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Life Sciences, Biophysics; 4SM; satellite derived bathymetry; water depth; water column correction; remote sensing; Landsat; San Lorenzo Channel
Online: 18 August 2017 (12:14:16 CEST)
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Satellite derived bathymetry methods over coastal areas were born to deliver basic and useful information like bathymetry. However, the process is not straightforward, the main limitation being the need of field data. The Self-calibrated Spectral Supervised Shallow-water Modeler (4SM) method was tested to obtain coastal bathymetry without the use of any field data. Using LANDSAT-8 multispectral images from 2013 to 2016, a bathymetric time series was produced. Groundtruthed depths and an alternative method, Stumpf’s Band Ratio Algorithm, were used to verify the results. Retrieved (4SM) vs groundtruthed depths scored an average r2 (0.90), and a low error (RMSE = 1.47 m). Also 4SM showed, over the whole time series, the same average accuracy of the control method (40%). Advantages, limitations and operability under complex atmosphere and water column conditions, and high and low-albedo bottom processing capabilities of 4SM are discussed. In conclusion, the findings suggest that 4SM is equally accurate as the commonly used Stumpf’s method, the only difference being the independence of 4SM to previous field data, and the potential to deliver bottom spectral characteristics for further modelling. 4SM represents a significative advance in coastal remote sensing potential to obtain bathymetry and optical properties of the marine bottom.
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Life Sciences, Immunology; influenza virus; apoptosis; antiviral agent; innate immunity; host response
Online: 14 August 2017 (04:41:22 CEST)
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Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral outbreaks, new treatments are urgently needed. Developing new virus control modalities requires better understanding of virus-host interactions. Here we describe how IAV infection triggers cellular apoptosis, and how this process can be exploited towards development of new therapeutics, which might be more effective than the currently available anti-influenza drugs.
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Life Sciences, Other; caffeic acid; caffeic acid phenethyl ester; CAPE; apotosis; cell cycle; proliferation; breast cancer; propolis
Online: 12 August 2017 (21:37:04 CEST)
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1) Background: Studies indicate that caffeic acid (CA), caffeic acid phenethyl ester (CAPE) are compounds with potent chemopreventive effects. Breast cancer is a common cancer among women worldwide. The study shows comparison of caffeic acid and its ester activity in the cells of breast cancer line MDA-MB-231; 2) Methods: The cells of MDA-MB-231 were treated by CA and CAPE with doses from 10 to 100 µM in time 24 h and 48 h. Cytotoxicity MTT test, apoptosis by Annexin V and cell cycle with Dead Cell Assay were performed; 3) Results: The cytotoxic activity was greater for CAPE comparing to CA, in both incubation time (same dosage). IC50 values for CAPE were 27.84 (24h) and 15.83 (48h) and >10000 (24h) and >1000 (48h) for CA. Polyphenols induced apoptosis, higher apoptotic effect observed for CAPE (dose dependent). CAPE induced cell cycle arrest in S phase (time and dose dependent). Dose dependent decline G0/G1 phase (48h) and elimination of phase G2/M (100 µM of CAPE). For CA, only after 48 hours, small effect of cell cycle at phase S (however dose dependent), and slight decline of phase G0/G1 and G2/M only for highest doses (50 and 100 µM); 4) Conclusions: Comparing CA and CAPE activity, on the MDA-MB-231, we clearly see better activity of CAPE, with the same dosage and experiment time.
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Life Sciences, Immunology; ALCL; ALK; thymus; lymphoma origins
Online: 12 August 2017 (21:30:37 CEST)
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T cell Non-Hodgkin lymphoma is a heterogeneous disease ranging from malignancies arising from thymic T cells halted in development, through to mature, circulating peripheral T cells. The latter cases are diagnostically problematic with many entering the category of peripheral T cell lymphoma, not otherwise specified (PTCL, NOS). Anaplastic Large Cell Lymphoma is one of the exceptions to this whereby aberrant expression of Anaplastic Lymphoma Kinase and distinctive presence of cell surface CD30 places this entity in its own class. Besides expression of a well-studied oncogenic translocation, ALCL, ALK+ may also have a unique pathogenesis with a thymic origin like T lymphoblastic lymphoma but a peripheral presentation akin to PTCL. This review discusses evidence towards the potential origin of ALCL, ALK+ and mechanisms that may give rise to its unique phenotype.
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Life Sciences, Other; neural network; potts model; latching; recursion
Online: 4 August 2017 (14:20:59 CEST)
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We study latching dynamics in the adaptive Potts model network, through numerical simulations with randomly and also weakly correlated patterns, and we focus on comparing its slowly and fast adapting regimes. A measure, Q, is used to quantify the quality of latching in the phase space spanned by the number of Potts states S, the number of connections per Potts unit C and the number of stored memory patterns p. We find narrow regions, or bands in phase space, where distinct pattern retrieval and duration of latching combine to yield the highest values of Q. The bands are confined by the storage capacity curve, for large p, and by the onset of finite latching, for low p. Inside the band, in the slowly adapting regime, we observe complex structured dynamics, with transitions at high crossover between correlated memory patterns; while away from the band latching transitions lose complexity in different ways: below, they are clear-cut but last so few steps as to span a transition matrix between states with few asymmetrical entries and limited entropy; while above, they tend to become random, with large entropy and bi-directional transition frequencies, but indistinguishable from noise. Extrapolating from the simulations, the band appears to scale almost quadratically in the p - S plane, and sublinearly in p - C. In the fast adapting regime the band scales similarly, and it can be made even wider and more robust, but transitions between anti-correlated patterns dominate latching dynamics. This suggest that slow and fast adaptation have to be integrated in a scenario for viable latching in a cortical system. The results for the slowly adapting regime, obtained with randomly correlated patterns, remain valid also for the case with correlated patterns, with just a simple shift in phase space.
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Life Sciences, Molecular Biology; ischemia-reperfusion injury (IRI), ω3-PUFA, AMP-activated protein kinase (AMPK), autophagy
Online: 4 August 2017 (12:56:08 CEST)
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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.
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Life Sciences, Microbiology; natural mineral water; free living protozoa; Nontuberculous mycobacteria; Legionella; qPCR
Online: 3 August 2017 (09:11:03 CEST)
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Italian Directives recommends the good quality of natural mineral waters but literature data assert a potential risk from several microorganisms colonizing wellsprings and mineral water bottling plants. Aim of study is the identification of microorganisms from spring waters (SW) and bottled mineral waters (BMW) samples. Methods: Routine microbiological indicators, Legionella spp., Nontuberculous mycobacteria (NTM), protozoa (FLA) and physical-chemical parameters were assessed in 24 SW and 10 BMW samples performing culture methods and molecular tests as PCR and qPCR. Results: In 33 out of 34 samples no cultivable bacteria were isolated with the exception of 83 CFU/L of Mycobacterium gilvum, detected in one warm rich-mineralized SW. qPCR showed the presence of Legionella genomic units in 24% of samples (mean 2,9x102±1,7x102 GU/L) and NTM genomic units in 18% of samples (mean 5,7x103±4,1x103 GU/L). Vermamoeba vermiformis and Acanthamoeba polyphaga were recovered respectively in 70% of BMW samples (counts from 1,3x103 to 1,2x105) and 42% of SW samples (counts from 1,1x103 to 1,3x104). Vahlkampfia spp. was detected in 42% of SW and 70% of BMW samples (mean 1,3x104 ±2,9x103 GU/L). Conclusion: The study highlights a low rate of microbial risk and the importance of risk assessment in natural mineral waters.
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Life Sciences, Molecular Biology; Rifampicin; insertion; biological cost; M. tuberculosis; resistance; structural bioinformatics
Online: 27 July 2017 (11:07:55 CEST)
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Rifampicin is one of the most important chemotherapeutic agents used in the treatment of tuberculosis. M. tuberculosis clinical strains resistant to rifampicin harbor mainly mutation in an 81-base pair region of rpoB. These mutations mainly consist of single amino acid substitutions. However insertions also can be related with rifampicin resistance strains. Herein, we described an insertion of 12 nucleotides in clinical isolates of M. tuberculosis resistant to rifampicin, all obtained from inmates. To evaluate the importance this insertion in surviving and drug resistance, it were carried out fitness experimental assays as well as in silico studies of 3D structural models, molecular docking simulations and virtual screening. The medical records of the seven patients showed all were previously treated to tuberculosis. Growth curves shown that the insertion determines a biological cost when compared to wild type rpoB and katG; or the double mutated rpoB S531L and katG S315T. From docking and molecular dynamics simulations it can be inferred that the insertion does not affect the process of synthesis of RNA transcripts. On the other hand, in the mutant RNAP-RIF complex rifampicin confirmed a low affinity interaction for the mutant form. Interesting, virtual screening for potential inhibitors for wtRNAP and mRNAP using a library of 1446 compounds approved by the FDA showed that the best ligands were mainly compounds with antibiotic activity, although the targets involved in the pharmacological action are other than RNAP. In conclusion, seven strains of M. tuberculosis RIF resistant that present an insertion of four amino acids in RNA polymerase showed by growth curve assays, a biological cost. Further, bioinformatics tools had characterized the putative drug resistance dynamic as well as the maintenance of RNA polymerase activity.
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Life Sciences, Microbiology; agavins; prebiotics; microbiota; overweight; body weight loss; short chain fatty acids
Online: 25 July 2017 (04:52:34 CEST)
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Agavins consumption has lead to accelerate body weight loss in mice. We investigated the changes on cecal microbiota and short chain fatty acids (SCFA) associated to body weight loss in overweight mice. Firstly, mice were fed with standard (ST5) or high fat (HF5) diet for 5 weeks. Secondly, overweight mice were shifted to standard diet alone (HF-ST10) or supplemented with agavins (HF-ST+A10) or oligofructose (HF-ST+O10), five more weeks. Cecal contents were collected before and after supplementation to determine microbiota and SCFA concentrations. At the end of first phase, HF5 mice showed a significant increase of body weight, which was associated with reduction of cecal microbiota diversity (PD whole tree; non-parametric t-test, P < 0.05), increased Firmicutes/Bacteroidetes ratio and reduced SCFA concentrations (t-test, P < 0.05). After diet shifted, HF-ST10 normalized its microbiota, increase its diversity and SCFA levels, whereas agavins (HF-ST+A10) or oligofructose (HF-ST+O10) led to partial microbiota restoration, with normalization of the Firmicutes/Bacteroides ratio as well as higher SCFA levels (P < 0.1). Moreover, agavins noticeably enriched Klebsiella and Citrobacter (LDA > 3.0); this enrichment has not been reported previously under a prebiotic treatment. In conclusion, agavins or oligofructose modulated cecal microbiota composition, reduced extent of diversity and increased SCFA. Furthermore, identification of bacteria enriched by agavins, opens opportunities to explore new probiotics.
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Life Sciences, Microbiology; Sulfur reduced species; Biofilms; Chalcopyrite, Biooxidation; Hydrophobicity
Online: 21 July 2017 (17:31:25 CEST)
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A bioelectrochemical study of charge transfer in the biofilm/chalcopyrite interface was performed to investigate the effect of surficial sulfur reduced species (SRS), as non-stochiometric compounds or polysulfides (Sn2-), and elemental sulfur (S0) on a biofilm structure during the earliest stages (1, 12 and 24 h) of chalcopyrite biooxidation by A. thiooxidans alone and adding Leptospirillum sp. The surface of massive chalcopyrite electrodes was exposed to the bacteria, which were analyzed electrochemically, spectroscopically, and microscopically. At the studied earlier times, charge transfer and significant differences in the biofilm structure were detected, depending on the presence of Leptospirillum sp. acting on A. thiooxidans biofilms. Such differences were a consequence of a continuous chalcopyrite pitting and promoting changes in biofilm hydropathy. A. thiooxidans modifies the reactive properties of SRS and favors an acidic dissolution, which shifts into ferric when Leptospirillum sp. is present. A. thiooxidans allows H+ and Fe3+ diffusion, and Leptospirillum sp. allows surpassing the charge transfer (reactivity) barrier between the mineral interface and the ions. The observed changes of hydropathy on the interface are associated to ions and electrons activity and transfer. Finally, a model of S0 biooxidation by A. thiooxidans alone or with Leptospirillum sp., is proposed.
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Life Sciences, Other; rapid light adaptation; glare; discrimination threshold; increment threshold; direct current electroretinogram
Online: 19 July 2017 (23:33:45 CEST)
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The excitation of the visual system increases with increasing retinal illumination. At the same time, the sensitivity of the system decreases (light adaptation). Higher excitation automatically results in a lower sensitivity. This study investigates whether this parallelism between the excitation and the sensitivity also applies in the dynamic case, that is, during the transition to a higher excitation level after an increase in the retinal illuminance. For this purpose, the courses of the subjective and the electroretinographic threshold during the transitional phase after a step of the adaptation illumination was determined by means of a special light-stimulation apparatus. As a measure of the course of the excitation during this time, the response ERG on the adaptation step was recorded with a special amplifier. The threshold curve always has an overswing, which shows subjectively very strong differences. It can be concluded that the glare caused by a sudden increase in illuminance is subjectively very different. The comparison between the response ERG on the adaptation step and the course of the electroretinographic increment threshold during this time shows a broad agreement between the two courses. It can thus be assumed that the sensitivity of the visual system follows the course of the excitation also in the dynamic case. In addition, the investigation shows that the glare experienced after a step in the illuminance clearly shows great subjective differences.
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Life Sciences, Other; Black polyethylene, Mulches, Allium sativum, Growth, Grass
Online: 19 July 2017 (22:50:23 CEST)
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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.
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Chenglin Zhang,
Jianbo Zhang,
Yan Fan,
Ming Sun,
Wendan Wu,
Wenda Zhao,
Xiaopeng Yang,
Linkai Huang,
Yan Peng,
Xiao Ma,
Xinquan Zhang
Life Sciences, Genetics; Festuca ovina L.; AFLP, genetic diversity; genetic barriers; environmental factors
Online: 18 July 2017 (10:05:56 CEST)
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Glaciation and mountain orogeny have generated new ecologic opportunities for plants, favoring an increase in the speciation rate. Moreover, they also act as corridors or barriers for plant lineages and populations. High genetic diversity ensures that species are able to survive and adapt. Gene flow is one of the most important determinants of the genetic diversity and structure of out-crossed species, and it is easily affected by biotic and abiotic factors. The aim of this study was to characterize the genetic diversity and structure of an alpine species, Festuca ovina L., in Xingjiang, China. A total of 100 individuals from 10 populations were analyzed using six amplified fragment length polymorphism (AFLP) primer pairs. A total of 583 clear bands were generated, of which 392 were polymorphic; thus, the percentage of polymorphic bands (PPB) was 67.24%. The total and average genetic diversities were 0.2722 and 0.2006 (0.1686-0.2225), respectively. The unweighted group method with arithmetic mean (UPGMA) tree, principal coordinates analysis (PCoA) and STRUCTURE analyses revealed that these populations or individuals could be clustered into two groups. The analysis of molecular variance analysis (AMOVA) suggested that most of the genetic variance existed within a population, and the genetic differentiation (Fst) among populations was 20.71%. The Shannon differentiation coefficient (G’st) among populations was 0.2350. Limited gene flow (Nm = 0.9571) was detected across all sampling sites. The Fst and Nm presented at different levels under the genetic barriers due to fragmentation. The population genetic diversity was significant relative to environmental factors such as temperature, altitude and precipitation.
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Life Sciences, Other; oncolytic virotherapy; combination therapy; mathematical model; immune system; cancer; immunotherapy
Online: 17 July 2017 (13:01:09 CEST)
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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.
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Life Sciences, Other; 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)
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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.
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Life Sciences, Molecular Biology; TGF-β; gastric cancer; microenvironment
Online: 14 July 2017 (11:59:25 CEST)
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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.
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Life Sciences, Biochemistry; insulin; phenolic derivatives; crystallography; powder diffraction
Online: 12 July 2017 (04:11:12 CEST)
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Human Insulin (HI) is a well-characterized natural hormone which regulates glycose levels into the blood-stream and is widely used for diabetes treatment. Numerous studies have manifested that despite significant efforts devoted to structural characterization of this molecule and its complexes with organic compounds (ligands), there is still a rich diagram of phase transitions and novel crystalline forms to be discovered. Towards the improvement of drug delivery, identification of new insulin polymorphs from polycrystalline samples, simulating the commercially available drugs, is feasible today via macromolecular X- ray powder diffraction (XRPD). This approach has been developed and is considered as a respectable method, which can be employed in biosciences for various purposes such as observing phase transitions and characterizing bulk pharmaceuticals. An overview of structural studies on human insulin complexes performed over the past decade employing both synchrotron and laboratory sources for XRPD measurements, is reported herein. This review aims to assemble all recent advances in diabetes treatment field in terms of drug formulation, verifying in parallel the efficiency and applicability of protein XRPD for quick and accurate preliminary structural characterization in large scale.
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Life Sciences, Biochemistry; DNA polymerase δ; PDIP46; poldip3; PDIP38; poldip2; DNA replication; enzyme regulation; DNA damage response; p12 subunit; E3 ligases; cell cycle
Online: 10 July 2017 (08:44:53 CEST)
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This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair. The second focus of the review involves the functions of two Pol δ binding proteins, PDIP46 and PDIP38, both of which are multi-functional proteins. PDIP46 is a novel activator of Pol δ4, and the impact of this function is discussed in relation to its potential roles in DNA replication. Several new models for the roles of Pol δ3 and Pol δ4 in leading and lagging strand DNA synthesis that integrate a role for PDIP46 are presented. PDIP38 has multiple cellular localizations including the mitochondria, the splicesosomes and the nucleus. It has been implicated in a number of cellular functions, including the regulation of specialized DNA polymerases, mitosis, the DNA damage response, Mdm2 alternative splicing and the regulation of the Nox4 NADPH oxidase.
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Life Sciences, Biochemistry; flavonoids; nitric oxide (•NO); nitrosation; nitrous acid; quinones; redox reactions; stomach; thiocyanic acid.
Online: 28 June 2017 (07:41:14 CEST)
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Foods are mixed with saliva in the oral cavity and swallowed. During staying in the stomach, saliva is contentiously provided to mix with the ingested foods. Because a salivary component nitrite is protonated to produce active nitrous acid at acidic pH, the redox reactions of nitrous acid with phenolic compounds in foods become possible in the stomach. In the reactions, nitrous acid is reduced to nitric oxide (•NO), producing various products from phenolic compounds. In the products, stable hydroxybezoyl benzofuranone derivatives, which are produced from quercetin and its 7-O-glucoside, are included. Caffeic acid, chlorogenic acid, and rutin are oxidized to quinones and the quinones can react with thiocyanic acid derived from saliva producing stable oxathiolone derivatives. 6,8-Dinitrosocatechis are produced from catechins by the redox reaction, and the dinitrocatechins are oxidized further by nitrous acid producing the quinones, which can make charge transfer complexes with the dinitrosocatechin and can react with thiocyanic acid producing the stable thiocyanate conjugates. In this way, various products can be produced by the reactions of salivary nitrite with dietary phenolic compounds, and reactive and toxic quinones formed by the reactions are postulated to be removed in the stomach by thiocyanic acid derived from saliva.
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Life Sciences, Immunology; autophagy； immune system； cancer；cell death；metabolic homeostasis
Online: 27 June 2017 (06:30:17 CEST)
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Autophagy is a highly conserved catabolic mechanism that mediates the degradation of damaged cellular components by inducing their fusion with lysosomes. This process provides cells with an alternative source of energy for the synthesis of new proteins and the maintenance of metabolic homeostasis in stressful environments. Numerous studies have demonstrated beneficial roles for the induction as well as the suppression of autophagy in cancer cells. Autophagy may induce either survival or death depending on the cell/tissue type. Radiation therapy is widely used therapeutic option to treat cancer, and it induces autophagy in human cancer cell line. Also, melatonin seems to affect cancer cell death via regulation of programmed cell death. In this review, we summarize the current understanding of autophagy and its regulation in cancer.
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Life Sciences, Biochemistry; proteins；time-varying； parallel； architectures；Conditional Random Fields (CRF)；Graphics Processing Units； Block Coordinate Descent algorithm
Online: 26 June 2017 (05:47:40 CEST)
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Proteins are the workhorses of the cell that perform biological functions by interacting with other proteins. Many statistical methods for protein-protein interaction (PPI) have been studied without considering time-dependent changes in networks and the functionalities. I introduced a novel method that models PPI networks as being dynamic in nature and evolving time-varying multivariate distribution with Conditional Random Fields (CRF). This research is directed towards implementing this new combinatorial algorithm on massively parallel architectures such as Graphics Processing Units (GPUs) for efficient computations for large scale bioinformatics datasets. I compared Conditional Random Fields (CRF) and the proposed novel method using CRF combined with the Block Coordinate Descent algorithm for human protein-protein interaction data set. Both are implemented on GPU-Accelerated Computing Architecture and the proposed novel method showed the advantages in predicting protein-protein interaction sites. I also show that the proposed approach is more efficient in 6.13% than standalone CRF++ in predicting protein-protein interaction sites.
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Life Sciences, Molecular Biology; food safety； GMO screening；GMO quantification; Maize； biometrology
Online: 26 June 2017 (03:52:29 CEST)
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Nowadays, genetically modified (GM) plants are widely used in commercial products. Cotton, soybean, maize, canola are the most widely consumed foods globally and their derived products have reached the global marketplace. Maize, specially has the greatest diversity of approved GM events globally (a total of 130 varieties approved in one or more countries) It is one of the most widely used staple food and feed ingredients, highly integrated into food and feed supply chains. Due to the fact that GMOs carry environmental risks and human health related risks it is required that the food and their ingredients that either contain GMOs or derived from GMOs should be labelled. In this study, we investigated the taxon-specific cauliflower mosaicvirus 35S promoter region (CaMV), Agrobacterium tumefaciens nonpalin synthase terminator (tNOS) gene and High Mobility Group (HMG) gene as a control gene in maize-containing foods that were obtained from grocery stores in Turkey. DNA extraction was performed by modified CTAB DNA extraction method for all samples and isolated DNA samples were checked by qPCR. Following extraction, the samples were analysed in 2% agarose gel electrophoreses. It was shown that the selected maize-containing foods in Turkey do not contain genetically modified using tNOS and CaMV.
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Life Sciences, Molecular Biology; Specnvezhenide; osteoarthritis; chondrocyte; NF-κB; wnt/β-catenin
Online: 16 June 2017 (04:20:07 CEST)
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As a chronic disease, osteoarthritis (OA) leads to degradation of both cartilage and subchondral bone, of which the development is related to proinflammatory cytokines like interleukin-1β. In the present study, the anti-inflammatory effect of Specnvezhenide in osteoarthritis and mechanism of it was studied in vitro and in vivo. The results showed that Specnvezhenide decreases interleukin-1β-induced expression of matix-degrading enzymes and reduces the activation of NF-κB and wnt/β-catenin pathways in vitro. Furthermore, Specnvezhenide treatment prevents the degeneration of both cartilage and subchondral bone in rats OA model. As conclusion, to the best of our knowledge, we report firstly that Specnvezhenide decreases interleukin-1β-induced inflammation on rat chondrocytes by inhibiting activation of NF-κB and wnt/β-catenin pathways, and has therapeutic potential in OA treatment.
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Life Sciences, Biochemistry; 8-prenylnaringenin; naringenin; cellular accumulation; glioblastoma; cytotoxicity; confocal microscopy
Online: 16 June 2017 (03:25:34 CEST)
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Gliomas are one of the most aggressive and treatment-resistant types of human cancer. One of the most promising field in gliomas cancer therapy is identification and evaluation of anticancer properties of compounds found in plants i.a. naringenin (N) and 8-prenylnaringenin (8PN). The prenyl group seem to be crucial to the anticancer activity of flavones, which may lead to enhanced cell membrane targeting and thus increased intracellular activity. Unfortunately, 8PN content in hop cones is from 10 to 100 times lower compared to other flavonoids i.e. xanthohumol. In this study we used a simple method for the synthesis of 8PN from isoxanthohumol, via O-demethylation with high, 97% of the isolated yield. Cellular accumulation and cytotoxicity of naringenin and 8-prenylnaringenin in normal (BJ) and cancer cells (U-118 MG) were also examined. Obtained data indicated that 8-prenylnaringenin exhibited higher toxicity against used cell lines than naringenin and both flavones inhibited stronger glioblastoma U-118 MG cells than normal fibroblasts. The anticancer properties of 8PN correlated with its significantly greater (37%), accumulation in glioblastoma cells than in normal fibroblasts. Additionally, naringenin indicated higher selectivity for glioblastoma as it was over 6 times more toxic for cancer than normal cells. Our results provide evidence that examined prenylated and non-prenylated flavanones have different biological activity against normal and cancer cell lines and this phenomenon may be useful in clinical practice to construct new, anticancer drugs for glioblastoma.
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Life Sciences, Other; human cytolytic fusion proteins; immunotherapy; microtubule associated protein tau (MAP); cancer; inflammatory diseases
Online: 15 June 2017 (12:02:31 CEST)
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Some of the most promising small molecule toxins used to generate antibody drug conjugates (ADCs) include anti-mitotic agents (e.g auristatin and its derivatives) which are designed to attack cancerous cells at their most vulnerable state during mitosis. We were interested to identify a human cystostatic protein eventually showing comparable activities and allowing the generation of corresponding targeted fully human cytolytic fusion proteins. Recently, we identified the human microtubule associated protein tau (MAP tau) which binds specifically to tubulin and modulates the stability of microtubules thereby blocking mitosis and presumably vesicular transport. By binding and stabilizing polymerized microtubule filaments, MAP tau-based fusion proteins skew microtubule dynamics towards cell cycle arrest and apoptosis. This biological activity makes rapidly proliferating cells (e.g cancer and inflammatory cells) an excellent target for MAP tau-based targeted treatments. Their superior selectivity for proliferating cells confers additional selectivity towards upregulated tumor-associated antigens at their surface, thereby preventing off-target related toxicity against normal cells bearing tumor-associated antigens at physiologically normal to low levels. In this review, we highlight recent findings on MAP tau-based targeted cytolytic fusion proteins reported in preclinical immunotherapeutic studies.
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Life Sciences, Microbiology; antimicrobial peptides; lipopeptides; cyclic lipopeptides Staphylococcus aureus; biofilm; culture media
Online: 13 June 2017 (06:09:47 CEST)
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Staphylococcus aureus bacteria are one of the leading microorganisms responsible for nosocomial infections as well as being the primary causative pathogen of skin and wound infections. Currently, the therapy of staphylococcal diseases faces many difficulties, due to a variety of mechanisms of resistance and virulence factors. Moreover, a number of infections caused by S. aureus is connected with biofilm formation that impairs effectiveness of the therapy. Short cationic lipopeptides that are designed on the basis of the structure of antimicrobial peptides structure are likely to provide a promising alternative to conventional antibiotics. Despite the fact that many research groups have proved a high antistaphylococcal potential of lipopeptides, the lack of unified protocols in determination of antimicrobial activity may be the reason of inconsistency of the results. The aim of this study was to learn how the use of various bacteriological media as well as solvents may affect activity of lipopeptides and their cyclic analogs.
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Life Sciences, Genetics; educational attainment; polygenes; polygenic selection; IQ; GWAS
Online: 8 June 2017 (08:11:07 CEST)
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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.
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Life Sciences, Molecular Biology; gibberellin; photoperiod; mutant; floral induction; flowering time
Online: 2 June 2017 (07:45:32 CEST)
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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.
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Hui Kong,
Xueqian Wang,
Rongfeng Shi,
Yan Zhao,
Jinjun Cheng,
Xin Yan,
Xiaoman Liu,
Yongzhi Wang,
Meiling Zhang,
Qingguo Wang,
Huihua Qu
Life Sciences, Other; pharmacokinetics; tissue distribution; indirect competitive enzyme-linked immunosorbent assay; puerarin
Online: 30 May 2017 (07:47:09 CEST)
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Puerarin (PUE) is a compound isolated from the roots of Pueraria lobata. We studied the pharmacokinetics and tissue distribution kinetics of PUE in Sprague-Dawley rats following intraperitoneal administration of three concentrations. Indirect competitive ELISA based on an anti-PUE monoclonal antibody was used to determine the concentration of PUE in the blood, heart, liver, spleen, lung, kidney, hippocampus, cerebral cortex, and striatum. The plasma and tissue distribution kinetic characteristics following a single injection of PUE (20, 40, and 80 mg/kg) were calculated using a non-compartment model. In the high-dose (80 mg/kg) and medium-dose (40 mg/kg) groups, the kinetic profile of PUE in blood and kidney samples showed two absorption peaks, while that of the other tissues showed only one peak. In the low-dose (20 mg/kg) group, there was only one peak, irrespective of the sample type. Pharmacokinetic parameters such as the area under the curve, Cmax, and Tmax varied according to the administered dose. AUC and Cmax values increased dose-dependently. PUE was widely distributed in areas of the brain such as the hippocampus, cerebral cortex, and striatum, providing a foundation for guiding the use of PUE in the treatment of cerebral ischaemic stroke and neurodegenerative diseases.
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Zhong Peng,
Sidi Liu,
Xiujuan Meng,
Wan Liang,
Biao Tang,
Yuanguo Wang,
Juping Duan,
Chenchao Fu,
Bin Wu,
Anhua Wu,
Chunhui Li
Life Sciences, Microbiology; Clostridium difficile; ST201; binary toxin-positive; whole genome sequencing; comparative genomic analysis
Online: 30 May 2017 (06:15:11 CEST)
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A novel binary toxin-positive non-027, non-078 Clostridium difficile strain designated LC693 whose sequence type was ST201 was isolated from the fecal sample of a patient with severe diarrhea in China. To understand the pathogenesis basis of C. difficile ST201, this recently recovered isolate LC693 was then chosen for whole genome sequencing. The project finally generated an estimated genome size of approximately 4.07 Mbp. The genome sequence was then analyzed together with the other two ST201 strains VL-0104 and VL-0391 and compared to the epidemic 027/ST1 and 078/ST11 strains. Phylogenetic analysis demonstrated that the ST201 strains belonged to clade 3. Genome size of the three ST201 strains ranged from 4.07 Mb~4.16 Mb, with an average GC content between 28.5%~28.9%. The ST201 genomes contained more than 40 antibiotic resistance genes and 15 of them were predicted to be associated with vancomycin-resistance, suggesting that they may have a strong antibiotic resistance. The ST201 strains contained a typical clade 3 specific PaLoc with a Tn6218 element inserted, and those genes harbored on their PaLoc that participated in the toxin expression and regulation were highly homologues to the epidemic 027 and 078 strains, with the exception of tcdC. A truncated TcdC was found in the ST201 strains, which is suggestive to have a contribution to the toxin production of the ST201 strains. In addition, the ST201 strains contained intact binary toxin coding and regulation genes, which is also proposed to contribute to the virulence. Genome comparison of the ST201 strains with the epidemic 027 and 078 strain identified 641 genes specific for the C. difficile ST201, and a number of them were predicted as fitness and virulence associated genes. The identification of those genes also contributes to the pathogenesis of the ST201 strain. To our knowledge, this is the first study that the genome sequence of C. difficile ST201 was discussed in detail, and the present study would have a contribution to understanding the pathogenesis basis of C. difficile ST201.
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Life Sciences, Biochemistry; loureirin B; Ins-1 cells; Insulin secretion; KATP channel; influx of Ca2+; expression of Cx43
Online: 26 May 2017 (04:52:12 CEST)
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The development of new diabetes drugs continues to be explored. Loureirin B, a flavonoid, extracted from Dracaena cochinchinensis, has been confirmed to increase insulin secretion and decrease blood glucose levels. For understanding the mechanism, a series of experiments had been employed based on computational methods and cell experiments. The insulin secretion significantly increased with the incubation of 0.01μM loureirin B for 4 hours. The viability of Ins-1 cells showed no significant difference with the treatment of loureirin B. Through computational methods, we hypothesized that loureirin B could interacts with KATP channels to promote insulin secretion. In cell experiments, it could be found that the current of KATP channel of Ins-1 cells was inhibited by the effect of loureirin B. After then, the voltage-dependent calcium channels were activated, the increase of Cx43 protein expression might mediate the Ca2+ to the intracellular. In summary, it could be concluded that loureirin B promoted insulin secretion mainly through inhibiting KATP current, the influx of Ca2+ to the Intracellular and the expression of Cx43.
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Life Sciences, Immunology; Zinc; infection; inflammation; homeostasis
Online: 24 May 2017 (08:48:15 CEST)
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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.
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Life Sciences, Endocrinology & Metabolomics; steroid; metabolism; anti-inflammatory drug; inhibition
Online: 24 May 2017 (08:25:26 CEST)
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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.
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Life Sciences, Genetics; educational attainment; polygenes; polygenic selection; IQ; GWAS
Online: 23 May 2017 (17:08:33 CEST)
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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.
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Life Sciences, Other; tooth wear; attrition; erosion; abrasion; palaeo-odontology
Online: 22 May 2017 (07:36:30 CEST)
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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.
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Life Sciences, Other; DNA fragmentation factors 40, DFF40, DNA fragmentation factors 45, DFF45, b-cell lymphoma 2, bcl-2, endometrium, menstrual cycle, uterine myometrium.
Online: 22 May 2017 (05:44:31 CEST)
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Abstract: DNA fragmentation factors 40 and 45 (DFF40 and DFF45) and B-cell lymphoma 2 (Bcl-2) expression were evaluated in the normal human endometrium and myometrium. DFF40, DFF45, and Bcl-2 expression was assessed via immunohistochemistry in the proliferative, secretory, and atrophic endometrium and myometrium collected postmenopausally and premenopausally during the proliferative and secretory phases of the menstrual cycle. The endometrium showed significantly higher DFF40 and DFF45 expression than that in the uterine myometrium; compared to the stroma, endometrial glands showed the highest expression in pre- and postmenopausal specimens. Glandular expression of DFF45 was dependent on the menstrual cycle, reaching its highest level in the secretory endometrium. The glandular expression of DFF40 and DFF45 was significantly lower in postmenopausal specimens than that in premenopausal tissue. No cycle-dependent changes were reported for stromal or myometrial DFF40 or DFF45 expression. Compared to the endometrial stroma and myometrium, Bcl-2 showed the highest expression in the glandular proliferative endometrium and the lowest expression in the stromal secretory endometrium and myometrium during the secretory phase of the cycle. DFF45 and Bcl-2 showed menstrual cycle-dependent expression, which was limited to the glandular layer of the endometrium.
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Life Sciences, Biophysics; cell fate decision; cancer attractors; gene network dynamics; EMT; drug resistance; intrinsically disordered proteins
Online: 17 May 2017 (06:25:17 CEST)
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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.
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Life Sciences, Biochemistry; Cholangiocarcinoma; DNA methylation; Tumor suppressor gene; microRNA; DNA methylation inhibitor
Online: 16 May 2017 (18:08:59 CEST)
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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.
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Life Sciences, Other; propolis; NIR spectroscopy; flavonoids; antioxidant capacity
Online: 12 May 2017 (05:53:14 CEST)
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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.
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Life Sciences, Other; indigenous goats; free range; milk production; milk composition
Online: 11 May 2017 (07:52:28 CEST)
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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.
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Life Sciences, Other; livestock; stover; lucerne; maize; bull; animals; dry matter; protein; cottonseed
Online: 11 May 2017 (05:04:11 CEST)
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The experiment was conducted at livestock research and development station surezai Peshawar during March 2012 to study the effect of cotton seed cake, Lucerne hay supplementation on intake of maize stover and weight gain by male sahiwal bull. Twelve (12) young Sahiwal bull breed, 280 kg average liveweight and 2 years of age were randomly put into 4 groups of 3 animals under intensive feeding system to determine the effect of different protein supplements on growth, and intake of chopped, dried maize stover. A control group was fed stover adlibitum only, and the other groups were fed daily 750 g cottonseed cake/head, 1 kg lucerne hay or 900 g of lucerne/cottonseed cake (66:34; w/w). Significant differences were observed on average daily live weight gains. Animals on lucerne and its mixture registered higher daily gains (243 g) and (330 g) respectively, followed by cottonseed cake (156 g); the control group lost weight (-8.0 g/d). Contrary to the live weight gains, animals fed on lucerne and its mixture had lower maize stover intakes, 3.35 kg DM/animal/day and 3.70 kg DM respectively, while those on cottonseed cake and the control group ingested respectively 4.72 kg DM and 4.16 kg DM maize Stover. It is concluded that during the critical period in the suburb of Peshawar, small-scale farmers can prevent loss in live weight by utilizing simple available rations.
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Life Sciences, Immunology; microbiome; probiotics, dietary supplements; nutrition; HIV infection, inflammation
Online: 8 May 2017 (12:10:17 CEST)
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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.
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Life Sciences, Molecular Biology; TRIM28; osteosarcoma; progression; E-cadherin
Online: 8 May 2017 (10:54:53 CEST)
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Tripartite motif containing 28 (TRIM28) is a transcriptional co-factor with pleiotropic biological activities, especially in tumor cells. In this study, expression levels of TRIM28 in osteosarcoma (OS) tissues and the correlations with clinicopathological variables were investigated in 87 OS cases, meanwhile, cell and animal experiments were performed to detect the biological functions of TRIM28. The results showed that TRIM28 was overexpressed in OS tissues compared with normal bones, and TRIM28 expression correlated significantly with tumor diameter (χ2 = 4.06, p=0.04), metastasis (χ2 =11.10, p< 0.01) and clinical stage (χ2 =15.50, p< 0.01). Furthermore, patients with high TRIM28 level always had poor survival (p < 0.01). Functionally, TRIM28 knockdown significantly inhabited cell ability of proliferation and migration in OS cell lines of in vitro and in vivo experiments. Additionally, TRIM28 could significantly inhibited E-cadherin expression in reducing the stability of the TRIM28 mRNA. Therefore, TRIM28 overexpression was correlated with malignant progression of OS and poor survival of OS patients, and TRIM28 pathway may be a therapeutic target for OS.
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Life Sciences, Biochemistry; alginate lyase; Vibrio sp.QD-5; alginate
Online: 8 May 2017 (09:27:58 CEST)
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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).
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Life Sciences, Molecular Biology; ABCC transporter; lateral roots; Triticum aestivum; auxin; transport inhibition
Online: 8 May 2017 (07:48:20 CEST)
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TaABCC13 is member of wheat ABCC subclass of transporters. The RNAi mediated silencing of this transporter in wheat results in lowering of seed phytic acid level and other developmental defects. In addition to that, wheat ABCC13 was involved in cadmium detoxification as evident by the complementation assays in yeast. The appearance of early lateral roots in these transgenic seedlings speculated the possibility for studying the role of localized auxin-mediated effects. In the current study, firstly, the expression of auxin related genes was studied in the transgenic roots. Enhanced expression of genes pertaining to either auxin biosynthesis or its transport was observed in transgenic wheat seedling roots suggesting the direct effect of the hormone. Further, the early emergence of lateral roots in transgenic wheat seedlings was affected due to the presence of auxin-transport inhibitor suggesting the direct effect of hormones in root development. In conclusion, herein we provide the novel evidence for the auxin mediated regulation of lateral root emergence in TaABCC13:RNAi seedlings.
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Life Sciences, Microbiology; core-shell; disinfection; Escherichia coli; nanoparticles; pathogens; silver; solar-photocatalysis; Staphylococcus aureus; water; zinc oxide
Online: 4 May 2017 (11:32:16 CEST)
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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 Ag@ZnO 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 Ag@ZnO 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 Ag@ZnO 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 Ag@ZnO core-shell nanoparticles have a good potential for application in solar photocatalytic disinfection of water borne pathogens.
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Life Sciences, Biochemistry; Vitamin E; vitamin A; maternal serum; lactation; liquid chromatography.
Online: 2 May 2017 (17:20:34 CEST)
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Vitamin A and E are important during pregnancy, the neonatal period, and childhood. The objective of this study was to assess whether maternal RRR-a-tocopherol supplementation affects serum and breast milk retinol. Serum was collected at baseline and twenty days later, and breast milk, at baseline, and on days 1, 7, and 20 after delivery. After the baseline serum collection, the supplemented group (n=16) received a single 400 IU of RRR-α-tocopherol. The control group (n=18) was only performed collections. Retinol and alpha tocopherol levels were determined by liquid chromatography. Serum retinol and alpha tocopherol at baseline and 20 days after delivery indicated proper vitamin A (> 20 µg/dL) and E (> 516 μg/dL) statuses in the control and supplemented groups (p > 0.05). Colostrum retinol levels on days 1 and 7 after delivery were significantly higher in the supplemented group (p = 0.018 and p = 0.012, respectively). Maternal vitamin E supplementation increased colostrum retinol by 52.23% and 111.2%, 24 hours and 7 days, respectively. However, retinol in mature milk did not differ between the groups (p > 0.05). In conclusion, the supplementation with 400 IU of RRR-α-tocopherol improved vitamin A bioavailability in breast milk.
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Life Sciences, Genetics; heat stress; cruciferae; ONSEN; retrotransposon
Online: 2 May 2017 (04:58:58 CEST)
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Transposable elements (TEs) are highly abundant in plant genomes. Environmental stress is one of the critical stimuli that activate TEs. We analyzed a heat-activated retrotransposon named ONSEN in cruciferous vegetables. The multiple copies of ONSEN-like elements (OLEs) were found in all the cruciferous vegetables that were analyzed. The copy number of OLE was abundant in Brassica oleracea, which includes cabbage, cauliflower, broccoli, Brussels sprout, and kale. Phylogenic analysis demonstrated that some OLEs transposed after the allopolyploidization of parental Brassica species. Furthermore, we found that the increasing number of OLEs in B. oleracea appeared to be induced transpositional silencing by epigenetic regulation, including DNA methylation. The results of this study would be relevant to the understanding of evolutionary adaptations to thermal environmental stress in different species.
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Life Sciences, Molecular Biology; fusion proteins; protein therapeutics; ricin; pokeweed antiviral protein; protein engineering; immunotoxins; ribosome-inactivating proteins.
Online: 1 May 2017 (10:51:21 CEST)
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Fusion protein therapeutics engineering is advancing to meet the need for novel medicine. Herein, we further characterize the development of novel RTA & PAP-S1 antiviral fusion proteins. In brief, RTA/PAP-S1 and PAP-S1/RTA fusion proteins were produced in both cell free and E. coli in vivo expression systems, purified by His-tag affinity chromatography, and protein synthesis inhibitory activity assayed by comparison to the production of a control protein, CalmL3. Results showed that the RTA/PAP-S1 fusion protein is amenable to standardized production and purification and has both increased potency and less toxicity compared to either RTA or PAP-S1 alone. Thus, this research highlights the developmental potential of novel fusion proteins with reduced cytotoxic risk and increased potency.
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Life Sciences, Other; Jivanti; Leptadenia reticulata; traditional medicine; herb; therapy; rasayana; galactagogue; pharmacology; biological activities; medicinal plant
Online: 1 May 2017 (10:25:26 CEST)
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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.
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Life Sciences, Cell & Developmental Biology; Spreading parameter; Cellular proliferation; Drug sensitivity; Substrates; Cancer cells
Online: 26 April 2017 (17:38:07 CEST)
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The interpretation of the local microenvironment of extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (PLLA and PCL) and collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter of (Nuclear/Cytoplasm) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity (IC50) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.
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Life Sciences, Molecular Biology; 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)
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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.
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Life Sciences, Biochemistry; GPCR; ubiquitination; β-arrestin; deubiquitinating enzyme; E3 ubiquitin ligase
Online: 21 April 2017 (06:23:26 CEST)
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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.
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Life Sciences, Biotechnology; lipid extracted microalgae, isoprenoids, detoxification
Online: 14 April 2017 (09:11:15 CEST)
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Microalgae are recognized as a third generation feedstock for biofuel production due to its rapid growth rate and lignin-free characteristic. In this study, the lipid extracted microalgae biomass residues was used as the material to produce isoprene, α-pinene and β-pinene with the engineered E. coli strain. We adopted an optimal sulfuric acid hydrolysis method to convert holocellulose into fermentable sugar efficiently (6.37 g/L) and explored a novel detoxification strategy (phosphoric acid/calcium hydroxide) to remove inhibitors notably. 55.32 % acetic acid, 99.19 % furfural and 98.22 % 5-HMF were cut down with the phosphoric acid/calcium hydroxide method, and the fermentation concentration of isoprene (223.23 mg/L), α-pinene (382.21 μg/L) and β-pinene (17.4 mg/L) using the detoxified hydrolysate as the carbon source account for approximately 86.02 %, 90.16 % and 88.32 % of those produced by the engineered E. coli strain fermented on pure glucose, respectively.
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Life Sciences, Microbiology; genistein; soy isoflavone extracts; anti-menopausal dietary supplements; bacterial growth; viability of human cells
Online: 13 April 2017 (05:33:06 CEST)
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Flavonoids, compounds present in many dietary supplements, affect growth of different bacterial species when tested as purified or synthetic substances. Here, we asked if soy isoflavone extracts, commonly used in many products sold as anti-menopausal dietary supplements, influence bacterial growth similarly to synthetic isoflavone, genistein. Four commercially available products were tested in amounts corresponding to genistein concentrations causing inhibition of growth of Vibrio harveyi (a model bacterium sensitive to this isoflavone) and Escherichia coli (a model bacterium resistant to genistein). Differential effects of various extracts on V. harveyi and E. coli growth, from stimulation, through no changes, to inhibition, were observed. Moreover, contrary to genistein, tested extracts caused a decrease (to different extends) in viability of human dermal fibroblasts. These results indicate that effects of various soy isoflavone extracts on bacterial growth and viability of human cells are different, despite similar declared composition of the commercially available products.
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Life Sciences, Endocrinology & Metabolomics; Keywords: vitamin D deficiency; diabetic retinopathy; meta-analysis.
Online: 11 April 2017 (06:16:22 CEST)
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Background: Diabetic retinopathy (DR) is one of the most prominent pathological microvascular complications in diabetes. A series of studies reported that vitamin D deficiency was associated with increased prevalence of retinopathy in diabetic patients but the results were inconsistent. In this study we focused on evaluating the relationship between vitamin D deficiency and DR by conducting a meta-analysis of observational studies. Methods: Systematic computerized searches were performed in PubMed, MEDLINE, and the Cochrane Library for relevant original articles till November 20, 2016. The pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated to assess the associated value of vitamin D deficiency to the risk of DR. 9 studies including 6332 participants were subjected to final analysis. Results: The results indicated that vitamin D deficiency increases the risk of DR (OR = 1.57, 95% CI 1.32-1.87) with a little heterogeneity (I2 = 23%). In addition, the subgroup analysis demonstrated that there were obvious heterogeneities in T2DM (I2 = 47.8%). Sensitivity analysis showed that the results were relatively stable and reliable. Conclusion: our meta-analysis demonstrated that vitamin D deficiency could increase the risk of DR.
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Life Sciences, Other; micronutrients; inadequacies; usual daily intake; China
Online: 10 April 2017 (06:10:20 CEST)
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The aim of this study was to examine usual daily micronutrient intake of Chinese children based on data from the 2011 China Health and Nutrition Survey. We analyzed data from 4 to 17-year-old participants, who provided dietary data on 3 consecutive days combined with the household weighing method in 2011. Usual daily intake of each nutrient was estimated using a mixed effects model based on the China Food Composition published in 2002 and 2004. The means, medians and percent below Estimated Average Requirements (EAR) were reported for selected micronutrients, including calcium, sodium, potassium, iron, zinc, selenium, vitamin A, thiamine, riboflavin and vitamin C. For sodium and potassium, means and the distribution of intakes were compared to the Adequate Intake (AI) level. The average usual daily intakes of all micronutrients increase with age and the intakes of boys higher than girls in the same age group. The average of calcium intakes increased from 272mg/d in 4-6y to 391mg/d in 14-17y, but the percentage of inadequate calcium intake remained very high (>96%). The prevalence of inadequacy of calcium was the highest among the mineral nutrients reported in this study. As the requirement of micronutrient increased with age, the percentage of subjects with inadequate intake increased in 11-17 age groups. Among the 14-17y, the percentages of study participants with dietary intakes of calcium, iron, zinc, selenium, vitamin A, thiamine, riboflavin and vitamin C below the EAR were 96.8%, 18.8%, 37.6%, 72.8%, 36.8%, 91.8%. 85.9% and 75.5%, respectively. Among the 11-13y, the percentages of study participants with dietary intakes of iron, zinc and vitamin A below the EAR were 23.5%, 41.5%, and 41.6%, respectively. Thus, the micronutrients deficiency is a problem in Chinese Children. Nutrition education and intervention programs are needed to address the nutritional gaps.
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Life Sciences, Molecular Biology; Lynch syndrome; segregation analysis; MSH6 gene; hereditary colorectal cancer; oligogenic model
Online: 5 April 2017 (03:04:02 CEST)
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Background: Lynch syndrome, the most frequent form of hereditary colorectal cancer and involves mutations in mismatch repair genes. The aim of this study was to identify mutations in MSH6 from 97 subjects negative for mutations in MLH1 and MSH2. Methods: By direct sequencing, we identified 27 MSH6 variants, of which, nine were novel. To verify the pathogenicity of these novel variants we performed in silico and segregation analyses. Results: Three novel variants were predicted by in silico analysis as damaging mutations and segregated with the disease phenotype. While, a novel frameshift deletion variant that was predicted to yield a premature stop codon, did not segregate with the LS phenotype in 3 of 4 cases in the family. Interestingly, another frame-shift variant identified in this study, already described in the literature, also did not segregate with the LS phenotype in 1 of 2 affected subjects in the family. In all affected subjects of both families, no mutation was detected in other MMR genes. Therefore, it is expected that within these families other genetic factors contribute to the disease either alone or in combination with MSH6 variants. Conclusion: We conclude that caution should be exercised in counseling for MSH6-associated LS family members.
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Life Sciences, Molecular Biology; NF-кB, Hypoxia, Inflammation, IKK, PHDs, Cancer, TAK1, FIH
Online: 31 March 2017 (17:21:52 CEST)
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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.
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Life Sciences, Biochemistry; green tea catechins; prostate cancer; chemoprevention; metabolism; nanoparticles; epigenetic; proteostasis
Online: 31 March 2017 (12:46:15 CEST)
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Green Tea Catechins (GTCs) are a family of chemically related compounds usually classified as antioxidant molecules. Epidemiological evidences, supported by interventional studies, highlighted a more than promising role for GTCs in human Prostate Cancer (PCa) chemoprevention.In the last decades many efforts have been made to gain new insights into the mechanism of action of GTCs. Now it is clear that GTCs anticancer action can no longer be simplistically limited to their direct antioxidant/pro-oxidant properties. Recent contributions to the advancement of knowledge in this field have shown that GTCs specifically interact with cellular targets including, cell surface receptors, lipid rafts and endoplasmic reticulum, modulate gene expression through direct effect on transcription factors or indirect epigenetic mechanisms, interfere with intracellular proteostasis at various levels. Many of the effects observed in vitro are dose and cell context dependent and take place at concentration that cannot be achieved in vivo.Poor intestinal absorption together with an extensive systemic and enteric metabolism influence GTCs bioavailability through still poor understood mechanisms. Recent efforts to develop delivery systems that increase GTCs overall bioavailability, by mean of biopolymeric nanoparticles, represent the main way to translate preclinical results in a real clinical scenario for PCa chemoprevention.
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Life Sciences, Virology; Filamentous phage; M13; gp1; Zonula occludens toxin (Zot); phage assembly; assembly 27 complex; ATPase; membrane protein; molecular hinge; secretion; Walker motifs
Online: 31 March 2017 (11:13:40 CEST)
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In contrast to lytic phages, filamentous phages are assembled in the inner membrane and secreted across the bacterial envelope without killing the host. For assembly and extrusion of the phage across the host cell wall, filamentous phages code for membrane-embedded morphogenesis proteins. In the outer membrane of E. coli, the protein gp4 forms a pore-like complex, while gp1 and gp11 form a complex in the inner membrane of the host. By comparing sequences with other filamentous phages, we identified putative Walker A and B motifs in gp1 with a conserved lysine in the Walker A motif (K14), and a glutamic and aspartic acid in the Walker B motif (D88, E89). In this work we demonstrate that both, Walker A and Walker B, are essential for phage production. The crucial role of these key residues suggest that gp1 is likely to be a molecular motor driving phage assembly. We further identified essential residues for the function of the assembly complex. Mutations in three out of six cysteine residues abolish phage production. Similarly, two out of six conserved glycine residues are crucial for gp1 function. We hypothesise that the residues represent molecular hinges allowing domain movement for nucleotide binding and phage assembly.
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Life Sciences, Biotechnology; bioethanol, fruits, Corn Threshing Residue, fermentation, distillation
Online: 30 March 2017 (17:49:30 CEST)
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Alcoholic fermentations were performed adapting the technology to exploit the residual thermal energy (hot water at 83-85°C) of a cogeneration plant and to valorize agricultural wastes. Substrates were apple, kiwifruit and peaches wastes and Corn Threshing Residue (CTR). Saccharomyces bayanus was chosen as biocatalyst. The fruits, fresh or blanched, were mashed; CTR was gelatinized and liquefied by adding Liquozyme® SC DS (Novozyme); saccharification simultaneous to fermentation was carried out using the enzyme Spirizyme® Ultra (Novozyme). Lab-scale static fermentations were carried out at 28°C and 35°C, using raw fruits, blanched fruits and CTR, monitoring the ethanol production. The highest ethanol production was reached with CTR (10,22%9 and among fruits with apple (8,71%). Distillations at low temperatures and under vacuum, to exploit warm water from cogeneration plant, were tested; distillation at 80°C and 200 mbar or 400 mbar allowed to recover 93,35 and 89,59 % of ethanol respectively. These results support a fermentation process coupled to a cogeneration plant, fed with apple wastes and with CTR when apple wastes are not available, where hot water from cogeneration plant is used in blanching and distillation phases. The scale up in a pilot plant was also carried out.
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Life Sciences, Biotechnology; Auxin, Cutting, Hybrid aspen, Rooting
Online: 30 March 2017 (16:22:32 CEST)
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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.
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Life Sciences, Other; olive pomace oil; fatty acid profile; total nitrogen content; total protein; olive pomace; biochemical characterization
Online: 20 March 2017 (08:40:46 CET)
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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.
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Life Sciences, Other; 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)
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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.
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Life Sciences, Cell & Developmental Biology; 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)
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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.
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Life Sciences, Biophysics; erythema; swimming; re-application; exposed skin surface; natural sunlight
Online: 17 March 2017 (04:59:23 CET)
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Background: The efficacy of sunscreen is evaluated by SPF values, which are quantitatively determined in laboratories on the backs of human subjects according to a standardized procedure. However, SPF cannot be directly translated to sunburn protection under real-life situations because actual efficacy depends on various factors related to human behaviors and environmental conditions. This study clinically evaluated the efficacy of two sunscreen sprays (SPF 30 and SPF 70) under natural sunlight exposure on healthy subjects at the beach. Methods: Twenty subjects were divided into two cells for the two sunscreen sprays (SPF 70 and SPF 30) in a single-center, actual usage test. The primary endpoint of the study was sunburn protection on the dorsal arms and the secondary endpoint was protection on the face and neck. Subjects stayed at the beach for 4 h after application of the sunscreens with normal beach activities. Subjects’ behavior at the beach, the amounts of sunscreen applied and reapplied, and environmental conditions were all recorded. Results: There was no significant sunburn for a majority of the subjects in either cell. However, neither sunscreen completely blocked the sunburn, especially for the face/neck area. We found that the SPF 70 sunscreen was more effective than the SPF 30 sunscreen. Conclusion: Modern sunscreen sprays, applied liberally, are effective in providing sunburn protection for the body in a beach setting.
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Life Sciences, Molecular Biology; genetic code; tRNA dimers; self-reference; modularity; error-compensation; metabolism chronology; protein stability; punctuation system
Online: 17 March 2017 (04:55:46 CET)
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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.
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Life Sciences, Other; cancer; incidence; endocrine disruptors; environmental exposure
Online: 16 March 2017 (06:42:22 CET)
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The aim of the present study was to investigate the incidence of breast (females), prostate, testicular and thyroid cancer in the Italian National Priority Contaminated Sites (NPCSs), served by cancer registries, where the presence of endocrine disruptors (EDs), reported to be linked to these tumors, was documented. Evidence of carcinogenicity of EDs present in NPCs was assessed based on evaluation by international scientific institutions/committees. Standardized Incidence Ratios (SIRs) were computed for each NPCS and cancer site with reference to the time window 1996-2005. Excess incidence of one or more cancer site at study was found in twelve out of fourteen NPCSs. Significantly increased SIRs were found for breast cancer in eight NPCSs, for prostate cancer in six, for thyroid cancer (both gender) in four and for testicular cancer in two. Non significantly increased SIRs were found in five NPCSs for testicular cancer and in two for thyroid cancer (males). Even if increased incidence of one or more cancer sites at study were found in several NPCSs, the ecological study design and the multifactorial etiology of the considered tumors do not allow reaching conclusions in terms of causal links with environmental contamination. In light of the observation of some excesses in SIRs, continuing epidemiological surveillance is warranted.
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Life Sciences, Molecular Biology; glucose transporter; GLUTs; chicken; avian; mammal; phylogenetic analysis
Online: 15 March 2017 (08:34:06 CET)
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The GLUT members belong to a family of glucose transporter proteins that facilitate glucose transport across the cell membrane. The mammalian GLUT family consists of thirteen members (GLUTs 1-12 and HMIT). Humans have a recently duplicated GLUT member, GLUT14. Avians express the majority of GLUT members. The arrangement of multiple GLUTs across all somatic tissues signifies the important role of glucose across all organisms. Defects in glucose transport have been linked to metabolic disorders, insulin resistance and diabetes. Despite the essential importance of these transporters, our knowledge regarding GLUT members in avians is fragmented. It has been clear that there are no chicken orthologs of mammalian GLUT4 and GLUT7. Our examination of GLUT members in the chicken revealed that some chicken GLUT members do not have corresponding orthologs in mammals. We review the information regarding GLUT orthologs and their function and expression in mammals and birds, with emphasis on chickens and humans.
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Life Sciences, Cell & Developmental Biology; Th17 cells; blood - brain barrier; chemokines; VCAM-1; neuroinflammation; multiple sclerosis
Online: 15 March 2017 (07:34:02 CET)
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The nature of the interaction between Th17 cells and the blood-brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). TNF-a or IL-17 stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express VCAM-1, the receptor responsible for inflammatory cell adhesion, which binds VLA-4 on migrating effector lymphocytes at the early stage of brain inflammation. The present study examines the effect of the pro-inflammatory cytokines TNF-a and IL-17 on the adherence of Th17 cells to bEnd.3 The bEnd.3 cells were found to increase production of CCL2 and CXCL1 after stimulation by pro-inflammatory cytokines, while CCL2, CCL5, CCL20 and IL17 induced Th17 cell migration through a bEnd.3 monolayer. This interaction between Th17 cells and the brain endothelium appears to be mediated by VCAM-1 and some chemotactic cytokines. This observation may suggest potential therapeutic targets for the prevention of autoimmune neuroinflammation development in the CNS.
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Life Sciences, Microbiology; water; physical; chemical; microbiological; quality; household; stored; source
Online: 14 March 2017 (10:49:43 CET)
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In this study, we evaluated the physicochemical and microbial qualities of source and stored household waters in some communities in Southwestern Nigeria using standard methods. Compared parameters include physicochemical constituents; Temperature (T), pH, Total Dissolved Solids (TDS), Total Hardness (TH), Biological Oxygen Demand (BOD), Magnesium ion (Mg2+) and Calcium ion (Ca2+) and microbiological parameters included Total Coliform Counts (TC), Faecal Coliform Counts (FC), Fungal Counts (Fung C), Heterotrophic Plate Counts (HPC). Comparing Stored and Source samples, the mean values of some physicochemical parameters of most of the stored water samples significantly (P<0.05) exceeded that of Sources and ranged in the following order: T (15.3±0.3oC - 28.3±0.5oC), pH (6.4±0.1 - 7.6±0.1), TDS (192.1±11.1 ppm - 473.7±27.9 ppm), TH (10.6±1.7 mg/L - 248.6±18.6 mg/L), BOD (0.5±0.0 mg/L - 3.2±0.3 mg/L), Mg2+ (6.5±2.4 mg/L - 29.1±3.2 mg/L) and Ca2+ (6.5±2.4 mg/L - 51.6±4.4 mg/L). The mean microbial counts obtained from microbial comparison of different points (Stored and Source) of collection showed that most of the stored water had counts significantly exceeding (P<0.05) those of the source water samples (cfu/100 mL) which ranged as follows: TC (3.1±1.5 - 156.8±42.9), FC (0.0±0.0 - 64.3±14.2) and HPC (47.8±12.1 - 266.1±12.2) across all sampled communities. Also, the predominant isolates recovered from the samples were identified as Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Enterobacter aerogenes, Aspergillus spp, Mucor spp, Rhizopus spp and Candida spp. The presence of these pathogenic and potentially pathogenic organisms in the waters and the high counts of the indicator organisms suggest the waters to be a threat to public health.
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Life Sciences, Molecular Biology; miRNAs; pre-miRNAs sequencing; Abelmoschus esculentus; Next generation sequencing; non-model plant
Online: 14 March 2017 (10:15:14 CET)
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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.
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Life Sciences, Other; mercury; exposure assessment; human health; artisanal and small-scale gold mining
Online: 14 March 2017 (08:40:59 CET)
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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.
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Life Sciences, Microbiology; Remotely Operated Vehicle; Metatranscriptomics; Niskin
Online: 10 March 2017 (10:50:15 CET)
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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.
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Life Sciences, Molecular Biology; ovarian cancer; melatonin; angiogenesis; VEGF; VEGFR; HIF-1α
Online: 6 March 2017 (06:34:02 CET)
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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.
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Life Sciences, Biotechnology; fumaric acid; purification; spent sulfite liquor; biorefineries
Online: 1 March 2017 (09:41:31 CET)
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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.
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Life Sciences, Molecular Biology; fructose; obesity; liver; aerobic exercise; strength exercise; combined exercise
Online: 28 February 2017 (12:02:06 CET)
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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.
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Life Sciences, Other; melatonin; testis; androgen production; oxidative stress; inflammation; infertility; Leydig cells; Sertoli cells; mast cells; macrophages
Online: 27 February 2017 (08:56:51 CET)
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Environmental darkness signal is transferred from the retina to the pineal gland triggering melatonin secretion. Melatonin influences the synthesis and release of the hypothalamic GnRH and the adenohypophyseal gonadotropin hormones and therefore, regulates testicular function in photoperiodic species. Besides the brain, direct actions of melatonin at the testicular level have also been described. Melatonin released from the pineal gland to the circulation is taken up by peripheral tissues including testes. Testicular synthesis of melatonin has also been reported. The two key somatic cell types in the testis, Leydig and Sertoli cells, express melatonergic receptors. Melatonin acts as a local modulator of the endocrine activity in Leydig cells. In Sertoli cells, melatonin influences the oxidation state and the energy metabolism, and consequently may regulate spermatogenesis. Melatonergic receptors were also described in testicular macrophages and mast cells of infertile patients. Whereas melatonin exerts anti-proliferative and anti-inflammatory effects on testicular macrophages, it provides protective effects against oxidative stress in testicular mast cells. These data pinpoints melatonin as a key player in the regulation of testicular physiology (i.e. steroidogenesis, spermatogenesis) mostly in seasonal breeders. More importantly, melatonin is also involved in the modulation of testicular inflammatory and oxidant/anti-oxidant states in patients with idiopathic infertility.
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Life Sciences, Molecular Biology; alfalfa; drought; microRNA; small RNA; differential expression
Online: 23 February 2017 (09:50:07 CET)
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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.
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Life Sciences, Biochemistry; albumin; oxidative stress; exercise; ultra-marathon mountain race; protein oxidation
Online: 17 February 2017 (15:02:03 CET)
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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.
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Beatrice Casini,
Francesco Aquino,
Michele Totaro,
Mario Miccoli,
Irio Galli,
Laura Manfredini,
Valentino Serini,
Anna Laura Costa,
Benedetta Tuvo,
Paola Valentini,
Gaetano Privitera,
Angelo Baggiani
Life Sciences, Microbiology; Hydrogen Peroxide; Legionella; Hospital; Disinfection
Online: 16 February 2017 (18:48:27 CET)
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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.
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Life Sciences, Other; tumor microenvironment; nanoparticle; nanotheronostics; probe; imaging
Online: 13 February 2017 (09:33:16 CET)
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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).
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Life Sciences, Virology; seroprevalence; WNV; blood donors; blood bank; Sudan
Online: 3 February 2017 (09:47:48 CET)
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Background: West Nile virus is one of the transfusion transmitted viral infections with worldwide distribution; it can cause severe disorders of the Central Nervous System. Aim: This research aimed to provide information about the seroprevalence of WNV among blood donors at Central Blood Bank, Khartoum State-Sudan. Materials & methods: Ninety sera specimen were randomly collected from blood donors at Central Blood Bank. All collected sera specimen were tested for the presence anti-West Nile virus (IgM & IgG) antibodies by using semi-quantitative indirect ELISA. Results: Out of Ninety blood donor sera, 40 (44.4 %) were reactive for anti-WNV IgG antibody, whereas 2 (2.2%) were reactive for anti-WNV IgM antibody. Conclusion & recommendations: In spite of higher percentage of Blood Donors at Central Blood Bank, Khartoum State-Sudan was exposed to West Nile virus, there were few recent cases. High care should be taken by health authorities for screening of blood donors, particularly when administered to immunocompromised patients.
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Life Sciences, Microbiology; Deformed cloacal region; Danio rerio; Live-Cell imaging; Salmonella infection; Immune response; Cloacitis
Online: 3 February 2017 (04:18:59 CET)
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Pathogenic Salmonella strains have a set of virulence factors allowing them to generate systemic infections and damage in a variety of hosts. Among these factors, bacterial proteins secreted by specialized systems are used to penetrate the host’s intestinal mucosa, through the invasion and destruction of specialized epithelial M cells in the intestine. On the other hand, numerous studies have demonstrated that humans, as well as experimental animal hosts, respond to Salmonella infection by activating both innate and adaptive immune responses. Here, through live cell imaging of S. Typhimurium infection of zebrafish larvae, we showed that besides the intestinal colonization, a deformed cloacae region and a concomitant accumulation of S. Typhimurium cells was observed upon bacterial infection. The swelling led to a persistent inflammation of infected larvae, although the infection was non-lethal. The in vivo inflammation process was confirmed by the co-localization of GFP-tagged S. Typhimurium with mCherry-tagged neutrophils at 72 hours post exposition. Our live-cell analyses suggest that Salmonella Typhimurium induce cloacitis-like symptoms in zebrafish larvae. Typhimurium induce cloacitis-like symptoms in zebrafish larvae.
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Life Sciences, Biochemistry; Aquatic-toxic effects; EU chemical regulation; Glyoxal-containing cellulose ether
Online: 31 January 2017 (12:10:39 CET)
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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.
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Life Sciences, Molecular Biology; blunt snout bream; high carbohydrate; transcriptome; metabolomics; insulin resistance; fatty liver disease
Online: 26 January 2017 (03:52:10 CET)
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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.
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Life Sciences, Molecular Biology; aldo-keto reductases; cigarette smoke; smokeless tobacco products; nicotine; oral cavity cells; xenobiotic metabolism
Online: 25 January 2017 (04:20:07 CET)
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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.
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Life Sciences, Molecular Biology; spermine; cyclooctaoxygen; DNA; selenium; glyphosate; AMPA
Online: 25 January 2017 (03:10:06 CET)
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Oxygen exists in two gaseous and six solid allotropic modifications. An additional allotropic modification of oxygen, the cyclooctaoxygen, was predicted to exist in 1990. The first synthesis and characterization of cyclooctaoxygen as its sodium crown complex, isolated in the form of three cytosine nucleoside hydrochloride complexes, was reported in 2016. Cyclooctaoxygen sodium was synthesized from atmospheric oxygen, or catalase effect-generated oxygen, under catalysis of cytosine nucleosides and either ninhydrin or eukaryotic low-molecular weight RNA. The cationic cyclooctaoxygen sodium complex was shown to bind RNA and DNA, to associate with single-stranded DNA and spermine phosphate, and to be essentially non-toxic to cultured mammalian cells at 0.1–1.0 mM concentration. We postulated that cyclooctaoxygen is formed in most eukaryotic cells from dihydrogen peroxide in a catalase reaction catalysed by cytidine and RNA. A molecular biological model was deduced for a first epigenetic shell of eukaryotic euchromatin. This model incorporates an epigenetic explanation for the interactions of the essential micronutrient selenium (as selenite) with eukaryotic euchromatin. The sperminium phosphate/cyclooctaoxygen sodium complex is calculated to cover the actively transcribed regions (2.6%) of bovine lymphocyte interphase genome. Cyclooctaoxygen seems to be naturally absent in hypoxia-induced highly condensed chromatin, taken as a model for eukaryotic metaphase/anaphase/early telophase mitotic chromatin. We hence propose that the cyclooctaoxygen sodium-bridged spermine phosphate and selenite coverage serves as an epigenetic shell of actively transcribed gene regions in eukaryotic ‘open’ euchromatin DNA. The total herbicide glyphosate (ROUNDUP) and its metabolite (aminomethyl)phosphonic acid (AMPA) are proved to represent ‘epigenetic poisons’, since they both selectively destroy the cyclooctaoxygen sodium complex. This definition is of reason, since the destruction of cyclooctaoxygen is sufficient to bring the protection shield of human euchromatin into collateral epigenetic collapse.
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Life Sciences, Biotechnology; magnetic hyperthermia; gene therapies; heat shock protein promoter; in vivo optical imaging; magnetic polymer-coated nanoparticles
Online: 24 January 2017 (04:14:19 CET)
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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.
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Maria Pitrone,
Giuseppe Pizzolanti,
Laura Tomasello,
Antonina Coppola,
Lorenzo Morini,
Gianni Pantuso,
Romina Ficarella,
Valentina Guarnotta,
Sebastio Perrini,
Francesco Giorgino,
Carla Giordano
Life Sciences, Endocrinology & Metabolomics; adipose derived stem cell (ASC); regenerative medicine; embryonic stem cell marker network
Online: 19 January 2017 (10:59:11 CET)
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The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90 and CD105 and NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.
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Songzi Zhang,
Huizhu Liu,
Yuxia Liu,
Jie Zhang,
Hongbo Li,
Weili Liu,
Guohong Cao,
Pan Xu,
Jinjin Zhang,
Changjun Lv,
Xiaodong Song
Life Sciences, Molecular Biology; idiopathic pulmonary fibrosis; miR-30a; TET1; Drp-1
Online: 16 January 2017 (04:44:44 CET)
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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.
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Life Sciences, Biotechnology; C-type lectin; agglutination; CRD; bacterial detection; E. coli
Online: 13 January 2017 (13:17:13 CET)
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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.
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Life Sciences, Molecular Biology; cancer; microRNA; gene therapy; oncogene; tumor suppressor gene
Online: 9 January 2017 (10:24:03 CET)
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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.
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Life Sciences, Molecular Biology; Sarcocystis neurona; EPM; docking; apicomplexans; phylogeny; homology modeling
Online: 9 January 2017 (05:19:32 CET)
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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.
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Life Sciences, Virology; H7N9 avian influenza; pseudovirus; neutralization assay; relative luminescence units (RLU)
Online: 6 January 2017 (10:21:52 CET)
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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.
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Life Sciences, Molecular Biology; symbiogenesis; eukaryogenesis; RNA world; expensive brain; human evolution; hydrothermal vent
Online: 4 January 2017 (07:34:07 CET)
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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.
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Life Sciences, Biochemistry; ATP-dependent proteolysis, Non-native membrane proteins, Periplasmic domain, Crystal structure, Photosystem II.
Online: 29 December 2016 (17:16:52 CET)
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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.
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Life Sciences, Microbiology; aflatoxin B1; transaminases; hepatocellular carcinoma; Saudi patients; liver dysfunction
Online: 29 December 2016 (10:59:51 CET)
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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.
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Life Sciences, Molecular Biology; zebrafish; models; evaluation; drugs; cardiotoxicity; genotoxicity
Online: 20 December 2016 (10:34:56 CET)
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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.