bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consolidated bioprocessing of corn cob-derived hemicellulose: engineered industrialSaccharomyces cerevisiaeas efficient whole cell biocatalysts
Authors: Cunha Joana T. , Romaní Aloia , Inokuma Kentaro , Johansson Björn , Hasunuma Tomohisa , Kondo Akihiko , Domingues Lucília 
Published: July 2020

AbstractConsolidated bioprocessing, which combines saccharolytic and fermentative abilities in a single microorganism, is receiving increased attention to decrease environmental and economic costs in lignocellulosic biorefineries. Nevertheless, the economic viability of lignocellulosic ethanol is also dependent of an efficient utilization of the hemicellulosic fraction, which is mainly composed of xylose and may comprise up to 40 % of the total biomass. This major bottleneck is mainly due to the necessity of chemical/enzymatic treatments to hydrolyze hemicellulose into fermentable sugars and to the fact that xylose is not readily consumed bySaccharomyces cerevisiae– the most used organism for large-scale ethanol production. In this work, industrialS. cerevisiaestrains, presenting robust traits such as thermotolerance and improved resistance to inhibitors, were evaluated as hosts for the cell-surface display of hemicellulolytic enzymes and optimized xylose assimilation, aiming at the development of whole-cell biocatalysts for consolidated bioprocessing of corn cob-derived hemicellulose. These modifications allowed the direct production of ethanol from non-detoxified hemicellulosic liquor obtained by hydrothermal pretreatment of corn cob, reaching an ethanol titer of 11.1 g/L corresponding to a yield of 0.328 gram per gram of potential xylose and glucose, without the need for external hydrolytic catalysts. Also, consolidated bioprocessing of pretreated corn cob was found to be more efficient for hemicellulosic ethanol production than simultaneous saccharification and fermentation with addition of commercial hemicellulases. These results show the potential of industrialS. cerevisiaestrains for the design of whole-cell biocatalysts and paves the way for the development of more efficient consolidated bioprocesses for lignocellulosic biomass valorization, further decreasing environmental and economic costs.
Chromosome-scale assembly of the coral endosymbiontSymbiodinium microadriaticumgenome provides insight into the unique biology of dinoflagellate chromosomes
Authors: Nand Ankita , Zhan Ye , Salazar Octavio R. , Aranda Manuel , Voolstra Christian R. , Dekker Job 
Published: July 2020

AbstractDinoflagellates are major primary producers in the world’s oceans, the cause of harmful algal blooms, and endosymbionts of marine invertebrates. Much remains to be understood about their biology including their peculiar crystalline chromosomes. Here we used Hi-C to order short read-based sub-scaffolds into 94 chromosome-scale scaffolds of the genome of the coral endosymbiontSymbiodinium microadriaticum. Hi-C data show that chromosomes are folded as linear rods within which loci separated by up to several Mb are highly packed. Each chromosome is composed of a series of structural domains separated by boundaries. Genes are enriched towards the ends of chromosomes and are arranged in unidirectional blocks that alternate between top and bottom strands. Strikingly, the boundaries of chromosomal domains are positioned at sites where transcription of two gene blocks converges, indicating a correlation between gene orientation, transcription and chromosome folding. Some chromosomes are enriched for genes involved in specific biological processes (e.g., photosynthesis, and nitrogen-cycling), and functionally related genes tend to co-occur at adjacent sites in the genome. All chromosomes contain several repeated segments that are enriched in mobile elements. The assembly of theS. microadriaticumgenome and initial description of its genetic and spatial organization provide a foundation for deeper exploration of the extraordinary biology of dinoflagellates and their chromosomes.
Arctic charr phenotypic responses to abrupt temperature change: an insight into how cold water fish could respond to extreme climatic events
Authors: Hooker Oliver E. , Adams Colin E. , Chavarie Louise 
Published: July 2020

ABSTRACTPhenotypic plasticity, the ability of an organism to express multiple phenotypes in response to the prevailing environmental conditions without genetic change, may occur as a response to anthropogenic environmental change. Arguably, the most significant future anthropogenic environment change is contemporary climate change. Given that increasing climate variability is predicted to pose a greater risk than directional climate change, we tested the effect of a water temperature differential of 4 ºC on the Arctic charr phenotypic response within a generation. We demonstrate that Arctic charr phenotype can respond rapidly and markedly to an environmental cue. The plastic response to different temperature regimes comprised a shift in the mean phenotype coupled with a reduction in the between-individual phenotypic variation in the expressed head shape. The magnitude of shape difference was cumulative over time but the rate of divergence diminished as fish became larger. Individuals raised in the elevated temperature treatment expressed a phenotype analogous to a benthivorous ecotype of this species rather than that of the parental pelagic feeding form. The response of cold-water freshwater species to temperature change is likely to be an interaction between the capacity of the organism for phenotypic plasticity, the speed of mean change in the environment (e.g., temperature), and the degree of short interval variation in the environment.
DiffNets: deep learning the structural determinants of proteins biochemical properties by comparing different structural ensembles
Authors: Ward Michael D. , Zimmerman Maxwell I. , Meller Artur , Chung Moses , Swamidass S.J. , Bowman Gregory R. 
Published: July 2020

AbstractUnderstanding the structural determinants of a protein’s biochemical properties, such as activity and stability, is a major challenge in biology and medicine. Comparing computer simulations of protein variants with different biochemical properties is an increasingly powerful means to drive progress. However, success often hinges on dimensionality reduction algorithms for simplifying the complex ensemble of structures each variant adopts. Unfortunately, common algorithms rely on potentially misleading assumptions about what structural features are important, such as emphasizing larger geometric changes over smaller ones. Here we present DiffNets, self-supervised autoencoders that avoid such assumptions, and automatically identify the relevant features, by requiring that the low-dimensional representations they learn are sufficient to predict the biochemical differences between protein variants. For example, DiffNets automatically identify subtle structural signatures that predict the relative stabilities of β-lactamase variants and duty ratios of myosin isoforms. DiffNets should also be applicable to understanding other perturbations, such as ligand binding.
Gut cancer increases the risk forDrosophilato be preyed upon by hunting spiders
Authors: Duneau David , Buchon Nicolas 
Published: July 2020

AbstractPredators are thought to prey on individuals that are in poor physical condition, although the evidence supporting this is ambiguous. We tested if sick individuals where more predated usingDrosophila melanogasterflies as manipulable preys. We asked whether hunting spiders, trapped from the wild, would selectively prey upon flies with compromised health (i.e. chronically infected or cancerous) versus healthy flies under laboratory conditions. Flies chronically infected with the bacteriumProvidencia rettgeri, a naturalDrosophilapathogen, were not selectively preyed upon by jumping spiders. We strengthened and confirmed our finding with another hunting spider species, small wolf spiders. We discuss that this result supports the hypothesis that chronic infection is associated with reduced symptoms notably to avoid the potentially deadly consequences of host predation on pathogens. We then induced colon cancer in some of the flies and asked whether the presence of cancer led to selective predation; there is little evidence for this, even in vertebrates. As the cancer developed, the incidence of predation by jumping spiders on the afflicted flies increased. We conclude that disease can have different lethal consequences through predation, even in invertebrate species, and that cancer is a factor in selective predation. Our results may explain why early tumours, but not metastasized cancers, are commonly detected in organisms in the wild, as cancer bearing individuals are rapidly eliminated due to the strong selective pressure against them.
Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits
Authors: Orchard Peter , Manickam Nandini , Varshney Arushi , Rai Vivek , Kaplan Jeremy , Lalancette Claudia , Gallagher Katherine , Burant Charles F. , Parker Stephen C.J. 
Published: July 2020

AbstractBackgroundSkeletal muscle accounts for the largest proportion of human body mass, on average, and is a key tissue in complex diseases, mobility, and quality of life. It is composed of several different cell and muscle fiber types.ResultsHere, we optimize single-nucleus ATAC-seq (snATAC-seq) to map skeletal muscle cell-specific chromatin accessibility landscapes in frozen human and rat samples, and single-nucleus RNA-seq (snRNA-seq) to map cell-specific transcriptomes in human. We capture type I and type II muscle fiber signatures, which are generally missed by existing single-cell RNA-seq methods. We perform cross-modality and cross-species integrative analyses on 30,531 nuclei, representing 11 libraries, profiled in this study, and identify seven distinct cell types ranging in abundance from 63% (type II fibers) to 0.9% (muscle satellite cells) of all nuclei. We introduce a regression-based approach to infer cell types by comparing transcription start site-distal ATAC-seq peaks to reference enhancer maps and show consistency with RNA-based marker gene cell type assignments. We find heterogeneity in enrichment of genetic variants linked to complex phenotypes from the UK Biobank and diabetes genome wide association studies in cell-specific ATAC-seq peaks, with the most striking enrichment patterns in muscle mesenchymal stem cells (∼3% of nuclei). Finally, we overlay these chromatin accessibility maps on GWAS data to nominate causal cell types, SNPs, and transcription factor motifs for creatinine levels and type 2 diabetes signals.ConclusionsThese chromatin accessibility profiles for human and rat skeletal muscle cell types are a useful resource for investigating specific cell types and nominating causal GWAS SNPs and cell types.
S-nitrosoglutathione reductase deficiency causes aberrant placental S-nitrosylation and preeclampsia
Authors: Kulandavelu Shathiyah , Dulce Raul A , Murray Christopher I , Bellio Michael A , Fritsch Julia , Kanashiro-Takeuchi Rosemeire , Arora Himanshu , Paulino Ellena , Soetkamp Daniel , Balkan Wayne , Van Eyk Jenny E , Hare Joshua M 
Published: July 2020

ABSTRACTPreeclampsia (PE), a leading cause of maternal and fetal mortality and morbidity, is characterized by an increase in S-nitrosylated (SNO) proteins and reactive oxygen species (ROS), suggesting a pathophysiologic role for dysregulation in nitrosylation and nitrosative stress. Here we show that mice lacking S-nitrosoglutathione reductase (GSNOR−/−), a denitrosylase regulating protein S-nitrosylation, exhibit a PE phenotype, including hypertension, proteinuria, renal pathology, cardiac concentric hypertrophy, decreased placental vascularization, and fetal growth retardation. ROS, nitric oxide (NO) and peroxynitrite levels are elevated. Importantly, mass spectrometry reveals elevated placental SNO-amino acid residues inGSNOR−/−mice. Ascorbate reverses the phenotype except for fetal weight, reduces the difference in the S-nitrosoproteome, and identifies a unique set of SNO-proteins inGSNOR−/−mice. Therefore, deficiency of GSNOR creates dysregulation of placental S-nitrosylation and preeclampsia in mice, which can be rescued by ascorbate. These findings offer valuable insights and therapeutic implications for PE.Abstract FigureGraphical Abstract:Dysregulation in nitrosylation contributes to nitroso-redox imbalance and nitrosative stress contributing to clinical features of PE including hypertension, proteinuria, concentric hypertrophy in the heart, decrease placental vascularization and fetal growth restriction. Antioxidant treatment rescued the PE-like phenotype in the mother.
6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro protease activities
Authors: Swaim Caleb D. , Perng Yi-Chieh , Zhao Xu , Canadeo Larissa A. , Harastani Houda H. , Darling Tamarand L. , Boon Adrianus C. M. , Lenschow Deborah J. , Huibregtse Jon M. 
Published: July 2020

AbstractA recently emerged betacoronavirus, SARS-CoV-2, has led to a global health crisis that calls for the identification of effective therapeutics for COVID-19 disease. Coronavirus papain-like protease (PLpro) is an attractive drug target as it is essential for viral polyprotein cleavage and for deconjugation of ISG15, an antiviral ubiquitin-like protein. We show here that 6-Thioguanine (6-TG) inhibits SARS-CoV-2 PLpro-catalyzed viral polyprotein cleavage and ISG15 deconjugation in cells and inhibits replication of SARS-CoV-2 in Vero-E6 cells and Calu3 cells at submicromolar levels. As a well-characterized FDA-approved orally delivered drug, 6-TG represents a promising therapeutic for COVID-19 and other emerging coronaviruses.One Sentence SummaryA repurposed drug that targets an essential enzymatic activity of SARS-CoV-2 represents a promising COVID-19 therapeutic.
RanDeL-seq: A high-throughput method to map viral cis- and trans-acting elements
Authors: Notton Timothy , Glazier Joshua J. , Saykally Victoria R. , Thompson Cassandra E. , Weinberger Leor S. 
Published: July 2020

AbstractIt has long been known that noncoding genomic regions can be obligateciselements acted uponin transby gene products. In viruses,ciselements regulate gene expression, encapsidation, and other maturation processes but mapping these elements relies on targeted iterative deletion or laborious prospecting for rare, spontaneously occurring mutants. Here, we introduce a method to comprehensively map viralcisandtranselements at single-nucleotide resolution by high-throughput random deletion. Variable-size deletions are randomly generated by transposon integration, excision, and exonuclease chewback, and then barcoded for tracking via sequencing (i.e.,Random-DeletionLibrarysequencing, RanDeL-seq). Using RanDeL-seq, we generated and screened >23,000 HIV-1 variants to generate a single-base resolution map of HIV-1’scisandtranselements. The resulting landscape recapitulated HIV-1’s knowncis-acting elements (i.e., LTR, Ψ, and RRE) and surprisingly indicated that HIV-1’s central DNA flap (i.e., central polypurine tract, cPPT to central termination sequence, CTS) is as critical as the LTR, Ψ, and RRE for long-term passage. Strikingly, RanDeL-seq identified a previously unreported ∼300bp region downstream of RRE extending to splice acceptor 7 that is equally critical for sustained viral passage. RanDeL-seq was also used to construct and screen a library of >90,000 variants of Zika virus (ZIKV). Unexpectedly, RanDeL-seq indicated that ZIKV’scis-acting regions are larger than the UTR termini, encompassing a large fraction of the non-structural genes. Collectively, RanDeL-seq provides a versatile framework for generating viral deletion mutants enabling discovery of replication mechanisms and development of novel antiviral therapeutics, particularly for emerging viral infections.ImportanceRecent studies have renewed interest in developing novel antiviral therapeutics and vaccines based on defective interfering particles (DIPs)—a subset of viral deletion mutant that conditionally replicate. Identifying and engineering DIPs requires that viralcis- andtrans-acting elements be accurately mapped. Here we introduce a high-throughput method (Random Deletion Library sequencing, RanDeL-seq) to comprehensively mapcis-andtrans-acting elements within a viral genome. RanDeL-seq identified essential cis elements in HIV, including the obligate nature of the once-controversial viral central poly-purine tract (cPPT) and identified a newcisregion proximal to the Rev responsive element (RRE). RanDeL-seq also identified regions of Zika virus required for replication and packaging. RanDeL-seq is a versatile and comprehensive technique to rapidly map cis and trans regions of a genome.
A model of population dynamics with complex household structure and mobility: implications for transmission and control of communicable diseases
Authors: Chisholm Rebecca H. , Crammond Bradley , Wu Yue , Bowen Asha C. , Campbell Patricia T. , Tong Steven Y. C. , McVernon Jodie , Geard Nicholas 
Published: July 2020

ABSTRACTHouseholds are known to be high-risk locations for the transmission of communicable diseases. Numerous modelling studies have demonstrated the important role of households in sustaining both communicable diseases outbreaks and endemic transmission, and as the focus for control efforts. However, these studies typically assume that households are associated with a single dwelling and have static membership. This assumption does not appropriately reflect households in some populations, such as those in remote Australian Indigenous communities, which can be distributed across more than one physical dwelling, leading to the occupancy of individual dwellings changing rapidly over time. In this study, we developed an individual-based model of an infectious disease outbreak in communities with demographic and household structure reflective of a remote Australian Indigenous community. We used the model to compare the dynamics of unmitigated outbreaks, and outbreaks constrained by a household-focused prophylaxis intervention, in communities exhibiting fluid versus stable dwelling occupancy. Our findings suggest that fluid dwelling occupancy can lead to larger and faster outbreaks, interfere with the effectiveness of household-focused interventions, and may contribute to the considerable burden of communicable diseases in communities exhibiting this type of structure.
Macro-scale models for fluid flow in tumour tissues: impact of microstructure properties
Authors: Vaghi Cristina , Fanciullino Raphaelle , Benzekry Sebastien , Poignard Clair 
Published: July 2020

AbstractUnderstanding the dynamics underlying fluid transport in tumour tissues is of fundamental importance to assess processes of drug delivery. Here, we analyse the impact of the tumour microscopic properties on the macroscopic dynamics of vascular and interstitial fluid flow by using formal asymptotic techniques.Here, we obtained different macroscopic continuum models that couple vascular and interstitial flows. The homogenization technique allows us to derive two macroscale tissue models of fluid flow that take into account the microscopic structure of the vessels and the interstitial tissue. Different regimes were derived according to the magnitude of the vessel wall permeability and the interstitial hydraulic conductivity. Importantly, we provide an analysis of the properties of the models and show the link between them. Numerical simulations were eventually performed to test the models and to investigate the impact of the microstructure on the fluid transport.Future applications of our models include their calibration with real imaging data to investigate the impact of the tumour microenvironment on drug delivery.
PCB126 exposure revealed alterations in m6A RNA modifications in transcripts associated with AHR activation
Authors: Aluru Neelakanteswar , Karchner Sibel I 
Published: July 2020

AbstractChemical modifications of proteins, DNA and RNA moieties play critical roles in regulating gene expression. Emerging evidence suggests these RNA modifications (epitranscriptomics) have substantive roles in basic biological processes. One of the most common modifications in mRNA and noncoding RNAs isN6-methyladenosine (m6A). In a subset of mRNAs, m6A sites are preferentially enriched near stop codons, in 3’ UTRs, and within exons, suggesting an important role in the regulation of mRNA processing and function including alternative splicing and gene expression. Very little is known about the effect of environmental chemical exposure on m6A modifications. As many of the commonly occurring environmental contaminants alter gene expression profiles and have detrimental effects on physiological processes, it is important to understand the effects of exposure on this important layer of gene regulation. Hence, the objective of this study was to characterize the acute effects of developmental exposure to PCB126, an environmentally relevant dioxin-like PCB, on m6A methylation patterns. We exposed zebrafish embryos to PCB126 for 6 hours starting from 72 hours post-fertilization and profiled m6A RNA using methylated RNA immunoprecipitation followed by sequencing (MeRIP-seq). Our analysis revealed 117 and 217 m6A peaks in the DMSO and PCB126 samples (FDR 5%), respectively. The majority of the peaks were preferentially located around the 3’UTR and stop codons. Statistical analysis revealed 15 m6A marked transcripts to be differentially methylated by PCB126 exposure. These include transcripts that are known to be activated by AHR agonists (e.g.,ahrra, tiparp, nfe2l2b) as well as others that are important for normal development (vgf, cebpd, foxi1). These results suggest thatenvironmental chemicals such as dioxin-like PCBs could affect developmental gene expression patterns by altering m6A levels. Further studies are necessary to understand the functional consequences of exposure-associated alterations in m6A levels.