Preprint
|
|
|
Life Sciences, Molecular Biology; ultrasound imaging; serum biomarker; steatohepatities; hepatocellular carcinoma
Online: 19 April 2018 (10:22:09 CEST)
|
|
Share this article with
×
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of lesions ranging from steatosis to a complex pattern, nonalcoholic steatohepatitis (NASH). Ultrasonography provides important information on hepatic architecture for steatosis. NASH patients have an increased risk of hepatocellular carcinoma. Early detection of NASH is critical for the clinicians to advice on necessary treatments to prevent the onset of hepatocellular carcinoma (HCC). In this study, we established a NASH-HCC mouse model using diethylnitrosamine as carcinogen to induce HCC and high fat diet to induce metabolic disorders. Characteristics of ultrasound imaging and potential serum biomarkers were investigated for detection of steatohepatitis and HCC in mice. The data suggested that the ultrasound imaging of hyperechoic mass was potentially linked to the gross finding of hepatocellular carcinoma nodule which was further confirmed by the histology. Positive correlation between serum fibroblast growth factor 15 and acoustic attenuation coefficient was found in steatohepatitis mice. Combing with the serum markers, the increased acoustic attenuation coefficient could be a useful diagnostic parameter of ultrasound imaging for nonalcoholic steatohepatitis detection. This study demonstrates that combination of serum fibroblast growth factor 15 and acoustic attenuation coefficient could be a sensitive marker for steatohepatitis and to predict carcinogenic initiation and progression of hepatocellular carcinoma in mice. These results might help for the design of ultrasound and surrogate markers in screening nonalcoholic steatohepatitis patients who could be at risk of hepatocellular carcinoma.
Preprint
|
|
|
Life Sciences, Biotechnology; sterol glycosyltransferase; O-methyltransferase; Streptomyces avermitilis MA-4680; biotransformation; Cholesterol-3-O-β-D-glucoside; GC-MS
Online: 19 April 2018 (09:31:06 CEST)
|
|
Share this article with
×
A sterol glycosyltransferases (SGT) gene (sav7185; accession number NP_828361) was isolated from Streptomyces avermitilis MA-4680. The full-length gene consists of 1284 nucleotides and encodes 427 amino acids with a calculated mass of 46.05 kDa. The gene was then cloned in pET28a vector and heterologously expressed in Escherichia coli BL21 (DE3) and was used for the biotransformation of cholesterol. This SGT protein showed favorable activity towards cholesterol tested in this study. Further, we tested the conversion of cholesterol to its methoxide using another Streptomyces O-methyltransferase (accession number KF420279). This O-methyltransferase (OMT) SpOMT2884, originating from Streptomyces peucetius ATCC 27952, was cloned, expressed, and applied for the production of methylated derivative. The GC-MS analysis confirmed the conversion of cholesterol into cholesterol-3-O-β-D-glucoside and a novel cholesterol-3-O-methoxide. Hence, these Streptomyces SGT and OMT could find applications for the derivatization of pharmaceutically significant sterols.
Preprint
|
|
|
Life Sciences, Biochemistry; Non-small cell lung cancer; Lambertianic acid; Apoptosis; TRAIL; XIAP; NF-B
Online: 18 April 2018 (15:25:10 CEST)
|
|
Share this article with
×
Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population and cleaved poly (ADP-ribose) polymerase (PARP) and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) and enhanced the activation of pro-apoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-B), inhibitory protein of kB family (p-IB) and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-B. Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-B in TRAIL resistant NSCLCs.
Preprint
|
|
|
Life Sciences, Biochemistry; axon guidance; DRS; HGPPS; CFEOM3; in silico; systems biology; PPI network
Online: 18 April 2018 (08:23:58 CEST)
|
|
Share this article with
×
Axon guidance is a crucial process for growth of the central and peripheral nervous systems. In this study, 3 axon guidance related disorders, namely- Duane Retraction Syndrome (DRS) , Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS) and Congenital fibrosis of the extraocular muscles type 3 (CFEOM3) were studied using various Systems Biology tools to identify the genes and proteins involved with them to get a better idea about the underlying molecular mechanisms including the regulatory mechanisms. Based on the analyses carried out, 7 significant modules have been identified from the PPI network. Five pathways/processes have been found to be significantly associated with DRS, HGPPS and CFEOM3 associated genes. From the PPI network, 3 have been identified as hub proteins- DRD2, UBC and CUL3.
Preprint
|
|
|
Life Sciences, Virology; alpha-sheet; cancerous tumors; capsid dynamics; drug delivery vehicles; native gel electrophoresis; neurodegenerative disease; pathogenic viruses
Online: 17 April 2018 (09:00:05 CEST)
|
|
Share this article with
×
Studies of phage capsids have at least three potential interfaces with nanomedicine. First, investigation of phage capsid states potentially will provide therapies targeted to similar states of pathogenic viruses. Recently detected, altered radius-states of phage T3 capsids include those probably related to intermediate states of DNA injection and DNA packaging (dynamic states). We discuss and test the idea that some T3 dynamic states include extended α-sheet in subunits of the capsid’s shell. Second, dynamic states of pathogenic viral capsids are possible targets of innate immune systems. Specifically, α-sheet-rich innate immune proteins would interfere with dynamic viral states via inter-α-sheet co-assembly. A possible cause of neurodegenerative diseases is excessive activity of these innate immune proteins. Third, some phage capsids appear to have characteristics useful for improved drug delivery vehicles (DDVs). These characteristics include stability, uniformity and a gate-like sub-structure. Gating by DDVs is needed for (1) drug-loading only with gate opened, (2) closed gate-DDV migration through circulatory systems (no drug leakage-generated toxicity), and (3) drug release only at targets. A gate-like sub-structure is the connector ring of double-stranded DNA phage capsids. Targeting to tumors of phage capsid-DDVs can possibly be achieved via the enhanced permeability and retention effect.
Preprint
|
|
|
Life Sciences, Biotechnology; bone graft, resorbable barrier, sinus lift, heterologous cortical lamina
Online: 16 April 2018 (13:53:55 CEST)
|
|
Share this article with
×
Abstract A variety of surgical techniques have been developed to reconstruct the posterior maxilla when bone volume is insufficient. A barrier membrane or bone window pushed inside the sinus cavity as the ‘‘roof’’ of the sinus cavity for preserve the space and help bone. The heterologous cortical lamina is used for the mechanical support, without any grafting material, of sinus membranes resulting in only bone tissue formation and not mixed with the graft.
Preprint
|
|
|
Life Sciences, Biotechnology; lignocellulosic biomass; laccases; peroxidases; green biochemical; acidophilic microbes
Online: 16 April 2018 (10:36:26 CEST)
|
|
Share this article with
×
Lignocellulosic feedstock (cellulose, hemicellulose and lignin) has been used for a variety of purposes. Among them, lignin can produce value-added chemicals having phenyl-propanoid subunits known as core lignin, possessing either C-C bonds or ether linkages. It can be depolymerized by microbial activity together with certain enzymes (laccases and peroxidases). Both acetic acid and formic acid production by certain fungi contribute significantly to lignin depolymerization. Natural organic acids production by fungi has many key roles in nature that are strictly dependent upon organic acid producing fungus type. Enzymatic conversion of lignocellulosic is beneficial over other physiochemical processes. Laccases, the copper containing proteins oxidize a broad spectrum of inorganic as well as organic compounds but most specifically phenolic compounds by radical catalyzed mechanism. Similarly, lignin peroxidases (LiP), the heme containing proteins perform a vital part in oxidizing a wide variety of aromatic compounds with H2O2. Lignin depolymerization yields polyaromatics, the important ones are BTX (Benzene, Xylene and Toluene), found in several different configurations. However, most modern aromatics complexes enhance the production of p-xylene, benzene and sometimes o-xylene respectively. Thus, this review will provide a concept that chemical and biological modifications of lignin yield certain value added and environment friendly chemicals.
Preprint
|
|
|
Life Sciences, Microbiology; drug resistance; Candida albicans; Candida glabrata; Galenia africana; fluconazole; broth microdilution; checkerboard; sensititre
Online: 13 April 2018 (03:49:28 CEST)
|
|
Share this article with
×
Candida infections have increased in recent years and are causing serious public health concern. In addition, Candida species are becoming resistant to numerous antifungal drugs. It is for this reason that alternative treatment options are being explored, using medicinal plants, to curb this trend of drug resistance. The aim of this study was to evaluate the anti-Candida activity of an ethanolic extract of Galenia africana (G. africana) alone and particularly in combination with fluconazole (FLC) against Candida albicans and Candida glabrata. The anti-Candida activity was evaluated using various techniques. The minimum inhibitory concentration (MIC) of the extract was 6.25 mg/ml for both Candida strains. After combining with FLC, G. africana exerted a strong synergistic effect against C. albicans and an indifferent effect against C. glabrata when interpreted by the fractional inhibitory concentration index (FICI) (0.36 and 1.002 for C. albicans and C. glabrata, respectively). Microscopic analysis revealed cell damage and decrease in cell size after G. africana treatment. Collectively, these results suggested that G. africana possessed antifungal activities against the Candida strains and a synergistic effect with FLC. Cell damage observed possibly contributed to this synergistic effect. This provides new information for the development of new antifungal agents.
Preprint
|
|
|
Life Sciences, Other; Wuchereria bancrofti antigen, lyophilization, dried blood spots, freeze-drying
Online: 12 April 2018 (16:18:09 CEST)
|
|
Share this article with
×
Antigen-based rapid diagnostic tests for Lymphatic filariasis do not come with quality control (QC) materials, and research and disease control programmes rely on stored positive plasma samples. This study was undertaken to evaluate the use of freeze-dried Wuchereria bancrofti antigen positive plasma samples to serve as QC materials for LF RDTs. 10 well characterized W. bancrofti positive samples were lyophilized and stored at 4°C, 28°C and 40°C. The samples were evaluated using the Filaria Test Strips before lyophilization and after one and three (3) months of storage. The sensitivity and stability of the lyophilized samples were evaluated. The results revealed a loss of sensitivity and stability with increasing temperature and duration of storage. The results are further discussed in terms of the use of Dried Blood Spot (DBS) in diagnostics studies on LF requiring quantitative assessments, and the need for thoughtful DBS preparation and storage.
Preprint
|
|
|
Life Sciences, Other; electronic nose; nanowire gas sensors; food quality control; Parmigiano Reggiano; multivariate data analysis; artificial neural network
Online: 12 April 2018 (06:25:29 CEST)
|
|
Share this article with
×
Parmigiano Reggiano cheese is one of the most appreciated and consumed food worldwide, especially in Italy, for its high content of nutrients and for its taste. However, these characteristics make this product subject to counterfeiting in different forms. In this study, a novel method based on an electronic nose has been developed in order to investigate the potentiality of this tool to distinguish rind percentage in grated Parmigiano Reggiano packages that should be lower than 18%. Different samples in terms of percentage, seasoning and rind working process were considered to tackle the problem at 360°. In parallel, GC-MS technique was used to give a name to the compounds that characterize Parmigiano and to relate them with sensors responses. Data analysis consisted of two stages: multivariate analysis (PLS) and classification made in a hierarchical way with PLS-DA ad ANNs. Results are promising in terms of correct classification of the samples. The classification rate is higher for ANNs than PLS-DA, reaching also 100% values.
Preprint
|
|
|
Cristiana Zanetti,
Angelo Gallina,
Alessia Fabbri,
Sofia Parisi,
Angela Palermo,
Katia Fecchi,
Zaira Boussadia,
Maria Carollo,
Mario Falchi,
Luca Pasquini,
Maria Luisa Fiani,
Massimo Sargiacomo
Life Sciences, Cell & Developmental Biology; Cholera toxin; exosomes; endocytic pathway; Caveolin-1; GM1 ganglioside
Online: 12 April 2018 (05:58:31 CEST)
|
|
Share this article with
×
Here we first report, how cholera toxin (CT) A subunit (CTA), the bacterial enzyme moiety responsible of cell signaling alteration, can take over the exosomal pathway, spread extracellularly and be transmitted in a cell population. A first evidence for long-term transmission of CT toxic effect via extracellular vesicles was obtained in CHO cells. To follow CT intracellular route towards exosome secretion we adopted a strategy apt to convert multivesicular body (MVB) derived exosomes in traceable fluorescent vectors. CT treated Me665 cells, a human melanoma cell line highly expressing caveolin-1 (Cav-1) and GM1, were used to purify and characterize fluorescent exosomes. Our results clearly show association of CT with exosomes together with typical exosomal markers and the HSP90 and PDI molecules, the required membrane translocation elements of CTA to the cytoplasm. Confocal microscopy proved direct CT containing fluorescent exo transfer into CHO cells coupled with the morphological cell change characteristic of CT action. Moreover, direct assessment of cAMP levels in Me665 cells treated with CT containing exo showed an efficient induction of cAMP increase comparable with CT alone. From our results, we can infer that CT can exploit exosome-mediated cell communication to target and extend its pathophysiological action throughout cell tissues.
Preprint
|
|
|
Life Sciences, Other; mycobacterium ulcerans; animal reservoir; transmission
Online: 11 April 2018 (13:54:56 CEST)
|
|
Share this article with
×
Mycobacterium ulcerans is the causative agent of the Buruli ulcer, also known, in Australia, as Daintree ulcer or Bairnsdale ulcer. This destructive skin disease is characterized by extensive and painless necrosis of the skin and soft tissue with the formation of large ulcers, commonly on the leg or arm. To date, 33 countries with tropical, subtropical and temperate climates in Africa, the Americas, Asia and the Western Pacific have reported cases of Buruli Ulcer. The disease is rarely fatal, although it may lead to permanent disability and/ or disfigurement if not treated appropriately or in time. It is the third most common mycobacterial infection in the world after tuberculosis and leprosy. The precise mode of transmission of M. ulcerans is yet to be elucidated. Nevertheless, it is possible that the mode of transmission varies with different geographical areas and epidemiological settings. The knowledge about the possible route of transmission and potential animal reservoir of M. ulcerans is poorly understood and still remains patchy. We conducted a systematic review with selected key words on PubMed and INFORMIT databases to aggregate available published data on animal reservoirs of M. ulcerans. After certain inclusion and exclusion criteria, a total of 17 studies were included in the review. A variety of animals, e.g rodents, shrews, possums (ringtail and brush tail), horses, dogs, alpacas, koalas and Indian flap-shelled turtles have been recorded as being infected with M. ulcerans around the world. The majority of studies included in this review identified animal reservoirs, either aquatic or terrestrial, as predisposing for the emergence and reemergence of M. ulcerans infection. Taken together, the selected studies in this systematic review and discussed so far, it is clear that exotic wildlife, aquatic animals and native mammals play a significant role as reservoirs for M. ulcerans.
Preprint
|
|
|
Sean M. Evans,
Haley E. Adcox,
Lauren VieBrock,
Ryan S. Green,
Alison Luce-Fedrow,
Suschsmita Chattopadhyay,
Ju Jiang,
Richard T. Marconi,
Daniel Paris,
Allen L. Richards,
Jason A. Carlyon
Life Sciences, Microbiology; scrub typhus; Orientia tsutsugamushi; Rickettsia; Rickettsiales; outer membrane protein A; Anaplasma
Online: 11 April 2018 (08:13:04 CEST)
|
|
|
Share this article with
×
Scrub typhus threatens one billion people in the Asia-Pacific area and cases have emerged outside this region. It is caused by infection with any of the multitude of strains of the bacterium, Orientia tsutsugamushi. A vaccine that affords heterologous protection and a commercially available molecular diagnostic assay are lacking. Herein, we determined that the nucleotide and translated amino acid sequences of outer membrane protein A (OmpA) are highly conserved among 51 O. tsutsugamushi isolates. Molecular modeling revealed the predicted tertiary structure of O. tsutsugamushi OmpA to be very similar to that of the phylogenetically related pathogen, Anaplasma phagocytophilum, including the location of a helix that contains residues functionally essential for A. phagocytophilum infection. PCR primers were developed that amplified ompA DNA from all O. tsutsugamushi strains, but not from negative control bacteria. Using these primers in quantitative real-time PCR enabled sensitive detection and quantitation of O. tsutsugamushi ompA DNA from organs of mice that had been experimentally infected with the Karp or Gilliam strains. The high degree of OmpA conservation among O. tsutsugamushi strains evidences its potential to serve as a molecular diagnostic target and justifies its consideration as a candidate for developing a broadly protective scrub typhus vaccine.
Preprint
|
|
|
Life Sciences, Genetics; genetic code, alphabet, unitary matrix, dyadic shift, decomposition, spectral presentation, fractal, tensor product, quantum informatics
Online: 10 April 2018 (16:20:14 CEST)
|
|
Share this article with
×
Information molecules of DNA and RNA should obey principles of quantum mechanics where unitary operators in form of unitary matrices have key meanings. Unitary matrices are the basis of calculations in quantum computers. This article presents some author's results, which show that matrix forms of the representation of structured systems of molecular-genetic alphabets can be considered as sets of sparse unitary matrices related with phenomenologic features of the degeneracy of the genetic code. These sparse unitary matrices have orthogonal systems of functions in their rows and columns. A complementarity exists among some unitary genetic matrices in relation each other. Decompositions of numeric genetic matrices into sets of sparse unitary matrices are connected with the logical operation of modulo-2 addition used in quantum computers as well. Tensor (or Kronecker) families of unitary genetic matrices with their fractal-like properties are also considered. The described results are discussed in the frame of development of quantum-information approaches for modeling genetic systems.
Preprint
|
|
|
Life Sciences, Other; metabolic syndrome; inflammation; index; Korea
Online: 10 April 2018 (09:50:20 CEST)
|
|
Share this article with
×
Inflammation is known to be risk factors for metabolic diseases. The purpose of this study was to develop a Food-based Index of Dietary Inflammatory Potential (FBDI) and conduct its validation assessment. This study analyzed raw data from Korean Genome and Epidemiology Study 2012–2014 data of 17,771 people. We carried out the correlation analysis between 51 food groups and hs-CRP. The FBDI was developed by multiple regression method with hs-CRP and selected 17 food group. For the validation of FBDI, 7795 people in the 6th Korea National Health and Nutrition Examination Survey (KNHAES) was used. Binary logistic regression analysis was used for risk analysis of metabolic syndrome and FBDI. The FBDI model included that 7 were composed of anti-inflammatory food groups and 3 of inflammatory food groups. The FBDI was calculated by multiplying the intake of food group by β coefficients. KNHAES were included in the validation of FBDI. The risk of metabolic syndrome was found to be 2.152 times higher in the group with the highest FBDI than in the group with the lowest one (95% Cl:1.458–3.178, p for trend = 0.000). This study developed FBDI reflecting food intake for Koreans, which showed a significant relationship with the risk of metabolic syndrome.
Preprint
|
|
|
Life Sciences, Immunology; omega-3 and omega-6 polyunsaturated fatty acids; colorectal cancer; cancer immune therapy
Online: 10 April 2018 (08:05:27 CEST)
|
|
|
Share this article with
×
Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been found to be modulators of immune function. Additionally, they may affect the growth of colorectal cancer (CRC). With the advent of novel treatment approaches in oncology targeting immune checkpoint inhibition and aiming to boost the immune response against tumors the exact role of n-3 and n-6 PUFA in inflammation as well as in CRC needs to be re-evaluated in order to understand potential interactions with these new treatment paradigms. Interestingly, for the cyclooxygenase (COX) inhibitor aspirin a possible synergistic effect together with a PD1-Ligand antibody has been shown. However, could n-3 PUFA be disadvantageous in the context of immune tumor therapy due to an immune suppressive effect that has been described for these fatty acids in the past, or could they also enhance the effect of immune checkpoint inhibition? In this paper, we discuss the current data regarding the immune modulatory as well as the anti-CRC effect of n-3 PUFA. Arguing towards an immune-activating effect of n-3 PUFA, we demonstrate the results of a pilot study. Here, we show that incubation of human peripheral blood mononuclear cells (PBMCs) with the n-3 PUFA docosahexaenoic acid (DHA) significantly decreases CRC-cell supernatant-triggered secretion of IL-10 and increases secretion of TNF-a, while the omega-6 polyunsaturated fatty acid (n-6 PUFA) arachidonic acid (AA) reduced TNF-a secretion. These changes in cytokine secretion upon incubation with DHA demonstrate a possible enhancing effect of n-3 PUFA on an anti-tumor immune response.
Preprint
|
|
|
Life Sciences, Biotechnology; anti-inflammatory agents; cancer; sponges
Online: 10 April 2018 (07:52:19 CEST)
|
|
Share this article with
×
Inflammation is a dynamic process, in which pro-inflammatory cytokines, such as tumor necrosis factor, interleukins and vascular endothelial growth factor have central roles. A number of drugs or active agents have been developed to treat inflammation, able to reduce the activity of specific cytokines or their receptors to block lymphocyte trafficking into tissues, to prevent the binding of monocyte-lymphocyte co-stimulatory molecules, or to deplete B lymphocytes. Furthermore, inflammation is a critical component of tumor progression, fostering new anti-inflammatory therapeutic approaches against cancer development. In the few last decades marine environment have been recognized to be a rich sources of bioactive metabolites with varied biological and pharmacological activities, including anti-inflammatory effects. A lot of marine phyla were considered for their significance respect to pharmacological active compounds, including bacteria, fungi, algae, soft corals, nudibranchs, bryozoans, tunicates and especially sponges. In particular, marine sponges have been considered as a gold mine because they contain different secondary metabolites and provide novel natural products with a remarkable chemical diversity. Considering that the last review on anti-inflammatory agents from marine sponges dates back to 2005, and after this many studies report results on the identification of natural compounds from sponges with this activity, here we report an update on anti-inflammatory agents, focusing our attention on marine sponges as promising their sources.
Preprint
|
|
|
Life Sciences, Virology; Zika virus; ZIKV; Rhesus macaques; Non-human primates; NHP; infection; natural history; Asian-lineage; African-lineage
Online: 9 April 2018 (03:53:26 CEST)
|
|
Share this article with
×
The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose dependent peak viral loads between days 2 and 5 post infection; and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assays lower limit of quantitation and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasures development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.
Preprint
|
|
|
Life Sciences, Molecular Biology; Alzheimer’s disease (AD); amyloid precursor protein (APP); familial AD (FAD); sporadic AD (SAD); BACE1 inhibitors; APP-independent generation of beta amyloid
Online: 6 April 2018 (15:16:08 CEST)
|
|
Share this article with
×
The present article analyzes the results of recent clinical trials of beta secretase inhibition in sporadic Alzheimer’ disease (SAD), considers the striking dichotomy between successes in tests of BACE1 inhibitors in healthy subjects and familial AD (FAD) models versus persistent failures of clinical trials and interprets it as a confirmation of key predictions for a mechanism of APP-independent, beta secretase inhibition-resistant production of beta amyloid in SAD, previously proposed by us. In the light of this concept, FAD and SAD should be regarded as distinctly different diseases as far as beta-amyloid generation mechanisms are concerned, and whereas beta secretase inhibition would be neither applicable nor effective in treatment of SAD, the BACE1 inhibitor(s) deemed failed in SAD trials could be perfectly suitable for treatment of FAD. Moreover, targeting the aspects of AD other than cleavages of the APP by beta and alpha secretases should have analogous impacts in both FAD and SAD.
Preprint
|
|
|
Life Sciences, Microbiology; membrane fatty acids composition; Staphylococcus aureus; staphyloxanthin; membrane fluidity; metabolic regulation
Online: 6 April 2018 (11:37:53 CEST)
|
|
Share this article with
×
Fatty acids play a major role in determining membrane biophysical properties. Staphylococcus aureus produces branched-chain fatty acids (BCFAs) and straight-chain fatty acids (SCFAs), and can incorporate exogenous SCFAs and straight-chain unsaturated fatty acids (SCUFAs). Many S. aureus strains produce the triterpenoid pigment staphyloxanthin, and the balance of BCFAs, SCFAs and staphyloxanthin determines membrane fluidity. Here, we investigated the relationship of fatty acid and carotenoid production in S. aureus using a pigmented strain (Pig1), its carotenoid-deficient mutant (Pig1ΔcrtM) and the naturally non-pigmented Staphylococcus argenteus that lacks carotenoid biosynthesis genes and is closely related to S. aureus. Fatty acid compositions in all strains were similar under a given condition indicating that staphyloxanthin does not influence fatty acid composition. Strain Pig1 had decreased membrane fluidity as measured by fluorescence anisotropy than the other strains under all conditions indicating that staphyloxanthin helps maintain membrane rigidity. We could find no evidence for correlation of expression of crtM and fatty acid biosynthesis genes. Supplementation of medium with glucose increased SCFA production and decreased BCFA and staphyloxanthin production, whereas acetate-supplementation also decreased BCFAs but increased staphyloxanthin production. We believe that staphyloxanthin levels are influenced more through metabolic regulation than responding to fatty acids incorporated into the membrane.
Preprint
|
|
|
Life Sciences, Virology; Zika virus; ZIKV-host interactions; viral pathogenesis; cell surface receptors; antiviral responses; viral counteraction; cytopathic effects; microcephaly; ZIKV-associated neurologic disorders
Online: 5 April 2018 (05:34:07 CEST)
|
|
Share this article with
×
The recent Zika virus (ZIKV) outbreak in Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies and Guillain-Barré syndrome. In responding to this global health outcry, unprecedented and world-wide efforts are taking place to study the ZIKV etiology. Much have been learned about this virus in the areas of epidemiology, clinical manifestation, viral sequences and protein structures, as well as effects of ZIKV infection on fetal brain development and microcephaly. However, the molecular mechanism underlying ZIKV-mediated neurologic disorders remains elusive. Some critical questions include: 1) what type of virologic changes has taken place that increased the viral virulence? 2) which ZIKV protein(s) is responsible for the enhanced viral pathogenicity? And 3) how the newly adapted and pathogenic ZIKV strains alter their interactions with host cells leading to neurologic disorders? The goal of this review is to explore the molecular insights into the ZIKV-host interactions with special focuses on host cell receptor usage for viral entry, host cellular and immune antiviral responses, ZIKV counteraction and ZIKV-induced cytopathic effects. Our hope with this literature review is to inspire additional studies focusing on molecular studies of ZIKV-host Interactions.
Preprint
|
|
|
Mikiko Watanabe,
Elena Gangitano,
Davide Francomano,
Eliana Addessi,
Raffaella Toscano,
Daniela Costantini,
Dario Tuccinardi,
Stefania Mariani,
Sabrina Basciani,
Giovanni Spera,
Lucio Gnessi,
Carla Lubrano
Life Sciences, Endocrinology & Metabolomics; garcinia mangostana; inflammation; insulin resistance; metabolic syndrome; diabetes; xanthones; mangostin; phytotherapy; dietary supplements
Online: 4 April 2018 (06:19:44 CEST)
|
|
Share this article with
×
Insulin resistance is the most important underlying cause of obesity and type 2 Diabetes (T2DM), and insulin sensitizing treatments have proved effective in preventing diabetes and inducing weight loss. Obesity and T2DM are also associated with increased inflammation. Mangosteen is a tropical tree, whose fruits, widely known for their antioxidant properties, have been recently suggested having a possible further role in the treatment of obesity and T2DM. The objective of this pilot study has been to evaluate safety, compliance and efficacy of mangosteen on insulin resistance, weight management, and inflammatory status in obese female patients with insulin resistance. 22 patients were randomized 1:1 to behavioral therapy alone or behavioral therapy and mangosteen and 20 completed the 26-week study. The mangosteen group reported a significant improvement in insulin sensitivity (HOmeostatic Model Assessment-Insulin Resistance, HOMA-IR -53.22% vs -15.23%, p=.0037), and a trend decrease in inflammation markers serum levels, together with trend greater weight loss and trend increased HDL levels. No side effect attributable to treatment was reported. Given the positive preliminary results we report and the excellent safety profile, we suggest a possible role of mangosteen in the treatment of obesity, insulin resistance and inflammation.
Preprint
|
|
|
Life Sciences, Biotechnology; electromyography; human-computer interface; motor control; pattern classification; artificial neural networks
Online: 4 April 2018 (05:07:22 CEST)
|
|
Share this article with
×
Recent advances in recording and real-time analysis of surface electromyographic signals (sEMG) have fostered the use of sEMG human-machine interfaces for controlling personal computers, prostheses of upper limbs, and exoskeletons among others. Despite a relatively high mean performance, sEMG-interfaces still exhibit strong variance in the fidelity of gesture recognition among different users. Here we systematically study the latent factors determining the performance of sEMG-interfaces in synthetic tests and in an arcade game. We show that the degree of muscle cooperation and the amount of the body fatty tissue are the decisive factors in synthetic tests. Our data suggest that these factors can only be adjusted by a long-term training, which promotes fine-tuning of low-level neural circuits driving the muscles. A short-term training has no effect on synthetic tests, but significantly increases the game scoring. This implies that it works at a higher decision-making level, not relevant for synthetic gestures. We propose a procedure that enables quantification of the gestures’ fidelity in a dynamic gaming environment. For each individual subject the approach allows identifying “problematic” gestures that decrease gaming performance. This information can be used for optimizing the training strategy and for adapting the signal processing algorithms to individual users, which could be a way for a qualitative leap in the development of future sEMG-interfaces.
Preprint
|
|
|
Life Sciences, Other; geospatial economic supply; biomass; risk assessment; vulnerability
Online: 4 April 2018 (04:17:33 CEST)
|
|
Share this article with
×
Assessing the economic supply of biomass in a geospatial context while accounting for risk from natural disasters was studied. Risk levels were estimated from a component of factors which included: population density, road density, federal ownership, U.S. Environmental Protection Agency ecoregions, and Presidential Disaster Declarations. The Presidential Disaster Declarations included risks due to: coastal storm, drought, fire, flood, freezing, hurricane, mud land slide, severe ices, severe storms, snow, tornado, and tropical storm. Presidential Disaster Declarations included summaries based on a short-term time period from 2000-2011, and on a long-term time period from 1964-2011. Risk categories were developed as a function of the number of disaster declarations, agricultural-to-forest land ratio, average road density, and average population density. A significant contribution of the research was the allocation of spatially explicit data using GIS technology at the 5-digit zip code tabulation area. The average area for 5-digit ZCTAs in the Eastern U.S. study region was approximately 169 kilometers2. Long-term risk (1964-2011) from disaster declarations had a greater impact on the economic availability of biomass supply relative to short-term declarations (2000-2011). The greatest risk to biomass supply came from population density relative to the other risk factors studies. Of the 25,044 total ZCTAs, 12,256 ZCTAs were in locations that did not include population density ≥ 150/km2, road density ≥ 14 km/km2, federal ownership, and US Environmental Protection Agency Level III ecoregions. Of the remaining 12,256 ZCTAs, 26.8% were considered to be moderate-to-high risk based on short-term declarations (2000-2011) and 29.4% were considered to be moderate-to-high risk based on long-term declarations (1964-2011). Lower risk locations for procuring biomass supply for both short-term and long-term declarations, across all risk factors, were in southern Georgia, South Carolina, and Texas.
Preprint
|
|
|
Yuan Li ,
Yan Li,
Xueyan Wang,
Hongyue Xu,
Chao Wang,
Yanan An,
Wenjing Luan,
Xuefei Wang,
Shulin Li,
Mingyuan Liu,
Xudong Tang,
Lu Yu
Life Sciences, Endocrinology & Metabolomics; cordycepin; adenosine A1 receptor; prolactin; anti-obesity
Online: 3 April 2018 (07:53:24 CEST)
|
|
Share this article with
×
Cordycepin is an extract from the insect fungus Cordyceps. militaris, which is a traditional medicine with various biological function. In previous studies, cordycepin had been reported with excellent anti-obesity effect, but the mechanism is unclear. A large quantity of evidences showed that prolactin plays an important part in body weight regulation, hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular mechanism of the anti-obesity effect of cordycepin by reducing prolactin release via an adenosine A1 receptor. In vivo, obese rats model was induced by high fat diet for 5 weeks, the serum and liver lipids coupling with serum prolactin were reduced by treatment of cordycepin, the results suggested that cordycepin is a potential drug for therapying obesity which could be related with prolactin. In vitro, cordycepin could inhibit prolactin secretion in GH3 cells via upregulating the expression of adenosine A1 receptor, the inhibition effect could be blocked by an antagonist of adenosine receptor A1 DPDPX, prolactin induced the upregulation of lipogenesis genes PRLR, and P-JAK2 in 3T3-L1 cells. Intriguingly, cordycepin would down-regulate the expression of prolactin receptor (PRLR). Thus, we concluded that cordycepin modulate body weight by reducing prolactin release via an adenosine A1 receptor.
Preprint
|
|
|
Life Sciences, Cell & Developmental Biology; minicircle; induced pluripotent stem cells; chondrogenesis; chondrocyte; bone morphogenetic proteins; transforming growth factors
Online: 2 April 2018 (09:59:50 CEST)
|
|
Share this article with
×
The human degenerative cartilage has low regenerative potential. Chondrocyte transplantation offers a promising strategy for cartilage treatment and regeneration. Currently chondrogenesis using human pluripotent stem cells are accomplished using human recombinant growth factors. Here, we differentiated human induced pluripotent stem cells (hiPSCs) into chondrocytes and cartilage pellet using minicircle vectors. Minicircles are used as a non-viral gene delivery system for gene therapy in various diseases. Non-viral gene delivery can produce growth factors without integrating into the host genome. Minicircle vectors containing bone morphogenetic protein 2 (BMP2) and transforming growth factor, beta 3 (TGFβ3) were successfully generated and delivered to hiPSC-derived outgrowth (OG) cells. Cell pellets generated using minicircle-transfected OG cells successfully differentiated into chondrogenic lineage. Chondrogenic pellets transfected with growth factor-encoding minicircles effectively recovered osteochondral defect in rat models. Taken together, this work shows the potential application of minicircles in cartilage regeneration using hiPSCs.
Preprint
|
|
|
Life Sciences, Genetics; colorectal cancer; gene expression; molecular classification; molecular subtyping
Online: 2 April 2018 (09:55:26 CEST)
|
|
|
Share this article with
×
Molecular classifications of colorectal cancer (CRC) are benefitting cancer research by providing insights into subtype-specific disease prognosis and better therapeutic intervention. So far different conventional DNA markers such as microsatellite instability (MSI), CpG island methylator phenotype (CIMP), chromosomal instability (CIN), and BRAF and KRAS mutations have been used to classify CRC patients but have not shown promising prognostic values. Here, for the first time, we show classification of CRC tumors from Saudi Arabian patients based on gene expression profile (GEP). An existing method of CRC subtyping has been applied to the GEP of tumors from Saudi CRC patients. Survival analysis was carried out on predicted CRC subtypes. In-silico functional analyses were conducted on the gene signature used for subtype prediction. The predicted subtypes showed distinct but statistically insignificant overall survival distribution (log-rank test, p = 0.069). Comparison of predicted subtypes in Saudi CRC patients with that of the French one showed significant dissimilarity in the two populations (Chi-square test, p = 0.0091). Functional analyses of the gene signature used for subtyping suggest their association with “cancer” and “gastrointestinal diseases”. Most of the signature genes were found differentially expressed in CRC tumors compared to adjacent normal tissues. Such a classification framework might help improve the treatment of colorectal cancer patients.
Preprint
|
|
|
Life Sciences, Other; wildfire; prescribed fire; smoke; particulate matter; public health; exposure
Online: 30 March 2018 (09:36:54 CEST)
|
|
Share this article with
×
Prescribed fire, intentionally ignited low-intensity fires, and managed wildfires, wildfires that are allowed to burn for land management benefit, could be used as a land management tool to create forests that are resilient to wildland fire. This could lead to fewer large catastrophic wildfires in the future. However, we must consider the public health impacts of the smoke that is emitted from wildland and prescribed fire. The objective of this synthesis is to examine the differences in ambient community-level exposures to particulate matter (PM2.5) from smoke in the United States from two smoke exposure scenarios – wildfire fire and prescribed fire. A systematic search was conducted to identify scientific papers to be included in this review. Web of Science Core Collection and PubMed for scientific papers, and Google Scholar were used to identify any grey literature or reports to be included in this review. Sixteen studies that examined particulate matter exposure from smoke were identified for this synthesis – nine wildland fire studies and seven prescribed fire studies. PM2.5 concentrations from wildfire smoke were found to be significantly lower than reported PM2.5 concentrations from prescribed fire smoke. Wildfire studies focused on assessing air quality impacts to communities that were nearby fires and urban centers that were far from wildfires. However, the prescribed fire studies used air monitoring methods that focused on characterizing exposures and emissions directly from and next to the burns. This review highlights a need for a better understanding of wildfire smoke impact over the landscape. It is essential for properly assessing population exposure to smoke from different fire types.
Preprint
|
|
|
Life Sciences, Genetics; RNA-seq; miRNA; pig; NGS; transcript analysis; muscle
Online: 30 March 2018 (06:02:33 CEST)
|
|
|
Share this article with
×
Recently, selection in pigs has been focused on improving the lean meat content in carcasses; this focus has been most evident in breeds constituting a paternal component in breeding. Such sire-breeds are used to improve the meat quantity of cross-breed pig lines. However, even in one breed, a significant variation in the meatiness level can be observed. In the present study, the comprehensive analysis of genes and microRNA expression profiles in porcine muscle tissue was applied to identify the genetic background of meat content. The comparison was performed between whole gene expression and miRNA profiles of muscle tissue collected from two sire-line pig breeds (Piertain, Hampshire). The RNA-seq approach allowed the identification of 627 and 416 differentially expressed genes (DEGs) between pig groups differing in terms of loin weight between Pietrain and Hampshire breeds, respectively. The comparison of miRNA profiles showed differential expression of 57 microRNAs for Hampshire and 34 miRNAs for Pietrain pigs. Next, 43 genes and 18 miRNAs were selected as differentially expressed in both breeds and potentially related to muscle development. According to Gene Ontology analysis, identified DEGs and microRNAs were involved in the regulation of the cell cycle, fatty acid biosynthesis and regulation of the actin cytoskeleton. The most deregulated pathways dependent on muscle mass were the Hippo signalling pathway connected with the TGF-beta signalling pathway and controlling organ size via the regulation of ubiquitin-mediated proteolysis, cell proliferation and apoptosis. The identified target genes were also involved in pathways such as the FoxO signalling pathway, signalling pathways regulating pluripotency of stem cells and the PI3K-Akt signalling pathway. The obtained results indicate molecular mechanisms controlling porcine muscle growth and development. Identified genes (SOX2, SIRT1, KLF4, PAX6 and genes belonging to the transforming growth factor beta superfamily) could be considered candidate genes for determining muscle mass in pigs.
Preprint
|
|
|
Life Sciences, Virology; RNA silencing; gemycircularvirus; mycovirus; antiviral; dicer
Online: 29 March 2018 (05:44:40 CEST)
|
|
Share this article with
×
This study aimed to demonstrate the existence of antiviral RNA silencing mechanisms in Sclerotinia sclerotiorum by probing wild-type and RNA-silencing-deficient strains of the fungus with an RNA virus and a circular DNA virus. Key silencing-related genes, specifically dicers, were disrupted in order to dissect the RNA silencing pathway and provide useful information on fungal control. Dicers Dcl-1, Dcl-2, and both Dcl-1/Dcl-2- genes were displaced by selective marker(s). Disruption mutants were then compared for changes in phenotype, virulence, susceptibility to viral infection, and small RNA accumulation compared to the wild-type strain. Disruption of Dcl-1 or Dcl-2 resulted in no changes in phenotype compared to wild-type S. sclerotiorum; however, the double dicer mutant strain exhibited slower growth. To examine the effect of viral infection on strains containing null-mutations of Dcl-1, Dcl-2 or both genes, mutants were transfected with full-length RNA transcripts of a hypovirus SsHV2L and copies of a single-stranded DNA mycovirus- SsHADV-1 as a synthetic virus. Results indicate that the ΔDcl-1/Dcl-2 double mutant which was slow growing without virus infection exhibited much more severe debilitation following virus infection. Altered colony morphology including: reduced pigmentation, significantly slower growth, and delayed sclerotial formation. Additionally, there is an absence of virus-derived small RNAs in the virus-infected ∆Dcl-1/Dcl-2 mutant compared to the virus-infected wild-type strain which displays a high percentage of virus-derived small RNA. The findings of these studies suggest that if both dicers are silenced, invasive nucleic acids which include mycoviruses ubiquitous in nature- can greatly debilitate the virulence of fungal plant pathogens.
Preprint
|
|
|
Life Sciences, Molecular Biology; CREBH; SREBP; LXRα; PPARα; lipid metabolism; transcription; FGF21
Online: 28 March 2018 (08:06:15 CEST)
|
|
Share this article with
×
The cyclic AMP-responsive element-binding protein H (CREBH, encoded by CREB3L3) is a membrane-bound transcriptional factor that primarily localizes in the liver and small intestine. CREBH governs triglyceride metabolism in the liver, which mediates the changes in gene expression governing fatty acid oxidation, ketogenesis, and apolipoproteins upregulating LPL activity. A deficiency of CREBH in mice leads to severe hypertriglyceridemia. CREBH, in synergy with PPARα, has a crucial role in upregulating Fgf21 expression, which is implicated in metabolic homeostasis. CREBH binds to and functions as a co-activator for both PPARα and LXRα in regulating gene expression of lipid metabolism. Furthermore, intestinal CREBH in overexpression reduces cholesterol absorption and suppresses high-cholesterol diet-induced fatty liver. Conversely, a deficiency of CrebH in mice fed on various high-fat diets leads to severe fatty liver. Thus, CREBH could be a therapeutic target in the treatment of metabolic diseases.
Preprint
|
|
|
Life Sciences, Biotechnology; Antivenom; snakebite; small molecule toxin inhibitors; oligonucleotides; antibodies; phage display; next generation antivenom; recombinant antivenom
Online: 27 March 2018 (13:41:46 CEST)
|
|
Share this article with
×
With the inclusion of snakebite envenoming on the World Health Organisation’s list of Neglected Tropical Diseases, an incentive has been established to promote research and development effort in novel snakebite antivenom therapies. Different technological approaches are being pursued by different research groups, including the use of small molecule inhibitors against enzymatic toxins, as well as peptide and oligonucleotide-based aptamers and antibody-based biotherapeutics against both enzymatic and non-enzymatic toxins. In this article, the most recent advances in these fields are presented, and the advantages, disadvantages, and feasibility of using different toxin-neutralizing molecules are reviewed. Particular focus within small molecules is directed towards the inhibitors, varespladib, batimastat, and marimastat, while in the field of antibody-based therapies, novel recombinant polyclonal plantivenom technology is discussed.
Preprint
|
|
|
Junko Masuda,
Tsukasa Shigehiro,
Takuma Matsumoto,
Ayano Satoh,
Akifumi Mizutani,
Chiho Umemura,
Shoki Saito,
Mayumi Kijihira,
Eiji Takayama,
Akimasa Seno,
Hiroshi Murakami,
Masaharu Seno
Life Sciences, Immunology; Myeloid-derived suppressor cells (MDSCs); dendritic cells (DCs); M1 macrophages; M2 macrophages; xenograft tumor; allograft tumor; lipopolysaccharide (LPS)
Online: 27 March 2018 (12:03:56 CEST)
|
|
Share this article with
×
Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with myeloid-derived suppressor cells (MDSCs) in tumor microenvironments regulates cancer progression. Immunodeficient mice lacking T cells are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The xenograft tumor microenvironment, comprising human cancer and mouse host cells, exhibits more complex bidirectional signaling and function than a syngeneic tumor microenvironment. Here human and mouse colorectal cancer cells were transplanted into nude mice to elucidate differences in macrophage, DC, and MDSC functions in human xenograft and mouse allograft tumor models. Plasma interferon-γ and interleukin-18 concentrations in the former model after intraperitoneal lipopolysaccharide (LPS) administration were significantly higher than those in the latter model and non-transplanted control group. Splenic MHC class I, II, and CD80 expression increased in CD11b+ and MDSC populations after LPS administration in only the xenograft tumor model. The number of CD80- and MRC1-expressing cells decreased upon LPS administration in only the xenograft tumor. These results suggxest that macrophages and DCs function normally in xenograft tumor models, whereas their functions in response to LPS administration vary in allograft tumor models.
Preprint
|
|
|
Life Sciences, Genetics; Phaseolus vulgaris L.; REML/BLUP; genetic diversity
Online: 26 March 2018 (10:35:00 CEST)
|
|
Share this article with
×
In the international scenario of agriculture, Brazil stands out as the main producer and consumer of common bean (Phaseolus vulgaris L.) The increase in the productive potential of the crop is mainly due to breeding programs. The objective of this study was to estimate genetic parameters, predict genotypic values with REML/BLUP (Restricted Maximum Likelihood/Best Linear Unbiased Prediction) and, based on these values, study the variability in common bean cultivars with carioca and black grain. Twenty three agromorphological descriptors were evaluated, among them grain yield. Deviance analysis detected significant differences between the cultivars in both groups. Selective accuracy (Ac) was considered high for most of the traits. Broad-sense heritability (hg2 ) ranged from 0.05 to 0.72, but it was low for the trait yield (YLD). In the carioca grain group, the hg2 values for the traits related to plant morphology were higher than in the black group. Nevertheless, the hg2 values in the black group were higher in relation to the pod and seed traits. The correlations for YLD were moderate but different in the two commercial groups studied. In the black group, variables related to the seed morphology were correlated with grain yield, and in the carioca group, traits related to seed quantity. Based on the groupings, variability among the cultivars was observed. Three distinct clusters were formed for the carioca group and four for the black group. Based on the predicted genetic values, genetic variability and the most adapted and stable cultivars were detected among the cultivars in the studied environments.
Preprint
|
|
|
Life Sciences, Other; arginase; nor-NOHA; NOHA; cancer
Online: 26 March 2018 (10:00:51 CEST)
|
|
Share this article with
×
L-arginine is involved in a number of biological processes in our bodies. Metabolism of L-arginine by the enzyme arginase has been found to be associated with cancer cell proliferation. Arginase inhibition has been proposed as a potential therapeutic means to inhibit this process. N-hydroxy-nor-L-Arg (nor-NOHA) and N (omega)-hydroxy-L-arginine (NOHA) has shown promise in inhibiting cancer progression through arginase inhibition. In this study, nor-NOHA and NOHA-associated genes and proteins were analyzed with several Bioinformatics and Systems Biology tools to identify the associated pathways and the key players involved so that a more comprehensive view of the molecular mechanisms including the regulatory mechanisms can be achieved and more potential targets for treatment of cancer can be discovered. Based on the analyses carried out, 3 significant modules have been identified from the PPI network. Five pathways/processes have been found to be significantly associated with nor-NOHA and NOHA associated genes. Out of the 1996 proteins in the PPI network, 4 have been identified as hub proteins-SOD, SOD1, AMD1, and NOS2. These 4 proteins have been implicated in cancer by other studies. Thus, this study provided further validation into the claim of these 4 proteins being potential targets for cancer treatment.
Preprint
|
|
|
Life Sciences, Biotechnology; batch; biopolyesters; bioreactor; cell recycling; continuous; chemostat; fed-batch; fermentation; pH-stat; polyhydroxyalkanoate (PHA)
Online: 21 March 2018 (13:01:12 CET)
|
|
Share this article with
×
Polyhydroxyalkanoates (PHA) are microbial biopolyesters utilized as “green plastics”. Their production under controlled conditions resorts to bioreactors operated in different modes. Because PHA biosynthesis constitutes a multiphase process, both feeding strategy and bioreactor operation mode need smart adaptation. Traditional PHA production setups based on batch, repeated batch, fed-batch or cyclic fed-batch processes are often limited in productivity, or display insufficient controllability of polyester composition. For highly diluted substrate streams like it is the case for (agro)industrial waste streams, fed-batch enhanced by cell recycling were recently reported as a viable tool to increase volumetric productivity. As emerging trend, continuous fermentation processes in single-, two-, and multi-stage setups are reported, which bring the kinetics of both microbial growth and PHA accumulation into agreement with process engineering, and allow tailoring PHA´s molecular structure. Moreover, we currently witness an increasing number of CO2-based PHA production processes using cyanobacteria; these light-driven processes resort to photobioreactors similar to those used for microalgae cultivation, and can be operated both discontinuously and continuously. This development goes in parallel to the emerging use of methane and syngas as an abundantly available gaseous substrates, which also calls for bioreactor systems with optimized gas transfer.
The review sheds light on the challenges of diverse PHA production processes in different bioreactor types and operational regimes using miscellaneous microbial production strains such as extremophilic Archaea, chemoheterotrophic eubacteria and phototrophic cyanobacteria. Particular emphasize is dedicated to the limitations and promises of different bioreactor-strain combinations, and to efforts devoted to upscaling these processes to industrially relevant scales.
Preprint
|
|
|
Life Sciences, Cell & Developmental Biology; induced cardiomyocyte; epigenetic reprogramming; cell division; cell-cycle synchronization; cell-cycle exit
Online: 21 March 2018 (05:29:25 CET)
|
|
|
Share this article with
×
Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of EdU+/αMHC-GFP+ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFPhigh iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFPlow cells; however, S-phase synchronization didn’t enhance the polycistronic-MGT reprogramming, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.
Preprint
|
|
|
Life Sciences, Biochemistry; connexins; gap junctions; transcription; translation; post-translational modifications; trafficking
Online: 20 March 2018 (05:27:38 CET)
|
|
Share this article with
×
Connexins are tetraspan transmembrane proteins that form gap junctions and facilitate direct intercellular communication, a critical feature for the development, function and homeostasis of tissues and organs. In addition, a growing number of gap junction-independent functions are being ascribed to these proteins. The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional level, and undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability and function. Here, we summarize these key regulatory events, with emphasis on how these affect their multi-functionality in health and disease.
Preprint
|
|
|
Life Sciences, Other; Origin of life; evolution; molecular evolution; prebiotic chemistry; peptides; vesicles
Online: 19 March 2018 (13:01:33 CET)
|
|
Share this article with
×
Based on a new model of a possible origin of life, we establish an efficient and stable system undergoing structural reproduction, self-optimization and molecular evolution. This system is being formed under realistic conditions by the interaction of two cyclic processes, one of which offering vesicles as the structural environment, the other supplying peptides from a variety of amino acids as versatile building blocks. We demonstrate that structures growing in a combination of both cycles have the potential to support their own existence, to undergo chemical and structural evolution and to develop unpredicted functional properties. The key mechanism is the mutual stabilization of the peptides by the vesicles and of the vesicles by the peptides together with a constant production and selection of both. The development of the proposed system over time not only would represent one of the principles of life, but could also be a model for the formation of self-evolving structures ultimately leading to the first living cell. The experiment yields clear evidence on a vesicle-induced accumulation of membrane-interacting peptide which could be identified by liquid chromatography combined with high-resolution mass spectroscopy. We found that the selected peptide has an immediate effect on the vesicles, leading to i) reduced vesicle size, ii) increased vesicle membrane permeability, and iii) improved thermal vesicle stability.
Preprint
|
|
|
Life Sciences, Other; buckwheat; CVD risk markers; meta-analysis
Online: 19 March 2018 (10:45:19 CET)
|
|
Share this article with
×
The effects of buckwheat intake on cardiovascular diseases (CVD) have not been systematically investigated. The aim of the present study was to comprehensively summarise studies in humans and animals evaluating the impact of buckwheat consumption on CVD risk markers and to conduct a meta-analysis of relevant data. Thirteen randomised, controlled human studies, two cross-sectional human studies and twenty-one animal studies were identified. Using random effects models, the weighted mean difference of post-intervention concentrations of blood glucose, total cholesterol and triglycerides were significantly decreased following buckwheat intervention compared with controls [differences in blood glucose: -0.85 mmol/L (95% CI: -1.31, -0.39), total cholesterol: 0.50 mmol/L (95% CI: -0.80, -0.20) and triglycerides: 0.25 mmol/L (95% CI: -0.49, -0.02)]. Responses of a similar magnitude were seen in two cross-sectional studies. For animal studies, nineteen of twenty-one studies showed a significant reduction in total cholesterol of between 12 and 54%, and fourteen of twenty studies showed a significant reduction in triglycerides of between 2 and 74%. All exhibited high unexplained heterogeneity. There was inconsistency in HDL cholesterol outcomes in both human and animal studies. It remains unclear whether increased buckwheat intake significantly benefits other markers of CVD risk, such as weight, blood pressure, insulin, and LDL-cholesterol, and underlying mechanisms responsible for any effects are unclear.
Preprint
|
|
|
Life Sciences, Virology; influenza; H1N1; mouse adaptation; deep sequencing; polymerase; PA; PB1; defective viral genomes
Online: 19 March 2018 (08:59:26 CET)
|
|
Share this article with
×
Mice are not natural hosts for influenza A viruses (IAVs), but they are useful models for studying antiviral immune responses and pathogenesis. Serial passage of IAV in mice invariably causes the emergence of adaptive mutations and increased virulence. Typically, mouse-adaptation studies are conducted in inbred laboratory strains BALB/c and C57BL/6, which have defects in the antiviral Mx1 gene that results in increased susceptibility to infection and disease severity. Here, we report the adaptation of IAV reference strain A/California/07/2009(H1N1) (a.k.a. CA/07) in outbred Swiss Webster mice. Serial passage led to increased virulence and lung titers, and dissemination of the virus to brains. We adapted a deep-sequencing protocol to identify and enumerate adaptive mutations across all genome segments. Among mutations that emerged during mouse-adaptation, we focused on amino acid substitutions in polymerase subunits: polymerase basic-1 (PB1) T156A and F740L, and polymerase acidic (PA) E349G. These mutations were evaluated singly and in combination in minigenome replicon assays, which revealed that PA E349G increased polymerase activity. By selectively engineering these three adaptive PB1 and PA mutations into the parental CA/07 strain, we demonstrated that adaptive mutations in polymerase subunits decreased the production of defective viral genome segments with internal deletions, and dramatically increased the release of infectious virions from mouse cells. Together, these findings increase our understanding of the contribution of polymerase subunits to successful host adaptation.
Preprint
|
|
|
Life Sciences, Genetics; repetitive elements; RNA-Seq; genomics; evolution; cytogenetics; supernumerary elements; extra chromosomes
Online: 19 March 2018 (08:33:48 CET)
|
|
|
Share this article with
×
B chromosomes (B) are supernumerary elements found in many taxonomic groups. Most B chromosomes are rich in heterochromatin and composed of abundant repetitive sequences, especially transposable elements (TEs). Bs origin is generally linked to the A chromosome complement (A). The first report of a B chromosome in African cichlids was on Astatotilapia latifasciata, which can harbor 0, 1 or 2 B chromosomes. Classical cytogenetics studies found high TE content on the species B chromosome. In this study, we aim to understand TE composition and expression on A. latifasciata genome and its relation to the B chromosome. We use bioinformatics analysis to explore TEs genome organization and also their composition on the B chromosome. Bioinformatics findings were validated by fluorescent in situ hybridization (FISH) and real-time PCR (qPCR). A. latifasciata has a TE content similar to other cichlid fishes and several expanded elements on its B chromosome. With RNA sequencing data (RNA-seq) we showed that all major TE classes are transcribed in brain, muscle and male/female gonads. The evaluation of TE expression between B- and B+ individuals showed that few elements have differential expression among groups and expanded B elements were not highly transcribed. Putative silencing mechanisms may the acting on the B chromosome of A. latifasciata to prevent adverse consequences of repeat transcription and mobilization in the genome.
Preprint
|
|
|
Anusha Chaparala,
Deepak Poudyal,
Erin E. Witalison,
Hossam Tashkandi,
Alexander A. Chumanevich,
Jenna L. Hofseth,
Douglas L. Pittman,
Michael D. Wyatt,
Anthony Windust,
Mitzi Nagarkatti,
Prakash Nagarkatti,
Lorne J. Hofseth
Life Sciences, Immunology; Inflammatory Bowel Diseases; ulcerative colitis; American ginseng; Panaxynol; macrophages
Online: 19 March 2018 (08:32:22 CET)
|
|
|
Share this article with
×
Ulcerative colitis has a significant impact on the quality of life for the patients, and can substantially increase the risk of colon cancer in patients suffering long-term. Conventional treatments provide only modest relief paired with a high risk of side effects, while complementary and alternative medicines can offer safe and effective options. Over the past decade, we have shown that American ginseng has anti-oxidant and anti-inflammatory properties that can suppress mouse colitis and prevent colitis associated colon cancer. With the goal of isolating a single active compound, we further fractionated the hexane fraction, and found the most abundant molecule in this fraction was the polyacetylene, Panaxynol. After isolating and characterizing Panaxynol, we tested the efficacy of Panaxynol in the treatment and prevention of colitis in mice and studied the mechanism of action. We demonstrate here that Panaxynol effectively treats colitis in a Dextran Sulfate Sodium mouse model by targeting macrophages for DNA damage and apoptosis. Positive outcomes from this study could take American ginseng one-step further towards becoming a conventional drug for the treatment of colitis, and possibility exploring other autoimmune diseases associated with macrophage dysfunction.
Preprint
|
|
|
Life Sciences, Cell & Developmental Biology; regenerative medicine; reprogramming; cardiac differentiation; secretoma; tissue engineering
Online: 15 March 2018 (05:02:41 CET)
|
|
Share this article with
×
Human induced pluripotent stem cells (hiPSCs) are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs) recapitulate phenotypic differences caused by genetic variations, making them human attractive disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as source cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs. We also cover the phenotypic characteristics of the hiPSCs derived CMs, their ability to rescue injured CMs through paracrine effects, the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their potential use in biomedical applications.
Preprint
|
|
|
Life Sciences, Virology; insect; RNAi; non-RNAi; defense systems; antiviral; insect pest control; bee health
Online: 12 March 2018 (05:18:25 CET)
|
|
Share this article with
×
RNAi is considered a major antiviral defense mechanism in insects but its relative importance compared to other antiviral pathways has not been evaluated comprehensively. Here, it is attempted to give an overview of the antiviral defense mechanisms in Drosophila that involve both RNAi and non-RNAi to acquire a sense of their relative importance. While RNAi is considered important in most viral infections, many other pathways can exist that confer antiviral resistance. It is noted that very few direct recognition mechanisms of virus infections have been identified in Drosophila and that the activation of immune pathways may be accomplished indirectly through cell damage incurred by viral replication. In several cases, protection against viral infection can be obtained in RNAi mutants by non-RNAi mechanisms, confirming the variability of the RNAi defense mechanism according to the type of infection and the physiological status of the host. This analysis invites to investigate more systematically the relative contribution of RNAi in the antiviral response and more specifically to ask whether RNAi efficiency is affected when other defense mechanisms predominate. While Drosophila can function as a useful model, this issue may be more critical for economically important insects that are either controlled (agricultural pests and vectors of diseases) or protected from parasite infection (beneficial insects as bees) by RNAi products.
Preprint
|
|
|
Life Sciences, Virology; tail tubular protein B; bacteriophage; biofilm; exopolysaccharide; hydrolytic activity
Online: 12 March 2018 (04:06:53 CET)
|
|
Share this article with
×
Background: Dual function tail tubular proteins (TTP) from lytic bacteriophage are novel interesting group of biologically active enzymes possessing antibiofilm activity. Surprisingly, apart from their structural function, they are also polysaccharide hydrolyzes destroying bacterial extracellular components. One of the representatives of this group is TTPB from KP32 phage. Here, we present its biological activity towards biofilm of E. cloacae ATCC 13047 strain and towards its exopolysaccharide (EPS). Methods: TTPB was overexpressed in E coli system, purified and tested towards the pathogenic bacteria using agar overlay method. Hydrolytic activity of TTPB against bacterial EPS has been performed by reducing sugar (RS) determination in TTPB/EPS mixture regarding the RS amount obtained after acidic hydrolysis. Antibiofilm activity of TTPB has been set down on one-day E. cloacae biofilm using a biochemical method. Finally, the synergistic activity of TTPB with kanamycin has been demonstrated. Results: For the first time the hydrolytic activity of TTPB towards bacterial EPS has been showed. TTPB releases about a half of the whole RS amount of E. cloacae ATCC 13047 EPS and can reduce its biofilm by over 60%. Destroying the bacterial biofilm the phage protein improves the antibiotic action increasing kanamycin effectiveness almost four times.
Preprint
|
|
|
Life Sciences, Other; biosensor; S-layer protein; crystalline 2D protein lattice; lipid membrane platform; linking matrix; bioreceptor; biomimetics
Online: 9 March 2018 (12:10:28 CET)
|
|
Share this article with
×
The present Feature Paper highlights the application of bacterial surface (S-) layer proteins as versatile components for the fabrication of biosensors. One technologically relevant feature of S‑layer proteins is their ability to self-assemble on many surfaces and interfaces to form a crystalline 2D protein lattice. The S-layer lattice on the surface of a biosensor becomes part of the interface architecture, linking the bioreceptor to the transducer interface, which may cause signal amplification. The S-layer lattice as ultrathin, highly porous structure with functional groups in a well-defined special distribution and orientation and an overall anti-fouling characteristics can significantly raise the limit in terms of variety and ease of bioreceptor immobilization, compactness of bioreceptor molecule arrangement, sensitivity, specificity, and detection limit for many types of biosensors. The present paper discusses and summarizes examples for the successful implementation of S-layer lattices on biosensor surfaces in order to give a comprehensive overview on the application potential of these bioinspired S-layer protein-based biosensors.
Preprint
|
|
|
Life Sciences, Other; polybrominated diphenyl ether; PBDE; BDE-47; adipose; transcriptomic; genomic; obesogen; complement and coagulation cascade; de novo lipogenesis; metabolism
Online: 8 March 2018 (03:10:13 CET)
|
|
|
Share this article with
×
For the majority of lipophilic compounds adipose tissue is traditionally considered as storage depot and only rarely as a target organ. Meanwhile, abnormalities in adipose tissue physiology induced by chemical exposures may contribute to the current epidemic of obesity and metabolic diseases. Polybrominated diphenyl ethers (PBDEs) is a group of lipophilic flame retardants found in majority of human samples in North America. Their ability to alter physiology of adipose tissue is unknown. We exposed pregnant mice to 0.2 mg/kg body weight/day of BDE-47 perinatally. Transcriptomic changes in gonadal adipose tissue were analyzed in male offspring using RNA-seq approach with subsequent bioinformatic analysis. Genes of coagulation and complement cascade, de novo lipogenesis, and xenobiotic metabolism were altered in expression in response to BDE-47 exposure. The affected molecular network included the following hubs: PPARα, HNF1A and HNF4. These findings suggest that adipose tissue should be considered a target tissue for BDE-47, in addition to its role as a storage depot. This study also builds a background for a targeted search of sensitive phenotypic endpoints of BDE-47 exposure, including lipid profile parameters and coagulation factors in circulation. Additional studies are needed to investigate the role of PBDEs as an obesogen.
Preprint
|
|
|
Life Sciences, Genetics; common shrew; meiotic chromosomes; Sorex araneus; synaptonemal complex; hybrids; MLH1
Online: 7 March 2018 (09:24:11 CET)
|
|
|
Share this article with
×
The hybrid zone between chromosome races of the common shrew (Sorex araneus) provides an exceptional model to study the potential role of chromosome rearrangements in the initial steps of speciation. The Novosibirsk and Tomsk races differ by a series of Robertsonian fusions with monobrachial homology. They form a narrow hybrid zone and generate hybrids with both simple (chain of three chromosomes) and complex (chain of eight or nine) synaptic configurations. Using immunolocalisation of the meiotic proteins, we examined chromosome pairing and recombination in males from the hybrid zone. Homozygotes and simple heterozygotes for Robertsonian fusions showed a low frequency of synaptic aberrations (< 10%). The carriers of complex synaptic configurations showed multiple pairing abnormalities, which might lead to reduced fertility. Recombination frequency in the proximal regions of most chromosomes of all karyotypes was much lower than in the other regions. The strong suppression of recombination in the pericentromeric regions and co-segregation of race specific chromosomes involved in the long chains would be expected to lead to linkage disequilibrium between genes located there. Genic differentiation, together with the high frequency of pairing aberrations in male carriers of the long chains, might contribute to maintenance of the narrow hybrid zone.
Preprint
|
|
|
Life Sciences, Biophysics; cryo-electron microscopy; air-water interface; conformational heterogeneity; focus gradient; radiation damage
Online: 6 March 2018 (07:17:15 CET)
|
|
Share this article with
×
With forty years of developments, bio-macromolecule cryo-electron microscopy has met its revolution of resolution and is playing a very important role in structural biology study. According to different specimen states, cryo-electron microscopy (cryo-EM) involves three specific techniques, single particle analysis (SPA), electron tomography and sub-tomogram averaging, and electron diffraction. All these three techniques have not realized their full potentials of solving structures of bio-macromolecules and therefore need to be developed in the future. In this review, the current existing bottlenecks of cryo-EM SPA are discussed with theoretical analysis, which includes air-water interface during specimen cryo-vitrification, bio-macromolecular conformational heterogeneity, focus gradient within thick specimen, and electron radiation damage. Besides, potential solutions of these bottlenecks are proposed and discussed, which are worthy of further investigations in the future.
Preprint
|
|
|
Life Sciences, Biotechnology; diffusion; gas transfer; fermentation; uptake rate; physio-chemical
Online: 2 March 2018 (07:01:22 CET)
|
|
Share this article with
×
Current education in biology is devoid of mathematics in many countries, probably because many relevant biological processes are explained from a qualitative point of view rather than addressing the quantitative aspects of these phenomena. Here, we employ a case study from the yeast physiology to illustrate the importance of numeracy skills for a deeper understanding of relevant biological problems. Yeast anaerobic growth on sugars is a widespread process as it is the basis for beer, bread, and winemaking and it is much akin to lactic acid fermentation in muscle cells in response to an increased energy demand. To study the physiology of yeasts under controlled conditions and being able to compare the results quantitatively, one ought to perform measurements and calculations involving concentrations of oxygen, biomass, and organic compounds. To set-up an “anaerobic” culture of Saccharomyces cerevisiae in a defined medium, one needs to calculate how much oxygen must enter the cultivation system, to meet the requirements for ergosterol and oleic acid biosyntheses, both of which require oxygen. Using basic physicochemical principles and simple mathematical skills, students will be able to compute the oxygen requirement for yeast growth under such “anaerobic” conditions.
Preprint
|
|
|
Life Sciences, Microbiology; antagonism; Bacillus velezensis; Penicillium roqueforti; silage; roquefortine C
Online: 1 March 2018 (14:24:15 CET)
|
|
Share this article with
×
In Belgium, silages are often infected by Penicillium roqueforti sensu lato (s.l.). These toxigenic fungi are well adapted to silage conditions, and their prevention during feed-out is difficult. Bacillus velezensis strain NRRL B-23189 has been reported to inhibit P. roqueforti s.s. conidiospore germination in vitro by the production of lipopeptides. In the present study, the antagonistic effect of this B. velezensis strain towards P. roqueforti s.l. was evaluated in vitro and in vivo. In vitro, corn silage conditions were simulated, and the impact of B. velezensis culture supernatant or cell suspension on P. roqueforti s.l. growth, conidiospore germination and survival and roquefortine C production was evaluated. The antagonism was promising, but growth of B. velezensis in corn silage infusion was poor. An in vivo experiment with microsilos containing a mixture of perennial ryegrass and white clover artificially contaminated with P. roqueforti s.l. was carried out to determine if B. velezensis cell suspension could be used as an antagonistic silage inoculant. The B. velezensis cell suspension applied was unsuccessful in reducing P. roqueforti s.l. numbers at desiling after 56 days compared to no additive application. However, feed-out of the silage was not simulated, so it remains elusive whether or not B. velezensis exerts antagonistic activity during this phase.
Preprint
|
|
|
Life Sciences, Molecular Biology; hypoxia; chromatin; transcriptional repression; repressor complexes; JmjC; histone methylation; HIF
Online: 1 March 2018 (06:36:57 CET)
|
|
Share this article with
×
Hypoxia, or reduced oxygen availability, has been studied extensively for its ability to activate specific genes. Hypoxia induced gene expression is mediated by the HIF transcription factors, although not exclusively so. Despite the great knowledge on the mechanisms by which hypoxia activates genes, much less is known about how hypoxia promotes gene repression. In this review, we discuss the potential mechanisms underlying hypoxia-induced transcriptional repression responses. We highlight HIF-dependent and independent mechanisms, but also the potential roles of dioxygenases with functions at the nucleosome and DNA level. Finally, we discuss recent evidence regarding the involvement of transcriptional repressor complexes in hypoxia.
Preprint
|
|
|
Life Sciences, Molecular Biology; ark shell; transcriptome; growth; metabolism; differentially expressed genes
Online: 1 March 2018 (04:47:45 CET)
|
|
Share this article with
×
To understand the molecular mechanism associated with growth variability in bivalves, the Solexa/Illumina technology was employed to analyze the transcriptomic profiles of extreme growth rate differences (fast- VS. slow-growing individuals) in one full-sib family of the ark shell Scapharca subcrenata. De novo assembly of S. subcrenata transcriptome yielded 276,082,016 raw reads, which were assembled into 98,502 unique transcripts by Trinity strategy. A total of 6,357 differentially expressed genes (DEGs) were obtained between fast- and slow-growing individuals, with 580 up-regulated expression and 5777 down-regulated expression. Functional annotation revealed that the largest proportion of DEGs were classified to the large or small subunit ribosomal protein, all of which showed significantly lower expression levels in fast-growing group than those in slow-growing group. GO enrichment analysis identified the maximum of DEGs to biological process, followed by molecular function and cellular component. Most of the top enriched KEGG pathways were related to energy metabolism, protein synthesis and degradation. These findings reveal the link between gene expression and contrasting phenotypes in ark shells, which support that fast-growing individuals may be resulted from decreased energy requirements for metabolism maintenance, accompanying with greater efficiency of protein synthesis and degradation in bivalves.
Preprint
|
|
|
Margarita Maria-Panou,
Emma L. Prescott,
Daniel L. Hurdiss,
Gemma Swinscoe,
Michael Hollinshead,
Laura G. Caller,
Ethan L. Morgan,
Louisa Carlisle,
Marietta Muller,
Michelle Antoni,
David Kealy,
Neil A. Ranson,
Colin M. Crump,
Andrew Macdonald
Life Sciences, Virology; polyomavirus; agnoprotein; virus exit
Online: 1 March 2018 (04:11:26 CET)
|
|
Share this article with
×
BK polyomavirus (BKPyV) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein do not propagate to wild-type levels and fail to release from host cells. Despite this, loss of agnoprotein does not impair virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-SNAP is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell.
Preprint
|
|
|
Life Sciences, Biotechnology; Alzheimer’s disease; biomimetic nanocarriers; blood-brain barrier; dementia; drug targeting; lipid cubic phases; nanoemulsion; SR-BI; scavenger receptors
Online: 28 February 2018 (07:49:13 CET)
|
|
Share this article with
×
Over past decades, a frequent co-morbidity of cerebrovascular pathology and Alzheimer's disease pathology has been observed. Numerous published studies indicate that preservation of healthy cerebrovascular endothelium can be an important therapeutic target. By incorporating appropriate drug(s) into biomimetic (lipid cubic-phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type 1 (i.e., SR-BI), and crosses the blood-brain barrier. This targeting allows for various Alzheimer’s-related cell types to be simultaneously searched out for localized drug treatment in vivo.
Preprint
|
|
|
Life Sciences, Biophysics; molecular dynamics simulation; RNA-binding; rev protein; rev response element (RRE); HIV-virus.
Online: 21 February 2018 (16:57:27 CET)
|
|
Share this article with
×
Nuclear export of viral mRNAs, is an essential step in the HIV replication cycle. This role is played by a small regulatory protein of HIV-1 called Rev.The N-terminal region of Rev contains an arginine-rich sequence. The arginine-rich motif (ARM) is located between amino acids 38-50 and forms an alpha-helical secondary structure. Expression of the structural proteins of human immunodeficiency virus type 1 requires the direct interaction of multiple copies of the viral Rev protein with its highly structured RNA target sequence, the Rev Response element (RRE). The major viral proteins are not produced if this transport of RNA is stopped. Therefore, knowledge of Rev structure is essential for understanding of its cooperative binding to the RRE, for understanding the mechanism of HIV infection and for the development of antiviral drugs that interfere with Rev’s essential functions and for acknowledgment of good candidate drugs for treatment of AIDS. To understand how REV interact with RRE element of HIV-RNA and its formation of oligomeric complex it is better to characterize the domain wise structure of REV with regard in function of each domain. Due to lack of structural data on Rev no single compound is reported as inhibitor of REV expect antiviral drugs. Identification of a high-affinity RNA-binding site for the human immunodeficiency virus type 1 Rev Protein is much more important. The ARM is a highly specific sequence which allows for the multimerization of Rev and also binding of REV with RNA. Here we are first time exploring the structural characteristics of REV protein both in free form and in complex with RNA at domain function level especially explore the role of ARM motif in REV HIV-1 protein as RNA binding sites by molecular dynamics (MD) simulation and homology modeling studies. Results indicate that the arginine-rich motif (ARM) is crucial in stability of this complex. The residues ARG38, 39, 41, 43, 44, 48, 50, and ASN40 are most interacting with nucleobases of RRE in Crystal structure of Rev and Rev-response-element RNA complex. Our study plays a major role in elaboration of binding of RNA with REV and pave the way for further investigation for therapeutically agent for HIV.
Preprint
|
|
|
Life Sciences, Virology; flavivirus; arbidol; umifenovir; antiviral activity; cytotoxicity; cell-type dependent antiviral effect
Online: 21 February 2018 (14:44:34 CET)
|
|
Share this article with
×
Arthropod-borne flaviviruses represent human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy is currently available. Arbidol (umifenovir) is a broad spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound showed activity against numerous DNA and RNA viruses. Its mode of action is based predominantly on the impairment of critical steps of virus-cell interaction. Here we demonstrate that arbidol possesses a micromolar inhibition activity (EC50 values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of arthropod-borne flaviviruses. Interestingly, no antiviral effect of arbidol is observed in porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-6), human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol presents a significant increasing in cytotoxicity profiles when tested in various cell lines in the order: Huh-7 < HBCA < PS < UKF-NB-6 < Vero with CC50 values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activity and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in treating flaviviral infections.
Preprint
|
|
|
Life Sciences, Other; Alcohol abuse, Alcohol beneficial effects, multi-organ effects of alcohol
Online: 19 February 2018 (14:30:39 CET)
|
|
Share this article with
×
Alcohol abuse can result in detrimental multisystem effects. Chronic alcohol abuse is known to be associated with pathophysiological changes in multiple organs often resulting in life threatening clinical outcomes e.g. breast and colon cancer, pancreatic disease, cirrhosis of the liver, diabetes, osteoporosis, arthritis, kidney disease, immune system dysfunction, hypertension, coronary artery disease, alcohol-induced cardiomyopathy and heart failure as well as central nervous system disorders. In this review article, we will discuss the multisystemic effects of alcohol abuse and explore in greater detail alcohol’s impact on two main systems that result in pathophysiological changes i.e. the cardiovascular and central nervous systems.
Preprint
|
|
|
Life Sciences, Other; chromatolysis, ribonuclease, angiogenin, endoplasmic reticulum, ribosome
Online: 16 February 2018 (16:19:57 CET)
|
|
Share this article with
×
After axonal injury, chromatolysis (fragmentation of Nissl substance) occurs in both intrinsic neurons (whose processes are within the CNS) and extrinsic neurons (whose axons extend outside the CNS). Electron microscopy shows that chromatolysis involves fission of the rough endoplasmic reticulum. In intrinsic neurons (which do not regenerate axons) or in extrinsic neurons denied axon regeneration, chromatolysis is often accompanied by degranulation (loss of ribosomes from rough endoplasmic reticulum), disaggregation of polyribosomes and degradation of monoribosomes into dust-like particles. Ribosomes and rough endoplasmic reticulum may also be degraded in autophagic vacuoles by Ribophagy and Reticulophagy, respectively. In other words, chromatolysis is disruption of parts of the protein synthesis infrastructure. Whereas some neurons may show transient or no chromatolysis, severely injured neurons can remain chromatolytic and never again synthesise normal levels of protein; some may atrophy or die. What molecule(s) cause fragmentation or degranulation of rough endoplasmic reticulum, disaggregation of polyribosomes and degradation of monoribosomes? Ribonucleases can modify (and perhaps fragment) rough endoplasmic reticulum; various endoribonucleases can degrade mRNA causing polyribosomes to unchain and disperse; they can disassemble monoribosomes; Ribonuclease 5 can control rRNA synthesis and degrade tRNA; Ribonuclease T2 can degrade ribosomes, rough endoplasmic reticulum and RNA within autophagic vacuoles; and Ribonuclease IRE1α acts as a stress sensor within the endoplasmic reticulum. Regeneration might be improved after axonal injury by protecting the protein synthesis machinery from catabolism; targeting ribonucleases could be a profitable strategy.
Preprint
|
|
|
Life Sciences, Cell & Developmental Biology; COX-2; breast cancer; PGE2; EP receptors; stem-like cells; metastasis; angiogenesis; lymphangiogenesis; MicroRNAs; triple negative breast cancer
Online: 13 February 2018 (09:16:54 CET)
|
|
Share this article with
×
G protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions as well as in the pathology of many diseases including cancer progression and metastasis. Only a few GPCR members have been exploited as targets for developing drugs with therapeutic benefit in cancer. Present review deals with the Prostaglandin E receptor EP4, a member of the EP family of GPCR, as a promising newer therapeutic target for treating breast cancer. We show that aberrant over-expression of cyclooxygenase (COX)-2, an inflammation-associated enzyme, occurring in 40-50% of breast cancer patients leads to tumor progression and metastasis due to multiple cellular events resulting from an increased prostaglandin (PG) E2 production in the tumor milieu. They include inactivation of host anti-tumor immune (NK and T) cells, increased immuno-suppressor function of tumor-associated macrophages, promotion of tumor cell migration, invasiveness and tumor-associated angiogenesis (due to upregulation of VEGF-A), lymphangiogenesis (due to upregulation of VEGF-C/D) and a stimulation of stem-like cell (SLC) phenotype in cancer cells. All these events were primarily mediated by activation of the PGE receptor EP4 on tumor or host cells. We show that selective EP4 antagonists (EP4A) could mitigate all these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs - miR526b and miR655, one of which (miR655) appears to be a potential blood biomarker in breast cancer patients, for monitoring SLC-ablative therapies such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents such as PD-1 or PD-L1 inhibitors.
Preprint
|
|
|
Marta Maciejewska,
Magdalena Calusinska,
Luc Cornet,
Delphine Adam,
Igor Pessi,
Sandrine Malchair,
Philippe Delfosse,
Denis Baurain,
Hazel Barton,
Monique Carnol,
Sébastien Rigali
Life Sciences, Microbiology; antibiotics; geomicrobiology; Illumina sequencing; microbiome diversity; Streptomyces; Cave microbiology
Online: 12 February 2018 (16:30:42 CET)
|
|
|
Share this article with
×
Moonmilk are cave carbonate deposits that host a rich microbiome including antibiotic-producing Actinobacteria making these speleothems appealing for bioprospecting. Here we investigated the taxonomic profile of the actinobacterial community of three moonmilk deposits of the cave “Grotte des Collemboles” via high-throughput sequencing of 16S rRNA amplicons. Actinobacteria was the most common phylum after Proteobacteria, ranging from 9 to 23% of the total bacterial population. Next to actinobacterial OTUs attributed to uncultured organisms at the genus level (~44%), we identified 47 actinobacterial genera with Rhodoccocus (4 OTUs, 17%) and Pseudonocardia (9 OTUs, ~16%) as the most abundant in terms of absolute number of sequences. Streptomycetes presented the highest diversity (19 OTUs, 3%), with most of OTUs unlinked to the culturable Streptomyces strains previously isolated from the same deposits. 43% of OTUs were shared between the three studied collection points while 34% were exclusive to one deposit indicating that distinct speleothems host their own population despite their nearby localization. This important spatial diversity suggests that prospecting within different moonmilk deposits should result in the isolation of unique and novel Actinobacteria. These speleothems also host a wide range of non-streptomycetes antibiotic-producing genera, and should therefore be subjected to methodologies for isolating rare Actinobacteria.
Preprint
|
|
|
Life Sciences, Endocrinology & Metabolomics; physical exercise; irisin; neurodegeneration; aging; Alzheimer’s disease
Online: 11 February 2018 (04:28:07 CET)
|
|
Share this article with
×
Irisin, a skeletal muscle-secreted myokine, produced in response to physical exercise, has protective functions in both the central and the peripheral nervous systems, including the regulation of brain-derived neurotrophic factors and modification of telomere length. Such beneficial effects may inhibit or delay the emergence of neurodegenerative diseases, including Alzheimer’s disease (AD). This review is based on the hypothesis that irisin produced by physical exercise helps control AD progression. Herein, we describe the physiology of irisin and its potential role in delaying or preventing AD. Although current and ongoing studies on irisin show promising results, further research is required to clarify its potential as a meaningful therapeutic target for treating human diseases.
Preprint
|
|
|
Life Sciences, Genetics; genetics; injury; sport; soccer; DNA; inflammation; football
Online: 9 February 2018 (02:24:40 CET)
|
|
|
Share this article with
×
Genetics plays an integral role in athletic performance and is increasingly becoming recognised as an important risk factor for injury. Ankle and knee injuries are the most common injuries sustained by soccer players. Often these injuries result in players missing training and matches, which can incur significant costs to clubs. This study aimed to identify genotypes associated with ankle and knee injuries in soccer players and how these impacted the number of matches played. 289 soccer players including 46 professional, 98 semi-professional and 145 amateur players were genetically tested. Ankle and knee injuries and the number of matches played were recorded during the 2014/15 season. Four genes were assessed in relation to injury. Genotypes found to be associated with injury included the TT genotype of the GDF5 gene, TT and CT genotypes of AMPD1 gene, TT genotype of COL5A1 and GG genotype of IGF2 gene. These genes were also associated with a decrease in the number of matches played.
Preprint
|
|
|
Life Sciences, Microbiology; external resistances; soil microbial fuel cells; paddy soil; Geobacter; arsenic; iron; organic matter
Online: 8 February 2018 (03:29:46 CET)
|
|
|
Share this article with
×
Soil microbial fuel cells (sMFC) are a novel technique that use organic matters in soils as an alternative energy source. External resistance (ER) is a key factor influencing sMFC performance and, furthermore, alters the soil’s biological and chemical reactions. However, little information is available on how the microbial community and soil component changes in sMFC with different ER. Therefore, the effects of anodes of sMFC at different ER (2000 Ω, 1000 Ω, 200 Ω, 80 Ω and 50 Ω) were examined by measuring organic matter (OM) removal efficiency, trace elements in porewater and bacterial community structure in contaminated paddy soil. The results indicated that ER has significant effects on sMFC power production, OM removal efficiency and bacterial beta diversity. Moreover ER influences iron, arsenic and nickel concentration as well in soil porewater. In particular, greater current densities were observed at lower ER (2.4mA, 50Ω) compared to a higher ER (0.3mA, 2000Ω). The removal efficiency of OM increased with decreasing ER whereas it decreased with soil distance away from the anode. Furthermore, principal coordinate analysis (PCoA) revealed that ER may shape the bacterial communities that develop in the anode vicinity but have minimal effect on that of the bulk soil. The current study illustrates that lower ER can be used to selectively enhance the relative abundance of electrogenic bacteria and lead to high OM removal.
Preprint
|
|
|
Life Sciences, Biotechnology; metals; dental regeneration; bioactivity; tissue regeneration; bone
Online: 6 February 2018 (05:25:46 CET)
|
|
Share this article with
×
The regeneration of bone tissue is a main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, while it should be resorbed even in the time frame needed for complete regeneration up to the condition of restitution ad integrum. In this context, the modes of action of CaP-based substitute materials have been frequently investigated and it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also on osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between the formation of new bone tissue and material degradation has not been found until now. The addition of different substances such as collagen or growth factors and also of different cell types have already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are differently used as basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designated for bone regeneration with the aim to give an overview of currently existing knowledge about the effects of metals in the field of bone regeneration.
Preprint
|
|
|
Life Sciences, Biochemistry; Alzheimer disease; Amyloid β-protein; Antibodies; Cross-reactions; Nucleotide aptamers; Oligonucleotide ligands; Systematic evolution of ligands by exponential enrichment; Specificity; Therapeutics
Online: 5 February 2018 (22:37:02 CET)
|
|
Share this article with
×
Aptamers are versatile oligonucleotide ligands used for molecular recognition of diverse targets. However, application of aptamers to the field of amyloid β-protein (Aβ) has been limited so far. Aβ is an intrinsically disordered protein that exists in a dynamic conformational equilibrium, presenting time-dependent ensembles of short-lived, metastable structures and assemblies that have been generally difficult to isolate and characterize. Moreover, despite understanding of potential physiological roles of Aβ, this peptide has been linked to the pathogenesis of Alzheimer disease, and its pathogenic roles remain controversial. Accumulated scientific evidence thus far highlights undesirable or nonspecific interactions between selected aptamers and different Aβ assemblies likely due to metastable nature of Aβ or inherent affinity of RNA oligonucleotides to β-sheet-rich fibrillar structures of amyloidogenic proteins. Accordingly, lessons drawn from Aβ–aptamer studies emphasize that purity and uniformity of the protein target and rigorous characterization of aptamers’ specificity are important for realizing and garnering the full potential of aptamers selected for recongizing Aβ or other intrinsically disordered proteins. This review summarizes studies of aptamers selected for recognizing different Aβ assemblies and highlights controversies, difficulties, and limitations of such studies.
Preprint
|
|
|
Life Sciences, Other; behaviour; castration; cattle; dehorning; buccal meloxicam; pain; topical anaesthetic; weight gain
Online: 31 January 2018 (13:56:25 CET)
|
|
|
Share this article with
×
The use of pain relief during castration and dehorning of calves on commercial beef operations can be limited by constraints associated with the delivery of analgesic agents. As topical anaesthetic (TA) and buccal meloxicam (MEL) are now available in Australia, offering practical analgesic treatments for concurrent castration and dehorning of beef calves, a study was conducted to determine their efficacy in providing pain relief when applied alone or in combination. Weaner calves were randomly allocated to; (1) no castration and dehorning / positive control (CONP); (2) castration and dehorning / negative control (CONN); (3) castration and dehorning with buccal meloxicam (BM); (4) castration and dehorning with topical anaesthetic (TA); and (5) castration and dehorning with buccal meloxicam and topical anaesthetic (BMTA). Weight gain, paddock utilisation, lying activity and behaviour following treatment were measured. CONP and BMTA calves had significantly greater weight gain than CONN calves (P < 0.001). CONN calves spent less time lying compared to BMTA calves on all days (P < 0.001). All dehorned and castrated calves spent more time walking (P = 0.024) and less time eating (P < 0.001) compared to CONP calves. There was a trend for CONP calves to spend the most time standing and CONN calves to spend the least time standing (P = 0.059). There were also trends for the frequency of head turns to be lowest in CONP and BMTA calves (P = 0.098) and tail flicks to be highest in CONN and BM calves (P = 0.061). The findings of this study suggest that TA and MEL can improve welfare and production of calves following surgical castration and amputation dehorning.
Preprint
|
|
|
Life Sciences, Microbiology; Neisseria meningitidis; glycoconjugate vaccines; protein-based vaccines, vaccine development
Online: 31 January 2018 (03:07:42 CET)
|
|
Share this article with
×
Neisseria meningitidis causes most cases of bacterial meningitis. Meningococcal meningitis is a public health burden to both developed and developing countries throughout the world. There are a number of vaccines (polysaccharide-based, glycoconjugate, protein-based and combined conjugate vaccines) that are approved to target five of the six disease-causing serogroups of the pathogen. Immunization strategies have been effective at helping to decrease the global incidence of meningococcal meningitis. Researchers continue to enhance these efforts through discovery of new antigen targets that may lead to a broadly protective vaccine and development of new methods of homogenous vaccine production. This review describes current meningococcal vaccines and discusses some recent research discoveries that may transform vaccine development against N. meningitidis in the future.
Preprint
|
|
|
Life Sciences, Other; P2Y, UTP, antagonist, natural products
Online: 30 January 2018 (13:34:32 CET)
|
|
Share this article with
×
P2Y2 and P2Y4 receptors are physiologically activated by UTP and are widely expressed in many cell types in humans. They promote an increase in intracellular calcium via PLCβ/ IP3 and act on ion flux and water secretion. P2Y2 plays an important role in inflammation and proliferation of tumor cells, which could be attenuated with the use of antagonists. However, little is known about the physiological functions related to P2Y4 due to the lack of selective ligands for these receptors, which can be solved through the search of novel compounds with antagonistic activity. In the present study, we have applied a methodology of calcium measurement to identify new antagonist candidates for these receptors. Firstly, we established optimal conditions for calcium assay using J774.G8, a murine macrophage cell line, which expresses functional P2Y2 and P2Y4 receptors. J774.G8 cells were loaded with 2 μM of Fluo-4 to test its sensitivity in responding calcium stimuli. ATP and ionomycin, known as inductors of intracellular calcium rise, were used to stimulate cells. The EC50 obtained were 11 μM and 103 nM, respectively. Subsequently, investigation of P2Y2 and P2Y4 expression was performed. These cells responded with EC50 of 1.021 μM to the UTP stimulation. Screening assays were performed and a total of 100 extracts from Brazilian natural products were tested. JA2, RA3, and RB3 extracts stood out for their ability to inhibit UTP-induced responses without causing cytotoxicity and presented IC50 of 32.32 μg/mL, 14.99 μg/mL, and 12.98 μg/mL, respectively. Collectively, our results point to the discovery of potential antagonists candidates from natural products for UTP-activated receptors.
Preprint
|
|
|
Life Sciences, Virology; human coronavirus; MERS-CoV; clinical features; upper respiratory tract infections; lower respiratory tract infections; respiratory viruses
Online: 30 January 2018 (09:52:03 CET)
|
|
Share this article with
×
Human coronaviruses cause both upper and lower respiratory tract infections in humans. In 2012 a sixth human coronavirus (hCoV) was isolated from a patient presenting with severe respiratory illness. The 60-year-old man died as a result of renal and respiratory failure after admission to a hospital in Jeddah, Saudi Arabia. The aetiological agent was eventually identified as a coronavirus and designated Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV has now been reported in more than 27 countries across the Middle East, Europe, North Africa and Asia. As of July 2017, 2040 MERS-CoV laboratory confirmed cases, resulting in 712 deaths, were reported globally, with a majority of these cases from the Arabian Peninsula. This review summarises the current understanding of MERS-CoV, with special reference to the (i) genome structure, (ii) clinical features, (iii) diagnosis of infection and (iv) treatment and vaccine development.
Preprint
|
|
|
Life Sciences, Microbiology; filamentous fungi; bioactive substances; antibiosis; phytopathogenic
Online: 29 January 2018 (08:34:07 CET)
|
|
Share this article with
×
Native strains of Trichoderma, isolated from mangrove sediments of PE, Brazil were determining their morphological and molecular characterization, and were investigated to assess of their biocontrol potential over the phytopathogenic Fusarium strains isolated from Caatinga soil, PE, Brazil. The Trichoderma strains were characterized by polyphasic approach, which combined their morphological characteristics, macro- and microculture results, growth evaluation by Tukey test, with significance of 5%. The DNA was extracted and the product was amplified with primers ITS 1 and 2, and sequenced. Trichoderma strains were compatible morphologically with the description of the genus. The molecular identification of Trichoderma, sequences of 500 bp were amplified, deposited in GenBank and used for phylogenetic analysis. The growth rate analysis showed rate of 0.1207 cmh-1 to Trichoderma strains and Fusarium spp. lower growth rate (0.031 cmh-1) was observed. The antibiosis tests showed the best antagonistic level of effectiveness to T. asperellum UCP 0149 against F. solani UCP 1395(82.2%) and F. solani UCP 1075(70.0%), followed of T. asperellum UCP 0319 against F. solani UCP1083 (73.4%), and T. asperellum UCP 0168 against F. solani UCP1098 (71.5%), respectively. The data obtained could serve as the basis for developing several biotechnological processes of safe use.
Preprint
|
|
|
Life Sciences, Biochemistry; sulfoxidation; epoxidation; two-component monooxygenase; flavoprotein; enantioselective biotransformation; fusion protein; protein linker; soil microorganism
Online: 25 January 2018 (17:14:33 CET)
|
|
|
Share this article with
×
VpStyA1 and VpStyA2B of Variovorax paradoxus EPS is annotated and characterized as the first representative of an E2-type styrene monooxygenase of proteobacteria. It comprises a single epoxidase (VpStyA1) and a fusion protein (VpStyA2B) which serves mainly as NADH:FAD-oxidoreductase. VpStyA2B had a Km of 33.6 ± 4.0 µM for FAD and a kcat of 22.3 ± 1.1 s-1. VpStyA2B and VpStyA1 showed monooxygenase activity on styrene of 0.14 U mg-1 and 0.46 U mg-1 as well as on benzyl methyl sulfide of 1.62 U mg-1 and of 3.11 U mg-1. A putative fusion region at position 408 (AREAV) was mutated to provide insights on VpStyA2B-function. The best mutant (408-AAAAA) obtained showed a 6.6-times higher affinity for FAD while keeping the NADH-affinity and -oxidation activity. Corresponding epoxidase activity increased (1.6-times). But, other mutants showed still NADH:FAD-oxidoreductase activity, but lost mostly their epoxidase activity indicating effects on the monooxygenase-part as well. Thus, this monooxygenase system represents an interesting candidate for biocatalyst development.
Preprint
|
|
|
Life Sciences, Other; Lactate dehydrogenase (LDH), Computed Tomography (CT), Glomerular filtration rate (GFR), C reactive protein (CRP), Angiotensin converting enzyme inhibitor (ACEI) Angiotensin receptor blocker (ARB), Kidney Urinary bladder ( KUB), Dimercapto Succinic Acid (DMSA)
Online: 24 January 2018 (11:41:15 CET)
|
|
Share this article with
×
Renal artery thrombosis is a sporadic serious clinical condition which potentially cause renal infarction. Diagnosis of renal infarction can be delayed or missed due to non specific clinical presentation and overlapping appearance of medical and surgical phenomena. Early diagnosis supported by biochemical and radiological findings while appropriate management potentially improve morbidity and mortality. Persistent abdominal or flank pain with raised LDH and proteinuria on background of thromboembolism risk factors supports the diagnosis. Despite the rarity of the disease rapid identification with prompt medical or endovascular intervention could prevent irreversible renal parenchymal damage.
Preprint
|
|
|
Yuan Hui,
Zhiming Wu,
Zhiran Qin,
Li Zhu,
Junhe Liang,
Xujuan Li,
Hanmin Fu,
Shiyu Feng,
Weiwei Xiao,
Qinghua Wu,
Bao Zhang,
Wei Zhao
Life Sciences, Virology; Zika virus; nucleic acid detection; micro-droplet digital polymerase chain reaction; real-time fluorescence quantitative polymerase chain reaction
Online: 24 January 2018 (04:21:18 CET)
|
|
Share this article with
×
Establishment of diagnostic methods with low detection limits plays a critical role in the maintenance of early diagnosis, prevention of serious neurological complications, and control of the spread of ZIKA. In this study, we established the micro-droplet digital polymerase chain reaction (ddPCR) and real-time fluorescent quantification PCR (qPCR) protocols for the detection of Zika virus based on the NS5 gene. For the Zika standard plasmid, the standard curve of R2 was 0.999, and the amplification efficiency was 92.203%, as determined by qPCR. Both ddPCR and qPCR were positive for cell culture of Zika nucleic acid.The minimum detection limit of ddPCR is 1–2 times lower than qPCR. Moreover, all tests of Dengue virus (1–4 serotypes) were negative in cell culture. Overall, these results suggested than ddPCR may have a lower limit of detection than qPCR.
Preprint
|
|
|
Loriano Ballarin,
Baruch Rinkevich,
Kerstin Bartscherer,
Artur Burzynski,
Sebastien Cambier,
Matteo Cammarata,
Isabelle Domart-Coulon,
Damjana Drobne,
Juanma Encinas,
Uri Frank,
Anne-Marie Geneviere,
Bert Hobmayer,
Helike Löhelaid,
Daniel Lyons,
Pedro Martinez,
Paola Oliveri,
Lorena Peric,
Stefano Piraino,
Andreja Ramšak,
Sebastian Rakers,
Fabian Rentzsch,
Amalia Rosner,
Tiago Henriques da Silva,
Ildiko Somorjai,
Sherif Suleiman,
Ana Varela Coelho
Life Sciences, Cell & Developmental Biology; aging; bioactive molecules; blue biotechnology; cancer; cell culture; COST Action; Europe; marine/aquatic invertebrates; regeneration; stem cells
Online: 24 January 2018 (04:14:56 CET)
|
|
Share this article with
×
The “stem cells” discipline represents one of the most dynamic areas in biomedicine. While adult marine/aquatic invertebrate stem cell (MISC) biology is of prime research and medical interest, studies on stem cells from organisms outside the classical vertebrate (e.g., human, mouse, zebrafish) and invertebrate (e.g., Drosophila, Caenorhabditis) models have not been pursued vigorously. Marine/aquatic invertebrates constitute the largest biodiversity and the widest phylogenetic radiation on Earth, from morphologically simple organisms (e.g. sponges, cnidarians), to the more complex mollusks, crustaceans, echinoderms and protochordates. These organisms illustrate a kaleidoscope of MISC-types that participate in the production of a large number of novel bioactive-molecules, many of which are of significant potential interest for human health. MISCs further participate in aging and regeneration phenomena, including whole-body regeneration. For years, the European MISC-community has been highly fragmented and scarce ties were established with biomedical industries in attempts to harness MISCs for human welfare. Thus, it is important to: i) consolidate the fragmented European community working on MISCs; ii) promote and coordinate European research on MISC biology; iii) stimulate young researchers to embark on research in MISC-biology; iv) develop, validate, and network novel MISC tools and methodologies; v) establish the MISC discipline as a forefront interest of biomedical disciplines, including nanobiomedicine; vi) establish collaborations with industries to exploit MISCs as sources of bioactive molecules. In order to fill the recognised gaps, the EC-COST Action 16203 “MARISTEM”, has recently been launched. At its initial stage the consortium unites 26 scientists from EC countries, Cooperating countries and Near Neighbor Countries.
Preprint
|
|
|
Life Sciences, Biotechnology; Biocompatibility; Biodegradability; Biopolyesters; Biopolymers; Composites; Drug Release; Implants; Polyhydroxyalkanoates; Scaffolds; Tissue Engineering
Online: 23 January 2018 (16:49:05 CET)
|
|
Share this article with
×
Polyhydroxyalkanotes (PHA) are bio-based microbial biopolyesters with stiffness, elasticity, crystallinity and degradability tunable by the monomeric composition, bio-production strategy and post-synthetic processing; they display biological alternatives for diverse technomers of petrochemical origin. This, together with the fact that their monomeric and oligomeric in vivo degradation products do not exert any toxic or elsewhere negative effect to living cells or tissue of humans or animals, makes them highly stimulating for various applications in the medical field. The article provides an overview of PHA application in the therapeutic, surgical and tissue engineering area, and reviews strategies to produce PHA at purity levels high enough to be used in vivo. Tested applications of differently composed PHA and advanced follow-up products as carrier materials for controlled in vivo release of anti-cancer drugs or antibiotics, as scaffolds for tissue engineering, as guidance conduits for nerve repair or as enhanced sutures, implants or meshes are discussed from both a biotechnological and a material-scientific perspective. Particular attention is devoted to the adaptation of traditional polymer processing techniques for production of medicine-related devices based on PHA, such as melt-spinning, melt extrusion, or solvent evaporation, and to emerging processing techniques like 3D-printing, computer-aided wet-spinning, laser perforation, or electrospinning.
Preprint
|
|
|
João C. P. Silva,
Marta Mota,
Fátima O. Martins,
Célia Nogueira,
Teresa Gonçalves,
Tatiana Carneiro,
Joana Pinto,
Daniela Duarte,
António S. Barros,
John G. Jones,
Ana M. Gil
Life Sciences, Endocrinology & Metabolomics; fructose; intestinal microbiota; short-chain fatty acids; metabolic profiling
Online: 23 January 2018 (05:31:27 CET)
|
|
|
Share this article with
×
Increased sugar intake is implicated in Type-2 diabetes and fatty liver disease. Mechanisms by which glucose and fructose components promote these conditions are unclear. We hypothesize that alterations in intestinal metabolite and microbiota profiles specific to each monosaccharide are involved. Two groups of six adult C57BL/6 mice were fed for 10-weeks with a diet where either glucose or fructose was the sole carbohydrate component (G and F, respectively). A third group was fed with normal chow (N). Fecal metabolites were profiled every 2-weeks by 1H NMR and microbial composition was analysed by real-time PCR (qPCR). Glucose tolerance was also periodically assessed. N, G and F mice had similar weight gains and glucose tolerance. Multivariate analysis of NMR profiles indicated that F mice were separated from both N and G, with decreased butyrate and glutamate and increased fructose, succinate, taurine, tyrosine and xylose. Compared to N and G, F mice showed a shift in microbe populations from gram-positive Lactobacillus spp. to gram-negative Enterobacteria species. Substitution of normal chow carbohydrate mixture by either pure glucose or fructose for 10 weeks did not alter adiposity or glucose tolerance. However, F G and N mice generated distinctive fecal metabolite signatures with incomplete fructose absorption as a dominant feature of F mice.
Preprint
|
|
|
Life Sciences, Biotechnology; extromphiles; extremophilic bacteria; enzymes; biotechnology application
Online: 22 January 2018 (10:22:21 CET)
|
|
Share this article with
×
Extremophilic bacteria are important groups of extremophilic organisms that have been studied during the last years. They are considered as a source of enzymes due to great diversity and can survive under extreme conditions. Many enzymes produced by these microorganisms are of great importance and have found applications in several industries. Due to their activity and stability under extreme conditions, these enzymes offer new alternatives for current biotechnological and industrial applications. They have a wide range of potential uses and have been a nuclear subject of many different investigations. To date, some of the enzymes produced by extremophilic bacteria are currently being assessed thier industrials applications. Despite, benefits that present these enzymes, their potentials remain largely unexplored. These enzymes pose new opportunities for new line of research, and biotechnological applications. This review provides a summary on diversity and biotechnological and industrial applications of some enzymes produced by extremophilic bacteria.
Preprint
|
|
|
Life Sciences, Immunology; microbes; autoimmunity; glycolipids,alpha-GalactosylCeramide; sulfatide; CD1d; NKT.
Online: 20 January 2018 (13:59:26 CET)
|
|
Share this article with
×
Natural killer T cells (NKT) are a subset of T lymphocytes bridging innate and adaptive immunity. These cells recognize self and microbial glycolipids bound to non-polymorphic and highly conserved CD1d molecules. Three NKT cell subsets, type I, II and NKT-like expressing different antigen receptors (TCR) were described and TCR activation promotes intracellular events leading to specific functional activities. NKT can exhibit different functions depending on the secretion of soluble molecules and the interaction with other cell types. NKT cells act as regulatory cells in the defence against infections but, on the other hand, their effector functions can be involved in the pathogenesis of several inflammatory disorders due to their exposure to different microbial or self antigens, respectively. A deep understanding of the biology and functions of type I, II and NKT-like cells as well as their interplay with cell types acting in innate (Neuthrophils, Innate Lymphoid cells, Machrophages and Dendritic cells) and adaptive immunity (CD4+,CD8+ and Double Negative T cells) should be important to design potential immunotherapies for infectious and autoimmune diseases.
Preprint
|
|
|
Longlong Si,
Kun Meng,
Zhenyu Tian,
Ziwei Zhang,
Veronica Soloveva,
Jiaqi Sun,
Haiwei Li,
Ge Fu,
Qing Xia,
Sulong Xiao,
Lihe Zhang,
Demin Zhou
Life Sciences, Virology; Ebola; influenza virus; HIV; envelope protein; membrane fusion inhibitor; HR2; pentacyclic triterpenoids
Online: 19 January 2018 (04:02:15 CET)
|
|
Share this article with
×
Recent years have witnessed a breakthrough in identification of a trimer-of-hairpins motif within viral envelopes that triggers a broad range of virus-host fusion. Identifying a domain capable of controlling virus-host fusion remains a challenge due to sequence diversity, heavy glycan shielding and multiple conformations. Here, we report that HR2, a prevalent heptad repeat sequence comprising an alpha-helical coil anchored in viral membranes, is an accessible site to triterpenes, a class of widely distributed natural products. Triterpenes and their derivatives inhibit the entry of Ebola, HIV, and influenza A viruses with distinct structure-activity relationships. Specifically, triterpenoid probes, upon activation by ultraviolet light, capture the viral envelope via crosslinking the HR2 coil. Profiling the Ebola HR2 sequence using amino acid substitution, surface plasmon resonance (SPR) and nuclear magnetic resonance (NMR) spectroscopy disclosed six constitutive residues that are accessible to triterpenoids, leading to wrapping of the hydrophobic helix by triterpenoids and blocking of the HR1-HR2 interaction, which is critical in the trimer-of-hairpins formation. This finding was also observed in the envelopes of HIV and influenza A viruses and might potentially extend to a broader variety of viruses. Our findings might translate into a shared mechanism that host utilize natural product triterpenoids to antagonize membrane fusion of respective viruses, complementing the current repertoire of antiviral agents.
Preprint
|
|
|
Life Sciences, Biotechnology; valinomycin; ionophore; molecular networking; genome mining; heterologous expression
Online: 18 January 2018 (16:45:50 CET)
|
|
|
Share this article with
×
Streptomyces genome analyses have revealed an enormous abundance of gene clusters codifying enzymes from secondary metabolism inferring that their potential to produce metabolites is underestimated. Among the mostly useful natural products, those biosynthesized by nonribosomal peptides synthetases share both high molecular complexity and therapeutic activity. A gene cluster encoding the biosynthesis of valinomycin, a depsipeptide ionophore, was annotated from the whole genome sequencing of the endophytic strain Streptomyces sp. CBMAI 2042 isolated from Citrus ssp. In the present study, we describe the association of fermentation process, molecular networking and mass spectrometry imaging which revealed the production of the ionophore by the endophytic strain. Additionally, the heterologous expression of the entire valinomycin gene cluster in S. coelicolor M1146 host was successfully promoted, representing an alternative and unique platform for production of new valinomycin derivatives in future studies.
Preprint
|
|
|
Life Sciences, Other; provenances, height, root-collar-diameter, survival, growth
Online: 18 January 2018 (16:39:53 CET)
|
|
Share this article with
×
The aims of the study were to evaluate seedling growth and survival of Prunus africana provenances in awi highland based on ecological requirement of the tree. We measured survival and growth of three P.africana provenances seedlings found in Ethiopia (provenances sources namely: Gedeo, Jibat and Munnessa). Design of experiment with randomized complete block design (RCBD) with three replications. Seedlings planted at 2m, 2.5m and 3m distance between plants, plot, and blocks respectively. A plot size of 10mx10m and 25 plants are found per plot (0.01ha). We used ANOVA to test differences in survival, and growth among provenances over time. Results concluded that, provenances have no significant variation among in establishment rate, plant height and collar diameter growth. Of these provenances, Jibat was the first in establishment (56%), second in height (1.97m) and diameter (2.89cm). Gedeo was stood first in height (2.30m) but second in establishment rate (52%) and thickness(3.45cm), but Munessa with very good growth in diameter(3.59cm) might be prefreed for bark extraction followed by Gedeo, last in height (1.75m),but established second (52%). Contrary to expectations, seedlings were still at substantial risk of mortality ≥3 years after planting. Probably the plants survival rate and growth probably affected by altitude, soil water potential, light exposure, and wild animal presence in the surrounding. In steep slope sites, canopy shade, existing weed vegetation as well as wild animals such as apes is unlikely to enhance seedling survival after planting. Our results suggest that seedling mean growth increased with 0.008mm thickness and 0.41mm per day while 2.8mm thickness and 146.8mm tall increment recorded in 2560meter elevated high land or injibara with mean value of 18.5°C and rain fall is 1300mm.
Preprint
|
|
|
Life Sciences, Biochemistry; DCP-LA; PKCε; protein tyrosine phosphatase 1B; Akt; GSK-3β; tauopathy
Online: 17 January 2018 (05:26:21 CET)
|
|
Share this article with
×
Abnormal Tau phosphorylation and aggregation into neuronal paired helical filaments and neurofibrillary tangles cause tauopathies, a class of neurodegenerative diseases, that include Alzheimer’s disease, frontotemporal dementia and parkinsonism linked to chromosome 17, progressive supranuclear palsy, Pick's disease, and corticobasal degeneration. Glycogen synthase kinase-3β (GSK-3β) is the most critical kinase to phosphorylate Tau. We have developed the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), with cyclopropane rings instead of cis-double bonds, as an anti-dementia drug. DCP-LA serves as a selective activator of PKCε and a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B). DCP-LA prevents Tau phosphorylation due to PKCε-mediated direct inactivation of GSK-3β, to PKCε/Akt-mediated inactivation of GSK-3β, and to receptor tyrosine kinase-mediated inactivation of GSK-3β in association with PTP1B inhibition. DCP-LA targeting GSK-3β, thus, could become a valid drug for treatment of tauopathies.
Preprint
|
|
|
Life Sciences, Biotechnology; ice-binding proteins; antifreeze proteins, cold finger, ice affinity purification.
Online: 16 January 2018 (07:56:40 CET)
|
|
Share this article with
×
Ice-binding proteins (IBPs) have several functions that permit their hosts to thrive in the presence of ice. The ability of IBPs to control ice growth makes them potential additives in various industries ranging from food storage and cryopreservation to anti-icing systems. For IBPs to be used in commercial applications, however, methods are needed to produce sufficient quantities of high-quality proteins. Here, we describe a new method for IBP purification, termed falling water ice purification (FWIP). The method is based on the affinity of IBPs for ice. A crude IBP solution is allowed to flow continuously over the large chilled vertical surface of a commercial ice machine. The temperature of the surface is lowered gradually until ice crystals are produced, to which the IBPs bind but other solutes do not. As in other ice affinity methods, FWIP does not require molecular tags and is suitable for purifying recombinant IBPs as well as IBPs from natural sources. The advantage of FWIP over other ice affinity methods is that it exploits an ice machine designed to produce large volumes of clear ice daily. This system can be easily scaled up and suits the purification of industrial quantities of IBPs. The FWIP method significantly advances the use of IBPs in research and industry.
Preprint
|
|
|
Life Sciences, Other; GIS, Groundwater, Physico- chemical parameters, Statistics
Online: 15 January 2018 (16:48:32 CET)
|
|
Share this article with
×
Groundwater is an important role of the environment in natural resources. The major sources of groundwater contamination in this study were open discharges of domestic sewage, inadequate sewerage system, open defecation, septic tanks, soak pits, contaminated water pools, unorganized solid waste dumping and use of fertilizers, pesticides for agriculture deteriorated the condition. In this present study revealed that the physical and chemical characteristics of ground water in different areas of Kannur district in Kerala have been determined different seasons with respect to its suitability for drinking and agricultural purposes. For this study the groundwater samples were collected during pre-monsoon and post-monsoon seasons from 70 wells representing the entire the study area. The groundwater samples were analyzed for Physico-chemical characteristics using standard techniques in laboratory and compared with standards. The samples were analyzed with reference to the WHO and BIS standards. The groundwater quality information of the entire study area have been prepared using statistical and GIS technique for all the parameters. This paper proved in GIS will be helpful for measuring, monitoring and managing the groundwater pollution in the study area and suggested to protect groundwater resources in the environment.
Preprint
|
|
|
Life Sciences, Microbiology; HEdefensin; Haemaphysalis longicornis; bacteria
Online: 12 January 2018 (08:25:56 CET)
|
|
Share this article with
×
Ticks are key vectors of some important diseases of humans and animals. Although they are carriers of disease agents, the viability and development of ticks are not harmed by the infectious agents due to their innate immunity. Antimicrobial peptides directly protect hosts against pathogenic agents such as viruses, bacteria, and parasites. Among the identified and characterized antimicrobial peptides, defensins have been considerably well studied. Defensins, which contain intramolecular disulfide bridges between cysteine residues, are commonly found among fungi, plants, invertebrates, and vertebrates. The sequence of the tick hemolymph defensin (HEdefensin) gene from the hard tick Haemaphysalis longicornis was analyzed after identification and cloning from a cDNA library. HEdefensin has a predicted molecular mass of 8.15 kDa and a theoretical isoelectric point of 9.48. Six cysteine residues were also identified in the amino acids. The synthetic HEdefensin peptide only showed antibacterial activity against Gram-positive bacteria such as Micrococcus luteus. A fluorescence propidium iodide exclusion assay also showed that HEdefensin increased the membrane permeability of M. luteus. Additionally, an indirect fluorescent antibody test showed that HEdefensin binds to M. luteus. These results suggested that HEdefensin strongly affects the innate immunity of ticks against Gram-positive bacteria.
Preprint
|
|
|
Life Sciences, Biotechnology; Activities of Daily Living (ADL); environment; sensors; mobile devices, framework; data acquisition; data processing; data fusion; pattern recognition; machine learning
Online: 8 January 2018 (11:34:36 CET)
|
|
Share this article with
×
Sensors available on mobile devices allow the automatic identification of Activities of Daily Living (ADL). This paper describes an approach for the creation of a framework for the identification of ADL, taking in account several concepts, including data acquisition, data processing, data fusion, pattern recognition, and machine learning. These concepts can be mapped in a module of the framework, including the use and creation of several algorithms. For the development of a framework that works in several conditions, e.g., without Internet connection, these algorithms should take in account the hardware and software limitations of the mobile devices to run all main tasks locally. The main purpose of this paper is related to the presentation the sensors, algorithms, and architecture of the proposed approach.
Preprint
|
|
|
Life Sciences, Biotechnology; orange peel essential oil; green extraction; liquid whole eggs; biopreservation; shelf-life
Online: 8 January 2018 (09:22:37 CET)
|
|
Share this article with
×
A possible way to valorize citrus peels, which are byproducts of the juice extraction industry, is to use them as natural biopreservatives. In this paper we present early results from a compared Solvent Free Microwave Extraction (SFME) with Hydro-Distillation (HD) and Cold Pressing (CP) of essential oils (EOs) using fresh orange peel (Citrus sinensis L. var. Valencia late), a by-product in the production of orange juice in Algeria. The EOs were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). All extracted C. sinensis EOs were chemotype limonene (94.64 to 95.48%). SFME is performed without added any solvent or water. SFME increases EO yield and eliminate wastewater treatment, resulting in a great progress in terms of time and cost efficiency. In its second part, the present study was conducted to evaluate “in vitro”, the antioxidant activities of Solvent Free Microwave (SFM) extracted orange EO by using the DPPH• (2,2-di-phenyl-1-picrilhydrazyl) free radical scavenging assay. The ability of orange EO to scavenge the free radical DPPH• was high, exceeding 80%. The result of the DPPH assay gives an IC50 range value of 89.25 μg/mL (0.09 mg/mL) for the studied sample. Accordingly to the scientific literature, C. sinensis EO tested in the present study presented strong antioxidant activity, when looking to its values of AAI = 1.12 μg/mL. The feasibility of biopreservation used EOs as an alternative to synthetic techniques for liquid whole egg (LWE) stored under commercial retail conditions was investigated. The orange EO extracted by SFM was screened for its antibacterial and antioxidant activities in LWE at concentrations of 0.1, 0.3 and 0.5%. The TBA-RS results showed that the EO treatments significantly (p < 0.05) reduced the lipid oxidation in LWE. The long term oxidative, microbial and organoleptical stability of the LWE during display was positively influenced by orange EO treatments. Therefore, the results obtained here confirm that EO treatment as a promising technology to extend the commercial shelf-life of liquid egg products during retail/display.
Preprint
|
|
|
Life Sciences, Microbiology; antimicrobial; Aplysia; biofilm; chemical defense; Escapin; L–amino acid oxidase
Online: 8 January 2018 (08:29:03 CET)
|
|
Share this article with
×
Many marine animals use chemicals to defend themselves and their eggs from predators. Beyond their ecologically relevant functions, these chemicals may also have properties that make them beneficial for humans, including with biomedical and industrial applications. For example, some chemical defenses are also powerful antimicrobial or anti-tumor agents with relevance to human health and disease. One such chemical defense, Escapin, an L–amino acid oxidase in the defensive ink of the sea hare Aplysia californica, and related proteins have been investigated for their biomedical properties. This review details our current understanding of Escapin’s antimicrobial activity, including the array of chemicals generated by Escapin’s oxidation of its major substrates, L–lysine and L–arginine, and mechanisms underlying these molecules’ bactericidal and bacteriostatic effects on planktonic cells and the prevention of formation and removal of bacterial biofilms. Models of Escapin’s effects are presented, and future directions are proposed.
Preprint
|
|
|
Eszter Szarka,
Petra Aradi,
Krisztina Huber,
Judit Pozsgay,
Lili Végh,
Anna Magyar,
Gergő Gyulai,
György Nagy,
Bernadette Rojkovich,
Eva Kiss,
Ferenc Hudecz,
Gabriella Sármay
Life Sciences, Immunology; rheumatoid arthritis; citrulline-peptides; autoantibody; affinity; cross-reaction; targeting
Online: 2 January 2018 (11:50:04 CET)
|
|
Share this article with
×
Background: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide antibodies (ACPAs) are responsible for disease onset and progression, however, our knowledge is limited on ligand binding affinities of autoantibodies with different citrulline-peptide specificity. Methods: Citrulline-peptide specific ACPA IgGs were affinity purified and tested by ELISA. Binding affinities of ACPA IgGs and serum antibodies were compared by surface plasmon resonance (SPR) analysis. Bifunctional nanoparticles harboring a multi-epitope citrulline-peptide and a complement activating peptide were used to induce selective depletion of ACPA producing B cells. Results: KD values of affinity purified ACPA IgGs varies between 10-6-10-8 M and inversely correlate with disease activity. Based on their cross-reaction with citrulline-peptides we designed a novel multi-epitope peptide, containing Cit-Gly and Ala-Cit motifs in two-two copies, separated with a short, neutral spacer. This peptide detects antibodies in RA sera with 66 % sensitivity and 98 % specificity in ELISA and is recognized by 90% of RA sera, while none of the healthy samples in SPR. When coupled to nanoparticles, the multi-epitope peptide specifically targets and depletes ACPA producing B cells ex vivo. Conclusions: The unique multi-epitope peptide designed on the basis of ACPA cross-reactivity might be suitable to develop better diagnostics and novel therapies for RA.
Preprint
|
|
|
Life Sciences, Biochemistry; graphene; electrochemical biosensors; cancer; diagnosis; electrical detection; Alzheimer’s disease; dementia; neurodegenerative disorders; cardiovascular; blood biomarkers; antibodies; proteins
Online: 2 January 2018 (05:21:45 CET)
|
|
Share this article with
×
We report on the development of chemical vapour deposition (CVD) based graphene field effect transistor (GFET) immunosensors for the sensitive detection of Human Chorionic Gonadotropin (hCG), a glycoprotein risk biomarker of certain cancers. The GFET sensors were fabricated on Si/SiO2 substrate using photolithography with evaporated chromium and sputtered gold contacts. GFET channels were functionalized with a linker molecule to immobile anti-hCG antibody on the surface of graphene. Binding reaction of the antibody with varying concentration levels of hCG antigen demonstrated the limit of detection of the GFET sensors to be below 1 pg/mL using four-probe electrical measurements. We also show annealing can significantly improve the carrier transport properties of GFETs and shift the Dirac point (Fermi level) with reduced p-doping in back-gated measurements. The developed GFET biosensors are generic and could find applications in a broad range of medical diagnostics in addition to cancer, such as neurodegenerative (Alzheimer’s, Parkinson’s and Lewy body) and cardiovascular disorders.
Preprint
|
|
|
Life Sciences, Biochemistry; purple sweetpotato; anthocyanin; polyphenolics; caffeoylquinic acid; temperature
Online: 25 December 2017 (10:01:14 CET)
|
|
Share this article with
×
The health benefits of purple sweetpotato, which is used as an edible food in its natural state and in processed foods and as a natural color pigment, have been recognized. In Japan, sweetpotato has been economically produced in regions below 36°4′N latitude, however, cultivation areas are beginning to expand further north. The anthocyanin and polyphenolics in purple sweetpotatoes cultivated in different locations; I (42°92′ N, 143°04′ E), II (35°99′ N, 140°01′ E), and III (31°72′ N, 131°03′ E), were compared over two years. Total anthocyanin and polyphenolic contents in purple sweetpotatoes tended to be high in location I. Their contents significantly differed over the two years in locations I and III and was dependent on temperature during cultivation. The anthocyanin and polyphenolic compositions differed between locations. The peonidin/cyanidin ratios were higher in location III compared with I and II in all varieties. The relative amount of chlorogenic acid was higher in location I, while the amount of 3,4- and 4,5-dicaffeoyolquinic acids were higher in location III, suggesting that the variability of the anthocyanin and polyphenolic content and composition was dependent on cultivation conditions. This study suggested that northern areas in Japan are an alternative production area and may yield higher amounts of anthocyanin and polyphenolics.
Preprint
|
|
|
Life Sciences, Biochemistry; epigenome; DNA modification; cytosine methylation; gene regulation; histone modification; 5-methylcytosine; stress response
Online: 25 December 2017 (09:43:03 CET)
|
|
Share this article with
×
Genome-wide epigenetic changes in plants are being reported during the development and environmental stresses, which are often correlated with gene expression at the transcriptional level. Sum total of the biochemical changes in nuclear DNA, post-translational modifications in histone proteins and variations in the biogenesis of non-coding RNAs in a cell is known as epigenome. These changes are often responsible for variation in expression of the gene without any change in the underlying nucleotide sequence. The changes might also cause variation in chromatin structure resulting into the changes in function/activity of the genome. The epigenomic changes are dynamic with respect to the endogenous and/or environmental stimuli which affect phenotypic plasticity of the organism. Both, the epigenetic changes and variation in gene expression might return to the pre-stress state soon after withdrawal of the stress. However, a part of the epigenetic changes may be retained which is reported to play role in acclimatization, adaptation as well as in the evolutionary processes. Understanding epigenome-engineering for improved stress tolerance in plants has become essential for better utilization of the genetic factors. This review delineates the importance of epigenomics towards possible improvement of plant’s responses to environmental stresses for climate resilient agriculture.
Preprint
|
|
|
Life Sciences, Other; RNA world; [GADV]-protein world; GADV hypothesis; origin of life; protein 0th-order structure; origin of protein; origin of genetic code; origin of gene
Online: 25 December 2017 (08:08:37 CET)
|
|
Share this article with
×
All life on Earth uses three integrated molecular systems in which genetic information contained in DNA base sequences is transmitted to ribosomes by RNA and a genetic code, then translated into the amino acid sequences of structural and catalytic proteins. Therefore, the most important point for understanding the origin of life is to determine how such systems could emerge from random processes on the early Earth. In this review, two alternatives are compared: the RNA world hypothesis and the [GADV]-protein world hypothesis. [GADV] refers to four amino acids, Gly [G], Ala [A], Asp [D] and Val [V] that are conserved in the amino acid sequences of many common proteins. Here I will argue that the origins of the three primary processes required for life to begin can be better explained by the GADV hypothesis than the RNA world hypothesis. The GADV hypothesis also incorporates a conversion process by which random polymers can evolve into proteins with ordered sequences.
Preprint
|
|
|
Life Sciences, Biochemistry; algae; Euglena; biotechnology; carbohydrates; N-glycan; sugar nucleotide
Online: 17 December 2017 (08:55:09 CET)
|
|
Share this article with
×
Euglena gracilis is an alga of great biotechnological interest and extensive metabolic capacity, able to make high levels of bioactive compounds, such as polyunsaturated fatty acids, vitamins and β-glucan. Previous work has shown that Euglena expresses a wide range of carbohydrate-active enzymes, suggesting an unexpectedly high capacity for the synthesis of complex carbohydrates for a single-celled organism. Here, we present an analysis of some of the carbohydrates synthesised by Euglena gracilis. Analysis of the sugar nucleotide pool showed that there are the substrates necessary for synthesis of complex polysaccharides, including the unusual sugar galactofuranose. Lectin- and antibody-based profiling of whole cells and extracted carbohydrates revealed a complex galactan, xylan and aminosugar based surface. Protein N-glycan profiling, however, indicated that just simple high mannose-type glycans are present and that they are partially modified with putative aminoethylphosphonate moieties. Together, these data indicate that Euglena possesses a complex glycan surface, unrelated to plant cell walls, while its protein glycosylation is simple. Taken together, these findings suggest that Euglena gracilis may lend itself to the production of pharmaceutical glycoproteins.
Preprint
|
|
|
Life Sciences, Virology; smallpox; vaccine; vaccinia; postexposure; MVA; LC16m8; Cidofovir; Tecovirimat; VIG; poly(I:C)
Online: 12 December 2017 (06:37:59 CET)
|
|
Share this article with
×
Declaration of smallpox eradication by the WHO on 1980 led to discontinuation of the world-wide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV) and the recent synthetic achievements, increases the threat of intentional or accidental release and reemergence of smallpox. Control of smallpox would require an emergency vaccination campaign as no other protective measure has been approved to achieve eradication and ensure world-wide protection. Experimental data in surrogate animal models support the assumption, based on anecdotal, uncontrolled historical data, that vaccination up to 4 days postexposure, confers effective protection. The long incubation period and the uncertainty of the exposure status in the surrounding population calls for the development and evaluation of safe and effective methods that would allow to extend the therapeutic window and to reduce the disease manifestations and vaccine adverse reactions. To achieve these goals, we need to evaluate the efficacy of novel and already licensed vaccines as a sole treatment or in conjunction with immune modulators and antiviral drugs. In this review, we address the available data, recent achievements and open questions.
Preprint
|
|
|
Marie-Cécile Alexandre-Gouabau,
Thomas Moyon,
Véronique Cariou,
Jean-Philippe Antignac,
El Mostafa Qannari,
Mikaël Croyal,
Mohamed Molamine,
Yann Guitton,
Agnès David-Sochard,
Hélène Billard,
Arnaud Legrand,
Cécile Boscher,
Dominique Darmaun,
Jean-Christophe Rozé,
Clair-Yves Boquien
Life Sciences, Other; breast milk lipidome, preterm infant, growth trajectory
Online: 11 December 2017 (15:53:33 CET)
|
|
|
Share this article with
×
Human milk is recommended for feeding preterm infant. Yet the potential impact of specific breast-milk lipid components on the initial growth rate of very-preterm infants has received scant attention. The current pilot study aims to determine whether breast-milk lipidome had any impact on the early growth pattern of preterm infants fed their own mother’s milk. A prospective monocentric observational birth cohort was established, enrolling 147 preterm infants, who received their own mother’s breast-milk throughout hospital stay. Among that cohort, infants who experienced slow (n=15) or fast (n=11) growth were selected, based on the change in their weight Z-score between birth and hospital discharge (-1.54± 0.42 and -0.48± 0.19 Z-score, respectively). Liquid chromatography-high resolution-mass spectrometry was used to obtain lipidomic signatures in breast-milk. Multivariate analyses made it possible to identify breast-milk lipid species that allowed clear-cut discrimination between the 2 infants’ groups. Validation of the selected biomarkers was performed by means of various multidimensional statistical techniques, false-discovery rate and ROC curve computation. Breast-milk associated with fast growth contained more medium chain-saturated fatty acid and -sphingomyelin, dihomo-γ-linolenic acid (DGLA)-containing phosphethanolamine, and less oleic acid-containing triglyceride and DGLA-oxylipin. Their predictive ability of preterm early-growth rate was validated in presence of confounding clinical factors.
Preprint
|
|
|
Life Sciences, Molecular Biology; spermine; cyclooctaoxygen; DNA; selenium; glyphosate; AMPA
Online: 4 December 2017 (13:03:14 CET)
|
|
Share this article with
×
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.
Preprint
|
|
|
Life Sciences, Virology; HIV-1; quasispecies; minority resistance mutations; HAART; drug resistance; undetectable viral load
Online: 4 December 2017 (09:34:16 CET)
|
|
Share this article with
×
Increased access to highly active antiretroviral therapy (HAART) by HIV+ individuals has become a reality worldwide. In Brazil, ART currently reaches over half of the HIV-infected subjects. In the context of a remarkable HIV-1 genetic variability, highly related variants, called quasispecies, are generated. HIV quasispecies generated during infection can influence virus persistence and pathogenicity, representing a challenge to treatment. However, the clinical relevance of minority quasispecies is still uncertain. For this study, we have determined the archived proviral sequences, viral subtype and drug resistance mutations from a cohort of HIV+ patients with undetectable viral load undergoing HAART as first-line therapy using next-generation sequencing for near full-length virus genome (NFLG) assembly. HIV-1 consensus sequences representing NFLG were obtained for eleven patients, while for another twelve varying genome coverage rates were obtained. Phylogenetic analysis showed the predominance of subtype B (83%; 19/23). Considering the minority variants, 18 patients carried archived virus harboring at least one mutation conferring antiretroviral resistance; for six patients, the mutations correlated with the current ARVs used. These data highlight the importance of monitoring HIV minority drug resistant variants and their clinical impact, to guide future regimen switches and improve HIV treatment success.