bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Immunoinformatics Study to Predict Epitopes in the Envelope Protein of SARS-COV-2
Authors: Jakhar Renu , Gakhar S.K 
Published: May 2020

AbstractCOVID-19 is a new viral emergent human disease caused by a novel strain of Coronavirus. This virus has caused a huge problem in the world as millions of the people are affected with this disease in the entire world. We aimed to design a peptide vaccine for COVID-19 particularly for the envelope protein using computational methods to predict epitopes inducing the immune system and can be used later to create a new peptide vaccine that could replace conventional vaccines. A total of available 370 sequences of SARS-CoV-2 were retrieved from NCBI for bioinformatics analysis using Immune Epitope Data Base (IEDB) to predict B and T cells epitopes. Then we docked the best predicted CTL epitopes with HLA alleles. CTL cell epitopes namely interacted with MHC class I alleles and we suggested them to become universal peptides based vaccine against COVID-19. Potentially continuous B cell epitopes were predicted using tools from IEDB. The Allergenicity of predicted epitopes was analyzed by AllerTOP tool and the coverage was determined throughout the worlds. We found these CTL epitopes to be T helper epitopes also. The B cell epitope, SRVKNL and T cell epitope, FLAFVVFLL were suggested to become a universal candidate for peptide-based vaccine against COVID-19. We hope to confirm our findings by adding complementary steps of bothin vitroandin vivostudies to support this new universal predicted candidate.
Robustification of RosettaAntibody and Rosetta SnugDock
Authors: Jeliazkov Jeliazko R. , Frick Rahel , Zhou Jing , Gray Jeffrey J. 
Published: May 2020

AbstractIn recent years, the observed antibody sequence space has grown exponentially due to advances in high-throughput sequencing of immune receptors. The rise in sequences has not been mirrored by a rise in structures, as experimental structure determination techniques have remained low-throughput. Computational modeling, however, has the potential to close the sequence–structure gap. To achieve this goal, computational methods must be robust, fast, easy to use, and accurate. Here we report on the latest advances made in RosettaAntibody and Rosetta SnugDock—methods for antibody structure prediction and antibody–antigen docking. We simplified the user interface, expanded and automated the template database, generalized the kinematics of antibody–antigen docking (which enabled modeling of single-domain antibodies) and incorporated new loop modeling techniques. To evaluate the effects of our updates on modeling accuracy, we developed rigorous tests under a new scientific benchmarking framework within Rosetta. Benchmarking revealed that more structurally similar templates could be identified in the updated database and that SnugDock broadened its applicability without losing accuracy. However, there are further advances to be made, including increasing the accuracy and speed of CDR-H3 loop modeling, before computational approaches can accurately model any antibody.
Net reductions in greenhouse gas emissions from feed additive use in California dairy cattle
Authors: Feng Xiaoyu , Kebreab Ermias 
Published: May 2020

AbstractThe livestock industry is one of the main contributors to greenhouse gas emissions and there is an increasing demand for the industry to reduce its carbon footprint. Several studies have shown that feed additives 3-nitroxypropanol and nitrate to be effective in reducing enteric methane emissions. The objective of this study was to estimate the net mitigating effect of using 3-nitroxypropanol and nitrate on total greenhouse gas emissions in California dairy industry. A life cycle assessment approach was used to conduct a cradle-to-farm gate environmental impact analysis based on dairy production system in California. Emissions associated with crop production, feed additive production, enteric methane, farm management, and manure storage were calculated and expressed as kg CO2equivalents (CO2e) per kg of energy corrected milk. The total greenhouse gas emissions from baseline, two 3-nitroxypropanol and three nitrate scenarios were 1.12, 0.993, 0.991, 1.08, 1.07, and 1.09 kg CO2e/kg energy corrected milk. The average net reduction rates for 3-nitroxypropanol and nitrate were 11.7% and 3.95%, respectively. In both cases, using the feed additives on the whole herd slightly improved overall carbon footprint reduction compared to limiting its use during lactation phase. Although both 3-nitroxypropanol and nitrate had effects on decreasing the total greenhouse gas emission, the former was much more effective with no known safety issues in reducing the carbon footprint of dairy production in California.
Genetical control of 2D pattern and depth of the primordial furrow that codes 3D shape of the rhinoceros beetle horn
Authors: Adachi Haruhiko , Matsuda Keisuke , Niimi Teruyuki , Kondo Shigeru , Gotoh Hiroki 
Published: May 2020

AbstractThe head horn of the Asian rhinoceros beetle develops as extensively folded primordia before unfurling into its final 3D shape at the pupal molt. The information of the final 3D structure of the beetle horn is encoded in the folding pattern of the developing primordia. However, the developmental mechanism underlying epithelial folding of the primordia is unknown. In this study, we addressed this gap in our understanding of the developmental patterning of the 3D horn shape of beetles by focusing on the formation of surficial furrows that become the bifurcated 3D shape of the horn. By gene knockdown screening via RNAi, we found that knockdown of the geneNotchdisturbed overall horn primordia furrow depth without affecting 2D furrow pattern. In contrast, knockdown ofCyclinEaltered 2D horn primordia furrow pattern without affecting furrow depth. From these results, depth and 2D pattern of primordial surficial furrow are likely to be regulated independently during the development and both of change can alter the final 3D shape.Author SummaryIn insects, some large structure is made under the old exoskeleton before the molting. Long horn of rhino-beetle is one of extreme cases. The beetle horn is compactly packed as furrowed primordia under the larval exoskeleton. At molting, the primordia is extended to form its final 3D horn shape as blowing up furrows like a balloon. This transformation from primordia to final horn does not required any living cell activities. Thus, characteristics of furrows of primordia actually determine the final 3D shape. However, molecular mechanisms and genetic basis of furrow formation is not well understood not only in beetle horn but also in any other insects. In this study, by using beetle horn as a model, we addressed what kind of genetic factors are contributed to primordial furrow formation. By gene knockdown screening, we found that knockdown of the geneNotchdisturbed primordial furrow depth without affecting 2D furrow pattern. In contrast, knockdown ofCyclinEaltered 2D furrow pattern without affecting furrow depth. In both case, final horn shapes were disturbed. From these results, we concluded that both of the depth and 2D pattern of primordial furrow can contribute final shape, but their development is controlled independently.
Chloroflexi persisting for millions of years in oxic and anoxic deep-sea clay
Authors: Vuillemin Aurèle , Kerrigan Zak , D’Hondt Steven , Orsi William D. 
Published: May 2020

AbstractChloroflexi are widespread in energy-limited subseafloor sediments, but how Chloroflexi respond to subseafloor energy limitation under oxic and anoxic conditions is poorly understood. Here, we characterize the diversity, abundance, activity, and metabolic potential of Chloroflexi in oxic and anoxic abyssal clay from three deep-sea cores covering up to 15 million years of sediment deposition, where Chloroflexi are a major component of the community throughout the entire cored sequence at all sites. In oxic red clay at two different sites, Chloroflexi communities exhibit net death over both 10-15 million year cored sequences, and gene expression was below detection despite the availability of oxygen as a high energy electron acceptor, indicating a reduced level of activity. In contrast at the anoxic site, Chloroflexi abundance and gene expression increase below the seafloor and peak in 2 to 3 million year old sediment. The anaerobic subseafloor Chloroflexi exhibited a homoacetogenic metabolism and potential for energetically efficient intracellular H2recycling that have been proposed to confer a fitness advantage in energy-limited subseafloor habitats. Our findings indicate that the expression of this energy efficient metabolism in Chloroflexi coincides with net growth over million year timescales in deep-sea anoxic clay.Significance statementChloroflexi are widespread in energy-limited subseafloor sediments, both in oxic subseafloor sediments that are energetically limited by the availability of electron donors (organic matter) and in anoxic sediments that are energetically limited by the availability of high energy terminal electron acceptors. How Chloroflexi respond to these different forms of energy limitation over long time scales is poorly understood. We present new data that demonstrates how key differences in metabolism are manifested in different communities of aerobic and anaerobic Chloroflexi subsisting over millions of years in oxic and anoxic deep-sea clay. These data provide new insights into how certain Chloroflexi respond to different types of long-term energy limitation.
Predicting the evolution of sexual dimorphism in gene expression
Authors: Houle David , Cheng Changde 
Published: May 2020

AbstractSexual dimorphism in gene expression is likely to be the underlying source of dimorphism in a variety of traits. Many analyses implicitly make the assumption that dimorphism only evolves when selection favors different phenotypes in the two sexes, although theory makes clear that it can also evolve as an indirect response to other kinds of selection. Furthermore, previous analyses consider the evolution of a single transcript or trait at a time, ignoring the genetic covariance with other transcripts and traits. We first show which aspects of the genetic-variance covariance matrix,G, affect dimorphism when these assumptions about selection are relaxed. We then reanalyze gene expression data fromDrosophila melanogasterwith these predictions in mind. Dimorphism of gene expression for individual transcripts shows the signature of both direct selection for dimorphism and indirect responses to selection. To account for the effect of measurement error on evolutionary predictions, we estimated aGmatrix for eight linear combinations of expression traits. Sex-specific genetic variances in female- and male-biased transcription, as well as one relatively unbiased combination were quite unequal, ensuring that most forms of selection on these traits will have large effects on dimorphism. Predictions of response to selection based on the wholeGmatrix showed that sexually concordant and antagonistic selection are equally capable of changing sexual dimorphism. In addition, the indirect responses of dimorphism due to cross-trait covariances were quite substantial. The assumption that sexual dimorphism in transcription is an adaptation is likely to be incorrect in many specific cases.
Exploring amino acid functions in a deep mutational landscape
Authors: Dunham Alistair , Beltrao Pedro 
Published: May 2020

AbstractAmino acids fulfil a diverse range of roles in proteins, each utilising its chemical properties in different ways in different contexts to create required functions. For example, cysteines form disulphide or hydrogen bonds in different circumstances and charged amino acids do not always make use of their charge. The repertoire of amino acid functions and the frequency at which they occur in proteins remains understudied. Measuring large numbers of mutational consequences, which can elucidate the role an amino acid plays, was prohibitively time consuming until recent developments in deep mutational scanning. In this study we gathered data from 28 deep mutational scanning studies, covering 6291 positions in 30 proteins, and used the consequences of mutation at each position to define a mutational landscape. We demonstrated rich relationships between this landscape and biophysical or evolutionary properties. Finally, we identified 100 functional amino acid subtypes with a data-driven clustering analysis and studied their features, including their frequencies and chemical properties such as tolerating polarity, hydrophobicity or being intolerant of charge or specific amino acids. The mutational landscape and amino acid subtypes provide a foundational catalogue of amino acid functional diversity, which will be refined as the number of studied protein positions increases.
The effect of autophagy and mitochondrial fission on Harderian gland is greater than apoptosis in male hamsters during different photoperiods
Authors: Wang Zhe , Xu Jin-Hui , Mou Jun-Jie , Zhao Xiang-Yu , Geng Xiao-Cui , Wu Ming , Xue Hui-Liang , Lei-Chen  , Xu Lai-Xiang 
Published: May 2020

AbstractPhotoperiod is an important factor of mammalian seasonal rhythm. We studied the morphological differences in HG which is a vital photosensitive organ of male striped dwarf hamsters (Cricetulus barabensis), under different photoperiods (short photoperiod, SP; moderate photoperiod, MP; long photoperiod, LP), and further investigated the molecular mechanisms related to these morphological differences. Results showed that body weight, carcass weight, and HG weight were lower in SP and LP. Protein expression of bax/bcl2 and Cytochrome C showed no significant differences, indicating that the level of apoptosis remained stable. Protein aggregation of LC3 and protein expression of LC3II/LC3I were higher in SP than. Furthermore, comparison of changes in the HG ultrastructure demonstrated autolysosome formation in the LP, which suggesting the lowest autophagy level in MP. Protein expression levels of ATP synthase and mitochondrial fission factor were highest in the MP, whereas citrate synthase, dynamin-related protein1, and fission1 remained unchanged in three groups. In summary, the significant up-regulation of autophagy under short and long photoperiod may be the main factor leading to the loss of HG weight and reduced mitochondrial energy supply.
Gene regulation gravitates towards either addition or multiplication when combining the effects of two signals
Authors: Sanford Eric M. , Emert Benjamin L. , Coté Allison , Raj Arjun 
Published: May 2020

AbstractSignals often ultimately affect the transcription of genes, and often, two different signals can affect the transcription of the same gene. In such cases, it is natural to ask how the combined transcriptional response compares to the individual responses. Mechanistic models can predict a range of combined responses, with the most commonly applied models predicting additive or multiplicative responses, but systematic genome-wide evaluation of these predictions are not available. Here, we performed a comprehensive analysis of the transcriptional response of human MCF-7 cells to two different signals (retinoic acid and TGF-β), applied individually and in combination. We found that the combined responses exhibited a range of behaviors, but clearly favored both additive and multiplicative combined transcriptional responses. We also performed paired chromatin accessibility measurements to measure putative transcription factor occupancy at regulatory elements near these genes. We found that increases in chromatin accessibility were largely additive, meaning that the combined accessibility response was the sum of the accessibility responses to each signal individually. We found some association between super-additivity of accessibility and multiplicative or super-multiplicative combined transcriptional responses, while sub-additivity of accessibility associated with additive transcriptional responses. Our findings suggest that mechanistic models of combined transcriptional regulation must be able to reproduce a range of behaviors.
Plasmodium falciparumReplication factor C subunit 1 is involved in genotoxic stress response
Authors: Sheriff O , Aniweh Y , Lai Soak-Kuan , Loo HL , Sze S. K , Preiser PR 
Published: May 2020

AbstractAbout half the world’s population is at risk of malaria, withPlasmodium falciparummalaria being responsible for the most malaria related deaths globally. Antimalarial drugs such as chloroquine and artemisinin are directed towards the proliferating intra-erythrocytic stages of the parasite, which is responsible for all the clinical symptoms of the disease. These antimalarial drugs have been reported to function via multiple pathways, one of which induces DNA damage via the generation of free radicals and reactive oxygen species. An urgent need to understand the mechanistic details of drug response and resistance is highlighted by the decreasing clinical efficacy of the front line drug, Artemisinin.The replication factor C subunit 1 protein is an important component of the DNA replication machinery and DNA damage response mechanism. Here we show the translocation of PfRFC1 from an intranuclear localization to the nuclear periphery indicating an orchestrated progression of distinct patterns of replication in the developing parasites. PfRFC1 responds to genotoxic stress via elevated protein levels in soluble and chromatin bound fractions.Reduction of PfRFC1 protein levels upon treatment with antimalarials suggests an interplay of replication and DNA repair pathways leading to cell death. Additionally, mislocalization of the endogenously tagged protein confirmed its essential role in parasites’ replication and DNA repair. This study provides key insights into DNA replication, DNA damage response and cell death inplasmodium falciparum.ImportanceFrontline drugs have been found to induce DNA damage in the human malaria parasitePlasmodium falciparum.The genotoxic stress response inPlasmodiumand the interplay between DNA damage repair, replication and activation of programmed cell death pathways remains largely undescribed. This study shows a distinct pattern of localization of PfRFC1 during replication and DNA repair. PfRFC1 responds to genotoxic stress with an increase in protein expression. Interfering with the RFC complex formation or mislocalization of PfRFC1 is associated with disrupted genotoxic stress response. Additionally, a reduction of PfRFC1 protein levels is observed upon treatment with antimalarial drugs or under apoptosis like conditions, highlighting the role of DEVD/G like motif in mediating programmed cell death in these parasites. This study sheds light on the role of PfRFC1 in differentially responding to replication, genotoxic stress and programmed cell death inPlasmodiumparasites.
COVID-19: The unreasonable effectiveness of simple models
Authors: Carletti Timoteo , Fanelli Duccio , Piazza Francesco 
Published: May 2020

AbstractWhen the novel coronavirus disease SARS-CoV2 (COVID-19) was officially declared a pandemic by the WHO in March 2020, the scientific community had already braced up in the effort of making sense of the fast-growing wealth of data gathered by national authorities all over the world. However, despite the diversity of novel theoretical approaches and the comprehensiveness of many widely established models, the official figures that recount the course of the outbreak still sketch a largely elusive and intimidating picture. Here we show unambiguously that the dynamics of the COVID-19 outbreak belongs to the simple universality class of the SIR model and extensions thereof. Our analysis naturally leads us to establish that there exists a fundamental limitation to any theoretical approach, namely the unpredictable non-stationarity of the testing frames behind the reported figures. However, we show how such bias can be quantified self-consistently and employed to mine useful and accurate information from the data. In particular, we describe how the time evolution of the reporting rates controls the occurrence of the apparent epidemic peak, which typically follows the true one in countries that were not vigorous enough in their testing at the onset of the outbreak. The importance of testing early and resolutely appears as a natural corollary of our analysis, as countries that tested massively at the start clearly had their true peak earlier and less deaths overall.
Differentiating COVID-19 from other types of pneumonia with convolutional neural networks
Authors: Ozsahin Ilker , Onyebuchi Confidence , Sekeroglu Boran 
Published: May 2020

AbstractINTRODUCTIONA widely-used method for diagnosing COVID-19 is the nucleic acid test based on real-time reverse transcriptase-polymerase chain reaction (RT-PCR). However, the sensitivity of real time RT-PCR tests is low and it can take up to 8 hours to receive the test results. Radiologic methods can provide higher sensitivity. The aim of this study is to investigate the use of X-ray and convolutional neural networks for the diagnosis of COVID-19 and to differentiate it from viral and/or bacterial pneumonia, as 2-class (bacterial pneumonia vs COVID-19 and viral pneumonia vs COVID-19) and 3- class (bacterial pneumonia, COVID-19, and healthy group (BCH), and among viral pneumonia, COVID- 19, and healthy group (VCH)) experiments.METHODS225 COVID-19, 1,583 healthy control, 2,780 bacterial pneumonia, and 1,493 viral pneumonia chest X-ray images were used. 2-class- and 3-class-experiments were performed with different convolutional neural network (ConvNet) architectures, with different variations of convolutional layers and fully-connected layers.RESULTSThe results showed that bacterial pneumonia vs COVID-19 and viral pneumonia vs COVID- 19 reached a mean ROC AUC of 97.32% and 96.80%, respectively. In the 3-class-experiments, macro-average F1 scores of 95.79% and 94.59% were obtained in terms of detecting COVID-19 among BCH and VCH, respectively.CONCLUSIONSThe ConvNet was able to distinguish the COVID-19 images among non-COVID-19 images, namely bacterial and viral pneumonia as well as normal X-ray images.
Doctoral Apprenticeships and the “ladder of opportunity”
Authors: Senior Rowena , Cleaver Elizabeth , Queiros Gilmar , King Helen , Barnett Kirstin 
Published: May 2020

PurposeThis discussion paper supports the new development of Apprenticeships at Level 8 of the UK’s Framework for Higher Education Qualifications (QAA, 2014). This exciting development, one that employers and universities had been waiting for paves the way for, apprenticeships, sold as the ladder of opportunity, to go all the way to the top.Design/methodology/approachHere, we explore in brief the emergence of the new apprenticeship landscape and the importance of the addition of this new highest of levels.FindingsImportantly, however, we make the case that such progress needs to be met with an equally progressive approach to the design of the new doctoral pathway.Research limitations/implicationsWe sketch out a possible shell for the assessment of a Doctoral Apprenticeship, one that allows for flexible occupationally relevant inputs to create an applicable role-based and academically rigourous whole.Originality/valueThe importance of such a design is discussed within the context of the potential for impact in three priority areas: social justice, broadening the talent pool and ensuring the relevance and sustainability of the doctoral award.