bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of NR4A Ligands that Directly Bind and Modulate the Orphan Nuclear Receptor Nurr1
Authors: Munoz-Tello Paola , Lin Hua , Khan Pasha , de Vera Ian Mitchelle S. , Kamenecka Theodore M. , Kojetin Douglas J. 
Published: May 2020

ABSTRACTNurr1/NR4A2 is an orphan nuclear receptor transcription factor implicated as a potential drug target for neurological disorders including Alzheimer’s and Parkinson’s diseases. Previous studies identified small molecule modulators of NR4A nuclear receptors including Nurr1 and Nur77/NR4A1; it remains unclear whether these ligands affect Nurr1 through direct binding or indirect non-binding mechanisms. We assessed a panel of twelve ligands reported to affect NR4A activity for Nurr1-dependent and Nurr1-independent transcriptional effects and binding to the Nurr1 ligand-binding domain (LBD). Most of the NR4A ligands show Nurr1-independent effects on transcription in a cell type-specific manner, suggesting they may function through binding to effector proteins whose downstream activities influence Nurr1 function. Protein NMR spectroscopy structural footprinting data show that 4-amino-7-chloroquinoline derivatives (amodiaquine and chloroquine) and cytosporone B directly bind the Nurr1 LBD. In contrast, other NR4A ligands including commercially available compounds such as C-DIM12, celastrol, camptothecin, IP7e, isoalantolactone, and TMPA do not bind the Nurr1 LBD. Interestingly, previous crystal structures indicate that cytosporone B analogs bind to surface pockets in the Nur77 LBD, but protein NMR data indicate cytosporone B likely binds to the Nurr1 orthosteric pocket. These findings should influence medicinal chemistry efforts that desire to optimize Nurr1-binding ligands as opposed to ligands that function through binding to Nurr1 effector proteins.
Coupling transcriptomics and behaviour to unveil the olfactory system ofSpodoptera exigualarvae
Authors: Llopis-Giménez Angel , Carrasco-Oltra Tamara , Jacquin-Joly Emmanuelle , Herrero Salvador , Crava Cristina M. 
Published: May 2020

AbstractChemoreception in insects is crucial for many aspects related to food seeking, enemy avoidance, and reproduction. Different families of receptors and binding proteins interact with chemical stimuli, including odorant receptors (ORs), ionotropic receptors (IRs), gustatory receptors (GRs), odorant binding proteins (OBPs) and chemosensory proteins (CSPs). In this work, we describe the chemosensory-related gene repertoire of the worldwide spread pestSpodoptera exigua(Lepidoptera: Noctuide) focusing on the transcripts expressed in larvae, which feed on many horticultural crops producing yield losses. A comprehensivede novoassembly that includes reads from chemosensory organs of larvae and adults, and other larval tissues, enabled us to annotate 200 candidate chemosensory-related genes encoding 63 ORs, 28 IRs, 38 GRs, 48 OBPs and 23 CSPs. Of them, 51 transcripts are new annotations. RNA-seq and reverse transcription PCR analyses show that 50 ORs are expressed in larval heads, and 15 OBPs are larva-specific. To identify candidate ecologically-relevant odours forS. exigualarvae, we set up behavioural experiments with different volatile organic compounds (VOCs). 1-hexanol triggers attraction at the three timepoints tested and linalool repels larvae at any timepoints. Other five VOCs elicit behavioural response at single timepoint. Lastly, we tested if pre-exposure to single VOCs influence the expression patterns of selected ORs and pheromone binding proteins (PBPs), showing a massive and general up-regulation of some ORs after 24h exposure. This work sets the basis for the study of chemosensation inS. exigualarvae, boosting further studies aimed to characterize chemosensory-related genes that underlie ecologically-relevant behaviours of larval stage.
Adaptation of utility functions to reward distribution in rhesus monkeys
Authors: Bujold Philipe M. , Ferrari-Toniolo Simone , Schultz Wolfram 
Published: May 2020

AbstractThis study investigated the influence of experienced reward distributions on the shape of utility functions inferred from economic choice. Utility is the hypothetical variable that appears to be maximized by the choice. Despite the generally accepted notion that utility functions are not insensitive to external references, the exact occurrence of such changes remains largely unknown. Here we benefitted from the capacity to perform thorough and extensive experimental tests of one of our evolutionary closest, experimentally viable and intuitively understandable species, the rhesus macaque monkey. Data from thousands of binary choices demonstrated that the animals’ preferences changed dependent on the statistics of recently experienced rewards and adapted to future expected rewards. The elicited utility functions shifted and extended their shape with several months of changes in the mean and range of reward distributions. However, the adaptations were usually not complete, suggesting that past experiences remained present when anticipating future rewards. Through modelling, we found that reinforcement learning provided a strong basis for explaining these adaptations. Thus, rather than having stable and fixed preferences assumed by normative economic models, rhesus macaques flexibly shaped their preferences to optimize decision-making according to the statistics of the environment.
Intrinsic ecological dynamics drive biodiversity turnover in model metacommunities
Authors: O’Sullivan Jacob D. , Terry J. Christopher D. , Rossberg Axel G. 
Published: May 2020

ABSTRACTTurnover of species composition through time is frequently observed in ecosystems. It is often interpreted as indicating the impact of changes in the environment. Continuous turnover due solely to ecological dynamics—species interactions and dispersal—is also known to be theoretically possible, however the prevalence of such autonomous turnover in natural communities remains unclear. Here we demonstrate that observed patterns of compositional turnover and other important macroecological phenomena can be reproduced in large spatially explicit model ecosystems, without external forcing such as environmental change or the invasion of new species into the model. These results imply that the potential role of autonomous turnover as a widespread and important natural process is underappreciated, challenging assumptions implicit in many observation and management tools. Quantifying the baseline level of compositional change would greatly improve ecological status assessments.One Sentence SummaryBiodiversity change previously attributed to external drivers is explainable as resulting from intrinsic ecosystem dynamics.
RiceLncPedia: a comprehensive database of rice long non-coding RNAs
Authors: Zhang Zhengfeng , Xu Yao , Yang Fei , Xiao Benze , Li Guoliang 
Published: May 2020

ABSTRACTLong non-coding RNAs (lncRNAs) play significant functions in various biological processes including differentiation, development and adaptation to different environments. Although multi research focused on lncRNAs in rice, the systematic identification and annotation of lncRNAs expressed in different tissues, developmental stages under diverse conditions are still scarce. This impacts the elucidation of their functional significance and the further research on them. Here, RiceLncPedia (http://218.199.68.191:10092/) is constructed including rice lncRNAs explored from 2313 publically available rice RNA-seq libraries and characterize them with multi-omics data sets. In the current version, RiceLncPedia shows 6978 lncRNAs with abundant features: (i) expression profile across 2313 rice RNA-seq libraries; (ii) an online genome browser for rice lncRNAs; (iii) genome SNPs in lncRNA transcripts; (iv) lncRNA associations with phenotype; (v) overlap of lncRNAs with transposons; and (vi) LncRNA-miRNA interactions and lncRNAs as the precursors of miRNAs. In total, RiceLncPedia imported numerous of rice lncRNAs during development under various environments as well as their features extracted from multi-omics data and thus serve as a fruitful resource for rice-related research communities. RiceLncPedia will be further updated with experimental validation, functions association and epigenetic characteristics to greatly facilitate future investigation on rice lncRNAs.
Using GC content to compare recombination patterns on the sex chromosomes and autosomes of the guppy,Poecilia reticulata, and its close outgroup species
Authors: Charlesworth Deborah , Zhang Yexin , Bergero Roberta , Graham Chay , Gardner Jim , Yong Lengxob 
Published: May 2020

Summary/AbstractGenetic and physical mapping of the guppy (P. reticulata) have shown that recombination patterns differ greatly between males and females. Crossover events occur evenly across the chromosomes in females, but in male meiosis they are restricted to the tip furthest from the centromere of each chromosome, creating very high recombination rates per megabase, similar to the high rates in mammalian sex chromosomes’ pseudo-autosomal regions (PARs). We here used the intronic GC content to indirectly infer the recombination patterns on guppy chromosomes. This is based on evidence that recombination is associated with GC-biased gene conversion, so that genome regions with high recombination rates should be detectable by high GC content. Using intron sequences, which are likely to be under weak selection, we show that almost all guppy chromosomes, including the sex chromosome (LG12) have very high GC values near their assembly ends, suggesting high recombination rates due to strong crossover localisation in male meiosis. Our test does not suggest that the guppy XY pair has stronger crossover localisation than the autosomes, or than the homologous chromosome in a closely related fish, the platyfish (Xiphophorus maculatus). We therefore conclude that the guppy XY pair has not recently undergone an evolutionary change to a different recombination pattern, or reduced its crossover rate, but that the guppy evolved Y-linkage due to acquiring a male-determining factor that also conferred the male crossover pattern. The results also identify the centromere ends of guppy chromosomes, which were not determined in the guppy genome assembly.
Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 infection in the lung epithelium
Authors: Schuler Bryce A. , Habermann A. Christian , Plosa Erin J. , Taylor Chase J. , Jetter Christopher , Kapp Meghan E. , Benjamin John T. , Gulleman Peter , Nichols David S. , Braunstein Lior Z. , Hackett Alice , Koval Michael , Guttentag Susan H. , Blackwell Timothy S. ,   Vanderbilt COVID-19 Consortium Cohort, Webber Steven A. , Banovich Nicholas E. , Kropski Jonathan A. , Sucre Jennifer M. S. ,   HCA Lung Biological Network
Published: May 2020

AbstractThe SARS-CoV-2 novel coronavirus global pandemic (COVID-19) has led to millions of cases and hundreds of thousands of deaths around the globe. While the elderly appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of the developing mouse lung with temporally-resolved RNA-in-situ hybridization (ISH) in mouse and human lung tissue, we found that expression of SARS-CoV-2 Spike protein primerTMPRSS2was highest in ciliated cells and type I alveolar epithelial cells (AT1), andTMPRSS2expression was increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases revealed SARS-CoV-2 RNA was detected most frequently in ciliated and secretory cells in the airway epithelium and AT1 cells in the peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressingTMPRSS2.Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in the lung epithelium, and suggest that developmental regulation ofTMPRSS2may underlie the relative protection of infants and children from severe respiratory illness.
Preprinting the COVID-19 pandemic
Authors: Fraser Nicholas , Brierley Liam , Dey Gautam , Polka Jessica K , Pálfy Máté , Nanni Federico , Coates Jonathon Alexis 
Published: May 2020

AbstractThe world continues to face a life-threatening viral pandemic. The virus underlying the COVID-19 disease, SARS-CoV-2, has caused over 98 million confirmed cases and 2.2 million deaths since January 2020. Although the most recent respiratory viral pandemic swept the globe only a decade ago, the way science operates and responds to current events has experienced a paradigm shift in the interim. The scientific community has responded rapidly to the COVID-19 pandemic, releasing over 125,000 COVID-19 related scientific articles within 10 months of the first confirmed case, of which more than 30,000 were hosted by preprint servers. We focused our analysis on bioRxiv and medRxiv, two growing preprint servers for biomedical research, investigating the attributes of COVID-19 preprints, their access and usage rates, as well as characteristics of their propagation on online platforms. Our data provides evidence for increased scientific and public engagement with preprints related to COVID-19 (COVID-19 preprints are accessed more, cited more, and shared more on various online platforms than non-COVID-19 preprints), as well as changes in the use of preprints by journalists and policymakers. We also find evidence for changes in preprinting and publishing behaviour: COVID-19 preprints are shorter and reviewed faster. Our results highlight the unprecedented role of preprints and preprint servers in the dissemination of COVID-19 science, and the impact of the pandemic on the scientific communication landscape.
The interaction of DNA repair factors ASCC2 and ASCC3 is affected by somatic cancer mutations
Authors: Jia Junqiao , Absmeier Eva , Holton Nicole , Pietrzyk-Brzezinska Agnieszka J. , Hackert Philipp , Bohnsack Katherine E. , Bohnsack Markus T. , Wahl Markus C. 
Published: May 2020

AbstractThe ASCC3 subunit of the activating signal co-integrator complex is a dual-cassette Ski2-like nucleic acid helicase that provides single-stranded DNA for alkylation damage repair by the α-ketoglutarate-dependent dioxygenase, AlkBH3. Other ASCC components integrate ASCC3/AlkBH3 into a complex DNA repair pathway. We mapped and structurally analyzed interacting ASCC2 and ASCC3 regions. The ASCC3 fragment comprises a central helical domain and terminal, extended arms that clasp the compact ASCC2 unit. ASCC2-ASCC3 interfaces are evolutionarily highly conserved and comprise a large number of residues affected by somatic cancer mutations. We quantified contributions of protein regions to the ASCC2-ASCC3 interaction, observing that changes found in cancers lead to reduced ASCC2-ASCC3 affinity. Functional dissection of ASCC3 revealed similar organization and regulation as in the spliceosomal RNA helicase, Brr2. Our results delineate functional regions in an important DNA repair complex and suggest possible molecular disease principles.
A three-dimensional thalamocortical dataset for characterizing brain heterogeneity
Authors: Prasad Judy A. , Balwani Aishwarya H. , Johnson Erik C. , Miano Joseph D. , Sampathkumar Vandana , de Andrade Vincent , Fezzaa Kamel , Du Ming , Vescovi Rafael , Jacobsen Chris , Kording Konrad P. , Gürsoy Doga , Gray-Roncal William , Kasthuri Narayanan , Dyer Eva L. 
Published: May 2020

AbstractNeural cytoarchitecture is heterogeneous, varying both across and within brain regions. The consistent identification of regions of interest is one of the most critical aspects in examining neurocircuitry, as these structures serve as the vital landmarks with which to map brain pathways. Access to continuous, three-dimensional volumes that span multiple brain areas not only provides richer context for identifying such landmarks, but also enables a deeper probing of the microstructures within. Here, we describe a three-dimensional X-ray microtomography imaging dataset of a well-known and validated thalamocortical sample, encompassing a range of cortical and subcortical structures. In doing so, we provide the field with access to a micron-scale anatomical imaging dataset ideal for studying heterogeneity of neural structure.
Is a Ring-arranged Vascular Pattern Unique to Stems? A Three Dimensional Reconstruction ofAnaxagorea(Annonaceae) Carpel Vasculature and its Evolutionary Implications
Authors: Li Ya , Du Wei , Chen Ye , Wang Shuai , Wang Xiao-Fan 
Published: May 2020

AbstractElucidating the origin of carpel has been a challenge in botany for a long time. The Unifying Theory suggested that the carpel originate from a composite organ comprising an ovule-bearing shoot and a foliar part enclosing the shoot. A logical inference from this theory is that placenta in angiosperms should have radiosymmetrical vasculature, just like that in a young branch.Anaxagoreais the most basal genus of the primitive angiosperm family, Annonaceae. The conspicuous carpel stipe makes it an ideal material for exploring the carpel vasculature. In this study, serial sections of flower and carpel were delineated inAnaxagorea luzonensisandA. javanica, and a three-dimensional model of the carpel vasculature was reconstructed. The results show that (1) vascular bundles at both the carpel stipe and the ovule/placenta are in a radiosymmetrical pattern, (2) the amphicribral bundles would develop into ring-arranged bundle complex with the carpel maturation, (3) the ovule/placenta bundles were separated from the bundles of the carpel wall, and, (4) all the radiosymmetrical vasculature (including amphicribral bundles and ring-arranged bundle complexes) in the carpel were fed by a larger radiosymmetrical bundle system. These results suggest that the radiosymmetrical pattern of carpel vasculature are in line with the Unifying Theory.
High-throughput immunoassays for SARS-CoV-2 – considerable differences in performance when comparing three methods
Authors: Ekelund Oskar , Ekblom Kim , Somajo Sofia , Pattison-Granberg Johanna , Olsson Karl , Petersson Annika 
Published: May 2020

AbstractBackgroundThe recently launched high-throughput assays for the detection of antibodies against SARS-CoV-2 may change the managing strategies for the COVID-19 pandemic. This study aimed at investigating the performance of three high-throughput assays and one rapid lateral flow test relative to the recommended criteria defined by regulatory authorities.MethodsA total of 133 samples, including 100 pre-pandemic samples, 20 samples from SARS-CoV-2 RT-PCR positive individuals, and 13 potentially cross-reactive samples were analysed with SARS-CoV-2 IgG (Abbott), Elecsys Anti-SARS-CoV-2 (Roche), LIAISON SARS-CoV-2 S1/S2 IgG (DiaSorin) and 2019-nCOV IgG/IgM Rapid Test (Dynamiker Biotechnology Co).ResultsAll assays performed with a high level of specificity; however, only Abbott reached 100% (95% CI 96.3-100). The pre-pandemic samples analysed with Roche, DiaSorin and Dynamiker Biotechnology resulted in two to three false-positive results per method (specificity 96.9-98.0%). Sensitivity differed more between the assays, Roche exhibiting the highest sensitivity (100%, CI 83.9-100). The corresponding figures for Abbott, DiaSorin and Dynamiker Biotechnology were 85.0%, 77.8% and 75.0%, respectively.ConclusionsThe results of the evaluated SARS-CoV-2 assays vary considerably as well as their ability to fulfil the performance criteria proposed by regulatory authorities. Introduction into clinical use in low-prevalent settings, should therefore, be made with caution.
Knowledge, attitude, and practices of Community pharmacists about COVID-19: A cross-sectional survey in two provinces of Pakistan
Authors: Muhammad Khayal , Saqlain Muhammad , Hamdard Ataullah , Naveed Muhammad , Umer Muhammad Farooq , Khan Siraj , Kamran Muhammad , Rashid Haroon , Kamran Sohail , Khan Muhammad Ijaz , Khan Faiz Ullah , Hussain Yaseen , Khan Zakir 
Published: May 2020

AbstractAmidst to current Coronavirus infectious disease 2019 (COVID-19) pandemic, the international pharmaceutical federation stated that pharmacists being a part of the healthcare system had a crucial role in the management cycle of COVID-19 outbreak. The purpose of this study was to assess the knowledge, attitude and practice of community pharmacists, to snapshot their current preparedness and awareness regarding COVID-19. An online survey was conducted among a sample of 393 community pharmacists from two provinces; Punjab and Khyber-Pakhtunkhwa, Pakistan during a period of strict lockdown (10th to 30th April 2020). A validated (Cronbach alpha= 0.077) self-administered questionnaire comprised of five sections (Demographics, source of information, knowledge, attitude, and practice) was used for data collection. Logistic regression was applied to find potential factors associated with good knowledge, attitude, and practice by using SPSS version 21. Of total 393 participants, 71.5% (n=281) had good knowledge, 44% (n=175) had positive attitude and 57.3% (n=225) had good practice regarding COVID-19. Social media (45.29%, n=178) was reported as the main source to seek information regarding COVID-19. Results revealed that the age of ≥26 years, Ph.D. degree level, and good knowledge were the substantial determinants (P<0.05) of a good attitude. Similarly, community pharmacist who had an experience of >5 years, hold a Ph.D. degree, good knowledge and good attitude had higher odds of good practice compared to reference categories (P<0.05). The findings demonstrated that the majority of community pharmacists had good knowledge, but had a poor attitude and practice towards the COVID-19. This study also highlighted the disparity in some aspects of knowledge, attitude, and practice that must be addressed in future educational, awareness, and counselling programs.
A Noncooperative Game Analysis for Controlling COVID-19 Outbreak
Authors: Bairagi Anupam Kumar , Masud Mehedi , Kim Do Hyeon , Munir Md. Shirajum , Al Nahid Abdullah , Abedin Sarder Fakhrul , Alam Kazi Masudul , Biswas Sujit , Alshamrani Sultan S , Han Zhu , Hong Choong Seon 
Published: May 2020

AbstractCOVID-19is a global epidemic. Till now, there is no remedy for this epidemic. However, isolation and social distancing are seemed to be effective to control this pandemic. In this paper, we provide an analytical model on the effectiveness of the sustainable lockdown policy that accommodates both isolation and social distancing features of the individuals. To promote social distancing, we analyze a noncooperative game environment that provides an incentive for maintaining social distancing. Furthermore, the sustainability of the lockdown policy is also interpreted with the help of a game-theoretic incentive model for maintaining social distancing. Finally, an extensive numerical analysis is provided to study the impact of maintaining a social-distancing measure to prevent the Covid-19 outbreak. Numerical results show that the individual incentive increases more than 85% with an increasing percentage of home isolation from 25% to 100% for all considered scenarios. The numerical results also demonstrate that in a particular percentage of home isolation, the individual incentive decreases with an increasing number of individuals.
Lung epithelial stem cells express SARS-CoV-2 entry factors: implications for COVID-19
Authors: Valyaeva Anna A. , Zharikova Anastasia A. , Kasianov Artem S. , Vassetzky Yegor S. , Sheval Eugene V. 
Published: May 2020

AbstractSARS-CoV-2 can infiltrate the lower respiratory tract, resulting in severe respiratory failure and a high death rate. Normally, the airway and alveolar epithelium can be rapidly reconstituted by multipotent stem cells after episodes of infection. Here, we analyzed published RNA-seq datasets and demonstrated that cells of four different lung epithelial stem cell types express SARS-CoV-2 entry factors, includingAce2. Thus, stem cells can be potentially infected by SARS-CoV-2, which may lead to defects in regeneration capacity partially accounting for the severity of SARS-CoV-2 infection and its consequences.