bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type I interferons act directly on nociceptors to produce pain sensitization: Implications for viral infection-induced pain
Authors: Barragan-Iglesias Paulino , Franco-Enzástiga Úrzula , Jeevakumar Vivekanand , Wangzhou Andi , Granados-Soto Vinicio , Campbell Zachary T. , Dussor Gregory , Price Theodore J. 
Published: December 2019

ABSTRACTOne of the first signs of viral infection is body-wide aches and pain. While this type of pain usually subsides, at the extreme, viral infections can induce painful neuropathies that can last for decades. Neither of these types of pain sensitization are well understood. A key part of the response to viral infection is production of interferons (IFNs), which then activate their specific receptors (IFNRs) resulting in downstream activation of cellular signaling and a variety of physiological responses. We sought to understand how type I IFNs (IFN-α and IFN-β) might act directly on nociceptors in the dorsal root ganglion (DRG) to cause pain sensitization. We demonstrate that type I IFNRs are expressed in small/medium DRG neurons and that their activation produces neuronal hyper-excitability and mechanical pain in mice. Type I IFNs stimulate JAK/STAT signaling in DRG neurons but this does not apparently result in PKR-eIF2α activation that normally induces an anti-viral response by limiting mRNA translation. Rather, type I interferons stimulate MNK-mediated eIF4E phosphorylation in DRG neurons to promote pain hypersensitivity. Endogenous release of type I IFNs with the double stranded RNA mimetic poly(I:C) likewise produces pain hypersensitivity that is blunted in mice lacking MNK-eIF4E signaling. Our findings reveal mechanisms through which type I IFNs cause nociceptor sensitization with implications for understanding how viral infections promote pain and can lead to neuropathies.SIGNIFICANCE STATEMENTIt is increasingly understood that pathogens interact with nociceptors to alert organisms to infection as well as to mount early host defenses. While specific mechanisms have been discovered for diverse bacteria and fungal pathogens, mechanisms engaged by viruses have remained elusive. Here we show that type 1 interferons, one of the first mediators produced by viral infection, act directly on nociceptors to produce pain sensitization. Type I interferons act via a specific signaling pathway (MNK-eIF4E signaling) that is known to produce nociceptor sensitization in inflammatory and neuropathic pain conditions. Our work reveals a mechanism through which viral infections cause heightened pain sensitivity
Quantitative measurements of hydroxyl radicals generated by irradiated titanium dioxide nanoparticle suspensions
Authors: Coral Jason A. , Kitchens Christopher L. 
Published: December 2019

ABSTRACTIncreased use of titanium dioxide (TiO2) nanoparticles in different applications has increased risk for adverse environmental implications based on an elevated likelihood of organism exposure. Anatase TiO2is photoactive with exposure to ultraviolet light. TiO2nanoparticle exposure to UV-A radiation in aquatic environments generates hydroxyl radical species, which may ultimately be responsible increased organism toxicity. The present research demonstrates that the rate of radical generation heavily depends on exposure conditions, particularly the presence of natural organic matter (NOM). Environmentally relevant concentrations of TiO2nanoparticles were co-exposed to increasing NOM amounts (measured as concentration of dissolved organic carbon (DOC)) and UV-A intensities. Hydroxyl radical generation rate was determined using fluorescence spectroscopy. Radical generation rate was positively correlated to increases in TiO2concentration and UV-A intensity, and negatively correlated to increased DOC concentration. Nanoparticle aggregation over time and decrease in light transmission from NOM had negligible contributions to the generation rate. This suggests the decreased radical generation rate is a result of radical quenching by NOM functionalities.D. magnatoxicity to hydroxyl radicals is also demonstrated to decreased following the addition of DOC. These results correlate with the rate generation data, indicating that DOC provides rate attenuation that is protection to organisms. These conclusions demonstrate the importance considering exposure conditions during TiO2toxicity testing, and during TiO2waste management and regulatory decisions.
Introducing divisive inhibition in the Wilson-Cowan model
Authors: Papasavvas Christoforos A. , Wang Yujiang 
Published: December 2019

AbstractBoth subtractive and divisive inhibition has been recorded in cortical circuits and recent findings suggest that different interneuronal populations are responsible for the different types of inhibition. This calls for the formulation and description of these inhibitory mechanisms in computational models of cortical networks. Neural mass and neural field models typically only feature subtractive inhibition. Here, we introduce how divisive inhibition can be incorporated in such models, using the Wilson-Cowan modelling formalism as an example. In addition, we show how the subtractive and divisive modulations can be combined. Including divisive inhibition in neural mass models is a crucial step in understanding its role in shaping oscillatory phenomena in cortical networks.
The Ortholog Conjecture Revisited: the Value of Orthologs and Paralogs in Function Prediction
Authors: Stamboulian Moses , Guerrero Rafael F. , Hahn Matthew W. , Radivojac Predrag 
Published: December 2019

AbstractThe computational prediction of gene function is a key step in making full use of newly sequenced genomes. Function is generally predicted by transferring annotations from homologous genes or proteins for which experimental evidence exists. The “ortholog conjecture” proposes that orthologous genes should be preferred when making such predictions, as they evolve functions more slowly than paralogous genes. Previous research has provided little support for the ortholog conjecture, though the incomplete nature of the data cast doubt on the conclusions. Here we use experimental annotations from over 40,000 proteins, drawn from over 80,000 publications, to revisit the ortholog conjecture in two pairs of species: (i)Homo sapiensandMus musculusand (ii)Saccharomyces cerevisiaeandSchizosaccharomyces pombe. By making a distinction between questions about the evolution of function versus questions about the prediction of function, we find strong evidence against the ortholog conjecture in the context of function prediction, though questions about the evolution of function remain difficult to address. In both pairs of species, we quantify the amount of data that must be ignored if paralogs are discarded, as well as the resulting loss in prediction accuracy. Taken as a whole, our results support the view that the types of homologs used for function transfer are largely irrelevant to the task of function prediction. Aiming to maximize the amount of data used for this task, regardless of whether it comes from orthologs or paralogs, is most likely to lead to higher prediction accuracy.
A Molecular Pathway for Arterial-Specific Association of Vascular Smooth Muscle Cells
Authors: Stratman Amber N. , Burns Margaret C. , Farrelly Olivia M. , Davis Andrew E. , Li Wenling , Pham Van N. , Castranova Daniel , Yano Joseph J. , Goddard Lauren M. , Nguyen Oliver , Galanternik Marina Venero , Bolan Timothy J. , Kahn Mark L. , Mukouyama Yohsuke , Weinstein Brant M. 
Published: December 2019

ABSTRACTThe preferential accumulation of vascular smooth muscle cells on arteries versus veins during early development is a well-described phenomenon, but the molecular pathways underlying this polarization are not well understood. During zebrafish embryogenesis thecxcr4areceptor (mammalian CXCR4) and its ligandcxcl12b(mammalian CXCL12) are both preferentially expressed on arteries at time points consistent with the arrival and differentiation of the first vascular smooth muscle cells (vSMCs). We show that autocrinecxcl12b/cxcr4activity leads to increased production of the vSMC chemoattractant ligandpdgfbby endothelial cellsin vitroand increased expression ofpdgfbby arteriesin vivo. Additionally, we demonstrate that expression of the well-characterized blood flow-regulated transcription factorklf2ain primitive veins negatively regulatescxcr4/cxcl12andpdgfbexpression, restricting vSMC recruitment to the arterial vasculature. Together, this signaling axis leads to the differential acquisition of smooth muscle cells at sites whereklf2aexpression is low and bothcxcr4aandpdgfbare co-expressed, i.e. arteries during early development.
Arrhythmic gut microbiome signatures for risk profiling of Type-2 Diabetes
Authors: Reitmeier Sandra , Kießling Silke , Clavel Thomas , List Markus , Almeida Eduardo L. , Ghosh Tarini S. , Neuhaus Klaus , Grallert Harald , Troll Martina , Rathmann Wolfgang , Linkohr Birgit , Franke Andre , Le Roy Caroline I. , Bell Jordana T. , Spector Tim , Baumbach Jan , O’Toole Peter W. , Peters Annette , Haller Dirk 
Published: December 2019

SummaryTo combat the epidemic increase in Type-2-Diabetes (T2D), risk factors need to be identified. Diet, lifestyle and the gut microbiome are among the most important factors affecting metabolic health. We demonstrate in 1,976 subjects of a prospective population cohort that specific gut microbiota members show diurnal oscillations in their relative abundance and we identified 13 taxa with disrupted rhythmicity in T2D. Prediction models based on this signature classified T2D with an area under the curve of 73%. BMI as microbiota-independent risk marker further improved diagnostic classification of T2D. The validity of this arrhythmic risk signature to predict T2D was confirmed in 699 KORA subjects five years after initial sampling. Shotgun metagenomic analysis linked 26 pathways associated with xenobiotic, amino acid, fatty acid, and taurine metabolism to the diurnal oscillation of gut bacteria. In summary, we determined a cohort-specific risk pattern of arrhythmic taxa which significantly contributes to the classification and prediction of T2D, highlighting the importance of circadian rhythmicity of the microbiome in targeting metabolic human diseases.
Diet-induced loss of adipose Hexokinase 2 triggers hyperglycemia
Authors: Shimobayashi Mitsugu , Shetty Sunil , Frei Irina C. , Wölnerhanssen Bettina K. , Weissenberger Diana , Dietz Nikolaus , Thomas Amandine , Ritz Danilo , Meyer-Gerspach Anne Christin , Maier Timm , Hay Nissim , Peterli Ralph , Rohner Nicolas , Hall Michael N. 
Published: December 2019

AbstractChronically high blood glucose (hyperglycemia) leads to diabetes, fatty liver disease, and cardiovascular disease. Obesity is a major risk factor for hyperglycemia, but the underlying mechanism is unknown. Here we show that a high fat diet (HFD) in mice causes early loss of expression of the glycolytic enzyme Hexokinase 2 (HK2) specifically in adipose tissue. Adipose-specific knockout ofHk2caused enhanced gluconeogenesis and lipogenesis in liver, a condition known as selective insulin resistance, leading to glucose intolerance. Furthermore, we observed reduced hexokinase activity in adipose tissue of obese and diabetic patients, and identified a loss-of-function mutation in thehk2gene of naturally hyperglycemic Mexican cavefish. Mechanistically, HFD in mice led to loss of HK2 by inhibiting translation ofHk2mRNA. Our findings identify adipose HK2 as a critical mediator of systemic glucose homeostasis, and suggest that obesity-induced loss of adipose HK2 is an evolutionarily conserved, non-cell-autonomous mechanism for the development of hyperglycemia.One Sentence SummaryLoss of the glycolytic enzyme Hexokinase 2 in adipose tissue is a mechanism underlying high blood glucose levels.
An Unconventional Melanin Biosynthetic Pathway inUstilago maydis
Authors: Reyes-Fernández Esmeralda Z. , Shi Yi-Ming , Grün Peter , Bode Helge B. , Bölker Michael 
Published: December 2019

ABSTRACTUstilago maydisis a phytopathogenic fungus responsible for corn smut disease. Although it is a very well established model organism for the study of plant-microbe interactions, its biosynthetic potential has not been totally explored. By analyzingU. maydisgenome, we identified a biosynthetic gene cluster whose activation led to the production of a black melanin pigment. Single deletion mutants of the cluster genes revealed that five encoded enzymes are required for the accumulation of the black pigment, including three polyketide synthases (pks3, pks4andpks5), a cytochrome P450 monooxygenase (cyp4) and a protein with similarity to versicolorin B-synthase (vbs1). Moreover, metabolic profiles of the mutants defective forpks3andpks4indicated that the products of these genes catalyze together the first step in the melanin biosynthetic pathway since none of the mutants accumulated any melanin or intermediate products. Mutants deleted forpks5produced orsellinic acid (OA) and triacetic acid lactone (TAL), suggesting that both products are produced by Pks3 and Pks4. It might thus demonstrate that Pks5 plays a role in a reaction downstream of that catalyzed by Pks3 and Pks4. OA and TAL were also found in extracts of acyp4deletion mutant along with several heterodimers of TAL and Pks5-derived orsellinic aldehyde compounds. According to their phenotypes and the intermediate products isolated from these strains, Cyp4 and Vbs1 seem to be involved in reactions downstream of Pks5. Our findings suggest thatU. maydissynthesizes a new melanin based on coumarin and pyran-2-one intermediates, while most fungal melanins are derived from 1,8-dihydroxynaphthalene (DHN) or L-3,4-dihydroxyphenylalanine (L-DOPA). Along with these observations, this work also provides an insight into the mechanisms of polyketide synthases in this filamentous fungus.IMPORTANCEUstilago maydisrepresents one of the major threats for maize plants since it is responsible for corn smut disease, which generates considerable economical losses around the world. Therefore, contributing to a better understanding of the biochemistry of defense mechanisms used byU. maydisto protect itself against harsh environments, as the synthesis of melanin, could provide improved biological tools for tackling the problem and protect the crops. In addition, the fact that this fungus synthesizes melanin in a very unique way, requiring more than one polyketide synthase for producing this secondary metabolite, gives a different perspective on the complexity of these multimodular enzymes and their evolution in the fungal kingdom.
Deep6mA: a deep learning framework for exploring similar patterns in DNA N6-methyladenine sites across different species
Authors: Li Zutan , Jiang Hangjin , Kong Lingpeng , Chen Yuanyuan , Zhang Liangyun , Pian Cong 
Published: December 2019

ABSTRACTN6-methyladenin(6mA) is an important DNA modification form associated with a wide range of biological processes. Identifying accurately 6mA sites on a genomic scale is crucial for understanding of 6mA’s biological functions. In this paper, we developed, without requiring any prior knowledge of 6mA and manually crafted sequence features, a deep learning framework named Deep6mA to identify DNA 6mA sites, and its performance is superior to other DNA 6mA prediction tools. Specifically, the 5-fold cross-validation on a benchmark dataset of rice gives the sensitivity and specificity of Deep6mA as 92.96% and 95.06%, respectively, and the overall prediction accuracy is 94%. Importantly, we find that the sequences with 6mA sites share similar patterns across different species. The model trained with rice data predicts well the 6mA sites of other three species:Arabidopsis thaliana,Fragaria vesca, andRosa chinensis, with a prediction accuracy over 90%. In addition, we find that (1) 6mA tends to occur at GAGG motifs, which means the sequence near the 6mA site may be conservative; (2) 6mA is enriched in the TATA box of the promoter, which may be the main source of its regulating downstream gene expression.
The voltage-sensing mechanism of the KvAP channel involves breaking of the S4 helix
Authors: Bignucolo Olivier , Bernèche Simon 
Published: December 2019

AbstractVoltage-gated ion channels allow ion permeation upon changes of the membrane electrostatic potential (Vm). Each subunit of these tetrameric channels is composed of six transmembrane helices, of which the anti-parallel helix bundle S1-S4 constitutes the voltage-sensor domain (VSD) and S5-S6 forms the pore domain. Here, using molecular dynamics (MD) simulations, we report novel responses of the archaebacterial potassium channel KvAP to cell polarization. We show that the S4 helix, which is straight in the experimental crystal structure solved under depolarized conditions (Vm ∼ 0), breaks into two segments when the cell is polarized (Vm << 0), and reversibly forms a single straight helix following depolarization of the cell (Vm =0). The outermost segment of S4 translates along the normal to the membrane, bringing new perspective to previously paradoxical accessibility experiments that were initially thought to imply the displacement of the whole VSD across the membrane. Our simulations of KvAP reveal that the breaking of S4 under polarization is not a feature unique to hyperpolarization activated channel, as might be suggested by recent cryo-EM structures and MD simulations of the HCN channel.
Major QTLs for seedling traits in barley using a DArT-based linkage map
Authors: Capo-chich Ludovic , Eldridge Sharla , Elakhdar Ammar , Kumamaru Toshihiro , Anyia Anthony O. 
Published: December 2019

AbstractSeed vigor is considered as the most critical stage for barley production, and cultivar with high early seedling vigour (ESV) allow plants to form a canopy more quickly. In this study, the QTLs of seedling vigour related-traits were investigated using 185 RILs derived from Xena and H94061120 using DArT approach. In total, 46 significant QTLs for ESV related-traits were detected. The total map length was 1075.1 cM with an average adjacent-marker distance of 3.28 cM. Fourteen QTLs for BY were found on all chromosomes, two of them co-located with QTLs on 1H for GY. The related-traits; LL1, LL2, LA1 and LDW1 had high heritability (>60%). Meanwhile, a significant correlation was observed between GY and BY, which provide the clear image of these traits in the selection process. Our results demonstrate that a pleiotropic QTL related to SLA2, BY, and GY was linked to to the DArT markers bPb-9280 and bPb-9108 on 1H, which could be used to significantly improve the seed vigor by marker-assisted selection and possible future map-based cloning of the gene of intrest.
Discovery of new mitochondrial DNA segregation machinery components inTrypanosoma brucei: a comparison of three approaches
Authors: Baudouin Hélène Clémentine Margareta , Pfeiffer Laura , Ochsenreiter Torsten 
Published: December 2019

AbstractTrypanosoma bruceiis a single celled eukaryotic parasite and the causative agent of human African sleeping sickness and Nagana in cattle. Aside from its medical relevanceT. bruceihas also been key to the discovery of several general biological principles including GPI-anchoring, RNA-editing and trans-splicing. The parasite contains a single mitochondrial organelle with a singular genome. Recent studies have identified several molecular components of the mitochondrial genome segregation machinery (tripartite attachment complex, TAC), which connects the basal body of the flagellum to the mitochondrial DNA ofT. brucei. The TAC component in closest proximity to the mitochondrial DNA is TAC102. Here we apply and compare three different approaches (proximity labeling, Immunoprecipitation and yeast two-hybrid) to identify novel interactors of TAC102 and subsequently verify their localisation. Furthermore, we establish the direct interaction of TAC102 and p166 in the unilateral filaments of the TAC.Subject areabiochemistry, molecular biology, cellular biology
Influence Of Urbanization On Ecological Status Of River In Amhara Region, Ethiopia 2019
Authors: Alie Melsew Setegn 
Published: December 2019

AbstractIntroductionUrbanization is one of the main causes for environmental problems due to the introduction of pollutants into water bodies. Lahi is crossing fintoselam. This river has long been used for a variety of purposes including source of public water supply, small scale irrigation, bathing, washing, animal watering, sand and stone dredging and recreation.ObjectiveTo assess the influence of Finoteselam town on ecological status of Lahi riverMethodsThe assessment were assessed using physicochemical parameters, physical habitat assessment, biotic indices /metrics, human activity by observation as well as macroinvertabretes samples from eleven sampling sites coded S1 to S11 along the river using the standard procedures. The assessments were involved in-situ measurements and collection of water samples in April 2019 then, analyzed the water samples in laboratory.ResultsThe biological analysis reveals a notable reduction of the diversity macroinvertabrates in the downstream direction where the minimum was at midstream sites. Upstream has significantly better macroinvertabrates assemblage than midstream (p-value<0.05). Physical habitat evaluation scores varied from 43 at S8 to 173 at S1 and relatively lower score were recorded at midstream sites. Low % of Ephemeroptera, Plecoptera and Trichoptera with high family biotic index and high % of Diptera with low biological monitoring working party also indicated water ecology deteriorated mainly at midstream sites. Multivariate analysis of classical analysis, canonical correspondence analysis and none metric multidimensional scaling also indicated ecological deterioration at midstream sites mainly at S5, S6, S7 and S8.ConclusionMidstream was relatively more polluted than upstream due to influence of pollutant from Finoteselam town. The ecological status of upstream segments of the river is very good with slight organic pollutions, and at midstream is poor and significant degree of organic pollutions; whereas the status of the downstream is fair with fairly substantial water pollution showing moderate ecological disturbance. In general, midstream the sampling stations show the deterioration in water ecology and thus necessitated a need for mitigation measure to save the Lahi.
Characterization of human-iPSCs derived spinal motor neurons by single-cell RNA sequencing
Authors: Thiry Louise , Hamel Regan , Pluchino Stefano , Durcan Thomas , Stifani Stefano 
Published: December 2019

AbstractHuman induced pluripotent stem cells (iPSCs) offer the opportunity to generate specific cell types from healthy and diseased individuals, allowing the study of mechanisms of early human development, modelling a variety of human diseases, and facilitating the development of new therapeutics. Human iPSC-based applications are often limited by the variability among iPSC lines originating from a single donor, as well as the heterogeneity among specific cell types that can be derived from iPSCs. The ability to deeply phenotype different iPSC-derived cell types is therefore of primary importance to the successful and informative application of this technology. Here we describe a combination of motor neuron (MN) derivation and single-cell RNA sequencing approaches to generate and characterize specific MN subtypes obtained from human iPSCs. Our studies provide evidence for rapid and robust generation of MN progenitor cells that can give rise to a heterogenous population of brainstem and spinal cord MNs. Approximately 58% of human iPSC-derived MNs display molecular characteristics of lateral motor column MNs, ∼19% of induced MNs resemble hypaxial motor column MNs, while ∼6% of induced MNs have features of medial motor column MNs. The present study has the potential to improve our understanding of iPSC-derived MN subtype function and dysfunction, possibly leading to improved iPSC-based applications for the study of human MN biology and diseases.