bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of feeding behaviour traits to predict efficiency traits in pigs using partial least square regression
Authors: Ewaoluwagbemiga E. , Bee G. , Kasper C. 
Published: November 2020

AbstractThe improvement of efficiency traits, such as protein efficiency (PE), digestible energy efficiency (EnE) and lipid gain (LipG), are relevant given their associations with environmental pollution, cost of productions, and the quality of meat. However, these traits are difficult traits to measure and usually require slaughtering of pigs. Efficiency traits are complex, and several factors, such as genetic predisposition, feed composition, but also individual feeding behaviour may contribute to efficiency. The objective of this study was therefore to evaluate the potential of using feeding behaviour traits to predict efficiency traits under dietary protein restriction. A total of 587 Swiss Large White pigs, consisting of 312 females and 275 castrated males, hadad libitumaccess to feed and water, and were fed a protein-reduced diet (80% of recommended digestible protein and essential amino acids) from 22.5 ± 1.6 to 106.6 ± 4.6 kg BW. Individual feed intake was monitored and carcass composition (lean and fat mass) at slaughter was determined by dual-energy X-ray absorptiometry (DXA). The PE and EnE were calculated as the ratio of protein or energy in the carcass (estimated by DXA) to the total protein or energy consumed. Feeding behaviour traits monitored were daily feed intake (DFI; g/day), feed intake per meal (FIM; g/meal), number of daily meals (NDM; meals/day), duration of meal (DUM; min/meal), feeding rate (FR; g/min), and feeder occupation (FO; min/day). A partial least square (PLS) regression was used to predict PE, EnE and LipG from feeding behaviour traits, while including farrowing series (for PE only), age at slaughter and body weight at slaughter. Accuracy of PLS regression was assessed based on RMSE and R2for calibration and validation sets, and on concordance correlation coefficient (CCC), which were estimated over 100 replicates of calibration and validation sets. Models with a number of latent variables of 5, 2 and 3 were identified as optimal for PE, EnE, and LipG, which explained 34.64%, 55.42% and 82.68% of the total variation in PE, EnE, and LipG, respectively. Significant CCC were found between predicted and observed values for PE (0.50), EnE (0.70), and LipG (0.90). In conclusion, individual feeding behaviour traits can better predict EnE and LipG than for PE under dietary protein restriction when fedad libitum.ImplicationsThis study suggests that five feeding behaviour traits, which are automatically recorded via feeder stations in large numbers with little effort, together with body weight and age, may be used to predict protein efficiency, energy efficiency and lipid gain in Swiss Large White pigs receiving a protein reduced diet with considerable accuracy. This will allow for easy collection of large amounts of data on these traits for precision feeding and genetic selection strategies, especially when additional traits are added in the future to further improve accuracy.
Gene expression profiling of malaria parasites reveals common virulence gene expression in adult first-time infected patients and severe cases
Authors: Wichers Jan Stephan , Tonkin-Hill Gerry , Thye Thorsten , Krumkamp Ralf , Kreuels Benno , Strauss Jan , von Thien Heidrun , Scholz Judith Anna Marie , Hansson Helle Smedegaard , Jensen Rasmus Weisel , Turner Louise , Lorenz Freia-Raphaella , Schöllhorn Anna , Bruchhaus Iris , Tannich Egbert , Fendel Rolf , Otto Thomas Dan , Lavstsen Thomas , Gilberger Tim-Wolf , Duffy Michael Frank , Bachmann Anna 
Published: November 2020

AbstractSequestration ofPlasmodium falciparum-infected erythrocytes to host endothelium through the parasite-derivedPfEMP1 adhesion proteins is central to the development of malaria pathogenesis.PfEMP1 proteins have diversified and expanded to encompass many sequence variants conferring each parasite a similar array of human endothelial receptor binding phenotypes. Here, we analyzed RNA-seq profiles of parasites isolated from 32P. falciparuminfected adult travelers returning to Germany. Patients were categorized into either malaria naïve (n=15) or pre-exposed (n=17), and into severe (n=8) or non-severe (n=24) cases. For differential expression analysis ofPfEMP1-encodingvargene transcripts werede novoassembled from RNA-seq data and, in parallel,varexpressed sequence tags were analyzed and used to predict the encoded domain composition of the transcripts. Both approaches showed in concordance that severe malaria was associated withPfEMP1 containing the endothelial protein C receptor (EPCR)-binding CIDRα1 domain, whereas CD36-bindingPfEMP1 was linked to non-severe malaria outcomes. First-time infected adults were more likely to develop severe symptoms and tended to be infected for a longer period. Thus, parasites with more pathogenicPfEMP1 variants are more common in patients with a naïve immune status and/or adverse inflammatory host responses to first infections favors growth of EPCR-binding parasites.
Genetic-epigenetic tissue mapping for plasma DNA: applications in prenatal testing, transplantation and oncology
Authors: Gai Wanxia , Zhou Ze , Agbor-Enoh Sean , Fan Xiaodan , Lian Sheng , Jiang Peiyong , Cheng Suk Hang , Wong John , Chan Stephen L. , Jang Moon Kyoo , Yang Yanqin , Liang Raymond H. S. , Chan Wai Kong , Ma Edmond S. K. , Leung Tak Y. , Chiu Rossa W. K. , Valantine Hannah , Chan K. C. Allen , Lo Y. M. Dennis 
Published: November 2020

AbstractWe developedGenetic-EpigeneticTissueMapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived. In lung-transplant recipients, we showed that, at 72 hours after transplantation, the lung contributed only a median of 17% to the plasma DNA carrying donor-specific alleles and hematopoietic cells contributed a median of 78%. In hepatocellular cancer patients, the liver was identified as the predominant source of plasma DNA carrying tumor-specific mutations. In a pregnant woman with lymphoma, plasma DNA molecules carrying cancer mutations and fetal-specific alleles were accurately shown to be derived from the lymphocytes and placenta, respectively. Analysis of tissue origin for plasma DNA carrying genetic variants is potentially useful for noninvasive prenatal testing, transplantation monitoring and cancer screening.
BAP1 constrains pervasive H2AK119ub1 to control the transcriptional potential of the genome
Authors: Fursova Nadezda A. , Turberfield Anne H. , Blackledge Neil P. , Findlater Emma L. , Lastuvkova Anna , Huseyin Miles K. , Dobrinić Paula , Klose Robert J. 
Published: November 2020

AbstractHistone-modifying systems play fundamental roles in gene regulation and the development of multicellular organisms. Histone modifications that are enriched at gene regulatory elements have been heavily studied, but the function of modifications that are found more broadly throughout the genome remains poorly understood. This is exemplified by histone H2A mono-ubiquitylation (H2AK119ub1) which is enriched at Polycomb-repressed gene promoters, but also covers the genome at lower levels. Here, using inducible genetic perturbations and quantitative genomics, we discover that the BAP1 deubiquitylase plays an essential role in constraining H2AK119ub1 throughout the genome. Removal of BAP1 leads to pervasive accumulation of H2AK119ub1, which causes widespread reductions in gene expression. We show that elevated H2AK119ub1 represses gene expression by counteracting transcription initiation from gene regulatory elements, causing reductions in transcription-associated histone modifications. Furthermore, failure to constrain pervasive H2AK119ub1 compromises Polycomb complex occupancy at a subset of Polycomb target genes leading to their derepression, therefore explaining the original genetic characterisation of BAP1 as a Polycomb group gene. Together, these observations reveal that the transcriptional potential of the genome can be modulated by regulating the levels of a pervasive histone modification, without the need for elaborate gene-specific targeting mechanisms.
Structure of the complete dimeric human GDAP1 core domain provides insights into ligand binding and clustering of disease mutations
Authors: Tuyet Nguyen Giang Thi , Sutinen Aleksi , Raasakka Arne , Muruganandam Gopinath , Loris Remy , Kursula Petri 
Published: November 2020

ABSTRACTCharcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders. Despite the common involvement of ganglioside-induced differentiation-associated protein 1 (GDAP1) in CMT, the protein structure and function, as well as the pathogenic mechanisms, remain unclear. We determined the crystal structure of the complete human GDAP1 core domain, which shows a novel mode of dimerization within the glutathione S-transferase (GST) family. The long GDAP1-specific insertion forms an extended helix and a flexible loop. GDAP1 is catalytically inactive towards classical GST substrates. Through metabolite screening, we identified a ligand for GDAP1, the fatty acid hexadecanedioic acid, which is relevant for mitochondrial membrane permeability and Ca2+homeostasis. The fatty acid binds to a pocket next to a CMT-linked residue cluster, increases protein stability, and induces changes in protein conformation and oligomerization. The closest homologue of GDAP1, GDAP1L1, is monomeric in its full-length form. Our results highlight the uniqueness of GDAP1 within the GST family and point towards allosteric mechanisms in regulating GDAP1 oligomeric state and function.
DHS-Crystallize: Deep-Hybrid-Sequence based method for predicting protein Crystallization
Authors: Alavi Azadeh , Ascher David B. 
Published: November 2020

AbstractThe key method for determining the structure of a protein to date is X-ray crystallography, which is a very expensive technique that suffers from high attrition rate. On the contrary, a sequence-based predictor that is capable of accurately determining protein crystallization property, would not only overcome such limitations, but also would reduce the trial-and-error settings required to perform crystallization. In this work, to predict protein crystallizability, we have developed a novel sequence-based hybrid method that employs two separate, yet fully automated, concepts for extracting features from protein sequences. Specifically, we use a deep convolutional neural network on a publicly available dataset to extract descriptive features directly from the sequences, then fuse such feature with structural-and-physio-chemical driven features (such as amino-acid composition or AAIndex-based physicochemical properties). Dimentionality reduction is then performed on the resulting features and the output vectors are applied to train optimized gradient boosting machine (XGBoostt). We evaluate our method through three publicly available test sets, and show that our proposed DHS-Crystallize algorithm outperforms state-of-the-art methods, and achieves higher performance compared to using DCNN-deriven features, or structural-and-physio-chemical driven features alone.
Plasma irradiation efficiently inactivates the coronaviruses mouse hepatitis virus and SARS-CoV-2
Authors: Morikawa Shigeru , Watanabe Shunpei , Fujii Hikaru , Tanaka Toshio , Arai Junichirou , Kyuwa Shigeru 
Published: November 2020

AbstractMany inactivation methods have been shown to inactivate SARS-CoV-2 for safe and efficient diagnostic methods. COVID-19 is caused by airborne infection of SARS-CoV-2, and therefore, methods of inactivating the virus efficiently and safely are crucial for reducing the risk of airborne infection. In this regard, the effect of plasma discharge on the infectivity of the coronaviruses mouse hepatitis virus (MHV) and SARS-CoV-2 was tested. Plasma discharge efficiently reduced the infectivity of both coronaviruses. Treatment of SARS-CoV-2 in culture medium with a plasma discharge resulted in 95.17% viral inactivation after plasma irradiation after 1 hour (hr), 99.54% inactivation after 2 hrs and 99.93% inactivation after 3 hrs. Similar results were obtained for MHV. The results indicated that plasma discharge effectively and safely inactivated the airborne coronaviruses and may be useful in minimizing the risk of airborne infection of SARS-CoV-2.
Cloning and Functional characterization of seed-specificLEC1Apromoter from peanut (Arachis hypogaeaL.)
Authors: Tang Guiying , Xu Pingli , Li Pengxiang , Zhu Jieqiong , Chen Guangxia , Shan Lei , Wan Shubo 
Published: November 2020

AbstractLEAFY COTYLEDON1 (LEC1) is a HAP3 subunit of CCAAT-binding transcription factor, which controls several aspects of embryo and postembryo development, including embryo morphogenesis, storage reserve accumulation and skotomorphogenesis. Herein, using the method of chromosomal walking, a 2707bp upstream sequence from the ATG initiation codon site ofAhLEC1Awhich is a homolog of ArabidopsisLEC1was isolated in peanut. Its transcriptional start site confirmed by 5’ RACE was located at 82 nt from 5’ upstream of ATG. The bioinformatics analysis revealed that there existed many tissue-specific elements and light responsive motifs in its promoter. To identify the functional region of theAhLEC1Apromoter, seven plant expression vectors expressing theGUS(β-glucuronidase) gene, driven by 5’ terminal series deleted fragments ofAhLEC1Apromoter, were constructed and transformed into Arabidopsis. Results of GUS histochemical staining showed that the regulatory region containing 82bp of 5’ UTR and 2228bp promoter could facilitate GUS to express preferentially in the embryos at different development periods of Arabidopsis. Taken together, it was inferred that the expression ofAhLEC1Aduring seed development of peanut might be controlled positively by several seed-specific regulatory elements, as well as negatively by some other regulatory elements inhibiting its expression in other organs. Moreover, theGUSexpression pattern of transgenic seedlings in darkness and in light was relevant to the light-responsive elements scattered inAhLEC1Apromoter segment, implying that these light-responsive elements harbored in theAhLEC1Apromoter regulate skotomorphogenesis of peanut seeds, andAhLEC1Aexpression was inhibited after the germinated seedlings were transferred from darkness to light.
A whole virion vaccine for COVID-19 produced via a novel inactivation method: results from animal challenge model studies
Authors: Ragan Izabela K , Hartson Lindsay M , Dutt Taru S , Obregon-Henao Andres , Maison Rachel M , Gordy Paul , Fox Amy , Karger Burton R , Cross Shaun T , Kapuscinski Marylee L , Cooper Sarah K , Podell Brendan K , Stenglein Mark D , Bowen Richard A , Henao-Tamayo Marcela , Goodrich Raymond P 
Published: November 2020

AbstractThe COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAX™) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this study provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have utility in the preparation of one such vaccine candidate.Author SummaryWe have developed a vaccine for COVID-19 which is prepared by a novel method for inactivation of a whole virion particle and tested it in a hamster animal model for its ability to protect against SARS-CoV-2 infection.
ILRUN downregulates ACE2 expression and blocks infection of human cells by SARS-CoV-2
Authors: Tribolet Leon , Alexander Marina R. , Brice Aaron M. , van Vuren Petrus Jansen , Rootes Christina L. , Mara Kostlend , McDonald Meg , Bruce Kerri L. , Gough Tamara J. , Shi Shuning , Cowled Christopher , Bean Andrew G. D. , Stewart Cameron R. 
Published: November 2020

ABSTRACTThe human protein-coding gene ILRUN (inflammation and lipid regulator with UBA-like and NBR1-like domain, previously C6orf106) is a recently-characterised inhibitor of the transcription regulators p300 and CREB-binding protein (CBP). Here we have utilised RNA-seq to define cellular pathways regulated by ILRUN in the context of severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) infection. We find that inhibition of ILRUN expression increases cellular expression of several members of the renin-angiotensin aldosterone system (RAAS), including the SARS-CoV-2 entry receptor angiotensin converting enzyme 2 (ACE2). Furthermore, inhibition of ILRUN results in increased SARS-CoV-2 replication. These data identify ILRUN as a novel inhibitor of SARS-CoV-2 replication and represents, to our knowledge, the first report of ILRUN as a regulator of the RAAS.SIGNIFICANCE STATEMENTThere is no doubt that the current rapid global spread of COVID-19 has had significant and far-reaching impacts on our health and economy and will continue to do so. Research in emerging infectious diseases, such as severe acute respiratory syndrome-associated coronavirus (SARS-CoV-2), is growing rapidly, with new breakthroughs in the understanding of host-virus interactions and the development of innovative and exciting therapeutic strategies and new knowledge and tools to better protect against the impacts of disease. The human protein-coding gene ILRUN is a recently-characterised inhibitor of the transcription regulators p300 and CREB-binding protein (CBP). Here we present the first evidence that ILRUN modulation has implications for SARS-CoV-2 infections. Virus infectivity assays confirmed that gene silencing of ILRUN had a proviral effect and increased SARS-CoV-2 replication, whilst over-expression of ILRUN inhibited SARS-CoV-2 production. Additionally, we observed that ILRUN also regulates the expression of key elements of the RAAS. These data have important implications for the development of antiviral strategies to deal with the current SARS-CoV-2 pandemic.
Lipid-specific protein oligomerization is regulated by two interfaces in Marburg virus matrix protein VP40
Authors: Amiar Souad , Husby Monica L. , Wijesinghe Kaveesha J. , Angel Stephanie , Bhattarai Nisha , Gerstman Bernard S. , Chapagain Prem P. , Li Sheng , Stahelin Robert V. 
Published: November 2020

SummaryMarburg virus major matrix protein (mVP40) dimers associate with anionic lipids at the plasma membrane and undergo a dynamic and extensive self-oligomerization into the structural matrix layer which confers the virion shape and stability. Using a myriad ofin vitroand cellular techniques, we present a mVP40 assembly model highlighting two distinct oligomerization interfaces (N-terminal domain (NTD) and C-terminal domain (CTD)) in mVP40. Cellular studies of NTD and CTD oligomerization interface mutants demonstrated the importance of each interface in the mVP40 matrix assembly through protein trafficking to the plasma membrane and homo-multimerization that induced protein enrichment, plasma membrane fluidity changes and elongations at the plasma membrane. A novel APEX-TEM method was employed to closely assess the ultrastructural localization of and formation of viral particles for wild type and mutants. Taken together, these studies present a mechanistic model of mVP40 oligomerization and assembly at the plasma membrane during virion assembly.
A metabolic coincidence mechanism controls winter photoperiodism in plants
Authors: Liu Wei , Feke Ann , Leung Chun Chung , Tarté Daniel A. , Yuan Wenxin , Vanderwall Morgan , Sager Garrett , Wu Xing , Schear Ariela , Clark Damon A. , Thines Bryan C. , Gendron Joshua M. 
Published: November 2020

AbstractPlants have served as a preeminent study system for photoperiodism because of their propensity to flower in concordance with the seasons. A nearly singular focus on understanding seasonal flowering has been to the detriment of discovering other photoperiod measuring mechanisms that may be necessary for vegetative health. Here we use bioinformatics to identify a group of winter photoperiod-induced genes in Arabidopsis and show that one,PP2-A13, is critical for fitness and survival, exclusively in winter-like photoperiods. We create a real-time photoperiod reporter, using thePP2-A13promoter driving luciferase, and show that winter photoperiod genes are regulated independent of the canonical CO/FT mechanism for photoperiodic flowering. The reporter then allows us to identify the first genetic and cellular drivers of winter photoperiodism and reveal a mechanism that relies on coincidence between light capture through photosynthesis and rhythmic metabolism. This work demonstrates that plants have distinct photoperiod measuring mechanisms that enact critical biological and developmental processes in different seasons.
Molecular basis for a germline-biased neutralizing antibody response to SARS-CoV-2
Authors: Clark Sarah A. , Clark Lars E. , Pan Junhua , Coscia Adrian , McKay Lindsay G.A. , Shankar Sundaresh , Johnson Rebecca I. , Griffiths Anthony , Abraham Jonathan 
Published: November 2020

AbstractThe SARS-CoV-2 viral spike (S) protein mediates attachment and entry into host cells and is a major target of vaccine and drug design. Potent SARS-CoV-2 neutralizing antibodies derived from closely related antibody heavy chain genes (IGHV3-53 or 3-66) have been isolated from multiple COVID-19 convalescent individuals. These usually contain minimal somatic mutations and bind the S receptor-binding domain (RBD) to interfere with attachment to the cellular receptor angiotensin-converting enzyme 2 (ACE2). We used antigen-specific single B cell sorting to isolate S-reactive monoclonal antibodies from the blood of a COVID-19 convalescent individual. The seven most potent neutralizing antibodies were somatic variants of the same IGHV3-53-derived antibody and bind the RBD with varying affinity. We report X-ray crystal structures of four Fab variants bound to the RBD and use the structures to explain the basis for changes in RBD affinity. We show that a germline revertant antibody binds tightly to the SARS-CoV-2 RBD and neutralizes virus, and that gains in affinity for the RBD do not necessarily correlate with increased neutralization potency, suggesting that somatic mutation is not required to exert robust antiviral effect. Our studies clarify the molecular basis for a heavily germline-biased human antibody response to SARS-CoV-2.