bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the relationship between cognitive empathy, age, and face perception using a sequential Bayesian analysis
Authors: Kist J.D. , Bethlehem R.A.I. , Stonier Barnaby , Sluijters Olivier , Crockford S. K. , de Jonge Elke , Freyberg Jan , Baron-Cohen Simon , Parsons O. E. 
Published: September 2020

AbstractThe ability to correctly identify emotions in social stimuli such as faces is proposed to affect one’s level of cognitive empathy. The Fusiform Face Area shows a heightened neural response during the perception of faces relative to objects. We tested whether neural responses to social stimuli were associated with performance in a measure of cognitive empathy, the ‘Reading the Mind in the Eyes’ Task. To quantify face perception, participants were presented with images during a fast serial presentation task which elicited a steady state visual evoked potential, measured using electroencephalography. A Sequential Bayesian Analysis was used to assess if face specific neural responses were associated with either cognitive empathy or age. Data were collected from a participant group of both neurotypical individuals and individuals on the autistic spectrum. We found no significant relationship between the face-specific neural signature, cognitive empathy or age. This study highlights the efficiency of the Sequential Bayesian Analysis as an effective method of participant recruitment.
An extended catalogue of tandem alternative splice sites in human tissue transcriptomes
Authors: Mironov Aleksei , Denisov Stepan , Gress Alexander , Kalinina Olga V. , Pervouchine Dmitri D. 
Published: September 2020

AbstractTandem alternative splice sites (TASS) is a special class of alternative splicing events that are characterized by a close tandem arrangement of splice sites. Most TASS lack functional characterization and are believed to arise from splicing noise. Based on the RNA-seq data from the Genotype Tissue Expression project, we present an extended catalogue of TASS in healthy human tissues and analyze their tissue-specific expression. The expression of TASS is usually dominated by one major splice site (maSS), while the expression of minor splice sites (miSS) is at least an order of magnitude lower. Among 73k miSS with sufficient read support, 12k (17%) are significantly expressed above the expected noise level, and among them 2k are expressed tissue-specifically. We found significant correlations between tissue-specific expression of RNA-binding proteins (RBP) and tissue-specific expression of miSS that is consistent with miSS response to RBP inactivation by shRNA. In combination with RBP profiling by eCLIP, this allowed prediction of novel cases of tissue-specific splicing regulation including a miSS in QKI mRNA that is likely regulated by PTBP1. According to the structural annotation of the human proteome, tissue-specific miSS are enriched within disordered regions, and indels induced by miSS are enriched with short linear motifs and post-translational modification sites. Nonetheless, more than 15% of tissue-specific miSS affect structured protein regions and may adjust protein-protein interactions or modify the stability of the protein core. The significantly expressed miSS evolve under the same selection pressure as maSS, while other miSS lack signatures of evolutionary selection and conservation. Using mixture models, we estimated that not more than 10% of maSS and not more than 50% of significantly expressed miSS are noisy, while the proportion of noisy splice sites among not significantly expressed miSS is above 70%.
Microbiome-based environmental monitoring of a dairy processing facility highlights the challenges associated with low microbial-load samples
Authors: McHugh Aoife J. , Yap Min , Crispie Fiona , Feehily Conor , Hill Colin , Cotter Paul D. 
Published: September 2020

AbstractFood processing environments can harbor microorganisms responsible for food spoilage or foodborne disease. Efficient and accurate identification of microorganisms throughout the food chain can allow the identification of sources of contamination and the timely implementation of control measures. Currently, microbial monitoring of the food chain relies heavily on culture-based techniques. These assays are determined on the microbes expected to be present in the environment, and thus do not cater for unexpected contaminants. Many culture-based assays are also unable to distinguish between undesirable taxa and closely related harmless species. Furthermore, even when multiple culture-based approaches are used in parallel, it is still not possible to comprehensively characterize the entire microbiology of a food-chain sample.High throughput DNA sequencing represents a potential means through which microbial monitoring of the food chain can be enhanced. While sequencing platforms, such as the Illumina MiSeq, NextSeq and NovaSeq, are most typically found in research or commercial sequencing laboratories, newer portable platforms, such as the Oxford Nanopore Technologies (ONT) MinION, offer the potential for rapid analysis of food chain microbiomes. In this study, having initially assessed the ability of rapid MinION-based sequencing to discriminate between different microbes within a simple mock metagenomic mixture of related food spoilage, spore-forming microorganisms. Subsequently, we proceeded to compare the performance of both ONT and Illumina sequencing for environmental monitoring of an active food processing facility.Overall, ONT MinION sequencing provided accurate classification to species level, which was comparable to Illumina-derived outputs. However, while the MinION-based approach provided a means of easy library preparations and portability, the high concentrations of DNA needed to run the rapid sequencing protocols was a limiting factor, requiring the random amplification of template DNA in order to generate sufficient material for analysis.
Human IFITM3 restricts Chikungunya virus and Mayaro virus infection and is susceptible to virus-mediated counteraction
Authors: Franz Sergej , Zillinger Thomas , Pott Fabian , Schüler Christiane , Dapa Sandra , Fischer Carlo , Passos Vânia , Stenzel Saskia , Chen Fangfang , Döhner Katinka , Hartmann Gunther , Sodeik Beate , Pessler Frank , Simmons Graham , Drexler Jan Felix , Goffinet Christine 
Published: September 2020

AbstractInterferon-induced transmembrane (IFITM) proteins restrict infection by enveloped viruses through interfering with membrane fusion and virion internalisation. The role of IFITM proteins during alphaviral infection of human cells and viral counteraction strategies remain largely unexplored. Here, we characterized the impact of IFITM proteins and variants on entry and spread of Chikungunya virus (CHIKV) and Mayaro virus (MAYV) in human cells, and provide first evidence for a CHIKV-mediated antagonism of IFITM proteins. IFITM1, 2 and 3 restricted infection at the level of alphavirus glycoprotein-mediated entry, both in the context of direct infection and during cell-to-cell transmission. Relocalization of normally endosomal IFITM3 to the plasma membrane resulted in the loss of its antiviral activity. rs12252-C, a naturally occurring variant ofIFITM3that has been proposed to associate with severe influenza in humans, restricted CHIKV, MAYV and influenza A virus infection as efficiently as wild-typeIFITM3. Finally, all antivirally active IFITM variants displayed reduced cell surface levels in CHIKV-infected cells involving a posttranscriptional process mediated by one or several non-structural protein(s) of CHIKV.
Detection of sexually antagonistic transmission distortions in trio datasets
Authors: Lucotte Elise A. , Albiñana Clara , Laurent Romain , Bhérer Claude ,   Genome of the Netherland Consortium, Bataillon Thomas , Toupance Bruno 
Published: September 2020

ABSTRACTSex dimorphisms are widespread in animals and plants, for morphological as well as physiological traits. Understanding the genetic basis of sex dimorphism and its evolution is crucial for understanding biological differences between the sexes. Genetic variants with sex-antagonistic effects on fitness are expected to segregate in populations at the early phases of sexual dimorphism emergence. Detecting such variants is notoriously difficult, and the few genome-scan methods employed so far have limited power and little specificity. Here, we propose a new framework to detect a signature of sexually antagonistic selection. We rely on trio datasets where sex-biased transmission distortions can be directly tracked from parents to offspring, and allows identifying signal of sexually antagonistic transmission distortions in genomic regions. We report the genomic location and recombination pattern surrounding 66 regions detected as potentially under sexually antagonist selection. We find an enrichment of genes associated with embryonic development within these regions. Last, we highlight two candidates regions for sexually antagonistic selection in humans.
Acquisition of Host Cytosolic Protein byToxoplasma gondiiBradyzoites
Authors: Kannan Geetha , Thaprawat Pariyamon , Schultz Tracey L. , Carruthers Vern B. 
Published: September 2020

ABSTRACTToxoplasma gondiiis a protozoan parasite that persists in the central nervous system as intracellular chronic stage bradyzoites that are encapsulated by a thick cyst wall. While the cyst wall separates bradyzoites from the host cytosol, it has been posited that small solutes can traverse the cyst wall to sustain bradyzoites. Recently it was found that host cytosolic macromolecules can cross the parasitophorous vacuole and are ingested and digested by actively replicating acute stage tachyzoites. However, the extent to which bradyzoites have an active ingestion pathway remained unknown. To interrogate this, we modified previously published protocols that look at tachyzoite acquisition and digestion of host proteins by measuring parasite accumulation of a host-expressed reporter protein after impairment of an endolysosomal protease (Cathepsin Protease L, CPL). Using two cystogenic parasite strains (ME49 and Pru), we demonstrate thatT. gondiibradyzoites can ingest host-derived cytosolic mCherry. Bradyzoites acquire host mCherry within 4 hours of invasion and post-cyst wall formation. This study provides direct evidence that host macromolecules can be internalized byT. gondiibradyzoites across the cyst wall in infected cells.
Refinement of a Cryo-EM Structure of hERG: Bridging Structure and Function
Authors: Khan H.M. , Guo J. , Duff H.J. , Tieleman D. P. , Noskov S. Y. 
Published: September 2020

AbstractThe humanether-a-go-go-related gene (hERG) encodes the voltage gated potassium channel (KCNH2 or Kv11.1, commonly known as hERG). This channel plays a pivotal role in the stability of phase 3 repolarization of the cardiac action potential. Although a high-resolution cryo-EM structure is available for its depolarized (open) state, the structure surprisingly did not feature many functionally important interactions established by previous biochemical and electrophysiology experiments. Using Molecular Dynamics Flexible Fitting (MDFF), we refined the structure and recovered the missing functionally relevant salt bridges in hERG in its depolarized state. We also performed electrophysiology experiments to confirm the functional relevance of a novel salt bridge predicted by our refinement protocol. Our work shows how refinement of a high-resolution cryo-EM structure helps to bridge the existing gap between the structure and function in the voltage-sensing domain (VSD) of hERG.Statement of SignificanceCryo-EM has emerged as a major breakthrough technique in structural biology of membrane proteins. However, even high-resolution Cryo-EM structures contain poor side chain conformations and interatomic clashes. A high-resolution cryo-EM structure of hERG1 has been solved in the depolarized (open) state. The state captured by Cryo-EM surprisingly did not feature many functionally important interactions established by previous experiments. Molecular Dynamics Flexible Fitting (MDFF) used to enable refinement of the hERG1 channel structure in complex membrane environment re-establishing key functional interactions in the voltage sensing domain.
Effects of underlying gene-regulation network structure on prediction accuracy in high-dimensional regression
Authors: Okinaga Yuichi , Kyogoku Daisuke , Kondo Satoshi , Nagano Atsushi J. , Hirose Kei 
Published: September 2020

AbstractMotivationThe least absolute shrinkage and selection operator (lasso) and principal component regression (PCR) are popular methods of estimating traits from high-dimensional omics data, such as transcriptomes. The prediction accuracy of these estimation methods is highly dependent on the covariance structure, which is characterized by gene regulation networks. However, the manner in which the structure of a gene regulation network together with the sample size affects prediction accuracy has not yet been sufficiently investigated. In this study, Monte Carlo simulations are conducted to investigate the prediction accuracy for several network structures under various sample sizes.ResultsWhen the gene regulation network was random graph, the simulation indicated that models with high estimation accuracy could be achieved with small sample sizes. However, a real gene regulation network is likely to exhibit a scale-free structure. In such cases, the simulation indicated that a relatively large number of observations is required to accurately predict traits from a transcriptome.Availability and implementationSource code athttps://github.com/keihirose/simrnetContacthirose@imi.kyushu-u.ac.jp
Mild reductions in guard cellsucrose synthase2 expression leads to slower stomatal opening and decreased whole plant transpiration in tobacco
Authors: Freire Francisco Bruno S. , Bastos Ricardo L. G. , Bret Raissa S. C. , Cândido-Sobrinho Silvio A. , Medeiros David B. , Antunes Werner C. , Fernie Alisdair R. , Daloso Danilo M. 
Published: September 2020

AbstractThe understanding of the dynamics of stomatal movements has increased substantially through genetic manipulation of plant metabolism either at the whole plant level or specifically in guard cells. However, the regulation of stomatal speediness remains not completely elucidated. Here we shown that reduced expression of guard cell sucrose synthase 2(NtSUS2) ofNicotiana tabacumL. altered the topology and the connectivity of the guard cell metabolic network and the accumulation of metabolites positively correlated with stomatal speediness during dark-to-light transition. This leads to a slower light-induced stomatal opening, lower steady-state stomatal conductance and a strong reduction (up to 44%) in daily whole plant transpiration in the transgenics, when compared to wild type plants. Furthermore, the transgenic lines transpired more or have lower reduction in whole plant transpiration under short water deficit periods, indicating a higher effective use of water under this condition. Our results collectively suggest that the regulation of stomatal movement and speediness involve a complex modulation of the guard cell metabolic network, in whichNtSUS2has an important role. The results are discussed on the role of guard cell metabolism for the regulation of both stomatal speediness and whole plant transpiration.
Cevipabulin-tubulin complex reveals a novel agent binding site on α-tubulin with tubulin degradation effect
Authors: Yang Jianhong , Yu Yamei , Li Yong , Yan Wei , Ye Haoyu , Niu Lu , Tang Minghai , Wang Zhoufeng , Yang Zhuang , Pei Heying , Wei Haoche , Zhao Min , Wen Jiaolin , Yang Linyu , Ouyang Liang , Wei Yuquan , Chen Qiang , Li Weimin , Chen Lijuan 
Published: September 2020

AbstractMicrotubule, composed of αβ-tubulin heterodimers, remains as one of the most popular anticancer targets for decades. To date, anti-microtubule drugs are mainly functionally divided into microtubule-destabilizing and microtubule-stabilizing agents while microtubule- or tubulin-degradation agents are rarely reported. Six known binding sites on tubulin dimer are identified with five sites on β-tubulin and only one site on α-tubulin (pironetin site), hinting compounds binding to α-tubulin are less well characterized. Cevipabulin, a microtubule-active antitumor clinical candidate, is widely accepted as a microtubule-stabilizing agent by binding to the vinblastine site. Our X-ray crystallography study reveals that, in addition binding to the vinblastine site, cevipabulin also binds to a novel site on α-tubulin (named the seventh site) which located near the nonexchangeable GTP. Interestingly, we find the binding of cevipabulin to the seventh site induces tubulin degradation. As the non-exchangeable GTP has structural role and is important for the stability of tubulin dimers, we propose and confirm the tubulin degradation mechanism as: Cevipabulin at the seventh site puts the αT5 loop outward to make the non-exchangeable GTP exchangeable, which reduces the stability of tubulin and results in its destabilization and degradation. Our results confirm a novel agent binding site on α-tubulin and shed light on the development of tubulin degraders as a new generation of anti-microtubule drugs targeting this novel site.
Selfish chromosomal drive shapes recent centromeric histone evolution in monkeyflowers
Authors: Finseth Findley R. , Nelson Thom C. , Fishman Lila 
Published: September 2020

AbstractUnder the selfish centromere model, costs associated with female meiotic drive by centromeres select on interacting kinetochore proteins to restore Mendelian inheritance. We directly test this model in yellow monkeyflowers (Mimulus guttatus), which are polymorphic for a costly driving centromere (D). We show that theDhaplotype is structurally and genetically distinct and swept to a high stable frequency within the past 1500 years. Quantitative genetic analyses reveal that variation in the strength of drive primarily depends on the identity of the non-Dcentromere, but also identified an unlinked modifier coincident with kinetochore protein Centromere-specific Histone 3 A (CenH3A). CenH3A has also experienced a recent (<1000 years) selective sweep in our focal population, consistent with ongoing interactions withDshaping its evolution. Together, our results demonstrate an active co-evolutionary arms race between the DNA and protein components of the meiotic machinery, with important consequences for individual fitness and molecular divergence.
Kinetic-Mechanistic Evidence for WhichE. coliRNA Polymerase-λPROpen Promoter Complex Initiates and for Stepwise Disruption of Contacts in Bubble Collapse
Authors: Plaskon Dylan , Henderson Kate , Felth Lindsey , Molzahn Cristen , Evensen Claire , Dyke Sarah , Shkel Irina , Record M. Thomas 
Published: September 2020

AbstractIn transcription initiation, specific contacts between RNA polymerase (RNAP) and promoter DNA are disrupted as the RNA-DNA hybrid advances into the cleft, resulting in escape of RNAP. From the pattern of large and small rate constants for steps of initiation at λPRpromoter at 19°C, we proposed that in-cleft interactions are disrupted in extending 3-mer to 5-mer RNA, −10 interactions are disrupted in extending 6-mer to 9-mer, and −35 interactions are disrupted in extending 10-mer to 11-mer, allowing RNAP to escape. Here we test this mechanism and determine enthalpic and entropic activation barriers of all steps from kinetic measurements at 25°C and 37°C. Initiation at 37°C differs significantly from expectations based on lower-temperature results. At low concentration of the second iNTP (UTP), synthesis of full-length RNA at 37°C is slower than at 25°C and no transient short RNA intermediates are observed, indicating a UTP-dependent bottleneck step early in the 37°C mechanism. Analysis reveals that the 37°C λPROC (RPO) cannot initiate and must change conformation to a less-stable initiation complex (IC) capable of binding the iNTP. We find that IC is the primary λPROC species below 25°C, and therefore conclude that IC must be the I3intermediate in RPOformation. Surprisingly, Arrhenius activation energy barriers to five steps where RNAP-promoter in-cleft and −10 contacts are disrupted are much smaller than for other steps, including a negative barrier for the last of these steps. We interpret these striking effects as enthalpically-favorable, entropically-unfavorable, stepwise bubble collapse accompanying disruption of RNAP contacts.SignificanceTranscription initiation is highly regulated. To understand regulation, mechanisms of initiation and escape of RNA polymerase (RNAP) from the promoter must be understood. RNAP forms a highly-stable open complex (RPO) with λPRpromoter at 37°C. From experiments determining effects of temperature on rate constants for each step of RNA synthesis, we find that RPOcannot bind the initiating nucleotides, that the I3intermediate and not RPOis the initiation complex, and that contacts of RNAP with single-stranded DNA of the discriminator and −10 region and with −35 duplex DNA are disrupted stepwise as the RNA-DNA hybrid moves into the cleft. Evidence is obtained for stepwise bubble collapse and base stacking accompanying disruption of interactions of the single-stranded discriminator and −10 regions with RNAP.
Control of feeding by Piezo-mediated gut mechanosensation inDrosophila
Authors: Min Soohong , Oh Yangkyun , Verma Pushpa , Van Vactor David , Suh Greg S.B. , Liberles Stephen D. 
Published: September 2020

SUMMARYAcross animal species, meals are terminated after ingestion of large food volumes, yet underlying mechanosensory receptors have so far remained elusive. Here, we identify an essential role forDrosophilaPiezo in volume-based control of meal size. We discover a rare population of fly neurons that express Piezo, innervate the anterior gut and crop (a food reservoir organ), and respond to tissue distension in a Piezo-dependent manner. Activating Piezo neurons decreases appetite, whilePiezoknockout and Piezo neuron silencing cause gut bloating and increase both food consumption and body weight. These studies reveal that disrupting gut distension receptors changes feeding patterns, and identify a key role forDrosophilaPiezo in internal organ mechanosensation.
Co-targeting myelin inhibitors and CSPGs markedly enhances regeneration of GDNF-stimulated, but not conditioning-lesioned, sensory axons into the spinal cord
Authors: Zhai Jinbin , Kim Hyukmin , Han Seung Baek , Manire Meredith , Yoo Rachel , Pang Shuhuan , Smith George M. , Son Young-Jin 
Published: September 2020

ABSTRACTA major barrier to intraspinal regeneration after dorsal root (DR) injury is the DR entry zone (DREZ), the CNS/PNS interface. DR axons stop regenerating at the DREZ, even if regenerative capacity is increased by a nerve conditioning lesion. This potent blockade has long been attributed to myelin-associated inhibitors and CSPGs, but incomplete lesions and conflicting reports have prevented conclusive agreement. Here we evaluated DR regeneration in mice, using novel strategies to facilitate complete lesions and analyses, selective tracing of proprioceptive and mechanoreceptive axons, and the first simultaneous targeting of Nogo/Reticulon-4, MAG, OMgp, CSPGs and GDNF. Co-eliminating myelin inhibitors and CSPGs elicited regeneration of only a few conditioning-lesioned DR axons across the DREZ. Their absence, however, markedly and synergistically enhanced regeneration of GDNF-stimulated axons, highlighting the importance of sufficiently elevating intrinsic growth capacity. We also conclude that myelin inhibitors and CSPGs are not the primary mechanism stopping axons at the DREZ.