bluuebunny/crossref_metadata_2025_split huggingface dataset:
In situstructure determination using single particle cryo-electron microscopy images
Authors: Cheng Jing , Li Bufan , Si Long , Zhang Xinzheng 
Published: September 2020

AbstractCryo-electron microscopy (cryo-EM) tomography is a powerful tool forin situstructure determination. However, this method requires the acquisition of tilt series, and its time consuming throughput of acquiring tilt series severely slows determination ofin situstructures. By treating the electron densities of non-target protein as non-Gaussian distributed noise, we developed a new target function that greatly improves the efficiency of the recognition of the target protein in a single cryo-EM image without acquiring tilt series. Moreover, we developed a sorting function that effectively eliminates the false positive detection, which not only improves the resolution during the subsequent structure refinement procedure but also allows using homolog proteins as models to recognize the target protein. Together, we developed anin situsingle particle analysis (isSPA) method. Our isSPA method was successfully applied to solve structures of glycoproteins on the surface of a non-icosahedral virus and Rubisco inside the carboxysome. The cryo-EM data from both samples were collected within 24 hours, thus allowing fast and simple structural determinationin situ.
Single-cell RNA-seq reveals early heterogeneity during ageing in yeast
Authors: Zhang Yi , Wang Jincheng , Sang Yuchen , Jin Shengxian , Wang Xuezheng , Azad Gajendra Kumar , McCormick Mark A. , Kennedy Brian K. , Li Qing , Wang Jianbin , Zhang Xiannian , Huang Yanyi 
Published: September 2020

AbstractThe budding yeastSaccharomyces cerevisiaehas relatively short lifespan and is genetically tractable, making it a widely used model organism in ageing research. Here, we carried out a systematic and quantitative investigation of yeast ageing with single-cell resolution through transcriptomic sequencing. We optimized a single-cell RNA sequencing (scRNA-seq) protocol to quantitatively study the whole transcriptome profiles of single yeast cells at different ages, finding increased cell-to-cell transcriptional variability during ageing. The single-cell transcriptome analysis also highlighted key biological processes or cellular components, including oxidation-reduction process, oxidative stress response (OSR), translation, ribosome biogenesis and mitochondrion that underlie ageing in yeast. Remarkably, we uncovered a molecular marker,FIT3, that was linked to mitochondrial DNA loss and indicated the early heterogeneity during ageing in yeast. We also analyzed the regulation of transcription factors and further characterized the distinctive temporal regulation of the OSR byYAP1and proteasome activity byRPN4during ageing in yeast. Overall, our data profoundly reveal early heterogeneity during ageing in yeast and shed light on the ageing dynamics at the single cell level.
The oriental fruit moth genome provides insights into evolutionary adaptation of tortricid pests
Authors: Song Wei , Cao Li-Jun , Yue Lei , Guo Shao-Kun , Chen Jin-Cui , Gong Ya-Jun , Fan Xu-Lei , Wei Shu-Jun 
Published: September 2020

AbstractMoths of the family Tortricidae (Insecta: Lepidoptera) usually distribute in temperate and tropical high upland regions. The oriental fruit moth (OFM)Grapholita molestais a globally important pest of stone and pome fruit from this family. In this study, we assembled a chromosome-level genome for the OFM and conducted a comparative genomic analysis with other lepidopterans. This genome was assembled to 28 chromosomes with a size of 517.71 Mb, an N50 of 19.5 Mb, and a BUSCO completeness of 97.1%. In total, 19968 protein-coding genes were predicted, among which 15269 were functionally annotated. We manually annotated ten gene families for 13 representative genomes from the Lepidopteran. In general, two tortricid moths have a moderate number of detoxification and receptor genes and the lowest number of HSP genes, congruent with their polyphagous dietary and pattern of distribution. However, the OFM has the highest number of P450, I Rs and ORs among all species. Compared to the other tortricid species of the codling mothCydia pomonella, the OFM has more genes in all gene families. Our results indicate that the high number of some detoxification and receptor genes may be related to the strong adaptation of OFM as a global pest. The high-quality genome of OFM provides an invaluable resource for understanding the ecology, genetics, and evolution of tortricid moths.
No evidence for cross-contextual consistency in spatial learning and behavioural flexibility in a passerine
Authors: Troisi CA , Cooke AC , Davidson GL , de la Hera I , Reichert MS , Quinn JL 
Published: September 2020

AbstractAlthough the evolution of cognitive differences among species has long been of interest in ecology, whether natural selection acts on cognitive processes within populations has only begun to receive similar attention. One of the key challenges is to understand how consistently cognitive traits within any one domain are expressed over time and across different contexts, as this has direct implications for the way in which selection might act on this variation. Animal studies typically measure a cognitive domain using only one task in one context, and assume that this captures the likely expression of that domain in different contexts. This deficit is not surprising because, from an ecologist’s perspective, cognitive tasks are notoriously laborious to employ, and for design reasons most tasks can only be deployed in a specific context. Thus our knowledge of whether individual differences in cognitive abilities are consistent across contexts is limited. Using a wild population of great tits (Parus major) we characterised consistency of two cognitive abilities, each in two different contexts: 1) spatial learning at two different spatial scales, and 2) behavioural flexibility as both performance in a detour reaching task and reversal learning in a spatial task. We found no evidence of a correlation between the two spatial learning speeds, or between the two measures of behavioural flexibility. This suggests that cognitive performance is highly plastic and sensitive to differences across tasks, or that variants of these well-known tasks may tap into different combinations of both cognitive and non-cognitive mechanisms, or that they simply do not adequately measure each putative cognitive domain. Our results highlight the challenges of developing standardised cognitive assays to explain natural behaviour and to understand the selective consequences of that variation.
Genomic diversity and evolution of coronavirus (SARS-CoV-2) in France from 309 COVID-19-infected patients
Authors: Levasseur Anthony , Delerce Jeremy , Caputo Aurelia , Brechard Ludivine , Colson Philippe , Lagier Jean-Christophe , Fournier Pierre-Edouard , Raoult Didier 
Published: September 2020

ABSTRACTThe novel coronavirus (SARS-CoV-2) causes pandemic of viral pneumonia. The evolution and mutational events of the SARS-CoV-2 genomes are critical for controlling virulence, transmissibility, infectivity, severity of symptoms and mortality associated to this infectious disease. We collected and investigated 309 SARS-CoV-2 genomes from patients infected in France. Detailed genome cartography of all mutational events (SNPs, indels) was reported and correlated to clinical features of patients. A comparative analysis between our 309 SARS-CoV-2 genomes from French patients and the reference Wuhan coronavirus genome revealed 315 substitution mutations and six deletion events: ten were in 5’/3’ UTR, 178 were nonsynonymous, 126 were synonymous and one generated a stop codon. Six different deleted areas were also identified in nine viral variants. In particular, 30 substitution mutations (18 nonsynonymous) and one deletion (Δ21765-21770) concerned the spike S glycoprotein. An average of 7.8 mutational events (+/- 1.7 SD) and a median of 8 (range, 7-9) were reported per viral isolate. Comparative analyses and clustering of specific mutational signatures in 309 genomes disclose several divisions in groups and subgroups combining their geographical and phylogenetic origin. Clinical outcomes of the 309 COVID-19-infected patients were investigated according to the mutational signatures of viral variants. These findings highlight the genome dynamics of the coronavirus 2019-20 and shed light on the mutational landscape and evolution of this virus. Inclusion of the French cohort enabled us to identify 161 novel mutations never reported in SARS-CoV-2 genomes collected worldwide. These results support a global and continuing surveillance of the emerging variants of the coronavirus SARS-CoV-2.
Method comparison studies of telomere length measurement using qPCR approaches: a critical appraisal of the literature
Authors: Lindrose Alyssa R. , McLester-Davis Lauren W. Y. , Tristano Renee I. , Kataria Leila , Gadalla Shahinaz M. , Eisenberg Dan T. A. , Verhulst Simon , Drury Stacy 
Published: September 2020

AbstractUse of telomere length (TL) as a biomarker for various environmental exposures and diseases has increased in recent years. Various methods have been developed to measure telomere length. PCR-based methods remain wide-spread for population-based studies due to the high-throughput capability. While several studies have evaluated TL measurement methods, the results have been variable. We conducted a literature review of TL measurement cross-method comparison studies that included a PCR-based method published between January 1, 2002 and May 25, 2020. A total of 25 articles were found that matched the inclusion criteria. Papers were reviewed for quality of methodologic reporting of sample and DNA quality, PCR assay characteristics, sample blinding, and analytic approaches to determine final TL. Overall, methodologic reporting was low as assessed by two different reporting guidelines for qPCR-based TL measurement. There was a wide range in the reported correlation between methods (as assessed by Pearson’s r) and few studies utilized the recommended intra-class correlation coefficient (ICC) for assessment of assay repeatability and methodologic comparisons. The sample size for nearly all studies was less than 100, raising concerns about statistical power. Overall, this review found that the current literature on the relation between TL measurement methods is lacking in validity and scientific rigor. In light of these findings, we present reporting guidelines for PCR-based TL measurement methods and results of analyses of the effect of assay repeatability (ICC) on statistical power of cross-sectional and longitudinal studies. Additional cross-laboratory studies with rigorous methodologic and statistical reporting, adequate sample size, and blinding are essential to accurately determine assay repeatability and replicability as well as the relation between TL measurement methods.
Seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar, northern India – a cross-sectional study
Authors: Salim Khan S Muhammad , Qurieshi Mariya Amin , Haq Inaamul , Majid Sabhiya , Bhat Arif Akbar , Nabi Sahila , Ganai Nisar Ahmad , Zahoor Nazia , Nisar Auqfeen , Chowdri Iqra Nisar , Qazi Tanzeela Bashir , Kousar Rafiya , Lone Abdul Aziz , Sabah Iram , Nabi Shahroz , Sumji Ishtiyaq Ahmad , Kawoosa Misbah Ferooz , Ayoub Shifana 
Published: September 2020

AbstractBackgroundPrevalence of IgG antibodies against SARS-CoV-2 infection provides essential information for deciding disease prevention and mitigation measures. We estimate the seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar.Methods2906 persons >18 years of age selected from hospital visitors across District Srinagar participated in the study. We tested samples for the presence of SARS-CoV-2 specific IgG antibodies using a chemiluminescent microparticle immunoassay-based serologic test.ResultsAge- and gender-standardized seroprevalence was 3.6% (95% CI 2.9% to 4.3%). Age 30-69 years, a recent history of symptoms of an influenza-like-illness, and a history of being placed under quarantine were significantly related to higher odds of the presence of SARS-CoV-2 specific IgG antibodies. The estimated number of SARS-CoV-2 infections during the two weeks preceding the study, adjusted for test performance, was 32602 with an estimated (median) infection-to-known-case ratio of 46 (95% CI 36 to 57).ConclusionsThe seroprevalence of SARS-CoV-2 specific IgG antibodies is low in the District. A large proportion of the population is still susceptible to the infection. A sizeable number of infections remain undetected, and a substantial proportion of people with symptoms compatible with COVID-19 are not tested.
Phasic modulation of visual representations during sustained attention
Authors: van Es Mats W.J. , Marshall Tom R. , Spaak Eelke , Jensen Ole , Schoffelen Jan-Mathijs 
Published: September 2020

AbstractSustained attention has long been thought to benefit perception in a continuous fashion, but recent evidence suggests that it affects perception in a discrete, rhythmic way. Periodic fluctuations in behavioral performance over time, and modulations of behavioral performance by the phase of spontaneous oscillatory brain activity point to an attentional sampling rate in the theta or alpha frequency range. We investigated whether such discrete sampling by attention is reflected in periodic fluctuations in the decodability of visual stimulus orientation from magnetoencephalographic (MEG) brain signals.In this exploratory study, human subjects attended one of two grating stimuli while MEG was being recorded. We assessed the strength of the visual representation of the attended stimulus using a support vector machine (SVM) to decode the orientation of the grating (clockwise vs. counterclockwise) from the MEG signal. We tested whether decoder performance depended on the theta/alpha phase of local brain activity. While the phase of ongoing activity in visual cortex did not modulate decoding performance, theta/alpha phase of activity in the FEF and parietal cortex, contralateral to the attended stimulus did modulate decoding performance. These findings suggest that phasic modulations of visual stimulus representations in the brain are caused by frequency- specific top-down activity in the fronto-parietal attention network.
Proteome dynamics during antibiotic persistence and resuscitation
Authors: Semanjski Maja , Gratani Fabio , Englert Till , Nashier Payal , Beke Viktor , Nalpas Nicolas , Germain Elsa , George Shilpa , Wolz Christiane , Gerdes Kenn , Macek Boris 
Published: September 2020

AbstractDuring antibiotic persistence, bacterial cells become transiently tolerant to antibiotics by restraining their growth and metabolic activity. Detailed molecular characterization of antibiotic persistence is hindered by low count of persisting cells and the need for their isolation. Here we used sustained addition of stable isotope-labeled lysine to selectively label the proteome duringhipA-induced persistence andhipB-induced resuscitation ofE. colicells in minimal medium after antibiotic treatment. Time-resolved, 24-hour measurement of label incorporation allowed detection of over 500 newly synthesized proteins in viable cells, demonstrating low but widespread protein synthesis during persistance. Many essential proteins were newly synthesized and several ribosome-associated proteins, such as RaiA and Sra showed high synthesis levels, pointing to their roles in maintenance of persistence. At the onset of resuscitation, cells synthesized the ribosome-splitting GTPase HflX and various ABC transporters, restored translation machinery and resumed metabolism by inducing glycolysis and biosynthesis of amino acids.
In silicocandidate variant and gene identification using inbred mouse strains
Authors: Munz Matthias , Khodaygani Mohammad , Aherrahrou Zouhair , Busch Hauke , Wohlers Inken 
Published: September 2020

ABSTRACTMice are the most widely used animal model to study genotype to phenotype relationships. Inbred mice are genetically identical, which eliminates genetic heterogeneity and makes them particularly useful for genetic studies. Many different strains have been bred over decades and a vast amount of phenotypic data has been generated. In addition, recently whole genome sequencing-based genome-wide genotype data for many widely used inbred strains has been released. Here, we present an approach forin silicofine-mapping that uses genotypic data of 37 inbred mouse strains together with phenotypic data provided by the user to propose candidate variants and genes for the phenotype under study. Public genome-wide genotype data covering more than 74 million variant sites is queried efficiently in real-time to provide those variants that are compatible with the observed phenotype differences between strains. Variants can be filtered by molecular consequences and by corresponding molecular impact. Candidate gene lists can be generated from variant lists on the fly. Fine-mapping together with annotation or filtering of results is provided in a Bioconductor package called MouseFM. In order to characterize candidate variant lists under various settings, MouseFM was applied to two expression data sets across 20 inbred mouse strains, one from neutrophils and one from CD4+T cells. Fine-mapping was assessed for about 10,000 genes, respectively, and identified candidate variants and haplotypes for many expression quantitative trait loci (eQTLs) reported previously based on these data. For albinism, MouseFM reports only one variant allele of moderate or high molecular impact that only albino mice share: a missense variant in theTyrgene, reported previously to be causal for this phenotype. Performingin silicofine-mapping for interfrontal bone formation in mice using four strains with and five strains without interfrontal bone results in 12 genes. Of these, three are related to skull shaping abnormality. Finally performing fine-mapping for dystrophic cardiac calcification by comparing 9 strains showing the phenotype with 8 strains lacking it, we identify only one moderate impact variant in the known causal geneAbcc6. In summary, this illustrates the benefit of using MouseFM for candidate variant and gene identification.
Evolution is in the details: Regulatory differences in modern human and Neanderthal
Authors: Barker Harlan R. , Parkkila Seppo , Tolvanen Martti E.E. 
Published: September 2020

AbstractTranscription factor proteins play a critical role in the regulation of eukaryote gene expression via sequence- specific binding to genomic locations known as transcription factor binding sites.We studied sites of genomic variation between modern human and Neanderthal promoters. We detected significant differences in the binding affinities of 110 transcription factors to the promoters of 74 target genes. The transcription factors were enriched for terms related to vision, motor neurons, homeobox, and brain, whereas the target genes and their direct interactors were enriched in terms related to autism, brain, connective tissue, trachea, prostate, skull morphology, and vision. Secondary analysis of single-cell data revealed that a subset of the identified transcription factors (CUX1, CUX2, ESRRG, FOXP1, FOXP2, MEF2C, POU6F2, PRRX1 and RORA) co-occur as marker genes in L4 glutamatergic neurons. The majority of these genes have known roles in autism and/or schizophrenia and are associated with human accelerated regions (elevated divergence in humans vs. other primates). These results support the value of gene regulation studies for the evolution of human cognitive abilities and the neuropsychiatric disorders that accompany it.
SARS-CoV-2 infection paralyzes cytotoxic and metabolic functions of the immune cells
Authors: Singh Yogesh , Trautwein Christoph , Fendel Rolf , Krickeberg Naomi , Berezhnoy Georgy , Bissinger Rosi , Ossowski Stephan , Salker Madhuri S. , Casadei Nicolas , Riess Olaf ,   the Deutsche COVID-19 OMICS Initiative (DeCOI)
Published: September 2020

AbstractThe SARS-CoV-2 virus is the causative agent of the global COVID-19 infectious disease outbreak, which can lead to acute respiratory distress syndrome (ARDS). However, it is still unclear how the virus interferes with immune cell and metabolic functions in the human body. In this study, we investigated the immune response in acute or convalescent COVID19 patients. We characterized the peripheral blood mononuclear cells (PBMCs) using flow cytometry and found that CD8+T cells were significantly subsided in moderate COVID-19 and convalescent patients. Furthermore, characterization of CD8+T cells suggested that patients with a mild and moderate course of the COVID-19 disease and convalescent patients have significantly diminished expression of both perforin and granzyme A in CD8+T cells. Using1H-NMR spectroscopy, we characterized the metabolic status of their autologous PBMCs. We found that fructose, lactate and taurine levels were elevated in infected (mild and moderate) patients compared with control and convalescent patients. Glucose, glutamate, formate and acetate levels were attenuated in COVID-19 (mild and moderate) patients. In summary, our report suggests that SARS-CoV-2 infection leads to disrupted CD8+T cytotoxic functions and changes the overall metabolic functions of immune cells.
EPAC regulates von Willebrand factor secretion from endothelial cells in a PI3K/eNOS-dependent manner during inflammation
Authors: Xiao Jie , Zhang Ben , Su Zhengchen , Liu Yakun , Shelite Thomas R. , Chang Qing , Wang Pingyuan , Bukreyev Alexander , Soong Lynn , Jin Yang , Ksiazek Thomas , Gaitas Angelo , Rossi Shannan L. , Zhou Jia , Laposata Michael , Saito Tais B. , Gong Bin 
Published: September 2020

AbstractCoagulopathy is associated with both inflammation and infection, including infection with the novel SARS-CoV-2 (COVID-19). Endothelial cells (ECs) fine tune hemostasis via cAMP-mediated secretion of von Willebrand factor (vWF), which promote the process of clot formation. Theexchangeprotein directlyactivated bycAMP (EPAC) is a ubiquitously expressed intracellular cAMP receptor that plays a key role in stabilizing ECs and suppressing inflammation. To assess whether EPAC could regulate vWF release during inflammation, we utilized ourEPAC1-null mouse model and revealed an increased secretion of vWF in endotoxemic mice in the absence of the EPAC1 gene. Pharmacological inhibition of EPAC1in vitromimicked theEPAC1−/− phenotype. EPAC1 regulated TNFα-triggered vWF secretion from human umbilical vein endothelial cells (HUVECs) in a phosphoinositide 3-kinases (PI3K)/endothelial nitric oxide synthase (eNOS)-dependent manner. Furthermore, EPAC1 activation reduced inflammation-triggered vWF release, bothin vivoandin vitro. Our data delineate a novel regulatory role of EPAC1 in vWF secretion and shed light on potential development of new strategies to controlling thrombosis during inflammation.Key PointPI3K/eNOS pathway-mediated, inflammation-triggered vWF secretion is the target of the pharmacological manipulation of the cAMP-EPAC system.