bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of paralogs in target enrichment data pinpoints multiple ancient polyploidy events inAlchemillas.l. (Rosaceae)
Authors: Morales-Briones Diego F. , Gehrke Berit , Huang Chien-Hsun , Liston Aaron , Ma Hong , Marx Hannah E. , Tank David C. , Yang Ya 
Published: August 2020

AbstractTarget enrichment is becoming increasingly popular for phylogenomic studies. Although baits for enrichment are typically designed to target single-copy genes, paralogs are often recovered with increased sequencing depth, sometimes from a significant proportion of loci, especially in groups experiencing whole-genome duplication (WGD) events. Common approaches for processing paralogs in target enrichment datasets include random selection, manual pruning, and mainly, the removal of entire genes that show any evidence of paralogy. These approaches are prone to errors in orthology inference or removing large numbers of genes. By removing entire genes, valuable information that could be used to detect and place WGD events is discarded. Here we use an automated approach for orthology inference in a target enrichment dataset of 68 species ofAlchemillas.l. (Rosaceae), a widely distributed clade of plants primarily from temperate climate regions. Previous molecular phylogenetic studies and chromosome numbers both suggested ancient WGDs in the group. However, both the phylogenetic location and putative parental lineages of these WGD events remain unknown. By taking paralogs into consideration, we identified four nodes in the backbone ofAlchemillas.l. with an elevated proportion of gene duplication. Furthermore, using a gene-tree reconciliation approach we established the autopolyploid origin of the entireAlchemillas.l. and the nested allopolyploid origin of four major clades within the group. Here we showed the utility of automated tree-based orthology inference methods, previously designed for genomic or transcriptomic datasets, to study complex scenarios of polyploidy and reticulate evolution from target enrichment datasets.
BayesFactorFMRI: Implementing Bayesian second-level fMRI analysis with multiple comparison correction and Bayesian meta-analysis of fMRI images with multiprocessing
Authors: Han Hyemin 
Published: August 2020

AbstractBayesFactorFMRI is a tool developed with R and Python to allow neuroimaging researchers to conduct Bayesian second-level analysis and Bayesian meta-analysis of fMRI image data with multiprocessing. This tool expedites computationally intensive Bayesian fMRI analysis through multiprocessing. Its GUI allows researchers who are not experts in computer programming to feasibly perform Bayesian fMRI analysis. BayesFactorFMRI is available via Zenodo and GitHub for download. It would be widely reused by neuroimaging researchers who intend to analyse their fMRI data with Bayesian analysis with better sensitivity compared with classical analysis while improving performance by distributing analysis tasks into multiple processors.
The N34S mutation of SPINK1 may impact the kinetics of trypsinogen activation to cause early trypsin release in the pancreas
Authors: Sun Zhuyezi , Kolossváry István , Kozakov Dima , Sahin-Tóth Miklós , Vajda Sandor 
Published: August 2020

ABSTRACTThe N34S variant of the trypsin inhibitor SPINK1 is the clinically most significant risk factor for chronic pancreatitis, but the underlying molecular mechanism could not be identified. Molecular dynamics simulations and docking of the generated conformational ensemble of SPINK1 to trypsin show that the mutation reduces the fraction of conformations that can directly participate in productive association, thereby reducing the association rate. The small change is difficult to detect by measuring the kinetics of SPINK1 binding to trypsin. However, kinetic modeling reveals that even a small change in the inhibition rate affects the trypsinogen to trypsin conversion rate at the early stage of the reaction when the trypsin concentration is very low, and the impact is substantially amplified by the autocatalytic mechanism of the conversion. Thus, the slightly reduced inhibition rate shortens the delay in the activation of trypsin release, which is therefore occurs within the pancreas.
Epigenetic compound screening uncovers small molecules for re-activation of latent HIV-1
Authors: Zutz Ariane , Chen Lin , Sippl Franziska , Schölz Christian 
Published: August 2020

AbstractDuring infection with the human immunodeficiency virus type 1 (HIV-1), latent reservoirs are established, which circumvent full eradication of the virus by antiretroviral therapy (ART) and are the source for viral rebound after cessation of therapy. As these reservoirs are phenotypically undistinguishable from infected cells, current strategies aim to reactivate these reservoirs, followed by pharmaceutical and immunological destruction of the cells.Here, we employed a simple and convenient cell-based reporter system, which enables sample handling under biosafety level (BSL)-1 conditions, to screen for compounds that were able to reactivate latent HIV-1. The assay showed a high dynamic signal range and reproducibility with an average Z-factor of 0.77, classifying the system as robust. The assay was used for high-throughput screening (HTS) of an epigenetic compound library in combination with titration and cell-toxicity studies and revealed several potential new latency reversing agents (LRAs). Further validation in well-known latency model systems verified earlier studies and identified two novel compounds with very high reactivation efficiency and low toxicity. Both drugs, namely N-hydroxy-4-(2-[(2-hydroxyethyl)(phenyl)amino]-2-oxoethyl)benzamide (HPOB) and 2',3'-difluoro-[1,1'-biphenyl]-4-carboxylic acid, 2-butylhydrazide (SR-4370), showed comparable performances to other already known LRAs, did not activate CD4+T-cells or caused changes in the composition of PBMCs as shown by flow cytometry analyses.Both compounds may represent an effective new treatment possibility for revocation of latency in HIV-1 infected individuals.
Potent anti-SARS-CoV-2 Antibody Responses are Associated with Better Prognosis in Hospital Inpatient COVID-19 Disease
Authors: Tighe Patrick J. , Urbanowicz Richard A. , Fairclough C. Lucy , McClure C. Patrick , Thomson Brian J. , Gomez Nancy , Chappell Joseph G. , Tsoleridis Theocharis , Loose Matthew , Carlile Matthew , Moore Christopher , Holmes Nadine , Sang Fei , Hrushikesh Divyateja , Clark Gemma , Temperton Nigel , Brooks Tim , Ball Jonathan K. , Irving William L. , Tarr Alexander W. 
Published: August 2020

AbstractCOVID-19 continues to cause a pandemic, having infected more than 20 million people globally. Successful elimination of the SARS-CoV-2 virus will require an effective vaccine. However, the immune correlates of infection are currently poorly understood. While neutralizing antibodies are believed to be essential for protection against infection, the contribution of the neutralizing antibody response to resolution of SARS-CoV-2 infection has not yet been defined. In this study the antibody responses to the SARS-CoV-2 spike protein and nucleocapsid proteins were investigated in a UK patient cohort, using optimised immunoassays and a retrovirus-based pseudotype entry assay. It was discovered that in severe COVID-19 infections an early antibody response to both antigens was associated with improved prognosis of infection. While not all SARS-CoV-2-reactive sera were found to possess neutralizing antibodies, neutralizing potency of sera was found to be greater in patients who went on to resolve infection, compared with those that died from COVID-19. Furthermore, viral genetic variation in spike protein was found to influence the production of neutralizing antibodies. Infection with the recently described spike protein variant 614G produced higher levels of neutralizing antibodies when compared to viruses possessing the 614D variant. These findings support the assertion that vaccines targeting generation of neutralizing antibodies may be useful at limiting SARS-CoV-2 infection. Assessment of the antibody responses to SARS-CoV-2 at time of diagnosis will be a useful addition to the diagnostic toolkit, enabling stratification of clinical intervention for severe COVID-19 disease.
A Single Chromosome Strain ofS. cerevisiaeExhibits Diminished Ethanol Metabolism and Tolerance
Authors: Doughty Tyler W. , Yu Rosemary , Chao Lucy Fang-I , Qin Zhongjun , Siewers Verena , Nielsen Jens 
Published: August 2020

AbstractThis study characterized the growth, metabolism, and transcriptional profile of aS. cerevisiaestrain with a single large chromosome that was constructed via successive chromosomal fusions. The single chromosome strain exhibited a longer lag phase, increased doubling time, and lower final biomass concentration compared with a wildtype strain when grown on YPD. These phenotypes were amplified when ethanol was added to the medium or used as the sole carbon source. RNAseq analysis showed diminished induction of genes involved in diauxic shift, ethanol metabolism, fatty-acid ß-oxidation, and methylglyoxal catabolism during growth on ethanol compared to the reference strain. Enzyme-constrained metabolic modeling predicted that decreased flux through these poorly induced enzymes results in diminished ATP formation and decreased biomass accumulation observed. Together, these observations suggest that switch-like control of carbon source dependent gene expression inS. cerevisiaerequires genome arrangement into multiple chromosomes.
Comprehensive genome sequencing analysis as a promising option in the prenatal diagnosis of fetal structural anomalies: a prospective study
Authors: Zhou Jia , Yang Ziying , Sun Jun , Liu Lipei , Zhou Xinyao , Liu Fengxia , Xing Ya , Cui Shuge , Xiong Shiyi , Liu Xiaoyu , Yang Yingjun , Wei Xiuxiu , Zou Gang , Wang Zhonghua , Wei Xing , Wang Yaoshen , Zhang Yun , Yan Saiying , Wu Fengyu , Zeng Fanwei , Duan Tao , Wang Jian , Yang Yaping , Peng Zhiyu , Sun Luming 
Published: August 2020

ABSTRACTPurposeGenome sequencing (GS) is a powerful tool for postnatal genetic diagnosis, but relevant clinical studies in the field of prenatal diagnosis are few. We aimed to evaluate the feasibility of GS as a first-line approach in prenatal diagnosis and compare its clinical value with the chromosomal microarray analysis (CMA) plus exome sequencing (ES) sequential testing.MethodsWe applied trio GS (∼40-fold) in parallel with CMA plus ES to investigate the genetic basis for structural or growth anomalies in 111 fetuses and compared their results.ResultsGS covered all genetic variants in 22 diagnosed cases detected by CMA plus ES, yielding a diagnostic rate of 19.8% (22/110). Moreover, GS provided more comprehensive and precise genetic information than CMA plus ES, revealing twin fetuses with an imbalanced translocation arising from a balanced paternal translocation and one fetus with an extra pathogenic variant in theGJA8gene, and incidentally identified intrauterine CMV infection in a growth-restricted fetus.ConclusionCompared with CMA plus ES, GS offers a more comprehensive view of the genetic etiology of fetal anomalies and provides clues for nongenetic factors such as intrauterine infection. Our study demonstrates the feasibility of GS as a promising first-line test in prenatal diagnosis.
Jaw Kinematics and Tongue Protraction-Retraction during Chewing and Drinking in the Pig
Authors: Olson Rachel A. , Montuelle Stéphane J. , Chadwell Brad A. , Curtis Hannah , Williams Susan H. 
Published: August 2020

ABSTRACTMastication and drinking are rhythmic and cyclic oral behaviors that require interactions between the tongue, jaw, and a food or liquid bolus, respectively. During mastication, the tongue transports and positions the bolus for breakdown between the teeth. During drinking, the tongue aids in ingestion and then transports the bolus to the oropharynx. The objective of this study is to compare jaw and tongue kinematics during chewing and drinking in pigs. We hypothesize there will be differences in jaw gape cycle dynamics and tongue protraction-retraction between behaviors. Mastication cycles had an extended slow-close phase, reflecting tooth-food-tooth contact, whereas drinking cycles had an extended slow-open phase, corresponding to tongue protrusion into the liquid. Drinking jaw movements were of lower magnitude for all degrees of freedom examined (jaw protraction, yaw, and pitch), and were bilaterally symmetrical with virtually no yaw. The magnitude of tongue protraction-retraction (Tx) was greater during mastication than drinking, but there were minimal differences in the timing of maximum and minimum tongue Tx relative to the jaw gape cycle between behaviors. However, during drinking, the tongue tip is often located outside the oral cavity for the entire cycle, leading to differences in behaviors in the timing of anterior marker maximum tongue Tx. This demonstrates that there is variation in tongue-jaw coordination between behaviors. These results show that jaw and tongue movements vary significantly between mastication and drinking, which hint at differences in the central control of these behaviors.Summary statementDifferences in the magnitude and timing of tongue and jaw movements and the anteroposterior positioning of the tongue during chewing and drinking demonstrate key differences in coordination of these behaviors.
Mutanofactin promotes bacterial adhesion and biofilm formation of cariogenicStreptococcus mutans
Authors: Li Zhong-Rui , Du Yongle , Sun Jin , Pan Aifei , Zeng Lin , Maboudian Roya , Burne Robert A. , Qian Pei-Yuan , Zhang Wenjun 
Published: August 2020

AbstractCariogenicStreptococcus mutansis known as a predominant etiological agent of dental caries due to its exceptional capacity in forming biofilms. From strains ofS. mutansisolated from dental plaque, we here discover a polyketide/non-ribosomal peptide biosynthetic gene cluster,muf, which directly correlates with a strong biofilm-forming capability. We then identify themuf-associated bioactive product, mutanofactin-697 that contains a novel molecular scaffold, along with its biosynthetic logic. Further mode-of-action studies reveal mutanofactin-697 binds toS. mutanscells nonspecifically, increases bacterial hydrophobicity, and promotes bacterial adhesion and subsequent biofilm formation. Our findings provide the first example of a microbial secondary metabolite promoting biofilm formation via a physicochemical approach, highlighting the significance of secondary metabolism in mediating critical processes related to the development of dental caries.
Deciphering the mechanical code of genome and epigenome
Authors: Basu Aakash , Bobrovnikov Dmitriy G. , Cieza Basilio , Qureshi Zan , Ha Taekjip 
Published: August 2020

AbstractSequence features have long been known to influence the local mechanical properties and shapes of DNA. However, a mechanical code (i.e. a comprehensive mapping between DNA sequence and mechanical properties), if it exists, has been difficult to experimentally determine because direct means of measuring the mechanical properties of DNA are typically limited in throughput. Here we use Loop-seq – a recently developed technique to measure the intrinsic cyclizabilities (a proxy for bendability) of DNA fragments in genomic-scale throughput – to characterize the mechanical code. We tabulate how DNA sequence features (distribution patterns of all possible dinucleotides and dinucleotide pairs) influence intrinsic cyclizability, and build a linear model to predict intrinsic cyclizability from sequence. Using our model, we predict that DNA mechanical landscape shapes nucleosome organization around the promoters of various organisms and at the binding site of the transcription factor CTCF, and that hyperperiodic DNA inC. elegansleads to globally curved DNA segments. By performing loop-seq on random libraries in the presence or absence of CpG methylation, we show that CpG methylation leads to global stiffening of DNA in a wide sequence context, and predict based on our model that CpG methylation widely changes the mechanical landscape around mouse promoters. It suggests how epigenetic modifications of DNA might alter gene expression and mediate cellular adaptation by affecting critical processes around promoters that require mechanical deformations of DNA, such as nucleosome organization and transcription initiation. Finally, we show that the genetic code and the mechanical code are linked: sequence-dependent mechanical properties of coding DNA constrains the amino acid sequence despite the degeneracy in the genetic code. Our measurements explain why the pattern of nucleosome organization along genes influences the distribution of amino acids in the translated polypeptide.
Light-emitting diode-based transcranial photoacoustic measurement of sagittal sinus oxyhemoglobin saturation in hypoxic neonatal piglets
Authors: Kang Jeeun , Koehler Raymond C. , Adams Shawn , Graham Ernest M. , Boctor Emad M. 
Published: August 2020

AbstractWe present a light-emitting diode (LED)-based transcranial photoacoustic measurement (LED-trPA) of oxyhemoglobin (HbO2) saturation at superior sagittal sinus (SSS) in hypoxic neonatal piglets. The optimal LED imaging wavelengths and frame averaging scheme were determined based onin vivocharacterization of transcranial sensitivity. Based on the framework (690/850 nm with >20 frame averaging), graded hypoxia was successfully identified in neonatal pigletsin vivowith less than 10.0 % of root mean squared error (RMSE). This preclinical study suggests the feasibility of a rapid, cost-effective, and safe LED-trPA monitoring of perinatal hypoxia-ischemia and prompt interventions for clinical use.
Climate change risk to southern African wild food plants
Authors: Wessels Carina , Merow Cory , Trisos Christopher H. 
Published: August 2020

AbstractClimate change is a threat to food security. Wild-harvested food plants (WFPs) are important for the diets of millions of people and contribute to food security, especially in rural and low-income communities, but little is known about climate change risk to these species. Using species distribution models, we examined climate change risk to 1190 WFP species used by 19 native language groups in southern Africa. We project that 40% of species will experience a decrease in range extent within southern Africa by 2060–2080 under a low warming scenario (Representative Concentration Pathway (RCP) 2.6), increasing to 66% under a high warming scenario (RCP 8.5). Decreases in geographic range are projected for >70% of WFP species traditionally used by some language groups. Loss of suitable climatic conditions is projected to decrease WFP species richness most in north-eastern southern Africa – with losses of >200 species – while increases in species richness are projected in the south and east of South Africa. Availability of WFP species for food security during lean times is also projected to change. Specifically, in south-eastern South Africa, local diversity of WFPs is projected to increase, while maize and sorghum yields decrease. However, this potential WFP nutritional safety net may be lost in central parts of the region, where declines in both crop yield and WFPs are projected. By looking beyond conventional crops to the exceptional diversity of WFPs, this research makes a first step towards understanding the linkages between WFPs, traditional knowledge, agriculture, food security, and climate change.
Cytochromeb6fcomplex inhibition by antimycin-A requires Stt7 kinase activation but not PGR5
Authors: Buchert Felix , Hippler Michael 
Published: August 2020

AbstractFerredoxin-plastoquinone reductase (FQR) activity during cyclic electron flow (CEF) was first ascribed to the cytochromeb6fcomplex (b6f). However, this was later dismissed sinceb6finhibition by antimycin-A (AA) could not be reproduced. AA presumably fails to ligate with haembh, at variance with cytochromebc1complex, owing to a specific Qi-site occupation inb6f. Currently, PROTON GRADIENT REGULATION5 (PGR5) and the associated PGR5-Like1 are considered as FQR in the AA-sensitive CEF pathway. Here, we show that theb6fis conditionally inhibited by AA in a PGR5-independent manner when CEF is promoted. AA inhibition, demonstrated by singleb6fturnover and electron transfer measurements, coincided with an altered Qi-site function which required Stt7 kinase activation by a strongly reduced plastoquinone pool. Thus, PGR5 and Stt7 were necessary forb6factivity and AA-sensitive electron transfer in CEF-favouring conditions. Extending previous findings, a new FQR activity model of theb6fis discussed.
Base pairing and stacking contributions to double stranded DNA formation
Authors: Zacharias Martin 
Published: August 2020

AbstractDouble-strand (ds)DNA formation and dissociation are of fundamental biological importance. The negatively DNA charge influences the dsDNA stability. However, the base pairing and the stacking between neighboring bases are responsible for the sequence dependent stability of dsDNA. The stability of a dsDNA molecule can be estimated from empirical nearest-neighbor models based on contributions assigned to base pair steps along the DNA and additional parameters due to DNA termini. In efforts to separate contributions it has been concluded that base-stacking dominates dsDNA stability whereas base-pairing contributes negligibly. Using a different model for dsDNA formation we re-analyze dsDNA stability contributions and conclude that base stacking contributes already at the level of separate ssDNAs but that pairing contributions drive the dsDNA formation. The theoretical model also predicts that stability contributions of base pair steps that contain only guanine/cytosine, mixed steps and steps with only adenine/thymine follows the order 6:5:4, respectively, as expected based on the formed hydrogen bonds. The model is fully consistent with available stacking data and nearest-neighbor dsDNA parameters. It allows to assign a narrowly distributed value for the effective free energy contribution per formed hydrogen bond during dsDNA formation of −0.72 kcal·mol-1based entirely on experimental data.
Emap2sec+: Detecting Protein and DNA/RNA Structures in Cryo-EM Maps of Intermediate Resolution Using Deep Learning
Authors: Wang Xiao , Alnabati Eman , Aderinwale Tunde W. , Venkata Subramaniya Sai Raghavendra Maddhuri , Terashi Genki , Kihara Daisuke 
Published: August 2020

AbstractAn increasing number of density maps of macromolecular structures, including proteins and protein and DNA/RNA complexes, have been determined by cryo-electron microscopy (cryo-EM). Although lately maps at a near-atomic resolution are routinely reported, there are still substantial fractions of maps determined at intermediate or low resolutions, where extracting structure information is not trivial. Here, we report a new computational method, Emap2sec+, which identifies DNA or RNA as well as the secondary structures of proteins in cryo-EM maps of 5 to 10 Å resolution. Emap2sec+ employs the deep Residual convolutional neural network. Emap2sec+ assigns structural labels with associated probabilities at each voxel in a cryo-EM map, which will help structure modeling in an EM map. Emap2sec+ showed stable and high assignment accuracy for nucleotides in low resolution maps and improved performance for protein secondary structure assignments than its earlier version when tested on simulated and experimental maps.