REVIEW Download: 2008| View: 893| Comments: 0 | doi:10.20944/preprints201609.0091.v1
Subject: Life Sciences, Biotechnology Keywords: biomaterial; scaffold; protein; keratin; tissue engineering
Online: 26 September 2016 (10:25:01 CEST)
In tissue engineering scaffolds take the place of the natural extra cellular matrix (ECM). The natural ECM is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The design aspect along with the choice of the material for the artificial scaffold is very crucial to cell differentiation, adhesion, proliferation, and the transport of the growth factors or other bio molecular signals. In addition to the material and design of the scaffolds, it is necessary to replicate the normal physiological situation if the scaffold has to function as an implant. The cells have to be located in the porous scaffold to form a three dimensional assembly. The article discusses the important factors to be considered while designing a scaffold for tissue engineering and regenerative medicine.
Mon, 1 August 2016
REVIEW Download: 1862| View: 1347| Comments: 0 | doi:10.20944/preprints201608.0005.v1
Online: 1 August 2016 (12:08:36 CEST)
The Leguminosae (legume family) is divided into three sub-families, the Caesalpiniodeae, Mimosoideae and Papilionoideae. Here, the literature on legume-rhizobia symbioses was reviewed, and genotypically characterised rhizobia related to the taxonomy of the legumes they were isolated from. Only data from field soils were considered. The objective of the work was to assess to what extent legume specificity for rhizobial symbiont is related to legume taxonomy. Bradyrhizobium spp. were the exclusive rhizobial symbionts of species in the Caesalpinioideae but data are limited. Where tested, species within the two Mimosoideae tribes, Ingeae and Mimoseae were nodulated by different rhizobial genera. Generally, Papilionoideae species with indeterminate nodules were promiscuous in relation to rhizobial symbionts but high specificity for rhizobial partners appears to hold at tribe level for the Fabeae (Rhizobium spp.), genus level for Medicago (Ensifer spp.), Cytisus (Bradyrhizobium spp.) and Lupinus (Bradyrhizobium spp.), and species level for Galega spp. (Neorhizobium galegeae), Hedysarum coronarium (Rhizobium sullae), Cicer arietinum (Mesorhizobium spp.) and New Zealand native Sophora spp. (Mesorhizobium spp.). High legume specificity for rhizobial symbionts was linked to specific rhizobial symbiosis genes. For Papilionoideae species with determinate nodules, the Dalbergieae were primarily nodulated by Bradyrhizobium but were promiscuous with respect to Bradyrhizobium spp. while those in the Desmodieae, Phaseoleae, Psoraleae and Loteae were promiscuous across different rhizobial genera. Possible advantages and disadvantages of high specificity or promiscuity are discussed.
Mon, 21 August 2017
ARTICLE Download: 1805| View: 766| Comments: 0 | doi:10.20944/preprints201708.0070.v1
Subject: Life Sciences, Other Keywords: stretch-shortening cycle; countermovement jump; force-time curve variables; eccentric; concentric; volleyball
Online: 21 August 2017 (09:08:50 CEST)
The importance of vertical jump in sport fields and rehabilitation is widely recognized. Furthermore, Force-Time variables of vertical jump are factors affecting jumping height. Exclusive review of each of this variables, in eccentric and concentric phases, can lead to a specific focus on them during jumping exercises. So, the aims of his study were to a) reviewing the relationship between force-time curve variables of eccentric and concentric phases with jump height and b) description of this variables in Iran national youth volleyball players society. This is an observational study. 12 elite volleyball player (Male, Iran national youth volleyball players, 17±0.7 years) have participated in this study. Correlation between Force-Time variables - included peak force (PF), relative peak force (RPP), peak power (PP), average power (AP), relative peak power (RPP), and Modified Reactive Strength Index (MRSI) - in eccentric and concentric phases and ultimate jump height has been studied. Results showed that the average power (r=0.7) and relative peak force (r=0.75) of concentric phase and MRSI (r=0.83) have significant correlation with ultimate jump height (JH). Relative peak power and average power of concentric phase can massively effect Jump Height in sports like volleyball, which vertical jump is an integral part of them. Focus on both of these factors, which has been studied in this research, in training programs, can improve athlete jump performance significantly.
Mon, 22 January 2018
REVIEW Download: 1740| View: 359| Comments: 0 | doi:10.20944/preprints201801.0198.v1
Subject: Life Sciences, Biotechnology Keywords: extromphiles; extremophilic bacteria; enzymes; biotechnology application
Online: 22 January 2018 (10:22:21 CET)
Extremophilic bacteria are important groups of extremophilic organisms that have been studied during the last years. They are considered as a source of enzymes due to great diversity and can survive under extreme conditions. Many enzymes produced by these microorganisms are of great importance and have found applications in several industries. Due to their activity and stability under extreme conditions, these enzymes offer new alternatives for current biotechnological and industrial applications. They have a wide range of potential uses and have been a nuclear subject of many different investigations. To date, some of the enzymes produced by extremophilic bacteria are currently being assessed thier industrials applications. Despite, benefits that present these enzymes, their potentials remain largely unexplored. These enzymes pose new opportunities for new line of research, and biotechnological applications. This review provides a summary on diversity and biotechnological and industrial applications of some enzymes produced by extremophilic bacteria.
Thu, 27 October 2016
ARTICLE Download: 1611| View: 1629| Comments: 2 | doi:10.20944/preprints201610.0119.v1
Online: 27 October 2016 (11:50:52 CEST)
Rosette caused by rose rosette virus (RRV) is the most devastating malady of rose in the United States. Because of the recent discovery of the virus and the completion of Koch’s postulates all assumptions about the disease are based on visual observations of material that may or may have not been infected by the virus. This study addresses several aspects of virus and disease epidemiology. Twenty rose genotypes were screened for mite and/or virus resistance. Phyllocoptes fructiphilus the only known vector of RRV, was able to establish, lay eggs and develop to nymphs and adults in all genotypes. ‘Stormy Weather’ shows resistance to the virus as assessed by both mite and cleft-grafting transmission experiments. The acquisition/latent and inoculation access periods were studied revealing long acquisition/latent periods but rapid inoculation time frames. The outputs of this study will assist in the better management of the vector and the disease. The resistant genotype identified could be used in areas with high disease pressure to minimize spread and for identification of the mechanisms behind resistance or as breeding material to incorporate virus resistance to new cultivars. The short inoculation access period indicates that chemical control for the vector may be a challenging undertaking.
Wed, 19 July 2017
ARTICLE Download: 1563| View: 469| Comments: 0 | doi:10.20944/preprints201707.0053.v1
Subject: Life Sciences, Other Keywords: Black polyethylene, Mulches, Allium sativum, Growth, Grass
Online: 19 July 2017 (22:50:23 CEST)
A field experiment to assess the effect of mulch on growth (days to maturity, plant height, leaf length and leaf number) of Garlic (Allium Sativum L.) was conducted in 2015 - 2016 at Addis Ababa University Selale campus, on demonstration field to identify optimum plant growth using different mulches for Garlic tested independently. The experiment was designed using randomized complete block. The analyzed result using ANOVA shows significance difference among the treatments. Plots treated with black polyethylene mulch and grass mulch enhanced maturity by about 114 and 116 days, respectively, while garlic in control showed slightly delayed maturity of 125 days. Maximum plant height (66.5 cm) was recorded in the plants mulched by black polyethylene mulch followed by grass mulch which records 62.3 cm and 52.3 cm, respectively. A highly significant variation (p<0.05) in the leaf length was observed at the different mulch treatments. Significantly maximum leaf number (15.3) was recorded in plants mulched with black polyethylene followed by grass mulch with 14.0 leaf number. Thus, black polyethylene and grass mulch performs better than control treatment in growth parameter evaluation of garlic plants under fiche condition.
Fri, 30 September 2016
ARTICLE Download: 1498| View: 1008| Comments: 0 | doi:10.20944/preprints201609.0124.v1
Subject: Life Sciences, Molecular Biology Keywords: breast cancer; immunosuppressive factor; biomarker; online database
Online: 30 September 2016 (09:34:30 CEST)
To screen and validate immunosuppressive factors in luminal- and basal-like breast cancer cell lines and tissue samples associated with malignant phenotypes. The mRNA microarray datasets, GSE40057 and GSE1561, were downloaded and remodelled. Differentially expressed genes (DEGs) were identified. Enrichment analyses performed and the online resources, GOBO and Kaplan-Meier Plotter, were employed to screen for immunosuppressive factors associated with breast cancer malignant phenotypes. qRT-PCR and western blot were used to validate the expression of CD274 and IL8 in cell lines and immunohistochemical detected the MIF and VEGFA on tissue microarrays. The results showed that CD274 and IL8 were both upregulated in basal-like cell lines. That MIF expression was dramatically increased in patients with breast cancer metastases (p<0.05) and that VEGFA expression positively correlates with breast cancer pathologic grade (p<0.05).During the formation and development of breast cancer, immune-related genes are always activated, and immunosuppressive factors CD274, IL8, MIF and VEGFA are upregulated. Such molecules could be used as biomarkers for breast cancer prognosis. However, because individual immune-related factors can play several biological roles, the mechanistic relationship between immunosuppressive factors and breast cancer malignant phenotypes and the feasibility of their application as drug targets require further investigation.
Wed, 17 August 2016
ARTICLE Download: 1477| View: 1124| Comments: 0 | doi:10.20944/preprints201608.0162.v1
Subject: Life Sciences, Microbiology Keywords: bacterial ghosts (BGs); Vibrio parahaemolyticus; chemically induced lysis; minimum inhibition concentration (MIC); sodium hydroxide (NaOH); lipopolysaccharides (LPS); endotoxic activity; macrophages; cytotoxicity; cytokine
Online: 17 August 2016 (10:26:00 CEST)
Acellular bacterial ghosts (BGs) are empty non-living bacterial cell envelopes, commonly generated by controlled expression of the cloned lysis gene E of bacteriophage PhiX174. In this study, Vibrio parahaemolyticus ghosts (VPGs) were generated by chemically induced lysis and the method is based on minimum inhibitory concentration (MIC) of sodium hydroxide (NaOH), acetic acid, boric acid, citric acid, maleic acid, hydrochloric acid and sulfuric acid. The MIC values of the respective chemicals were 3.125, 6.25, < 50.0, 25.0, 6.25, 1.56 and 0.781 mg/ml. Except boric acid, the lysis efficiency was reached more than 99.99% at 5 min after treatment of all chemicals. Among those chemicals, NaOH-induced VPGs showed completely DNA-free that was confirmed by quantitative real-time PCR. Besides, lipopolysaccharides (LPS) extracted from the NaOH-induced VPGs showed no distinctive band on SDS-PAGE gel after silver staining. On the other hand, LPS extracted from wild-type bacterial cells as well as the organic acids-induced VPGs showed triple major bands and LPS extracted from the inorganic acids-induced VPGs showed double bands. It suggests that some surface structures in LPS of the NaOH-induced VPGs may be lost, weakened or modified by the MIC of NaOH. Nevertheless, Limulus amoebocyte lysate assay revealed that there is no significant difference in endotoxic activity between the NaOH-induced VPGs and wild-type bacterial cells. Macrophages exposed to the NaOH-induced VPGs at 0.5 × 106 CFU/mL showed cell viability of 97.9%, however the MIC of NaOH did not reduce the cytotoxic effect of wild-type bacterial cells. Like Escherichia coli LPS, the NaOH-induced VPGs are an excellent activator of pro-inflammatory cytokines (IL-1β and iNOS), anti-inflammatory cytokine (IL-10) and dual activities (IL-6) in the stimulated macrophage cells. On the other hand, the induction of TNF-α mRNA was remarkable in the macrophages exposed with wild-type cells. Scanning electron microscopy showed the formation of trans-membrane lysis tunnel structures in the NaOH-induced VPGs. SDS-PAGE and agarose gel electrophoresis also confirmed that cytoplasmic proteins and genomic DNA released from the VPGs to culture medium through the lysis tunnel structures. Taken together, all these results indicated that the NaOH-induced VPGs show the potency of safe, economical and effective inactivated bacterial vaccine candidate.
Mon, 20 March 2017
ARTICLE Download: 1459| View: 733| Comments: 0 | doi:10.20944/preprints201703.0150.v1
Subject: Life Sciences, Other Keywords: olive pomace oil; fatty acid profile; total nitrogen content; total protein; olive pomace; biochemical characterization
Online: 20 March 2017 (08:40:46 CET)
In this study, the olive pomace was considered because of its importance in the environment. So, this study carried out to estimate the total nitrogen content and the fatty acids profile of olive pomace. The olive pomace samples were collected from Irbid, Jarash, Ajloun and Mafraq during the harvesting season 2014 to study the biochemical characteristics of fatty acid composition and the total nitrogen (TN) content. The total nitrogen content was determined by standard Kjeldahl method and the fatty acid profile was detected by gas chromatography (GC). The results show that the total nitrogen content ranged from (0.39 ± 0.0) to (0.62 ± 0.02) with statistically significant difference suggesting that the composition of matrices and their percentage may be responsible for composition of amendments. The calculated total protein percentage ranged between (2.43 ± 0.00) to (3.87 ± 0.17). Also, 13 different fatty acids were quantitatively profiled and quantitated. Oleic acid (C 18:1) was found to be the highest percentage of all other fatty acids and ranged between (59.03%) and (63.81%), moreover the C 18:1/C 18:2 (oil quality) was calculated and C.V% showed variation meaning that nutritional implication could affect the oxidative stability of oils. In conclusion, OP by-product could give a sustainable and alternative-cheap source for fertilizers, pharmaceutical industries, cosmetics and other industries.
Thu, 4 August 2016
ARTICLE Download: 1422| View: 1133| Comments: 0 | doi:10.20944/preprints201608.0040.v1
Subject: Life Sciences, Microbiology Keywords: seeds; ELISA; Fusarium; morphological data analysis; mycotoxins; phylogenetic analysis S
Online: 4 August 2016 (10:12:54 CEST)
Adlay seed samples were collected from 3 adlay growing regions (Yeoncheon, Jeonnam and Eumseong regions) in Korea during 2012. Among all the samples collected, 400 seeds were tested for fungal occurrence by standard blotter and test tube agar methods and different taxonomic groups of fungal genera were detected. The most predominant fungal genera encountered were Fusarium, Phoma, Alternaria, Cladosporium, Curvularia, Cochliobolus and Leptosphaerulina. The occurrence of Fusarium species were 45.6% and based on the combined sequences of two protein coding genes, EF-1a, Beta-tubulin and phylogenetic analysis, 10 species were characterized as F. incarnatum (11.67%), F. kyushense (10.33%), F. fujikuroi (8.67%), F. concentricum (6.00%), F. asiaticum (5.67%), F. graminearum (1.67%), F. miscanthi (0.67%), F. polyphialidiom (0.33%), F. armeniacum (0.33%) and F. thapsinum (0.33%). The ability of these isolates to produce mycotoxins fumonisin (FUM) and zeralenone (ZEN) were tested by ELISA quantitative analysis method. The result revealed that fumonisin (FUM) was produced only by F. fujikuroi and zeralenone (ZEN) by F. asiaticum & F. graminearum. Mycotoxigenic species were then examined for their morphological characteristics to confirm their identity. Morphological observations of the species correlated well with their molecular identification and confirmed as F. asiaticum, F. fujikuroi and F. graminearum.
Thu, 3 November 2016
ARTICLE Download: 1327| View: 1386| Comments: 0 | doi:10.20944/preprints201611.0023.v1
Subject: Life Sciences, Other Keywords: anti-yeast; enzyme inhibitors; Terminalia mantaly; Combretaceae
Online: 3 November 2016 (09:35:17 CET)
The chemical investigation of the anti-yeast methanol extract from the stem bark of Terminalia mantaly led to the isolation of seven compounds: 3-O-methyl-4-O-α-rhamnopyranoside ellagic acid (1), 3-O-mehylellagic acid (2), arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid (3), arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid glucopyranoside (4), 2α,3α,24-trihydroxyolean-11,13(18)-dien-28-oïc acid (5), stigmasterol (6), stigmasterol 3-O-β-D-glucopyranoside (7). Their structures were established by means of spectroscopic analysis and comparison with published data. Compounds 1-5 were tested in vitro for activity against three pathogenic yeast isolates, Candida albicans, Candida parapsilosis and Candida krusei. The activity of compounds 1, 2 and 4 were comparable to that of the reference compound fluconazole (MIC values below 32 µg/ml) against the three tested yeast isolates. They were also tested for inhibitory properties against four enzymes of metabolic significance: Glucose-6-Phosphate Deshydrogenase (G6PD), human erythrocyte Carbonic anhydrase I and II (hCA I and hCA II), Glutathione S-transferase (GST). Compound 4 showed highly potent inhibitory property against the four tested enzymes with overall IC50 values below 4 µM and inhibitory constant (Ki) <3 µM.
Tue, 28 February 2017
REVIEW Download: 1310| View: 1139| Comments: 0 | doi:10.20944/preprints201702.0103.v1
Subject: Life Sciences, Molecular Biology Keywords: fructose; obesity; liver; aerobic exercise; strength exercise; combined exercise
Online: 28 February 2017 (12:02:06 CET)
Fructose consumption has been growing exponentially and, concomitant with this, the increase in the incidence of obesity and associated complications has followed the same behavior. Studies indicate that fructose may be a carbohydrate with greater obesogenic potential than other sugars. In this context, the liver seems to be a key organ for understanding the deleterious health effects promoted by fructose consumption. Fructose promotes complications in glucose metabolism, accumulation of triacylglycerol in the hepatocytes and alterations in the lipid profile, which, associated with an inflammatory response and alterations in the redox state, will imply a systemic picture of insulin resistance. However, physical exercise has been indicated for the treatment of several chronic diseases. In this review, we show how each exercise protocol (aerobic, strength or a combination of both) promote improvements in the obesogenic state created by fructose consumption as an improvement in the serum and liver lipid profile (HDL increase and decrease TG and LDL levels) and a reduction of markers of inflammation caused by an excess of fructose. Therefore, it is concluded that the practice of aerobic physical exercise, strength or a combination of both is essential for attenuating the complications developed by the consumption of fructose.
Mon, 1 May 2017
REVIEW Download: 1300| View: 592| Comments: 0 | doi:10.20944/preprints201705.0012.v1
Subject: Life Sciences, Other Keywords: Jivanti; Leptadenia reticulata; traditional medicine; herb; therapy; rasayana; galactagogue; pharmacology; biological activities; medicinal plant
Online: 1 May 2017 (10:25:26 CEST)
Leptadenia reticulata (Ritz.) Wight (Asclepiadaceae), a traditional medicinal plant species, is widely used in traditional medicine to treat various ailments such as tuberculosis, hematopoiesis, emaciation, cough, dyspnea, fever, burning sensation, night blindness, cancer, and dysentery. In Ayurveda, it is known for its revitalizing, rejuvenating, and lactogenic properties. This plant is one of the major ingredients in many commercial herbal formulations, including Speman, Envirocare, Calshakti, Antisept, and Chyawanprash. The therapeutic potential of this herb is because of the presence of diverse bioactive compounds such as α-amyrin, β-amyrin, ferulic acid, luteolin, diosmetin, rutin, β-sitosterol, stigmasterol, hentriacontanol, a triterpene alcohol simiarenol, apigenin, reticulin, deniculatin, and leptaculatin. However, most biological studies on L. reticulata are restricted to crude extracts, and many biologically active compounds are yet to be identified in order to claim the traditional uses of L. reticulata into evidence-based uses. At present, L. reticulata is a threatened endangered plant because of overexploitation, unscientific harvesting, and habitat loss. The increased demand from pharmaceutical, nutraceutical, and veterinary industries has prompted its large-scale propagation. However, its commercial cultivation is hampered because of the non-availability of genuine planting material and the lack of knowledge on its agronomical practices. In this regard, micropropagation technique will be useful to obtain true-to-type L. reticulata planting materials from an elite germplasm to meet the current demand. Adopting other biotechnological approaches such as synthetic seed technology, cryopreservation, cell culture, and genetic transformation can warrant conservation as well as increased metabolite production from L. reticulata. The present review summarizes scientific information on the botanical, agronomical, phytochemical, pharmacological, and biotechnological aspects of L. reticulata. This comprehensive information will certainly allow better utilization of this industrially important herb towards the discovery of lead drug molecules.
Fri, 29 July 2016
ARTICLE Download: 1265| View: 1119| Comments: 0 | doi:10.20944/preprints201607.0096.v1
Subject: Life Sciences, Other Keywords: number of paralogs; comparative genomics; combinatorial optimization; Mycoplasmas; Halophiles; Orientia; Mycobacterium leprae; genome size
Online: 29 July 2016 (16:24:29 CEST)
The existence of multiple copies of genes is a well-known phenomenon. A gene family is a set of sufficiently similar genes, formed by gene duplication. In earlier works conducted on limited number of completely sequenced and annotated genomes it was found that size of gene family and size of genome are positively correlated. Additionally, it was found that several atypical microbes deviated from the observed general trend. In this study, we reexamined these associations on a larger dataset consisting of 1484 prokaryotic genomes and using several ranking approaches. We applied ranking methods in such a way that genomes with lower number of paralogs would have lower rank. Until now only simple ranking methods were used; we applied the Kemeny optimal aggregation approach as well. Regression and correlation analysis were utilized in order to accurately quantify and characterize the relationships between measures of paralog indices and genome size. In addition, boxplot analysis was employed as a method for outlier detection. We found that, in general, all paralog indexes positively correlate with an increase of genome size. As expected, different groups of atypical prokaryotic genomes were found for different types of paralog quantities.
Fri, 23 September 2016
ARTICLE Download: 1258| View: 828| Comments: 0 | doi:10.20944/preprints201609.0080.v1
Subject: Life Sciences, Genetics Keywords: Anatolian Black; East Anatolian Red; South Anatolian Red; Turkish Grey; Holstein Friesian; Innate immunity; Next Generation Sequencing; TLR2; TLR4; TLR6
Online: 23 September 2016 (05:44:43 CEST)
In recent years, the focus of disease resistance and susceptibility studies in cattle have been on determining patterns in the innate immune response of key proteins, such as Toll-like receptors (TLR). In the bovine genome, there are 10 TLR family members and, of these, TLR2, TLR4 and TLR6 are specialized in recognition of bacterial ligands. Indigenous cattle breeds of Anatolia have been reported to show fewer signs of clinical bacterial infections, such as bovine tuberculosis and mastitis, and it is hypothesized that this might be due to a less stringent genetic selection during breeding. In contrast, Holstein-Friesian cattle have been under strong selection for milk production, which may have resulted in greater susceptibility to diseases. To test this hypothesis, we have compared the TLR2, TLR4 and TLR6 genes of Anatolian Black (AB), East Anatolian Red (EAR), South Anatolian Red (SAR), Turkish Grey (TG), and Holstein (HOL) cattle using Next Generation Sequencing. The SAR breed had the most variations overall, followed by EAR, AB, TG and HOL. TG had the most variations for TLR2 whereas SAR had the most variations in TLR4 and TLR6. We compared these variants with those associated with disease and susceptibility traits. We used exon variants to construct haplotypes, investigated shared haplotypes within breeds and determined candidate haplotypes for disease resistance phenotype in Anatolian cattle breeds.
Tue, 23 August 2016
REVIEW Download: 1238| View: 1254| Comments: 0 | doi:10.20944/preprints201608.0195.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: green anole; tail autotomy; regeneration; microRNAs; Anolis carolinensis
Online: 23 August 2016 (11:25:42 CEST)
Regeneration of lost tail is of great importance to lizards. Anolis carolinensis, a green lizard, is capable of regenerating its tail efficiently after autotomy. Hence, it is considered as a model organism in regeneration study. A. carolinensis shed its tail in order to distract the predator’s attention and thus makes a way to escape. Restoring of the amputated tail takes several days and the mechanism is currently clearly understood. Although save its life, tail regeneration is associated with the impairment of several vital functions in Anoles. In addition, various differences have been observed between original and regenerated tail in terms of mechanism and structure. To date, very little work has been conducted on tail autotomy and regeneration at molecular and genetic level. The genes responsible for regeneration in anoles are identified recently. These genes are evolutionarily conserved through all tetrapod vertebrates. They are, however, in a state of ‘switched-off’ in other vertebrates including humans. Consequently, a throughout study of these so called ‘switched-off’ genes may provide a way of restoring lost organs in human, and thus could revolutionize the modern medical science.
Tue, 20 December 2016
REVIEW Download: 1230| View: 907| Comments: 0 | doi:10.20944/preprints201612.0103.v1
Subject: Life Sciences, Molecular Biology Keywords: zebrafish; models; evaluation; drugs; cardiotoxicity; genotoxicity
Online: 20 December 2016 (10:34:56 CET)
Embryonic and larval Danio rerio is increasingly used as a toxicological model to conduct rapid in vivo tests and developmental toxicity assays; the zebrafish features as high genetic homology to mammals; robust phenotypes; and its value in high-throughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. New methodologies of genome editing as CRISPR/Cas9; ZFN or Talen make it a suitable model to perform studies to pair human genetic diseases as well. This review surveys recent studies; employing zebrafish as experimental model; comparing it with other in vivo and in vitro models; presenting zebrafish as a potent vertebrate tool to evaluate drug toxicity to facilitate more extensive; easy and comprehensive knowledge of new generation drugs.
Fri, 27 January 2017
ARTICLE Download: 1224| View: 635| Comments: 0 | doi:10.20944/preprints201701.0127.v1
Online: 27 January 2017 (03:55:50 CET)
The majority of polygenic selection signal of educational attainment GWAS hits is confined to a handful of SNPs within genomic regions replicated across GWAS publications. A polygenic score comprising 9 SNPs predicts population IQ (r=0.9), outperforming 99.9% of the polygenic scores obtained from sets of random SNPs. Its predictive power remains unaffected after controlling for spatial autocorrelation. Even random polygenic scores are moderate predictors of population IQ, and their predictive power increases logarithmically with the number of SNPs, indicating an exponential reduction in noise.Thus, the predictive power of polygenic scores has to be scaled in proportion to the number of SNPs composing them.
Fri, 6 January 2017
ARTICLE Download: 1208| View: 974| Comments: 0 | doi:10.20944/preprints201701.0033.v1
Subject: Life Sciences, Virology Keywords: H7N9 avian influenza; pseudovirus; neutralization assay; relative luminescence units (RLU)
Online: 6 January 2017 (10:21:52 CET)
In March 2013, a novel avian influenza A H7N9 virus was emerged in China, which cause rapidly progressive pneumonia and with a high fatality rate. Serologic studies to evaluate neutralizing antibodies of infected patients and birds are invaluable tools for immunogenicity research of H7N9 and epidemiological investigation. Conventional neutralization assays are laborious and time-consuming which also hampered by biosafety requirement. In this study, We construct and produce pseudovirus bearing the full-length hemagglutinin (HA) of H7N9 virus in the Env-defective, luciferase-expressing HIV-1 backbone. The production of lentiviral pseudovirus was analysed by HA gene specific real-time reverse-transcription PCR, transmission electron microscopy (TEM), and Western Blot assay to prove the nucleic acid replication, the morphology of virus, and the expression of HA protein in pseudovirus. After that pseudovirus based inhibition assay was established to detect neutralizing antibodies of a panel of serum samples. Our results demonstrated that H7N9 pseudovirus which had single-cycle infection was generated. By comparing the neutralization antibody titers, pseudovirus based neutralization test could be recognized as an alternative of conventional microneutralization (MN). Hence, we conclude that it is possible to use pseudovirus inhibition assay to screen sera samples, as well as evaluate vaccine-induced neutralizing antibodies against H7N9 virus.
Mon, 8 August 2016
ARTICLE Download: 1184| View: 986| Comments: 0 | doi:10.20944/preprints201608.0072.v1
Subject: Life Sciences, Biotechnology Keywords: forest residue; pretreatment; liquefaction; enzymatic hydrolysis/saccharification; fermentation; high titer bioethanol; detoxification
Online: 8 August 2016 (10:39:56 CEST)
This study evaluated batch fermentation modes, namely, separate hydrolysis and fermentation (SHF), Quasi-simultaneous saccharification and fermentation (Q-SSF), and simultaneous saccharification and fermentation (SSF), and fermentation conditions, i.e., enzyme and yeast loadings, nutrient supplementation and sterilization, on high titer bioethanol production from SPORL-pretreated Douglas-fir forest residue without detoxification. The result indicated Q-SSF and SSF were obviously superior to SHF operation in terms of ethanol yield. The enzyme loading showed a strong positive correlation between enzyme loading and the ethanol yield. The nutrient supplementation and sterility was not necessary for ethanol production from SPORL-pretreated Douglas-fir. The yeast loading showed no significant influence on the ethanol yield for typical SSF conditions. The terminal ethanol titer of 43.2 g/L, or 75.1% theoretical based on glucose, mannose, and xylose theoretical was achieved when SSF was conducted at the condition of following: whole slurry solids loading of 15%, enzyme loading of 20 FPU/g glucan, 1.8 g/kg (wet) yeast loading, without nutrition supplementation and sterilization, at 38°C, on shake flask at 150 rpm for 96h. It is believed that with mechanical mixing, enzyme loading can be substantially reduced with affect ethanol yield by using a long fermentation time.
Thu, 26 January 2017
ARTICLE Download: 1178| View: 1057| Comments: 0 | doi:10.20944/preprints201701.0117.v1
Subject: Life Sciences, Molecular Biology Keywords: blunt snout bream; high carbohydrate; transcriptome; metabolomics; insulin resistance; fatty liver disease
Online: 26 January 2017 (03:52:10 CET)
A high intake of carbohydrates, associated with obesity, is one of the major causes of fatty liver disease in humans. This study investigated how high carbohydrate intake induces fatty liver disease in Blunt snout bream (Megalobrama amblycephala). Blunt snout bream were fed a high-carbohydrate diet (HCBD) for 60 days. Their growth indices were evaluated, and the transcriptomes, metabolites, biochemistry, and histology of their blood and livers were analyzed. The final weight, weight gain, specific growth rate, and feed conversion ratio were all higher in the HCBD group than in the control group, but not significantly so (P > 0.05). The hepatosomatic index (HSI) differed significantly in the two groups (P < 0.05), and the metabolomics results showed that a high carbohydrate intake induced significant increases in plasma α/β-glucose, succinate, and tyrosine, which could increase hepatic glycogen and triglyceride. Low levels of betaine were also found in the livers of the HCBD group. The histology and blood biochemistry results suggested abnormal liver, with excessive lipid accumulation and liver damage. A transcriptome analysis and quantitative reverse transcription–PCR (RT–qPCR) indicated that the expression of the factors INSR, IRS, PI3K, PDK, AKT, ACC, IL6, AP1, ChREBP-MLX, PEPCK, and FBP in the insulin signaling pathway was significantly upregulated and that of SOCS3, GSK3β, and AMPK significantly downregulated in the HCBD. This pattern is associated with the nonalcoholic fatty liver disease (NAFLD) pathway. This study extends our understanding of how high carbohydrate causes increased fat deposition in the liver, enhanced glycolysis (α/β-glucose) in the plasma, and reduced betaine in the liver. This leads to activation of hepatocyte insulin resistance and lipogenesis by regulating the expression of genes related to fatty liver disease.
Mon, 8 January 2018
ARTICLE Download: 1169| View: 766| Comments: 0 | doi:10.20944/preprints201801.0055.v1
Subject: Life Sciences, Biotechnology Keywords: orange peel essential oil; green extraction; liquid whole eggs; biopreservation; shelf-life
Online: 8 January 2018 (09:22:37 CET)
A possible way to valorize citrus peels, which are byproducts of the juice extraction industry, is to use them as natural biopreservatives. In this paper we present early results from a compared Solvent Free Microwave Extraction (SFME) with Hydro-Distillation (HD) and Cold Pressing (CP) of essential oils (EOs) using fresh orange peel (Citrus sinensis L. var. Valencia late), a by-product in the production of orange juice in Algeria. The EOs were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). All extracted C. sinensis EOs were chemotype limonene (94.64 to 95.48%). SFME is performed without added any solvent or water. SFME increases EO yield and eliminate wastewater treatment, resulting in a great progress in terms of time and cost efficiency. In its second part, the present study was conducted to evaluate “in vitro”, the antioxidant activities of Solvent Free Microwave (SFM) extracted orange EO by using the DPPH• (2,2-di-phenyl-1-picrilhydrazyl) free radical scavenging assay. The ability of orange EO to scavenge the free radical DPPH• was high, exceeding 80%. The result of the DPPH assay gives an IC50 range value of 89.25 μg/mL (0.09 mg/mL) for the studied sample. Accordingly to the scientific literature, C. sinensis EO tested in the present study presented strong antioxidant activity, when looking to its values of AAI = 1.12 μg/mL. The feasibility of biopreservation used EOs as an alternative to synthetic techniques for liquid whole egg (LWE) stored under commercial retail conditions was investigated. The orange EO extracted by SFM was screened for its antibacterial and antioxidant activities in LWE at concentrations of 0.1, 0.3 and 0.5%. The TBA-RS results showed that the EO treatments significantly (p < 0.05) reduced the lipid oxidation in LWE. The long term oxidative, microbial and organoleptical stability of the LWE during display was positively influenced by orange EO treatments. Therefore, the results obtained here confirm that EO treatment as a promising technology to extend the commercial shelf-life of liquid egg products during retail/display.
Thu, 24 November 2016
ARTICLE Download: 1168| View: 910| Comments: 0 | doi:10.20944/preprints201611.0125.v1
Subject: Life Sciences, Virology Keywords: Lamin, EBV latency, transformation, epigenetic regulation, activated B cell
Online: 24 November 2016 (17:53:07 CET)
Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.
Sat, 8 October 2016
ARTICLE Download: 1155| View: 950| Comments: 0 | doi:10.20944/preprints201610.0021.v1
Subject: Life Sciences, Genetics Keywords: SET; I2PP2A; ZFX; transcriptional regulation; gynecologic cancers
Online: 8 October 2016 (10:52:00 CEST)
SET protein carries out multiple functions including those for protein phosphatase 2A (PP2A) inhibition, histone modification, DNA repair and gene regulation. SET overexpression has been detected in brain neurons of Alzheimer's disease patients, follicle theca cells of Polycystic Ovary Syndrome (PCOS) patients, and ovarian cancer cells, indicating that SET may play a pathological role for these disorders. SET transcript 2, produced by a specific promoter, represents a major transcript variant in different cell types. In this study, we characterized the transcriptional activation of human SET transcript 2 promoter in HeLa cells. Promoter deletion experiments and co-transfection assays indicated that ZFX, the Zinc finger and X-linked transcription factor, was able to transactivate the SET promoter. A proximal promoter region containing four ZFX-binding sites was found to be critical for the ZFX-mediated transactivation. Mutagenesis study indicated that the site located closest to the transcription start site accounted for most of the ZFX-mediated transactivity. Manipulation of ZFX levels by overexpression or siRNA knockdown confirmed the significance and specificity of the ZFX-mediated SET promoter activation. Chromatin immunoprecipitation results verified the binding of ZFX to its cognate site in the SET promoter. These findings have led to identification of ZFX as an upstream factor regulating SET gene expression. More studies are required to define the in vivo significance of this mechanism, and specifically, its implication for several benign and malignant diseases related to SET dysregulation.
Wed, 10 August 2016
ARTICLE Download: 1122| View: 1299| Comments: 0 | doi:10.20944/preprints201608.0111.v1
Subject: Life Sciences, Other Keywords: Erigeron floribundus; essential oil; antimicrobial; NadD; Trypanosoma brucei; cytotoxicity; antioxidant; limonene; caryophyllene oxide
Online: 10 August 2016 (12:36:57 CEST)
Erigeron floribundus (Asteraceae) is an herbaceous plant widely used in the Cameroonian traditional medicine to treat various diseases of microbial and non-microbial origin. In the present study we evaluated the in vitro biological activities displayed by the essential oil obtained from the aerial parts of E. floribundus, namely the antioxidant, antimicrobial and antiproliferative activities. Moreover, we investigated the inhibitory effects of E. floribundus essential oil on nicotinate mononucleotide adenylyltransferase (NadD), a promising new target for developing novel antibiotics, and Trypanosoma brucei, the protozoan parasite responsible for Human African trypanosomiasis. The essential oil composition was dominated by spathulenol (12.2%), caryophyllene oxide (12.4%) and limonene (8.8%). The E. floribundus oil showed a good activity against Staphylococcus aureus (IZD of 14 mm, MIC of 512 µg/mL). Interestingly, it inhibited the NadD enzyme from S. aureus (IC50 of 98 µg/mL), with no effects on mammalian orthologue enzymes. In addition, T. brucei proliferation was inhibited with IC50 values of 33.5 µg/mL with the essential oil and 5.6 µg/mL with the active component limonene. The essential oil exhibited strong cytotoxicity on HCT 116 colon carcinoma cells with an IC50 value of 14.89 µg/mL, and remarkable ferric reducing antioxidant power (TEAC= 411.9 μmol TE/g).
Mon, 24 October 2016
ARTICLE Download: 1101| View: 1150| Comments: 0 | doi:10.20944/preprints201610.0102.v1
Subject: Life Sciences, Microbiology Keywords: dental caries; Streptococcus mutans; lactic acid bacteria; biofilm; glucosyltransferases
Online: 24 October 2016 (09:37:48 CEST)
Consumption of refined foods and beverages high in sugar make the teeth susceptible to the formation of biofilm, and lead to dental caries and diseases of the oral cavity such as periodontitis and periodontal disease. The aim of the present study was to determine the ability of selected probiotics to inhibit growth and biofilm formation by the cariogenic bacterium Streptococcus mutans in vitro. We screened strains of latic acid bacteria (LAB) (n=120) from the Bioresources Collection and Research Center (BCRC), saliva of healthy adults and infant stool. The antimicrobial activity of LAB in vitro was evaluated by agar spot culture and co-culture of the S. mutans strains. We determined the effect of heating and dilution factors (2- and 4-fold) on the antagonistic activity of LAB. Antagonistic substances in the spent culture suspensions (SCS) of LAB were precipitated by extraction with ammonium sulphate and chloroform to characterise the protein and lipophilic fractions. Results of co-culturing show that the SCS of the three LAB strains (Lactobacillus pentosus 13-1, 13-4 and Lactobacillus crispatus BCRC 14618) subjected to heat treatment showed significantly high antimicrobial activity. We found that substances produced by L. pentosus 13-4 which have the potential to exhibit antimicrobial properties might be lipophilic proteins. Additionally, we infer that the mechanism of reducing biofilm formation by Lactobacillus strains is associated with sucrose-dependent cell–cell adhesion and the gtfC level of glucosyltransferases (Gtfs) in the biofilm. Native LAB strains screened in our study may be used in chewing gums and other processed foods for preventing tooth decay.
Thu, 23 February 2017
ARTICLE Download: 1093| View: 752| Comments: 0 | doi:10.20944/preprints201702.0085.v1
Subject: Life Sciences, Molecular Biology Keywords: alfalfa; drought; microRNA; small RNA; differential expression
Online: 23 February 2017 (09:50:07 CET)
Alfalfa, an important legume forage, is an ideal crop for sustainable agriculture and a potential bioenergy plant. Drought, one of the most common environmental stresses, substantially affects plants’ growth, development and productivity. MicroRNAs (miRNAs) are newly discovered gene expression regulators that have been linked to several plant stress responses. To elucidate the role of miRNAs in drought stress regulation of alfalfa, a high-throughput sequencing approach was used to analyze 12 small RNA libraries comprising of 4 samples, each with 3 biological replicates. We identified 348 known miRNAs, belonging to 80 miRNA families, from the 12 libraries and 281 novel miRNAs using Mireap software. 18 known miRNAs in roots and 12 known miRNAs in leaves were screened out as drought-responsive miRNAs. Except for miR319d and miR157a which were upregulated under drought stress, the expression pattern of drought-responsive miRNAs were different between roots and leaves in alfalfa. This is the first study discovering miR157a, miR1507, miR3512, miR3630, miR5213, miR5294, miR5368 and miR6173 are drought-responsive miRNAs. Target transcripts of drought-responsive miRNAs were computationally predicted. All 447 target genes for the known miRNAs were predicted using an online tool. This study provides a significant insight on understanding drought-responsive mechanisms of alfalfa.
Fri, 30 September 2016
ARTICLE Download: 1076| View: 861| Comments: 0 | doi:10.20944/preprints201609.0123.v1
Subject: Life Sciences, Biochemistry Keywords: carbonic anhydrase; acetylcholinesterase; β-Lactam; 2-Azetidinone; enzyme inhibition; enzyme purification
Online: 30 September 2016 (05:38:45 CEST)
β-Lactams are pharmacologically important compounds because of their various biological uses, including antibiotic and so on. β-Lactams were synthesized from benzylidene-inden derivatives and acetoxyacetyl chloride. The inhibitory effect of these compounds was also examined for human carbonic anhydrase I and II (hCA I, and II) and acetylcholinesterase (AChE). The results reveal that β-lactams are inhibitors of hCA I, II and AChE. The Ki values of β-lactams (2a-k) were 0.44-6.29 nM against hCA I, 0.93-8.34 nM against hCA II, and 0.25-1.13 nM against AChE. Our findings indicate that β-lactams (2a-k) inhibit both CA isoenzymes and AChE at low nanomolar concentrations.
Mon, 10 October 2016
REVIEW Download: 1076| View: 1030| Comments: 0 | doi:10.20944/preprints201610.0028.v1
Subject: Life Sciences, Biochemistry Keywords: mercury; antioxidants; cardiovascular diseases; cardiotoxicity; chelating agents
Online: 10 October 2016 (09:49:50 CEST)
Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence show that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.
Thu, 4 August 2016
REVIEW Download: 1059| View: 1010| Comments: 0 | doi:10.20944/preprints201608.0043.v1
Subject: Life Sciences, Virology Keywords: enveloped viruses; viral glycoproteins; endoplasmic reticulum-associated degradation; ERAD; unfolded protein response; UPR; ER stress
Online: 4 August 2016 (11:44:59 CEST)
Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed potentiating or inhibiting viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.
Mon, 17 July 2017
ARTICLE Download: 1052| View: 1334| Comments: 2 | doi:10.20944/preprints201707.0041.v1
Subject: Life Sciences, Other Keywords: pine nut; pine nut syndrome (PNS); pine mouth syndrome (PMS); non-wood forest products; Leptoglossus occidentalis (Western conifer seed bug); Sphaeropsis sapinea (sphaeropsis blight)
Online: 17 July 2017 (05:58:34 CEST)
Pine nuts are non-wood forest products (NWFP) with constantly growing market notwithstanding a series of phytosanitary issues and related trade problems. The aim of paper is to review the literature on the relationship between phytosanitary problems and trade development. Production and trade of pine nuts in Mediterranean Europe have been negatively affected by the spreading of Sphaeropsis sapinea (a fungus) associated to an adventive insect Leptoglossus occidentalis (fungal vector), with impacts on forest management activities, production and profitability and thus in value chain organization. Reduced availability of domestic production in markets with growing demand has stimulated the import of pine nuts. China has become a leading exporter of pine nuts, but its export is affected by a symptom associated to the nuts of some pine species: the ‘pine nut syndrome’ (PNS). Most of the studies embraced during the review are associated to PNS occurrence associated to the nuts of Pinus armandii. In the literature review we highlight the need for a comprehensive and interdisciplinary approach to the analysis of the pine nuts value chain organisation, where research on food properties and clinical toxicology be connected to breeding and forest management, forest pathology and entomology and trade development studies.
Thu, 8 June 2017
ARTICLE Download: 1046| View: 1631| Comments: 0 | doi:10.20944/preprints201706.0039.v1
Subject: Life Sciences, Genetics Keywords: educational attainment; polygenes; polygenic selection; IQ; GWAS
Online: 8 June 2017 (08:11:07 CEST)
Background: The genetic variants identified by three large genome-wide association studies (GWAS) of educational attainment and the largest intelligence GWAS were used to test a polygenic selection model. Methods: Average frequencies of alleles with positive effect (polygenic scores or PS) were compared across populations (N=26) using data from 1000 Genomes. Factor analysis was used to extract a signal of polygenic selection. Results: A polygenic selection factor of educational attainment GWAS hits is high among a handful of SNPs within genomic regions replicated across GWAS publications and it is highly correlated to the genetic intelligence factor (r= 0.96). These factors are both highly predictive of average population IQ (r=0.9), and are robust to tests of spatial autocorrelation. Several Monte Carlo simulations yielded highly significant p values. Furthermore, the polygenic selection model shows high replicability, with the EA and intelligence factor scores being virtually identical to those from an older study (r=0.96-0.99). A larger sample of populations (N=53) produced similar results. Conclusion: This study shows robust results after accounting for spatial autocorrelation and Monte Carlo simulation using random SNPs and shows robust reproducibility of results from a previous study.
Fri, 14 October 2016
ARTICLE Download: 1040| View: 1156| Comments: 0 | doi:10.20944/preprints201610.0054.v1
Subject: Life Sciences, Genetics Keywords: energy metabolism; respiration; fermentation; auxotrophy; retrograde response
Online: 14 October 2016 (10:58:50 CEST)
Background: The control of energy metabolism is fundamental for cell growth and function, and anomalies are implicated in complex diseases and ageing. It is important for cells to carefully tune metabolic pathways to optimize their function in response to different nutrient or physiological conditions. Metabolism in yeast cells can be easily manipulated by supplying different carbon sources: on glucose yeast rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. The growth medium and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in key energy metabolism pathways were coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that the acetyl-CoA synthase, rather than the citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: These systematic and targeted analyses provide a rich framework of the genetic and regulatory basis of fundamental metabolic states to guide future studies on energy metabolism in fission yeast and beyond. Our study pinpoints weaknesses of commonly used auxotroph mutants for investigating energy metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.
Mon, 13 February 2017
REVIEW Download: 1037| View: 925| Comments: 0 | doi:10.20944/preprints201702.0037.v1
Subject: Life Sciences, Other Keywords: tumor microenvironment; nanoparticle; nanotheronostics; probe; imaging
Online: 13 February 2017 (09:33:16 CET)
Long gone was the time when tumors were thought to be insular masses of cells, residing independently at specific sites in an organ. Now, researchers gradually realize that tumors interact with the extracellular matrix (ECM), blood vessels, connective tissues and immune cells in their environment, which is now known as the tumor microenvironment (TME). It is found that the interactions between tumors and their surrounding promote tumor growth, invasion and metastasis. The dynamics and diversity of TME cause the tumors to be heterogeneous and thus pose a challenge for cancer diagnosis, drug design and therapy. As TME is significant in enhancing tumor progression, it is vital to identify the different components in the TME. This review explores how different factors in the TME supply tumors with the required growth factors and signaling molecules to proliferate, invade and metastasis. We also examine the development of TME-targeted nanotheranostics over the recent years for cancer therapy, diagnosis and anticancer drug delivery system. This review further discusses the limitations and future perspective of nanoparticle based theranostics when used in combination with current imaging modalities like Optical Imaging, Magnetic Resonance Imaging (MRI) and Nuclear Imaging (PET and SPECT).
Thu, 29 December 2016
ARTICLE Download: 1033| View: 942| Comments: 2 | doi:10.20944/preprints201612.0142.v1
Subject: Life Sciences, Microbiology Keywords: aflatoxin B1; transaminases; hepatocellular carcinoma; Saudi patients; liver dysfunction
Online: 29 December 2016 (10:59:51 CET)
Background: Exposure to chronic low levels of aflatoxin B1 (AFB1) contamination can lead to immune suppression and nutritional consequences that might greatly contributed in the increase of hepatocellular carcinoma (HCC). The toxicity of AFB1 is greatly vary between different population, affected by age, gender, and environmental factors. Material and subjects: Aflatoxin B1 (AFB1) was measured in 50 blood samples collected from non B, C hepatitis viruses and non CMV-Ab liver disease patients from different general hospitals and polyclinic in KSA during period 01-2013 to 06-2014. All Patients demonstrate elevation of ALT and AST with unknown etiology. Serum samples were obtained and kept at −20 °C for AFB1detection. Results: Out of the 50 blood samples, 38 demonstrate a detectable serum level of AFB1 while the remaining 12 patients were AFB1 negative and used as control participants. While AST was non-significantly different in AFB1 exposed patients, ALT was significantly higher in AFB1 positive samples compared to control AFB1-negative. AFB1 was positively correlated with AST and ALT as liver function enzymes and with age as a risk factor of long duration of AFB1 chronic exposure. Multiple linear regression analysis ascertained the association between AFB1 chronic exposure and ALT increase in liver dysfunction Saudi patients. Conclusion: Measurement of elevated ALT as marker of liver injury in AFB1 chronically exposed Saudi patients can help to avoid the future development of HCC. Moreover, early detection of AFB1 exposure, together with early vaccination against HBV and HCV can remove the synergistic effects of these two etiological factors and thus decrease the risk of developing liver cancer.
Mon, 9 January 2017
REVIEW Download: 1032| View: 978| Comments: 0 | doi:10.20944/preprints201701.0046.v1
Subject: Life Sciences, Molecular Biology Keywords: cancer; microRNA; gene therapy; oncogene; tumor suppressor gene
Online: 9 January 2017 (10:24:03 CET)
MicroRNAs (miRNAs) are a kind of conserved small non-coding RNAs that participate in regulating gene expression by targeting multiple molecules. Early studies have shown that the expression of miRNAs changes significantly in different tumor tissues and cancer cell lines. It is well acknowledged that such variation is involved in almost all biological processes, including cell proliferation, mobility, survival and differentiation. Increasing experimental data indicate that miRNA dysregulation is a biomarker of several pathological conditions including cancer, and that miRNA can exert a causal role, as oncogenes or tumor suppressor genes, in different steps of the tumorigenic process. Anticancer therapies based on miRNAs are currently being developed with a goal to improve outcomes of cancer treatment. In our present study, we review the function of miRNAs in tumorigenesis and development, and discuss the latest clinical applications and strategies of therapy targeting miRNAs in cancer.
ARTICLE Download: 1030| View: 904| Comments: 0 | doi:10.20944/preprints201701.0040.v1
Subject: Life Sciences, Molecular Biology Keywords: Sarcocystis neurona; EPM; docking; apicomplexans; phylogeny; homology modeling
Online: 9 January 2017 (05:19:32 CET)
The apicomplexan parasite, Sarcocystis neurona causes the degenerative neurological equine protozoal myeloencephalitis (EPM) disease of horses. Due to its host range expansion, S. neurona is an emerging threat that requires close monitoring. In apicomplexans, protein kinases (PKs) have been implicated in a myriad of critical functions such as host cell invasion, cell cycle progression and host immune responses evasion. Here, we used various bioinformatics methods to define the kinome of S. neurona and phylogenetic relatedness of its PKs to other apicomplexans. Further, three-dimensional (3D) homology models for selected S. neurona putative PKs were constructed and evaluated for inhibitor docking. We identified 92 putative PKs clustering within the AGC, CAMK, CK1, CMGC, STE, TKL, aPK and OPK groups. Although containing the universally conserved PKA (AGC group), S. neurona kinome was devoid of PKB and PKC, but contained the six apicomplexan conserved CDPKs (CAMK group). The OPK group was represented by ROPKs 19A, 27, 30, 33, 35 and 37, but was devoid of the virulence-associated ROPKs 5, 6, 18 and 38. Two out of the three S. neurona CK1 enzymes had high sequence similarities to T. gondii TgCK1-α and TgCK1-β and the Plasmodium PfCK1. Docking of four inhibitors onto homology models of putative ROP27 and PKA indicated that inhibition of S. neurona PKs is feasible, but needs to be experimentally tested. The essentiality of apicomplexan PKs makes the elucidation of S. neurona kinome a key milestone for development of novel therapeutics for EPM.
Thu, 24 November 2016
ARTICLE Download: 1019| View: 950| Comments: 0 | doi:10.20944/preprints201611.0121.v1
Subject: Life Sciences, Other Keywords: tissue microarray; immunohistochemistry; cancer imaging; tyrosine kinase receptor; normal tissue; colon cancer
Online: 24 November 2016 (11:07:23 CET)
Targeted image-guided oncologic surgery (IGOS) relies on the recognition of cell surface-associated proteins, which should be abundantly present on the tumor cells but preferably absent on cells in surrounding healthy tissue. The transmembrane receptor tyrosine kinase EphA2, a member of the A class of the Eph receptor family, has been reported to be highly overexpressed in several tumor types including breast, lung, brain, prostate, and colon cancer, and is considered amongst the most promising cell membrane-associated tumor antigens by the NIH. Another member of the Eph receptor family belonging to the B class, EphB4, has also been found to be up-regulated in multiple cancer types. In this study, EphaA2 and EphB4 are evaluated as target for IGOS of colorectal cancer by immunohistochemistry (IHC) using a tissue microarray (TMA) consisting of 168 pairs of tumor and normal tissue. The IHC sections were scored for staining intensity and percentage of cells stained. The results show a significantly enhanced staining intensity and more widespread distribution in tumor tissue compared with adjacent normal tissue for EphA2 as well as EphB4. Based on its more consistently higher score in colorectal tumor tissue compared to normal tissue, EphB4 appears to be an especially promising candidate for IGOS of colorectal cancer.
Fri, 25 November 2016
ARTICLE Download: 1012| View: 816| Comments: 0 | doi:10.20944/preprints201611.0128.v1
Subject: Life Sciences, Other Keywords: time slice LC-SPE-NMR/MS; GC-MS; LC-MS/MS; triterpenoid saponins; Barbarea vulgaris
Online: 25 November 2016 (10:04:12 CET)
Recently the number of studies investigating triterpenoid saponins has drastically increased due to their diverse and potentially attractive biological activities. Currently the literature contains chemical structures of few hundreds of triterpenoid saponins of plant and animal origin. Triterpenoid saponins consist of a triterpene aglycone with one or more sugar moieties attached to it. However, due to similar physico-chemical properties, isolation and identification of a large diversity of triterpenoid saponins remain challenging. This study demonstrates a methodology to screen saponins using hyphenated analytical platforms, GC-MS, LC-MS/MS, and LC-SPE-NMR/MS, in the example of two different phenotypes of the model plant Barbarea vulgaris (winter cress), glabrous (G) and pubescent (P) type that are known to differ by their insect resistance. The proposed methodology allows for detailed comparison of saponin profiles from intact plant extracts as well as saponin aglycone profiles from hydrolysed samples. Continuously measured 1D proton NMR data during LC separation along with mass spectrometry data revealed significant differences, including contents of saponins, types of aglycones and numbers of sugar moieties attached to the aglycone. A total of 49 peaks were tentatively identified as saponins from both plants; they are derived from eight types of aglycones and with 2–5 sugar moieties. Identification of two previously known insect-deterrent saponins, hederagenin cellobioside and oleanolic acid cellobioside, demonstrated the applicability of the methodology for relatively rapid screening of bioactive compounds.
Tue, 31 January 2017
CASE REPORT Download: 1011| View: 922| Comments: 0 | doi:10.20944/preprints201701.0136.v1
Subject: Life Sciences, Biochemistry Keywords: Aquatic-toxic effects; EU chemical regulation; Glyoxal-containing cellulose ether
Online: 31 January 2017 (12:10:39 CET)
The objective of this study is to investigate the aquatic-toxic effects of glyoxal-containing cellulose ether with four different glyoxal concentrations (0, 1.4, 2.3 and 6.3%) in response to global chemical regulations, e.g., European Union Classification, Labeling and Packaging (EU CLP). Tests of the aquatic-toxic effects of glyoxal-containing cellulose ether on 11 freeze-dried microbial strains, Microcystis aeruginosa, Daphnia magna and zebrafish embryos were designed as an initial stage for toxicity screening, and were performed with the standardized toxicity test guidelines. Glyoxal-containing cellulose ether showed no significant toxic effects in the toxicity tests for the 11 freeze-dried microbial strains, Daphnia magna and zebrafish embryos. Alternatively, 6.3% glyoxal-containing cellulose ether led to more than a 60% reduction of Microcystis aeruginosa growth after 7 days of exposure. Approximately 10% developmental abnormalities (e.g., bent spine) in zebrafish embryos were also observed in the group exposed to 6.3% glyoxal-containing cellulose ether after 6 days of exposure. These results imply that <6.3% glyoxal-containing cellulose ether results in non-toxic effects on the acute toxicity of aquatic organisms. However, ≥6.3% glyoxal-containing cellulose ether may affect the health of aquatic organisms with long-term exposure. In order to better evaluate the eco-safety of cellulosic products contained in glyoxal, further studies regarding the toxic effects of glyoxal-containing cellulose ether with long-term exposure are required. The results from this study allow us to evaluate the auatic-toxic effects of glyoxal-containing cellulosic products, under EU chemical regulations, on the health of aquatic organisms.
Thu, 8 December 2016
ARTICLE Download: 1011| View: 978| Comments: 0 | doi:10.20944/preprints201612.0044.v1
Subject: Life Sciences, Biochemistry Keywords: Polyalthia suaveolens; Uvaria angolensis; Monodora tenuifolia; Plasmodium falciparum K1; toxicity; antimalarial
Online: 8 December 2016 (08:59:49 CET)
The present study aimed at investigating the in vitro and in vivo susceptibility of malaria parasites to crude extracts and fractions from Polyalthia suaveolens, Uvaria angolensis, and Monodora tenuifolia. The ethanolic extracts were prepared by maceration, and were further partitioned using water, dichloromethane, hexane, and methanol. The most promising fraction was subjected to column chromatography and the sub-fractions tested for activity in vitro. The antiplasmodial effect of extracts and fractions was tested against the Chloroquine resistant (PfK1) strain in 96 wells microtiter plate format using SYBR green florescence assay. The promising fraction was further assessed for cytotoxicity and acute toxicity in Swiss albino mice and subsequently against the rodent malaria parasite, P. berghei. Qualitative phytochemical screening was also performed on the promising fraction. The methanol fractions exerted the overall better effect with that of the twigs of P. suaveolens (PStw(Ace)) showing the highest potency with a IC50 value of 3.24 µg/mL followed by the fractions of leaf of M. tenuifolia (MoTel(Ace), IC50= 3.84 µg/ml) and stem bark of P. suaveolens (IC50= 4.90 µg/ml). The phytochemical screening showed the presence of alkaloids, lactones, and phenols in the more active fraction of P. suaveolens (PStw(Ace)). The chromatographic fractionation of this fraction led to 12 sub-fractions with PS8 sub-fraction being the most active (IC50= 4.42 µg/mL). In vivo, oral administration of 2000 mg/kg b.w of fraction PStw(Ace) in mice showed no signs of toxicity. Also, fraction PStw(Ace) at 400 mg/kg b.w exerted the highest suppressive effect against P. berghei strain B throughout the 4 days experiment (% parasitaemia below 5.2%). Overall, the results achieved supported the use of the three plants in the traditional treatment of malaria in Cameroon. More interestingly, the methanolic fraction of the twigs extract from P. suaveolens might be of interest in future development of an antimalarial phytodrug.
Thu, 17 November 2016
ARTICLE Download: 1000| View: 1051| Comments: 0 | doi:10.20944/preprints201611.0093.v1
Subject: Life Sciences, Molecular Biology Keywords: diabetes mellitus; cardiomyopathy; hyperglycemia; oxidative stress; aspalathin; Nrf2
Online: 17 November 2016 (11:07:56 CET)
Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.
Fri, 12 May 2017
ARTICLE Download: 981| View: 913| Comments: 0 | doi:10.20944/preprints201705.0106.v1
Subject: Life Sciences, Other Keywords: propolis; NIR spectroscopy; flavonoids; antioxidant capacity
Online: 12 May 2017 (05:53:14 CEST)
Propolis is a bee product widely used as a dietary supplement and included in sweets or baby foods due to its well-known antioxidant and nutritional properties that are directly correlated with its phenolic composition. For this reason, this study analysed the total contents of flavones and flavonols, flavanones and dihydroflavonols, and the antioxidant capacity by using the methods of ABTS and linoleic acid/β-carotene in 99 samples of propolis from Spain and Chile. A rapid method was developed for quantifying these parameters in raw propolis using near infrared (NIR) spectroscopy with an optical fibre probe of remote reflectance applied directly to the ground up sample. The models developed allow the determination of the total of flavones and flavonols (0-183 mg rutin/ g propolis), of the total of flavanones and dihydroflavonols (9-109 mg pinocembrin/ g propolis extract), and the antioxidant capacity by the ABTS method (0-3212 nmolesTrolox/ mg of propolis) and of linoleic acid/β-carotene (22-86% inhibition). The NIR spectroscopy models were applied in external validation to different samples of the calibration group, which led to the conclusion that the methods developed provide significantly identical data to the initial chemical data of reference.
Mon, 24 October 2016
ARTICLE Download: 979| View: 1233| Comments: 0 | doi:10.20944/preprints201610.0101.v1
Subject: Life Sciences, Immunology Keywords: reactive oxygen species (ROS); asthma; montelukast; long-acting β2 agonist (LABA); corticosteroid; monocyte
Online: 24 October 2016 (05:50:30 CEST)
Asthma is a chronic inflammatory airway disease induced by many environmental factors. The inhalation of allergens and pollutants promote the reactive oxygen species (ROS) production leading to airway inflammation, hyper-responsiveness and remodeling in allergic asthma. The effects of asthma medications on ROS production are unclear. The present study investigated the anti-ROS effects of current asthma medications including inhaled corticosteroid (ICS; budesonide and fluticasone), leukotriene receptor antagonist (LTRA; montelukast), long acting β2 agonists (LABAs; salmeterol and formoterol) and a new extra-LABA (indacaterol). The human monocyte cell line THP-1 cells were pre-treated with different concentrations of the asthma medications at different time-points after hydrogen peroxide (H2O2) stimulation. H2O2 production was measured with DCFH-DA by flow cytometry. Montelukast, fluticasone and salmeterol suppressed H2O2-induced ROS production. Indacaterol enhanced H2O2-induced ROS production. Budesonide and formoterol alone had no anti-ROS effects, but the combination of these two drugs significantly suppressed H2O2-induced ROS production. Different asthma medications have different anti-ROS effects on monocytes. The combination therapy with LABA and ICS seemed not be the only choice for asthma control. Montelukast may be also a good supplemental treatment for the poorly-controlled asthma because of its powerful anti-ROS effects. Our findings provide a novel therapeutic view in asthma.
Wed, 9 November 2016
REVIEW Download: 971| View: 785| Comments: 0 | doi:10.20944/preprints201611.0055.v1
Subject: Life Sciences, Biotechnology Keywords: hybridization analysis; nucleic acids; optical biosensors; electrochemical biosensors; micromechanical (piezoelectric) sensors
Online: 9 November 2016 (10:28:58 CET)
In review, the operating principles of the most common bio sensing devices, detection methods and the identification sensitivity of analyzed molecules were shown. The central focus was done on hybridization analysis of nucleic acids (NA), which are considered to be one of the most important analytes in terms of diagnostic point of view. Constructions enabling to transfer the fact of formation of nucleotide probe/target complex in to detectable signal by optical, electrochemical or micromechanical (piezoelectric) sensors were presented in this review.
Wed, 25 January 2017
ARTICLE Download: 965| View: 1028| Comments: 0 | doi:10.20944/preprints201701.0111.v1
Subject: Life Sciences, Molecular Biology Keywords: aldo-keto reductases; cigarette smoke; smokeless tobacco products; nicotine; oral cavity cells; xenobiotic metabolism
Online: 25 January 2017 (04:20:07 CET)
Smoking has been established as a major risk factor for developing oral squamous cell carcinoma (OSCC), but less attention has been paid to the effects of smokeless tobacco products. Our objective is to identify potential biomarkers to distinguish the biological effects of combustible tobacco products from those of non-combustible using oral cell lines. Normal human gingival epithelial cells (HGEC), non-metastatic (101A) and metastatic (101B) OSCC cell lines were exposed to different tobacco product preparations (TPPs) including cigarette smoke total particulate matter (TPM), whole-smoke conditioned media (WS-CM), smokeless tobacco extract in complete artificial saliva (STE), or nicotine (NIC) alone. We performed microarray-based gene expression profiling and found 3456 probe sets from 101A, 1432 probe sets from 101B, and 2717 probe sets from HGEC to be differentially expressed. Gene Set Enrichment Analysis (GSEA) revealed xenobiotic metabolism and steroid biosynthesis were the top two pathways that were upregulated by combustible but not by non-combustible TPPs. Notably, aldo-keto reductase genes, AKR1C1 and AKR1C2, were the core genes in the top enriched pathways and were statistically upregulated more than 8 fold by combustible TPPs. Our qRT-PCR results statistically support AKR1C1 as a potential biomarker for differentiating the biological effects of combustible from non-combustible tobacco products.
Thu, 29 December 2016
ARTICLE Download: 955| View: 896| Comments: 0 | doi:10.20944/preprints201612.0145.v1
Subject: Life Sciences, Biochemistry Keywords: ATP-dependent proteolysis, Non-native membrane proteins, Periplasmic domain, Crystal structure, Photosystem II.
Online: 29 December 2016 (17:16:52 CET)
Prompt removal of misfolded membrane proteins and misassembled membrane protein complexes is essential for membrane homeostasis. However, the elimination of these toxic proteins from the hydrophobic membrane environment has high energetic barriers. Transmembrane FtsH is the only known ATP-dependent protease responsible for this task, unlike other well-studied soluble ATP-dependent proteases. The mechanisms by which FtsH recognizes, unfolds, translocates, and proteolyzes its substrates remain unclear. Here, we report the crystal structures of the Thermotoga maritima FtsH periplasmic domain (PD) in an associative trimeric state at a 1.5-1.95 Å resolution. We also describe the pH-dependent oligomerization states of the isolated PD using dynamic light scattering. These observations help us understand how FtsH recognizes membrane-anchored misfolded proteins.
Mon, 16 January 2017
ARTICLE Download: 949| View: 872| Comments: 0 | doi:10.20944/preprints201701.0074.v1
Subject: Life Sciences, Molecular Biology Keywords: idiopathic pulmonary fibrosis; miR-30a; TET1; Drp-1
Online: 16 January 2017 (04:44:44 CET)
Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung ﬁbrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.
Thu, 17 November 2016
ARTICLE Download: 943| View: 929| Comments: 0 | doi:10.20944/preprints201611.0094.v1
Subject: Life Sciences, Molecular Biology Keywords: diabetes mellitus; hyperglycemia; cardiomyopathy; lipid toxicity; polyphenols; aspalathin
Online: 17 November 2016 (11:19:37 CET)
Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocytes model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 hours before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. STRING analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, Cd36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results propose that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.
REVIEW Download: 940| View: 979| Comments: 0 | doi:10.20944/preprints201611.0087.v1
Online: 17 November 2016 (10:40:58 CET)
Oxidative stress occurs when cells are exposed to elevated levels of reactive oxygen species that could damage biological molecules. One bacterial response to oxidative stress involves disulfide bond formation either between protein thiols or between protein thiols and low-molecular-weight thiols. Bacillithiol was recently identified as a major low-molecular-weight thiol in Bacillus subtilis and related Firmicutes. Four genes (bshA, bshB1, bshB2 and bshC) are involved in bacillithiol biosynthesis. The bshA and bshB1 genes are part of a seven-gene operon (ypjD), which includes the essential gene cca, encoding CCA-tRNA nucleotidyltransferase. The inclusion of cca in the operon containing bacillithiol biosynthetic genes suggests that the integrity of the 3’ terminus of tRNAs may also be important in oxidative stress. Addition of the 3´ terminal CCA sequence by CCA-tRNA nucleotidyltransferase to give a mature tRNA and functional molecules ready for aminoacylation plays an essential role during translation and expression of the genetic code. Any defects in these processes, for example, the accumulation of shorter and defective tRNAs under oxidative stress, could exert a deleterious effect on cells. This review summarizes the physiological link between tRNACys regulation and oxidative stress in Bacillus.
Thu, 4 May 2017
ARTICLE Download: 924| View: 627| Comments: 0 | doi:10.20944/preprints201705.0041.v1
Subject: Life Sciences, Microbiology Keywords: core-shell; disinfection; Escherichia coli; nanoparticles; pathogens; silver; solar-photocatalysis; Staphylococcus aureus; water; zinc oxide
Online: 4 May 2017 (11:32:16 CEST)
Water borne pathogens present a threat to human health and their disinfection from water poses a challenge, prompting search for newer methods and newer materials. Disinfection of Gram-negative bacterium Escherichia coli and Gram-positive coccal bacterium Staphylococcus aureus in aqueous matrix was achieved within 60 and 90 minutes respectively at 35⁰C using solar-photocatalysis mediated by sonochemically synthesized [email protected] core-shell nanoparticles. The efficiency of the process increased with increase in temperature and at 55⁰C the disinfection could be achieved in 45 and 60 min respectively for the two bacteria. A new ultrasound assisted chemical precipitation technique was used for the synthesis of [email protected] core-shell nanoparticles. The characteristics of the synthesized material were established using physical techniques. The material remained stable even at 400o C. Disinfection efficiency of the [email protected] core-shell nanoparticles was confirmed in case of real world water samples from pond, river, municipal tap and was found to be better than that of pure ZnO and TiO2 (Degussa P25). When the nanoparticle based catalyst was recycled and reused for subsequent disinfection experiments, its efficiency did not change remarkably even after three cycles. The sonochemically synthesized [email protected] core-shell nanoparticles have a good potential for application in solar photocatalytic disinfection of water borne pathogens.
Wed, 12 October 2016
ARTICLE Download: 922| View: 848| Comments: 0 | doi:10.20944/preprints201610.0041.v1
Subject: Life Sciences, Microbiology Keywords: RNA; DNA; Repetitive sequences; RNA stem loops; RNA group identities
Online: 12 October 2016 (10:58:59 CEST)
Current knowledge of the RNA world indicates two different genetic codes being present throughout the living world. In contrast to non-coding RNAs that are built of repetitive nucleotide syntax, the sequences that serve as templates for proteins share – as main characteristics – a non-repetitive syntax. The differences in their syntax structure is coherent with the difference of the functions they represent. Whereas non-coding RNAs build groups that serve as regulatory tools in nearly all genetic processes, the coding sections represent the evolutionarily successful function of the genetic information storage medium. The DNA genomes themselves are rather inactive, whereas the non-coding RNA domain is highly active, even as non-random genetic innovation operators. This indicates that repetitive syntax is the essential pre-requisite for RNA interactions to install variable RNA-group-identities, whereas the non-repetitive syntax serves as a stable conservation tool for successful selection processes out of RNA-groups cooperation and competition. The interaction opportunities of RNA loops with repetitive syntax are higher than with non-repetitive ones. Interestingly, these two genetic codes resemble the function of all natural languages, i.e., (a) everyday language use for organization and coordination of biotic group behavior, and (b) artificial (instrumental) language use for conservation of blueprints for complex protein-body constructions.
Tue, 2 August 2016
OPINION Download: 920| View: 1175| Comments: 0 | doi:10.20944/preprints201608.0016.v1
Subject: Life Sciences, Molecular Biology Keywords: parallel DNA; antiparallel DNA; PCR; CRISPR; nucleic acid hybridization; microarray; siRNA
Online: 2 August 2016 (10:42:27 CEST)
Many fundamental molecular techniques (PCR, Microarray, Southern and northern hybridization, siRNA, CRISPR/Cas9 etc.) developed so far shows errors. I wish to highlight these molecular techniques are developed on basis of Watson-Crick DNA model, ignoring the concept of parallel stranded DNA. Through this opinion article, I wish to highlight specificity and accuracy of these molecular techniques can be enhanced by considering both parallel and anti parallel hybridization of DNA. Hopefully my views will also solve issue of irreproducibility in life science research.
Mon, 6 March 2017
ARTICLE Download: 919| View: 1200| Comments: 0 | doi:10.20944/preprints201703.0026.v1
Subject: Life Sciences, Molecular Biology Keywords: ovarian cancer; melatonin; angiogenesis; VEGF; VEGFR; HIF-1α
Online: 6 March 2017 (06:34:02 CET)
Angiogenesis is a hallmark of ovarian cancer (OC) it promotes rapid cell growth and the associated metastasis. Identifying new bioactive compounds to target angiogenesis may provide valuable paradigms as therapeutic strategies. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa. After the rats developed serous papillary OC, half of the animals received i.p. injections of melatonin (200 µg/100 g body weight/day) for 60 days. Serum levels of melatonin were higher following therapy, and the expression of its receptor MT1R was significantly increased in OC-bearing rats, regardless of ethanol intake. TGFB1, a transforming growth factor-beta1, was reduced only after melatonin treatment. Importantly, vascular endothelial growth factor (VEGF) was severely reduced after melatonin therapy in animals given or not given ethanol. Conversely, the levels of VEGF receptor 1 (VEGFR1) was diminished after ethanol consumption, regardless of melatonin therapy, and VEGFR2 was only reduced following melatonin. Hypoxia-inducible factor (HIF)-1α was augmented with ethanol consumption, and notably, melatonin significantly reduced their levels. Collectively, our results suggest that melatonin attenuates angiogenesis in OC of an animal model of ethanol consumption; this provides a possible complementary therapeutic opportunity for concurrent OC chemotherapy.
Wed, 17 May 2017
REVIEW Download: 916| View: 647| Comments: 0 | doi:10.20944/preprints201705.0129.v1
Subject: Life Sciences, Biophysics Keywords: cell fate decision; cancer attractors; gene network dynamics; EMT; drug resistance; intrinsically disordered proteins
Online: 17 May 2017 (06:25:17 CEST)
Waddington’s epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of “landscape” in the context of dynamical system theory represents a high-dimensional cell state space, in which each cell phenotype is considered as an “attractor” that is determined by interactions among multiple variables (molecular players), and is buffered against environmental fluctuations. Further, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes. Here, we discuss these phenotypic transitions in cancer from a dynamical systems perspective and invoke the concept of “cancer attractors” – hidden stable states of the underlying regulatory network that are not occupied by normal cells. Using epithelial-to-mesenchymal transition (EMT), cancer stem-like properties, metabolic reprogramming and the emergence of drug/hormone resistance as examples, we illustrate how phenotypic plasticity in cancer cells enables them to acquire hybrid phenotypes (such as hybrid epithelial/mesenchymal and hybrid metabolic phenotypes) that tend to be more aggressive and notoriously resilient to drug/hormone treatment. Furthermore, we highlight multiple factors that may give rise to phenotypic plasticity in cancer cells, such as (a) multi-stability or oscillatory behaviors governed by underlying regulatory networks involved in cell-fate decisions in cancer cells, and (b) network rewiring due to conformational dynamics of intrinsically disordered proteins (IDPs) that are highly enriched in cancer cells. We conclude by discussing why a therapeutic approach that promotes ‘recanalization’, i.e. the exit from “cancer attractors” and re-entry into “normal attractors”, is more likely to succeed rather than a conventional approach that targets individual molecules/pathways.
Tue, 11 December 2018
ARTICLE Download: 915| View: 4484| Comments: 0 | doi:10.20944/preprints201812.0137.v1
Subject: Life Sciences, Other Keywords: microscopy, fluorescence, machine learning, deep learning, inverse problems, image reconstruction, image restoration, super-resolution, deconvolution, spectral unmixing
Online: 11 December 2018 (17:03:14 CET)
Deep Learning is a recent and important addition to the computational toolbox available for image reconstruction in fluorescence microscopy. We review state-of-the-art applications such as image restoration, super-resolution, and light-field imaging, and discuss how the latest Deep Learning research can be applied to other image reconstruction tasks such as structured illumination, spectral deconvolution, and sample stabilisation. Despite its successes, Deep Learning also poses significant challenges, has often misunderstood capabilities, and overlooked limits. We will address key questions, such as: What are the challenges in obtaining training data? Can we discover structures not present in the training data? And, what is the danger of inferring unsubstantiated image details?
Mon, 30 October 2017
REVIEW Download: 912| View: 924| Comments: 0 | doi:10.20944/preprints201710.0185.v1
Subject: Life Sciences, Biochemistry Keywords: epigenome; DNA modification; cytosine methylation; gene regulation; histone modification; 5-methylcytosine; stress response
Online: 30 October 2017 (15:55:41 CET)
Genome-wide epigenetic changes in plants are being reported during the development and environmental stresses, which are often correlated with gene expression at the transcriptional level. Sum total of the biochemical changes in nuclear DNA, post-translational modifications in histone proteins and variations in the biogenesis of small non-coding RNAs in a cell is known as epigenome. These changes are often responsible for variation in expression of the gene without any change in the underlying nucleotide sequence. The changes might also cause variation in chromatin structure resulting into the changes in function/activity of the genome. The epigenomic changes are dynamic with respect to the endogenous and/or environmental stimuli which affect phenotypic plasticity of the organism. Both, the epigenetic changes and variation in gene expression might return to the pre-stress state soon after withdrawal of the stress. However, a part of the epigenetic changes may be retained which is reported to play role in acclimatization, adaptation as well as in the evolutionary processes. Understanding epigenome-engineering for improved stress tolerance in plants has become essential for better utilization of the genetic factors. This review delineates the importance of epigenomics towards possible improvement of plant’s responses to environmental stresses for climate resilient agriculture.
Wed, 5 October 2016
ARTICLE Download: 902| View: 828| Comments: 0 | doi:10.20944/preprints201610.0012.v1
Online: 5 October 2016 (15:08:32 CEST)
Bio-molecular reagents like antibodies required in experimental biology are expensive and their effectiveness, among other things, is critical to the success of the experiment. Although such resources are sometimes donated by one investigator to another through personal communication between the two, there is no previous study to our knowledge on the extent of such donations, nor a central platform that directs resource seekers to donors. In this paper, we describe, to our knowledge, a first attempt at building a web-portal titled Bio-Resource Exchange that attempts to bridge this gap between resource seekers and donors in the domain of experimental biology. Users on this portal can request for or donate antibodies, cell-lines and DNA Constructs. This resource could also serve as a crowd-sourced database of resources for experimental biology. Further, in order to index donations outside of our portal, we mined scientific articles to find instances of donations of antibodies and attempted to extract information about these donations at the finest granularity. Specifically, we extracted the name of the donor, his/her affiliation and the name of the antibody for every donation by parsing the acknowledgements sections of articles. To extract annotations at this level, we propose two approaches – a rule based algorithm and a bootstrapped relation learning algorithm. The algorithms extracted donor names, affiliations and antibody names with average accuracies of 57% and 62% respectively. We also created a dataset of 50 expert-annotated acknowledgements sections that will serve as a gold standard dataset to evaluate extraction algorithms in the future. Contact: [email protected], [email protected] Database URL: http://tonks.dbmi.pitt.edu/brx Supplementary information: Supplementary data are available at Database online.
Wed, 10 August 2016
ARTICLE Download: 900| View: 968| Comments: 0 | doi:10.20944/preprints201608.0114.v1
Subject: Life Sciences, Biophysics Keywords: 8-OHdG (8-hydroxy- 2-deoxyguanosine), vitamin A, vitamin C, vitamin E, ROS (reactive oxygen species), TAS (total antioxidant status)
Online: 10 August 2016 (16:49:20 CEST)
The present study was aimed to evaluate the levels of oxidative stress markers in breast diseases by measuring the 8-hydoxy-2-deoxyguanosine (8-OHdG), vitamin A, vitamin C, vitamin E and total antioxidant status (TAS) alterations in relation to cell proliferation activity and disease progression. Significant increases in the level of oxidative damage marker 8-OHdG and cell proliferation activity were observed in breast carcinoma patients in comparison to benign and normal controls, which were accompanied by significant decrease in non enzymatic antioxidants and TAS concentrations. 8-OHdG and cell proliferation level were negatively correlated with non enzymatic antioxidants viz., Vitamin A, Vitamin C, vitamin E level and total antioxidant activity. Altered levels of biomarkers of oxidative stress and cell proliferation activity amongst the malignant, benign and controls suggest a correlation of increased oxidative stress and cell proliferation activity in the progression of disease in breast carcinoma patients. Among the oxidative stress markers and cell proliferation index, decreased level of vitamin A, vitamin C, vitamin E, TAS and increased level of 8-OHdG, cell proliferation index emerged as best predicted biomarkers for subjects with malignancy and benign breast disease.
Fri, 1 February 2019
ARTICLE Download: 898| View: 2215| Comments: 0 | doi:10.20944/preprints201902.0004.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: artificial intelligence; machine learning; live-cell imaging; super-resolution microscopy; classification; segmentation
Online: 1 February 2019 (09:00:39 CET)
Artificial Intelligence based on Deep Learning is opening new horizons in Biomedical research and promises to revolutionize the Microscopy field. Slowly, it now transitions from the hands of experts in Computer Sciences to researchers in Cell Biology. Here, we introduce recent developments in Deep Learning applied to Microscopy, in a manner accessible to non-experts. We overview its concepts, capabilities and limitations, presenting applications in image segmentation, classification and restoration. We discuss how Deep Learning shows an outstanding potential to push the limits of Microscopy, enhancing resolution, signal and information content in acquired data. Its pitfalls are carefully discussed, as well as the future directions expected in this field.
Thu, 11 May 2017
ARTICLE Download: 882| View: 699| Comments: 0 | doi:10.20944/preprints201705.0095.v1
Subject: Life Sciences, Other Keywords: indigenous goats; free range; milk production; milk composition
Online: 11 May 2017 (07:52:28 CEST)
This study was conducted to evaluate the yield and quality parameters of milk from 60 indigenous South African goats of different genotypes namely Nguni, Boer and Non- descript reared under a free ranging system. Milk yield and quality parameters (milk fat, protein, lactose, solid non-fat and minerals) from Nguni (10), Boer (10) and Non-descript (10) goats was measured and analysed per week at each stage of lactation. Result showed that, Nguni goats produced (1.2±0.09, 1.3±0.11 and 1.2±0.07 litres per day) more milk (P ˂ 0.05) at early, mid and late stages of lactation than Boer (0.6±0.10, 1.0±0.17 and 0.6±0.09 litres per day) and Non-descript (0.3±0.10, 0.3±0.12 and 0.3±0.09 litres per day) goats, respectively. The mean value of milk fat, protein and lactose content from Nguni goat was (3.98, 3.54 and 5.31); Boer goat (2.9, 3.59 and 5.04) and Non-descript goat (4.05, 3.39 and 5.02), respectively. There was significant effect (P ˂ 0.05) of genotypes on milk fat, milk magnesium and sodium contents of Nguni, Boer and Non-descript goats. It could be concluded that, Nguni goat produced more milk than Boer and Non-descript goats, but the Non-descript goat had higher mean percentage of milk fat compared to Nguni and Boer goats.
Thu, 16 February 2017
ARTICLE Download: 880| View: 941| Comments: 0 | doi:10.20944/preprints201702.0063.v1
Subject: Life Sciences, Microbiology Keywords: Hydrogen Peroxide; Legionella; Hospital; Disinfection
Online: 16 February 2017 (18:48:27 CET)
Objectives: To evaluate the effectiveness of hydrogen peroxide (HP) use in the hospital water network disinfection to control Legionella spp. colonization. Methods: Following the detection of high levels of Legionella contamination in a 136-bed general hospital water network, an HP treatment of the hot water (25 mg/L) was adopted. During a period of 34 months, the effectiveness of HP on Legionella colonization was assessed. Legionella was isolated in accordance with ISO-11731 and identification was carried out by sequencing of the mip gene. Results: Before HP treatment L.pneumophila sg 2-15 was isolated in all sites with a mean count of 9950±8279 CFU/L. After one month of HP-treatment, we observed the disappearance of L. pneumophila 2-15, however other Legionella species never cultured before appeared; Legionella pneumophila 1 was isolated in 1 out of 4 sampling sites (2,000 CFU/L) and other non-pneumophila species in all sites (mean load 3,000 ±2887 CFU/L). Starting from September 2013, HP-treatment was modified adding food-grade polyphosphates and in the following months we observed a progressive reduction of the mean load of all species (p<0.05), until to a substantial disappearing of Legionella colonization. Conclusion: Hydrogen peroxide demonstrated a good efficacy in controlling Legionella. Although in the initial phases of treatment it seemed unable to eliminate all the species, by keeping HP levels to 25 mg/L and adding food-grade polyphosphates, a progressive and complete control of colonisation was obtained.
Fri, 21 April 2017
REVIEW Download: 877| View: 583| Comments: 0 | doi:10.20944/preprints201704.0135.v1
Subject: Life Sciences, Biochemistry Keywords: GPCR; ubiquitination; β-arrestin; deubiquitinating enzyme; E3 ubiquitin ligase
Online: 21 April 2017 (06:23:26 CEST)
G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors that control many cellular processes and consequently often serve as drug targets. These receptors undergo a strict regulation by mechanisms such as internalization and desensitization, which are strongly influenced by posttranslational modifications. Ubiquitination is a posttranslational modification with a broad range of functions that is currently gaining increased appreciation as a regulator of GPCR activity. The role of ubiquitination in directing GPCRs for lysosomal degradation has already been well-established. Furthermore, this modification can also play a role in targeting membrane and endoplasmic reticulum-associated receptors to the proteasome. Most recently, ubiquitination was also shown to be involved in GPCR signaling. In this review, we present current knowledge on the molecular basis of GPCR regulation by ubiquitination, and highlight the importance of E3 ubiquitin ligases, deubiquitinating enzymes and β-arrestins. Finally, we discuss classical and newly-discovered functions of ubiquitination in controlling GPCR activity.
Wed, 2 November 2016
ARTICLE Download: 869| View: 903| Comments: 0 | doi:10.20944/preprints201611.0015.v1
Subject: Life Sciences, Biophysics Keywords: cardiac transmural heterogeneity; electromechanical coupling; mechano-calcium-electric feedback; cardiac modeling; cardiomyocyte
Online: 2 November 2016 (06:58:53 CET)
Myocardial heterogeneity is an attribute of the normal heart. We have developed integrative models of cardiomyocytes from the subendocardial (ENDO) and subepicardial (EPI) ventricular regions that take into account experimental data on specific features of intracellular electromechanical coupling in the guinea pig heart. The models adequately simulate experimental data on the action potential and contraction of the ENDO and EPI cells. The modeling results predict that heterogeneity in the parameters of calcium handling and myofilament mechanics in isolated ENDO and EPI cardiomyocytes via cooperative mechanisms of mechano-calcium-electric feedback are essential to produce the differences in Ca2+ transients and contraction profiles and may further enhance transmural differences in the electrical properties between the cells. Simulation results predict that ENDO cells have greater sensitivity to changes in afterload than EPI cells. These data are important for understanding the behavior of cardiomyocytes in the intact heart.
Wed, 4 January 2017
HYPOTHESIS Download: 867| View: 1505| Comments: 0 | doi:10.20944/preprints201701.0016.v1
Subject: Life Sciences, Molecular Biology Keywords: symbiogenesis; eukaryogenesis; RNA world; expensive brain; human evolution; hydrothermal vent
Online: 4 January 2017 (07:34:07 CET)
Currently there is little doubt left on the symbiogenetic nature of eukaryotes - genomes of archaeon and bacterium participated in shaping a genome of last eukaryotic common ancestor in equal albeit asymmetric manner, while a merger event itself indicated the advent of a new domain of life. The “symbiogenetic” framework of interaction of two partners is proposed, outlining similar steps essential for three major advents: the origin of life, the origin of complex life and the origin of humans. Given the immense importance of proper energy source for the evolution of life it seems plausible that for any principal increase in complexity, a partnership with a novel energy donor is required. Moreover, a “language” elaborated in the course of communication of partners might have been a prerequisite for a subsequent increase in complexity. Transitions, which led to RNA-protein world, eukaryotes and human brain, resulted in advent of complex languages via communication onsets between two entities in close partnership. Accordingly this further facilitated formation of first cells, multicellular organisms and human society.
Fri, 2 June 2017
ARTICLE Download: 864| View: 738| Comments: 0 | doi:10.20944/preprints201706.0015.v1
Subject: Life Sciences, Molecular Biology Keywords: gibberellin; photoperiod; mutant; floral induction; flowering time
Online: 2 June 2017 (07:45:32 CEST)
Flower bud formation and flowering in chrysanthemum occur under short day conditions (SD), but the molecular basis for the switch to reproductive growth is less well understood than in model plants. Here, a spontaneous mutant able to flower under long days is described. In an attempt to reveal the pathway(s) involved in the formation of flower buds under contrasting daylengths, transcriptome sequencing was carried out in plants grown both under SD and under long day conditions (LD). A number of differentially transcribed genes involved in the various known flowering pathways were identified. Both circadian clock genes and CmFTL3 were up-regulated under SD, thereby inducing floral bud formation and flowering. The gibberellin (GA) signalling pathway-related genes GA20ox and GID1 were up-regulated in the mutant under LD, while the catabolic gene GA2ox and GAI was down-regulated, thereby inducing the transcription of CmFTL1, SOC1 and LFY. The GA content of the leaf was higher in the mutant than in the wild type under LD. When treated with GA, the mutant flowered earlier under both SD and LD, but there was no other detectable phenotype difference between the two lines. The indication was that the photoperiod pathway majorly regulates flower bud formation and flowering time in chrysanthemum under SD. GA signalling pathway only plays a subsidiary role for flowering. However, the GA signalling pathway predominated for flowering under LD.
Wed, 7 December 2016
REVIEW Download: 860| View: 888| Comments: 0 | doi:10.20944/preprints201612.0041.v1
Subject: Life Sciences, Other Keywords: crown of thorns starfish; Great Barrier Reef; nutrient enrichment; larval survivorship
Online: 7 December 2016 (11:18:50 CET)
The Great Barrier Reef (GBR) is currently experiencing widespread crown of thorns starfish (CoTS) outbreaks as part of the fourth wave of outbreaks since 1962. It is believed that outbreaks have become more frequent on the GBR and elsewhere in the Indo-Pacific associated with anthropogenic causes. The two widely accepted potential causes are (1) anthropogenic nutrient enrichment leading to increased biomass of phytoplankton, the food of the planktonic stage of larval CoTS; and (2) overfishing of predators on the juvenile to adult stages of CoTS, for example, commercial fished species such as coral trout. In this study, we show the evidence for the nutrient enrichment causation hypothesis is strong based on a large number of recent studies in the GBR. We also hypothesise that secondary outbreaks in the region between Cairns and Townsville can also be enhanced by nutrient enriched conditions associated with the annual nutrient discharge from Wet Tropics rivers.
Mon, 22 May 2017
REVIEW Download: 852| View: 553| Comments: 0 | doi:10.20944/preprints201705.0159.v1
Online: 22 May 2017 (07:36:30 CEST)
A review of the surface ablation of hominin teeth by attrition, abrasion and erosive wear. The occurrence of these lesions is explored in a sample of South African fossil australopithecine dentitions revealing excessive wear. Interpretation of the nature of the dietary components causing such wear in the absence of carious erosion provides insight into the ecology of the Plio-pleistocene epoch (1-2 million years ago). Fossil teeth inform much of the living past by their retained evidence after death. Tooth wear is the ultimate forensic evidence of lives lived.
Thu, 30 March 2017
ARTICLE Download: 851| View: 822| Comments: 0 | doi:10.20944/preprints201703.0218.v1
Online: 30 March 2017 (16:22:32 CEST)
In the present study, an attempt was made to induce rooting from single-node cuttings of hybrid aspen (Populus tremula L. ×P. tremuloides Michx.) with different concentrations of IAA, IBA and NAA during rooting. Among the three auxins used, NAA showed more effective induction on rooting as compared to IAA and IBA at the whole level. Thereafter, NAA was used further in experiments for anatomical and biochemical investigation. The results showed that it took 12 days from the differentiation of primordium to the appearance of young adventitious roots with NAA application. It was found that endogenous IAA, ZR and GA3 levels increased, but ABA decreased in cuttings with 0.54 mM NAA treatment. In contrast to the endogenous IAA level, NAA had negative effect on IAA-oxidase (IAAO) activity. Similarly, the decreased peroxidase (POD) activity, consistent with down-regulation of expressed levels of POD1 and POD2, was observed in NAA-treated cuttings. Whereas, NAA resulted in a higher activity in polyphenol oxidase (PPO) compared to the control cuttings. Collectively, the study highlighted that 0.54 mM NAA is efficient on rooting in hybrid aspen, and its effect on metabolic changes during rooting is discussed, which provide valuable information for propagating hybrid aspen.
Fri, 14 July 2017
REVIEW Download: 849| View: 558| Comments: 0 | doi:10.20944/preprints201707.0035.v1
Online: 14 July 2017 (11:59:25 CEST)
Gastric cancer is an intractable disease with a high incidence of peritoneal dissemination and obstructive symptoms (e.g. ileus, jaundice, and hydronephrosis) arising from accompanying marked fibrosis. Microenvironmental interactions between cancer cells and stromal cells are the suggested cause of the disease. Transforming growth factor (TGF-β) is an intriguing cytokine exhibiting dual roles in malignant disease, acting as an important mediator of cancer invasion, metastasis, and angiogenesis as well as exhibiting antitumor functions. Moreover, the TGF-β pathway contributes to the generation of a favorable microenvironment for tumor growth and metastasis throughout the steps of carcinogenesis. Among these effects, TGF-β induces the epithelial-to-mesenchymal transition with prometastatic functions, contributes to the conversion of stromal cells to carcinoma-associated fibroblasts, and suppresses the function of immune cells, which compromises the antitumor immune response, leading to cancer progression and stromal fibrosis. In this review, we address the role of the essential TGF-β signaling pathway in the regulation of the activities of components of the tumor microenvironment of gastric cancer and how this contributes to tumor progression and stromal fibrosis. We then explore the potential to optimize therapy that inhibits TGF-β signaling in the preclinical and clinical settings of gastric cancer.
Tue, 6 December 2016
ARTICLE Download: 844| View: 899| Comments: 0 | doi:10.20944/preprints201612.0031.v1
Subject: Life Sciences, Other Keywords: helminth infection; microbiota; 16S rRNA Gene; taxonomic tree; classification; SMART-scan method; transfer learning
Online: 6 December 2016 (08:23:46 CET)
Human microbiome data from genomic sequencing technologies is fast accumulating, giving us insights into bacterial taxa that contribute to health and disease. Predictive modeling of such microbiota count data for classification of human infection from parasitic worms such as helminths can help in detection and management across global populations. Real-world datasets of microbiome experiments are typically sparse containing hundreds of measurements for bacterial species, of which only a few are detected in the bio-specimens that are analyzed. This feature of microbiome data produces the challenge of needing more observations for accurate predictive modeling and has been dealt with previously using different methods of feature reduction. To our knowledge, integrative methods such as transfer learning has not been explored in the microbiome domain yet, as a way to deal with data sparsity by incorporating knowledge of different but related datasets. One way of incorporating this knowledge is by using a meaningful mapping among features of these datasets. In this paper, we claim that this mapping would exist among members of each individual cluster grouped based on phylogenetic dependency among taxa and their association to the phenotype. We validate our claim by showing that models incorporating associations in such a grouped feature space result in no performance deterioration for the given classification task. In this paper, we test our hypothesis using classification models that detect helminth infection in microbiota of human fecal samples obtained from Indonesia and Liberia countries. In our experiments, we first learn binary classifiers for helminth infection detection by using Naive Bayes, Support Vector Machines, Multilayer Perceptrons, and Random Forest methods. In the next step, we add taxonomic modeling using the SMART-scan module to group the data, and learn classifiers using the same four methods, to test the validity of the achieved groupings. We observed a 6% to 23% and 7% to 26% performance improvement based on the Area Under ROC Curve (AUC) and Balanced Accuracy(Bacc) measures, respectively, over 10 runs of 10-fold cross-validation. These results show that using phylogenetic dependency for grouping our microbiota data actually results in a noticeable improvement in classification performance for helminth infection detection. These promising results from this feasibility study demonstrate that methods such as SMART-scan can be utilized in the future for knowledge transfer from different but related microbiome datasets by phylogenetically-related functional mapping, to enable novel integrative biomarker discovery.
Mon, 20 March 2017
REVIEW Download: 844| View: 805| Comments: 0 | doi:10.20944/preprints201703.0148.v1
Subject: Life Sciences, Other Keywords: microcystin; saxitoxin; cylindrospermopsin; anatoxin-a; anatoxin-a(S); cyanobacteria; organic anion transporting polypeptide; phosphatase inhibitor; acetylcholinesterase; neurotoxicity; water quality; eutrophication; drinking water
Online: 20 March 2017 (06:17:48 CET)
Cyanobacteria are ubiquitous phototrophic bacteria that inhabit diverse environments across the planet. They dominate many eutrophic lakes impacted by excess nitrogen (N) and phosphorus (P) forming dense accumulations of biomass known as cyanobacterial harmful algal blooms or cyanoHABs. Their dominance in eutrophic lakes is attributed to a variety of unique adaptations including N and P concentrating mechanisms, N fixation, colony formation that inhibits predation, vertical movement via gas vesicles, and the production of toxic or otherwise bioactive molecules. While some of these molecules have been explored for their medicinal benefits, others are potent toxins harmful to humans, animals, and other wildlife known as cyanotoxins. In humans these cyanotoxins affect various tissues, including the liver, central and peripheral nervous system, kidneys, and reproductive organs among others. They induce acute effects at low doses in the parts-per-billion range and some are tumor promoters linked to chronic diseases such as liver and colorectal cancer. The occurrence of cyanoHABs and cyanotoxins in lakes presents challenges for maintaining safe recreational aquatic environments and the production of potable drinking water. CyanoHABs are a growing problem in the North American (Laurentian) Great Lakes basin. This review summarizes information on the occurrence of cyanoHABs in the Great Lakes, toxicological effects of cyanotoxins, and appropriate numerical limits on cyanotoxins in finished drinking water.
Tue, 20 December 2016
REVIEW Download: 843| View: 786| Comments: 0 | doi:10.20944/preprints201612.0097.v2
Subject: Life Sciences, Microbiology Keywords: pathogens; Legionella; amoeba; protozoa; biofilm; antibacterial; antimicrobial; cooling towers; biocides; polyvalent metals
Online: 20 December 2016 (10:26:22 CET)
Application of toxic antibacterial agents is considered necessary to control prevalent fresh water microorganisms in evaporative cooling water systems, but these agents can adversely affect the environment and human health. Alternatively, natural antibacterial water chemistry has been applied in industrial cooling water systems for over 10 years with excellent results. The tower water chemistry method concentrates natural salts in highly-softened water to produce elevated pH and dissolved solids, with low calcium and magnesium. This practice conserves water while generating only a small volume of non-toxic natural salt concentrate for cost efficient separation and disposal if required. This review presents a novel perspective of natural antimicrobial chemistry for inhibiting parasitic microbiome functional relationships within the bio-triad of Legionella outbreaks, "Trojan Protozoans" and biofilms. The review further examines practical application and function of polyvalent metal ions in the inhibition of biofilms. Reducing global dependence on toxic antibacterial agents discharged to the environment is an emerging concern due to their impact on the natural microbiome, plants, animals and humans. Discharge of antibacterial agents also contributes to development of pathogen resistance. Use of natural antibacterial chemistry can play a key role in managing the cooling water environment in a more ecologically sustainable manner.
Fri, 31 March 2017
REVIEW Download: 838| View: 705| Comments: 0 | doi:10.20944/preprints201703.0240.v1
Subject: Life Sciences, Molecular Biology Keywords: NF-кB, Hypoxia, Inflammation, IKK, PHDs, Cancer, TAK1, FIH
Online: 31 March 2017 (17:21:52 CEST)
Cancer is often characterised by the presence of hypoxia and inflammation. Paramount to the mechanisms controlling cellular responses under such stress stimuli, are the transcription factor families of Hypoxia Inducible Factor (HIF) and Nuclear Factor of kappa-light-chain-enhancer of activated B cells (NF-кB). Although, a detailed understating of how these transcription factors respond to their cognate stimulus is well established, it is now appreciated that HIF and NF-кB undergo extensive crosstalk, in particular in pathological situations such as cancer. Here, we focus on the current knowledge on how HIF is activated by inflammation and how NF-кB is modulated by hypoxia. We summarise the evidence for the possible mechanism behind this activation and how HIF and NF-кB function impacts cancer, focusing on colorectal, breast and lung cancer. We discuss possible new points of therapeutic intervention aiming to harness the current understanding of the HIF-NF-кB crosstalk.
Wed, 24 May 2017
ARTICLE Download: 837| View: 679| Comments: 0 | doi:10.20944/preprints201705.0174.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: steroid; metabolism; anti-inflammatory drug; inhibition
Online: 24 May 2017 (08:25:26 CEST)
In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3’-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair which holds considerable advantages over urinalysis for anti-doping tests.
Mon, 8 May 2017
REVIEW Download: 836| View: 540| Comments: 0 | doi:10.20944/preprints201705.0062.v1
Subject: Life Sciences, Immunology Keywords: microbiome; probiotics, dietary supplements; nutrition; HIV infection, inflammation
Online: 8 May 2017 (12:10:17 CEST)
Microbiota plays a key role in various body’s functions, physiological, metabolic and immunological processes, through different mechanisms such as the regulation of the development and/or functions of different types of immune cells in the intestines. Several evidences indicate that alteration in the gut microbiota can influence infectious and non-infectious diseases. Bacteria that resides on the mucosal surface or within the mucus layer participate in interactions with the host immune system, and a healthy gut microbiota is essential for the development of mucosal immunity. The immunomodulatory activity of probiotics has been proposed in several bowel disorders or in aging-related dysfunctions. In HIV infected patients, the intestinal immune system is affected and inflammation persists during ART therapy too. Several studies are in progress to investigate the ability of probiotics to modulate epithelial barrier functions, microbiota composition and microbial translocation in HIV infection. This mini-review aims to suggest how the use of probiotics is beneficial not only in maintaining a healthy status but also to improve conditions in HIV subjects.
ARTICLE Download: 834| View: 786| Comments: 0 | doi:10.20944/preprints201705.0055.v1
Online: 8 May 2017 (09:27:58 CEST)
The string of bacteria, Vibrio. sp. QD-5 utilizing alginate, was separated from rotten kelp. The results of genome sequencing showed that the strain QD-5 contained four alginate lyase genes.One of the alginate genes Aly-IV was cloned and linked to the plasmid pET-22b (+). The heterologous expressed alginate lyase aly-IVwas characterized，which possessed the theoretical molecular mass of 62 kDa, and theoretical isoelectric point (pI) of 5.12. - The enzyme aly-IV was purified and the activity reached 1256.78 U/mg, with optimal temperature of 35 oC and pH value of 8.9. Nurtured in the temperature below 25 oC for 30 minutes, the activity was almost stable. The result also suggested that the activity of enzyme was strongly affected by - NaCl whose optimal concentration was 15 mM in a lab environment The TLC and ESI-TOF-MS analysis suggested that the enzyme aly-IV could degrade sodium alginate and polyG in endo-lytic type, producing monomer, dimer and trimmer. So, aly-IV can also be widely applied to make large scale preparation of alginate oligosaccharides with low degree of polymerization (DP).
Fri, 10 March 2017
TECHNICAL NOTE Download: 830| View: 1516| Comments: 0 | doi:10.20944/preprints201703.0057.v1
Subject: Life Sciences, Microbiology Keywords: Remotely Operated Vehicle; Metatranscriptomics; Niskin
Online: 10 March 2017 (10:50:15 CET)
The development of low-cost, open-source Remotely Operated Vehicle (ROV) systems has provided almost unrestricted access for researchers looking to monitor the marine environment in ever greater resolution. Sampling microbial communities from the marine environment, however, still usually relies on Niskin-bottle sampling (ROV or CTD based), a method which introduces an inaccuracy and variability that is incompatible with metatranscriptomic analysis. Here, we describe a versatile, easily-replicated platform which achieves in situ mRNA preservation, via the addition of RNAlater to filtered microbial cells, to enhance ROV or CTD functionality.
Sun, 11 February 2018
REVIEW Download: 818| View: 481| Comments: 0 | doi:10.20944/preprints201712.0023.v2
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: physical exercise; irisin; neurodegeneration; aging; Alzheimer’s disease
Online: 11 February 2018 (04:28:07 CET)
Irisin, a skeletal muscle-secreted myokine, produced in response to physical exercise, has protective functions in both the central and the peripheral nervous systems, including the regulation of brain-derived neurotrophic factors and modification of telomere length. Such beneficial effects may inhibit or delay the emergence of neurodegenerative diseases, including Alzheimer’s disease (AD). This review is based on the hypothesis that irisin produced by physical exercise helps control AD progression. Herein, we describe the physiology of irisin and its potential role in delaying or preventing AD. Although current and ongoing studies on irisin show promising results, further research is required to clarify its potential as a meaningful therapeutic target for treating human diseases.
Mon, 17 July 2017
REVIEW Download: 812| View: 1068| Comments: 0 | doi:10.20944/preprints201707.0045.v1
Subject: Life Sciences, Other Keywords: oncolytic virotherapy; combination therapy; mathematical model; immune system; cancer; immunotherapy
Online: 17 July 2017 (13:01:09 CEST)
After decades of research, oncolytic virotherapy has recently advanced to clinical application, and currently a multitude of novel agents and combination treatments are being evaluated for cancer therapy. Oncolytic agents preferentially replicate in tumor cells, inducing tumor cell lysis and complex anti-tumor effects, such as innate and adaptive immune responses and the destruction of tumor vasculature. With the availability of different vector platforms and the potential of both genetic engineering and combination regimens to enhance particular aspects of safety and efficacy, the identification of optimal treatments for patient subpopulations or even individual patients becomes a top priority. Mathematical modeling can provide support in this arena by making use of experimental and clinical data to generate hypotheses about the mechanisms underlying complex biology and, ultimately, predict optimal treatment protocols. Increasingly complex models can be applied to account for therapeutically relevant parameters such as components of the immune system. In this review, we describe current developments in oncolytic virotherapy and mathematical modeling to discuss the benefit of integrating different modeling approaches into biological and clinical experimentation. Conclusively, we propose a mutual combination of these fields of research for more efficient development and effective treatments.
Mon, 25 December 2017
REVIEW Download: 810| View: 542| Comments: 0 | doi:10.20944/preprints201710.0185.v3
Subject: Life Sciences, Biochemistry Keywords: epigenome; DNA modification; cytosine methylation; gene regulation; histone modification; 5-methylcytosine; stress response
Online: 25 December 2017 (09:43:03 CET)
Genome-wide epigenetic changes in plants are being reported during the development and environmental stresses, which are often correlated with gene expression at the transcriptional level. Sum total of the biochemical changes in nuclear DNA, post-translational modifications in histone proteins and variations in the biogenesis of non-coding RNAs in a cell is known as epigenome. These changes are often responsible for variation in expression of the gene without any change in the underlying nucleotide sequence. The changes might also cause variation in chromatin structure resulting into the changes in function/activity of the genome. The epigenomic changes are dynamic with respect to the endogenous and/or environmental stimuli which affect phenotypic plasticity of the organism. Both, the epigenetic changes and variation in gene expression might return to the pre-stress state soon after withdrawal of the stress. However, a part of the epigenetic changes may be retained which is reported to play role in acclimatization, adaptation as well as in the evolutionary processes. Understanding epigenome-engineering for improved stress tolerance in plants has become essential for better utilization of the genetic factors. This review delineates the importance of epigenomics towards possible improvement of plant’s responses to environmental stresses for climate resilient agriculture.
Fri, 17 March 2017
ARTICLE Download: 807| View: 1013| Comments: 0 | doi:10.20944/preprints201612.0068.v2
Subject: Life Sciences, Cell & Developmental Biology Keywords: modulation of nuclear gene expression; mitochondrial 18 kDa translocator protein (TSPO); TSPO ligand; PK 11195; 2-Cl-MGV-1; retrograde mitochondrial-nuclear signaling pathway; microscopy; mitochondria; cell nucleus
Online: 17 March 2017 (17:28:28 CET)
It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 minutes, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with reverse transcriptase (RT) real-time -PCR. At the time points of 15, 30, 45, and 60 minutes, as well as 3 and 24 hours of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 hours of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.
Tue, 25 April 2017
ARTICLE Download: 798| View: 874| Comments: 0 | doi:10.20944/preprints201704.0154.v1
Subject: Life Sciences, Molecular Biology Keywords: water bridging; dipole waves; coherent states; polymerase chain reaction; DNA amplification; DNA transduction; enzyme catalytic activity; fractal-like self-similarity
Online: 25 April 2017 (04:24:21 CEST)
We discuss the role of water bridging the DNA-enzyme interaction by resorting to recent 1 results showing that London dispersion forces between delocalized electrons of base pairs of DNA 2 are responsible for the formation of dipole modes that can be recognized by Taq polymerase. 3 We describe the dynamical origin of the high efficiency and precise targeting of Taq activity in 4 PCR. The spatiotemporal distribution of interaction couplings, frequencies, amplitudes, and phase 5 modulations comprise a pattern of fields instantiating the electromagnetic image of DNA in its 6 water environment, which is what the polymerase enzyme actually recognizes at long range. The 7 experimental realization of PCR amplification, achieved through replacement of the DNA template 8 by the treatment of pure water with electromagnetic signals recorded from viral and bacterial DNA 9 solutions, is found consistent with the gauge theory paradigm of quantum fields.
Fri, 17 March 2017
REVIEW Download: 796| View: 701| Comments: 0 | doi:10.20944/preprints201703.0031.v2
Subject: Life Sciences, Molecular Biology Keywords: genetic code; tRNA dimers; self-reference; modularity; error-compensation; metabolism chronology; protein stability; punctuation system
Online: 17 March 2017 (04:55:46 CET)
The proposal that the genetic code was formed on the basis of protein synthesis directed by tRNA dimers is reviewed and updated. The tRNAs paired through the anticodon loops are an indication on the process. Dimers are considered mimics of the ribosomes – structures that hold tRNAs together and facilitate the transferase reaction, and of the translation process – anticodons are at the same time codons for each other. The primitive protein synthesis system gets stabilized when the product peptides are able to bind the producers therewith establishing a self-stimulating production cycle. The chronology of amino acid encoding starts with Glycine and Serine, indicating the metabolic support of the Glycine-Serine C1-assimilation pathway, which is also consistent with evidence on origins of bioenergetics mechanisms. Since it is not possible to reach for substrates simpler than C1 and compounds in the identified pathway are apt for generating the other central metabolic routes, it is considered that protein synthesis is the beginning and center of a succession of sink-effective mechanisms that drive the formation and evolution of the metabolic flow system. Plasticity and diversification of proteins construct the cellular system following the orientation given by the flow and implementing it. Nucleic acid monomers participate in bioenergetics and the polymers are conservative memory systems for the synthesis of proteins. Protoplasmic fission is the final sink-effective mechanism, part of cell reproduction, guaranteeing that proteins don’t accumulate to saturation, which would trigger inhibition.
Tue, 24 January 2017
ARTICLE Download: 796| View: 870| Comments: 0 | doi:10.20944/preprints201701.0105.v1
Subject: Life Sciences, Biotechnology Keywords: magnetic hyperthermia; gene therapies; heat shock protein promoter; in vivo optical imaging; magnetic polymer-coated nanoparticles
Online: 24 January 2017 (04:14:19 CET)
The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and non-invasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected sub-cutaneously with Matrigel™ to generate so called pseudo tumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 hours after heating. We showed that dextran-coated magnetic iron oxide nanoparticles dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as non-invasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.
Tue, 23 May 2017
ARTICLE Download: 793| View: 1627| Comments: 0 | doi:10.20944/preprints201701.0127.v3
Subject: Life Sciences, Genetics Keywords: educational attainment; polygenes; polygenic selection; IQ; GWAS
Online: 23 May 2017 (17:08:33 CEST)
Background: The genetic variants identified by three large genome-wide association studies (GWAS) of educational attainment were used to test a polygenic selection model. Methods: Average frequencies of alleles with positive effect (polygenic scores or PS) were compared across populations (N=26) using data from 1000 Genomes. A null model was created using frequencies of random SNPs. Results: Polygenic selection signal of educational attainment GWAS hits is high among a handful of SNPs within genomic regions replicated across GWAS publications. A polygenic score comprising 9 SNPs predicts population IQ (r=0.88), outperforming 99% of the polygenic scores obtained from sets of random SNPs (Monte Carlo p= 0.011). Its predictive power remains unaffected after controlling for spatial autocorrelation (Beta= 0.83). The largest polygenic score (161 SNPs) exhibits similar predictive power (Beta=0.8). Random polygenic scores are moderate predictors of population IQ (thanks to spatial autocorrelation), and their predictive power increases logarithmically with the number of SNPs, indicating an exponential reduction in noise. Conclusion: This study provides guidance for using GWAS hits together with random SNPs for testing polygenic selection using Monte Carlo simulations.
Fri, 13 January 2017
ARTICLE Download: 783| View: 902| Comments: 0 | doi:10.20944/preprints201701.0071.v1
Subject: Life Sciences, Biotechnology Keywords: C-type lectin; agglutination; CRD; bacterial detection; E. coli
Online: 13 January 2017 (13:17:13 CET)
Lectins are carbohydrate-interacting proteins playing a pivotal role in multiple physiological and developmental aspects of all organisms. They can specifically interact with different bacterial and viral pathogens through the carbohydrate-recognition domains (CRD). In addition, lectins are also of biotechnological interest because of their potential use as biosensor for capturing and identification of bacterial species. In this work, we have characterized the bacterial agglutination properties of three C-type lectins from the Lepidoptera Spodoptera exigua. One of these lectins, BLL2, was able to agglutinate cells from a broad range of bacterial species at an extremely low concentration, becoming a very interesting protein to be used as biosensor or other biotechnological applications involving bacterial capturing.
Tue, 16 May 2017
REVIEW Download: 779| View: 570| Comments: 0 | doi:10.20944/preprints201705.0127.v1
Subject: Life Sciences, Biochemistry Keywords: Cholangiocarcinoma; DNA methylation; Tumor suppressor gene; microRNA; DNA methylation inhibitor
Online: 16 May 2017 (18:08:59 CEST)
Cholangiocarcinoma is an epithelial malignancy arising in the region between the intrahepatic bile ducts and the ampulla of Vater at the distal end of the common bile duct. The effect of current chemotherapy regimens against cholangiocarcinoma is limited, and the prognosis of patients with cholangiocarcinoma is poor. Aberrant DNA methylation and histone modification induce silencing of tumor suppressor genes and chromosomal instability during carcinogenesis. Studies have shown that the tumor suppressor genes and microRNAs (miRNAs) including MLH1, p14, p16, DAPK, miR-370 and miR-376c are frequently methylated in cholangiocarcinoma. Silencing of these tumor suppressor genes and miRNAs plays critical roles in the initiation and progression of cholangiocarcinoma. In addition, recent studies have demonstrated that DNA methylation inhibitors induce expression of endogenous retroviruses and exert the anti-tumor effect of via an anti-viral immune response. Aberrant DNA methylation of tumor suppressor genes and miRNAs could be a powerful biomarker for diagnosis and treatment of cholangiocarcinoma. Epigenetic therapy with DNA methylation inhibitors hold considerable promise for the treatment of cholangiocarcinoma through re-activation of tumor suppressor genes and miRNAs as well as induction of an anti-viral immune response.
Fri, 16 December 2016
ARTICLE Download: 770| View: 1264| Comments: 0 | doi:10.20944/preprints201612.0089.v1
Subject: Life Sciences, Other Keywords: origin of life; selection; accumulation; prebiotic chemistry; molecular evolution; vesicles
Online: 16 December 2016 (08:46:10 CET)
A basic problem in all postulated pathways of prebiotic chemistry is the low concentration which generally is expected for interesting reactants in fluid environments. Even though compounds like nucleobases, sugars or peptides principally may form spontaneously under environmental conditions, they will always be rapidly diluted in an aqueous environment. In addition, any such reaction leads to side products which often exceed the desired compound and generally hamper the first steps of a subsequent molecular evolution. Therefore, a mechanism of selection and accumulation of relevant prebiotic compounds seems to be crucial for molecular evolution. A very efficient environment for selection and accumulation can be found in the fluid continuum circulating in tectonic fault zones. Vesicles which form spontaneously at a depth of approximately 1 km present a selective trap for amphiphilic molecules, especially for peptides composed of hydrophilic and hydrophobic amino acids in a suitable sequence. The accumulation effect is shown in a numeric simulation on a simplified model. Further, possible mechanisms of a molecular evolution in vesicle membranes are discussed. Altogether, the proposed scenario can be seen as an ideal environment for constant, undisturbed molecular evolution in and on cell-like compartments, the latter offering preferential starting conditions for a subsequent RNA world.
Thu, 3 November 2016
ARTICLE Download: 768| View: 758| Comments: 0 | doi:10.20944/preprints201611.0026.v1
Subject: Life Sciences, Other Keywords: system structure; organised complexity; organisation; models of organisation; whole-part graphs; synexions; organised sets; organisation interaction; in-formation
Online: 3 November 2016 (10:41:01 CET)
Warren Weaver, writing about the function that science should have in mankind’s developing future, ideas and ideals, proposed to classify scientific problems into ‘problems of simplicity’, ‘problems of disorganised complexity’, and ‘problems of organised complexity’ — the huge complementary class to which all biological, human, and social problems belong. Problems of simplicity have few components and variables and have been extensively addressed in the last 400 years. Problems of disorganised complexity have a huge number of individually erratic components and variables, but possess collective regularities that can be analysed by resourcing to stochastic methods. Yet, problems of organised complexity do not yield easily to classical or statistical treatment since interrelations among phenomenon elements change during its evolution alongside commonly used state variables, affecting behaviour and outcome. Moreover, organisation, the focal point in this complementary class, is still an elusive concept despite the gigantic efforts undertaken since a century ago to tame it. This paper addresses the description, representation and study of phenomena in the ‘problems of organised complexity’ class. Grounded on relational mathematical constructs, a theoretical framework providing operational definitions and schemes for formally modelling organisations and interaction of organisations is introduced. This framework extends the general systems’ concept and provides a novel perspective for addressing organised complexity phenomena as a collection of interacting organisations.
Tue, 14 March 2017
ARTICLE Download: 761| View: 781| Comments: 0 | doi:10.20944/preprints201703.0076.v1
Subject: Life Sciences, Other Keywords: mercury; exposure assessment; human health; artisanal and small-scale gold mining
Online: 14 March 2017 (08:40:59 CET)
Artisanal and small-scale gold mining (ASGM) has been an important source of income for communities in the Madre de Dios River Basin in Peru for hundreds of years. However, in recent decades, the scale of ASGM activities in the region has increased dramatically, and exposures to a variety of occupational and environmental hazards related to ASGM, including mercury, are becoming more widespread. The aims of our study were to: (1) examine patterns in the total hair mercury level of human participants in several communities in the region and compare these results to the 2.2 µg/g total hair mercury level equivalent to the World Health Organization (WHO) Expert Committee of Food Additives (JECFA)’s Provisional Tolerable Weekly Intake (PTWI); and (2), to measure the mercury levels of paco (Piaractus brachypomus) fish raised in local aquaculture ponds, in order to compare these levels to the EPA Fish Tissue Residue Criterion of 0.3 µg Hg/g fish (wet weight). We collected hair samples from 80 participants in four communities (one control and three where ASGM activities occurred) in the region, and collected 111 samples from fish raised in 24 local aquaculture farms. We then analyzed the samples for total mercury. Total mercury levels in hair were statistically significantly higher in the mining communities than in the control community, and increased with increasing distance away from the Madre de Dios headwaters (as the crow flies), did not differ by sex, and frequently exceeded the reference level. Regression analyses indicated that higher hair mercury levels were associated with residence in ASGM communities. The analysis of paco fish samples found no samples that exceeded the EPA tissue residue criterion. Collectively, these results align with other recent studies showing that ASGM activities are associated with elevated human mercury exposure. The fish farmed through the relatively new process of aquaculture in ASGM areas appeared to have little potential to contribute to human mercury exposure. More research is needed on human health risks associated with ASGM to discern occupational, residential, and nutritional exposure, especially through tracking temporal changes in mercury levels as fish ponds age, and assessing levels in different farmed fish species. Additionally, research is needed to definitively determine that elevated mercury levels in humans and fish result from the elemental mercury from mining, rather than from a different source, such as the mercury released from soil erosion during deforestation events from mining or other activities.
Mon, 21 November 2016
ARTICLE Download: 754| View: 875| Comments: 0 | doi:10.20944/preprints201611.0108.v1
Subject: Life Sciences, Molecular Biology Keywords: contrast induced nephropath; acute myocardial infarction
Online: 21 November 2016 (12:13:30 CET)
Background: The morbidity of myocardial infarction is keeping raise in this decade. Because of high safety and operability , percutaneous coronary intervention(PCI) has been used to conquer this disease for more than 20 years.An important complication of PCI is contrast induced nephropathy(CIN), which raises our attention. Previously, we started a study to explore the correlation between acute kidney injury and myonecrosis after scheduled percutaneous coronary intervention. Our study showed that the rate of CI-AKI in patients with post-procedural myocardial injury and undergoing elective PCI was higher than that in patients free of injury. Methods: In this study,forty male rats were randomly divided into four groups: control group (n=8), CM group (n=12), AMI group (n=8) and AMI+CM group (n=12), then velocity of renal artery blood flow (VRABF), computer tomography (CT), serum creatinine(Scr), reactive oxidative species (ROS), periodic acid-Schiff (PAS) and TUNEL were used to estimate the injury of kidney. We analyzed 327 non-ST-segment elevation acute coronary syndrome subjects undertaking elective PCI. Serum levels of creatinine (SCr) and the eGFR before coronary angiography, and 24–72 h after contrast administration were recorded to assess the renal function. Results: The data showed that VRABF was lower in AMI+CM group than CM group from 0 minute to 24h and CT number in cortex was higher in AMI+CM group than CM group at 4-hour. As well as the level of Scr in AMI+CM group displayed a significantly increase at 24-hour compared with CM group. The histopathologic scores and percentage of tubular cell apoptosis were higher in AMI+CM group at 24-hour. In 327 patients, we found that CI-AKI occurred more often in subjects with post-procedural myonecrosis (PMN) than in those without PMN (20.8% versus 5.8%, respectively, P=0.001). Conclusion: Compared to the elective patient, the injury of CIN exhibited a higher severity in AMI patient.
Fri, 4 August 2017
ARTICLE Download: 753| View: 782| Comments: 0 | doi:10.20944/preprints201708.0015.v1
Subject: Life Sciences, Molecular Biology Keywords: ischemia-reperfusion injury (IRI), ω3-PUFA, AMP-activated protein kinase (AMPK), autophagy
Online: 4 August 2017 (12:56:08 CEST)
Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). ω3-Polyunsaturated fatty acids (ω3-PUFAs) show protective effects against various renal injuries. It was recently reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham (n = 10), fat-1 sham (n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI (n = 15). Kidneys and blood were harvested 24 h after IRI. Renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of LC3, Beclin-1, and Atg7; lower amounts of p62; and higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more AMPK activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.
Wed, 1 March 2017
ARTICLE Download: 750| View: 693| Comments: 0 | doi:10.20944/preprints201703.0004.v1
Subject: Life Sciences, Biotechnology Keywords: fumaric acid; purification; spent sulfite liquor; biorefineries
Online: 1 March 2017 (09:41:31 CET)
Fumaric acid is a chemical building block with many applications, namely in the polymer industry. The fermentative production of fumaric acid from renewable feedstock is a promising and sustainable alternative to petroleum-based chemical synthesis. The use of existing industrial side-streams as raw-material within biorefineries potentially enable production costs competitive against current chemical processes, while preventing the use of refined sugars competing with food and feed uses and avoiding purposely grow crops requiring large areas of arable land. However, most industrial side streams contain a diversity of molecules that will add complexity to the purification of fumaric acid from the fermentation broth. A process for the recovery and purification of fumaric acid from complex fermentation medium containing spent sulfite liquor (SSL) as carbon source was developed and is herein described. A simple two-stage precipitation procedure involving separation unit operations, pH and temperature manipulation and polishing through the removal of contaminants with activated carbon allowed the recovery of fumaric acid with 68.3% recovery yield with specifications meeting the requirements of the polymer industry. Further, process integration opportunities were implemented that allowed minimizing the generation of waste streams containing fumaric acid which enabled increasing the yield to 81.4% while keeping the product specifications.
Wed, 24 May 2017
REVIEW Download: 744| View: 589| Comments: 0 | doi:10.20944/preprints201705.0176.v1
Online: 24 May 2017 (08:48:15 CEST)
Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors or differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B, a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.
Tue, 14 March 2017
ARTICLE Download: 742| View: 1160| Comments: 0 | doi:10.20944/preprints201703.0081.v1
Subject: Life Sciences, Molecular Biology Keywords: miRNAs; pre-miRNAs sequencing; Abelmoschus esculentus; Next generation sequencing; non-model plant
Online: 14 March 2017 (10:15:14 CET)
MicroRNAs (miRNAs) are crucial regulatory RNAs, originated from hairpin precursors. For the past decade, researchers are focusing extensively on miRNA profiles in various plants. However studies on precursor miRNAs (pre-miRNAs) global profiling stay static even in model plants. Here, for the first time in a non-model plant, Abelmoschus esculentus with negligible genome information, we are reporting the global profiling to characterize the miRNAs and their associated pre-miRNAs by applying next generation sequencing approach. Preliminarily we performed sRNA (small RNA) sequencing with five biological replicates of leaf samples to attain 207,285,863 reads and data analysis using miRPlant keyed out 128 known and 845 novel miRNA candidates. With the objective to seize their associated hairpin precursors, we accomplished pre-miRNA sequencing to attain 83,269,844 reads. The paired end reads are merged, adaptor trimmed and the resulting 40-241 nt (nucleotide) sequences were picked out for analysis by using perl scripts from miRGrep tool and in-house built shell script for Minimum Fold Energy Index (MFEI) calculation. Applying stringent criteria of dicer cleavage pattern and perfect stem loop structure revealed precursors for 57 known miRNAs of 15 families and 18 novel miRNAs. Quantitative Real Time (qRT) PCR was performed to determine the expression of selected miRNAs.
Fri, 17 February 2017
ARTICLE Download: 741| View: 748| Comments: 0 | doi:10.20944/preprints201702.0070.v1
Subject: Life Sciences, Biochemistry Keywords: albumin; oxidative stress; exercise; ultra-marathon mountain race; protein oxidation
Online: 17 February 2017 (15:02:03 CET)
The aim of this study was to examine the oxidation of human serum albumin (HSA) caused by oxidative stress after an exhaustive exercise such as ultra-marathon race. Thus, blood samples from 12 adult runners who underwent a 103 km mountain ultra-marathon race were collected pre- and 24, 48 and 72 h post race. HSA was partially purified using affinity chromatography and then was subjected to Western blot analysis for disulfide dimers determination, indicating oxidation. The results were correlated with those from a previous study in which the same samples were analyzed using different oxidative stress markers and a good correlation with protein carbonyls (PC) at all time points was observed. Moreover there was a significant correlation with static oxidation-reduction potential (sORP) at 24 h, and a negative correlation with capacity oxidation-reduction potential (cORP) at 24 and 48 h. In addition, an individual analysis of albumin dimers exhibited great inter-individual differences. This inter-individual variability in the oxidation of HSA may suggest different interventions (e.g. through diet) in order to confront the effects on athletes’ organism after a strenuous exercise. In conclusion, this study supported the importance of the assessment of albumin dimers as a predictive marker for exercise-induced oxidative stress.
Tue, 30 May 2017
ARTICLE Download: 733| View: 728| Comments: 0 | doi:10.20944/preprints201705.0210.v1
Subject: Life Sciences, Other Keywords: pharmacokinetics; tissue distribution; indirect competitive enzyme-linked immunosorbent assay; puerarin
Online: 30 May 2017 (07:47:09 CEST)