bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural and cognitive correlates of performance in dynamic multi-modal settings
Authors: Dziego Chloe A. , Bornkessel-Schlesewsky Ina , Jano Sophie , Chatburn Alex , Schlesewsky Matthias , Immink Maarten A. , Sinha Ruchi , Irons Jessica , Schmitt Megan , Chen Steph , Cross Zachariah R. 
Published: March 2022

ABSTRACTThe endeavour to understand human cognition has largely relied upon investigation of task-related brain activity. However, resting-state brain activity can also offer insights into individual information processing and performance capabilities. Previous research has identified electroencephalographic resting-state characteristics (most prominently: the individual alpha frequency; IAF) that predict cognitive function. However, it has largely overlooked a second component of electrophysiological signals: aperiodic 1/factivity. The current study examined how both oscillatory and aperiodic resting-state EEG measures, alongside traditional cognitive tests, can predict performance in a dynamic and complex, semi-naturalistic cognitive task. Participants’ resting-state EEG was recorded prior to engaging in a Target Motion Analysis (TMA) task in a simulated submarine control room environment (CRUSE), which required participants to integrate dynamically changing information over time. We demonstrated that the relationship between IAF and cognitive performance extends from simple cognitive tasks (e.g., digit span) to complex, dynamic measures of information processing. Further, our results showed that individual 1/fparameters (slope and intercept) differentially predicted performance across practice and testing sessions, whereby flatter slopes were associated with improved performance during learning, while higher intercepts were linked to better performance during testing. In addition to the EEG predictors, we demonstrate a link between cognitive skills most closely related to the TMA task (i.e., spatial imagery) and subsequent performance. Overall, the current study highlights (1) how resting-state metrics – both oscillatory and aperiodic - have the potential to index higher-order cognitive capacity, while (2) emphasising the importance of examining these electrophysiological components within more dynamic settings and over time.
Full-length transcriptome maps of reef-building coral illuminate the molecular basis of calcification, symbiosis, and circadian genes
Authors: Han Tingyu , Liao Xin , Zhu Yunchi , Liu Yunqing , Lu Na , Li Yixin , Guo Zhuojun , Chen J.-Y. , He Chunpeng , Lu Zuhong 
Published: March 2022

AbstractBackgroundReef-building corals are critical species for sustaining coral reefs and are highly threatened by global climate change. However, relevant transcriptomic data largely rely on short-read sequencing, which severely limits the understanding of coral molecular mechanisms and leaves many important biological questions unresolved.ResultsWe sequenced the full-length transcriptomes of four common and frequently dominant reef-building corals, including two Robusta clade species, Pocillopora damicornis and Pocillopora verrucosa, and two Complexa clade species, Acropora muricata and Montipora foliosa, using the PacBio Sequel II platform. We obtained information on gene functions, structures and expression profiles. Among them, a comparative analysis of biomineralization-related genes provided insights into the molecular basis of coral skeletal density. The gene expression profiles of the symbiote Symbiodiniaceae were also isolated and annotated from the holobiont sequence data; these profiles showed more highly convergent traits related to gene structure and expression level than those of coral hosts. Interestingly, we observed that intracellular algal cells share some evolutionary convergence between intracellular symbiosis in corals and intracellular digestion in amphioxus. Finally, a phylogenetic analysis of key circadian clock genes among 27 evolutionarily representative species indicated that there are four key members in early metazoans, including cry genes; Clock or Npas2; cyc or Arntl; and tim, while per, as the fifth member, occurs in Bilateria.ConclusionsOur work overcomes the incompleteness of short-read sequencing and illuminates the molecular basis of calcification, symbiosis, and circadian genes, thus providing a foundation for further work on the manipulation of skeleton production or symbiosis to promote the survival of these important organisms.
Spontaneous suppressors against debilitating transmembrane mutants of CaMdr1 disclose novel interdomain communication via Signature motifs of the Major Facilitator Superfamily
Authors: Sharma Suman , Banerjee Atanu , Moreno Alexis , Redhu Archana Kumari , Falson Pierre , Prasad Rajendra 
Published: March 2022

ABSTRACTThe Major Facilitator Superfamily (MFS) includes multiple families of proteins operating as uniporters, symporters and antiporters for a wide spectrum of substrates. Among them, the multidrug resistance-1 drug:H+ antiporter CaMdr1 from Candida albicans is responsible for the efflux of structurally-diverse antifungals. MFS share a common fold of 12-14 transmembrane helices (TMHs) forming two N- and C-domains. Each domain is arranged in a pseudo symmetric fold of two tandems of 3-TMHs that alternatively expose the drug-binding site towards the inside or the outside of the yeast to promote drug binding and release. MFS show a high primary structure diversity and few conserved Signature motifs, each thought to have a common function in the superfamily, although not yet clearly established. Here, we provide new information on these motifs by having screened a library of 64 drug transport-deficient mutants and their corresponding suppressors spontaneously rescuing the deficiency. We found that five strains recovered the drug-resistance capacity by expressing CaMdr1 with a secondary mutation. The pairs of debilitating/rescuing residues are distributed either in the same TMH (T127ATMH1->G140DTMH1) or 3-TMHs repeat (F216ATMH4->G260ATMH5), at the hinge of 3-TMHs repeats tandems (R184ATMH3->D235HTMH4, L480ATMH10->A435TTMH9), and finally between the N- and C-domains (G230ATMH4->P528HTMH12). Remarkably, most of these mutants belongs to the different Signature motifs, highlighting a mechanistic role and interplay thought to be conserved among MFS. Results point also to the specific role of TMH11 in the interplay between the N- and C-domains in the inward- to outward-open conformational transition.
Mechanical activation of mitochondrial energy metabolism during cell differentiation
Authors: Wang Zong-Heng , Combs Christian , Zhao Wenjing , Knutson Jay , Lilly Mary , Xu Hong 
Published: March 2022

AbstractIn multicellular lives, differentiation of many types of stem and progenitor cells is often accompanied by a metabolic transition from glycolysis to mitochondrial oxidative phosphorylation. The mechanisms driving this metabolic transition in vivo are largely unknown. Here, we show that, during differentiation of the Drosophila female germline cyst, the surrounding somatic cells compress the cyst and increase the tension of cyst cells’ membranes. Transmembrane channel-like, an evolutionarily conserved ion channel involved in mechanosensation, maintains cytosolic Ca2+ levels in compressed differentiating cysts. Cytosolic Ca2+ induces transcriptional activation of oxidative phosphorylation through a CaMKI-Fray-JNK signaling relay. Our findings demonstrate a molecular link between cell mechanics and mitochondrial energy metabolism, with implications in other developmentally orchestrated metabolic transitions in mammals.One-Sentence SummaryMechanical forces from the surrounding tissue activate mitochondrial energy metabolism in differentiating cells in vivo.
LSMMD-MA: Scaling multimodal data integration for single-cell genomics data analysis
Authors: Meng-Papaxanthos Laetitia , Zhang Ran , Li Gang , Cuturi Marco , Noble William Stafford , Vert Jean-Philippe 
Published: March 2022

AbstractMotivationModality matching in single-cell omics data analysis—i.e., matching cells across data sets collected using different types of genomic assays—has become an important problem, because unifying perspectives across different technologies holds the promise of yielding biological and clinical discoveries. However, single-cell dataset sizes can now reach hundreds of thousands to millions of cells, which remains out of reach for most multi-modal computational methods.ResultsWe propose LSMMD-MA, a large-scale Python implementation of the MMD-MA method for multimodal data integration. In LSMMD-MA we reformulate the MMD-MA optimization problem using linear algebra and solve it with KeOps, a CUDA framework for symbolic matrix computation in Python. We show that LSMMD-MA scales to a million cells in each modality, two orders of magnitude greater than existing implementations.AvailabilityLSMMD-MA is freely available at https://github.com/google-research/large_scale_mmdmaContactlpapaxanthos@google.com
Prevalence of Bourbon and Heartland viruses in field collected ticks at an environmental field station in St. Louis County, Missouri, USA
Authors: Aziati Ishmael D , McFarland Derek , Antia Avan , Joshi Astha , Aviles-Gamboa Anahi , Lee Preston , Harastani Houda , Wang David , Adalsteinsson Solny A. , Boon Adrianus C. M. 
Published: March 2022

ABSTRACTHeartland and Bourbon viruses are pathogenic tick-borne viruses putatively transmitted by Amblyomma americanum, an abundant tick species in Missouri. To assess the prevalence of these viruses in ticks, we collected 2778 ticks from 8 sampling sites at Tyson Research Center, an environmental field station within St. Louis County and close to the City of St. Louis, from May - July in 2019 and 2021. Ticks were pooled according to life stage and sex, grouped by year and sampling site to create 355 pools and screened by RT-qPCR for Bourbon and Heartland viruses. Overall, 14 (3.9%) and 27 (7.6%) of the pools were positive for Bourbon virus and Heartland virus respectively. In 2019, 11 and 23 pools were positive for Bourbon and Heartland viruses respectively. These positives pools were of males, females and nymphs. In 2021, there were 4 virus positive pools out of which 3 were positive for both viruses and were comprised of females and nymphs. Five out of the 8 sampling sites were positive for at least one virus. This included a site that was positive for both viruses in both years. Detection of these viruses in an area close to a relatively large metropolis presents a greater public health threat than previously thought.
First description of aYersinia pseudotuberculosisclonal outbreak in France, confirmed using a new core genome multilocus sequence typing method
Authors: Savin Cyril , Guern Anne-Sophie Le , Chereau Fanny , Guglielmini Julien , Heuzé Guillaume , Demeure Christian , Pizarro-Cerdá Javier 
Published: March 2022

AbstractYersinia pseudotuberculosisis an enteric pathogen causing mild enteritis that can lead to mesenteric adenitis and septicemia in elderly patients. Most cases are sporadic, but outbreaks have already been described in different countries. We report for the first time aY. pseudotuberculosisclonal outbreak in France, that occurred in 2020. An epidemiological investigation pointed towards the consumption of tomatoes as the likely source of contamination. TheYersiniaNational Reference Laboratory (YNRL) developed a new cgMLST scheme with 1,921 genes specific toY. pseudotuberculosisthat identified the clustering of isolates associated to the outbreak and allowed to perform molecular typing in real time. In addition, this method allowed to retrospectively identify isolates belonging to this cluster from earlier in 2020. This method, which does not require specific bioinformatic skills, is now used systematically at the YNRL and proves to display an excellent discriminatory power and is available to the scientific community.
Spatial turnover of soil viral populations and genotypes overlain by cohesive responses to moisture in grasslands
Authors: Santos-Medellín Christian , Estera-Molina Katerina , Yuan Mengting , Pett-Ridge Jennifer , Firestone Mary K. , Emerson Joanne B. 
Published: March 2022

AbstractAlthough soil viral abundance, diversity, and potential roles in microbial community dynamics and biogeochemical cycling are beginning to be appreciated1–5, little is known about the patterns and drivers of soil viral community composition that underlie their contributions to terrestrial ecology. Here, we analyzed 43 soil viromes from a precipitation manipulation experiment in a Mediterranean grassland in California, USA. We recovered 5,315 viral population sequences (vOTUs), and viral community composition exhibited a highly significant distance-decay relationship within the 18 m long field. This pattern was recapitulated in the microheterogeneity of 130 prevalent vOTUs (detected in >=90% of the viromes), which tended to exhibit significant negative correlations between genomic similarity of their predominant allelic variants and distance. Although spatial turnover was also observed in the bacterial and archaeal communities from the same soils, the signal was dampened relative to the viromes, suggesting differences in assembly drivers at local scales for viruses and their microbial hosts and/or differences in the temporal scales captured by viromes and total DNA. Despite the overwhelming spatial signal, vOTUs responsive to a decrease in soil moisture were significantly enriched in a predicted protein-sharing subnetwork of 326 vOTUs linked to 191 known actinobacteriophages, suggesting a genomically cohesive viral response to soil moisture evocative of environmental filtering, potentially by way of actinobacterial hosts. Overall, soil viral ecological processes appear to be highly constrained in space and tightly coupled to the heterogeneous, dynamic soil environment and thus fundamentally different from those of their well-mixed and more thoroughly studied marine counterparts.
Revealing within-species diversity in uncultured human gut bacteria with single-cell long-read sequencing
Authors: Kogawa Masato , Nishikawa Yohei , Saeki Tatsuya , Yoda Takuya , Arikawa Koji , Takeyama Haruko , Hosokawa Masahito 
Published: March 2022

AbstractBacterial genome structure changes dynamically, and structural variants can change bacterial phenotype; However, obtaining the complete genome and analyzing genome structure of uncultured bacteria has been challenging. We aimed to develop a single-cell amplified genome long-read assembly (scALA) workflow to construct circular single-cell amplified genomes (cSAGs) from long-read single-cell sequencing data of targeted uncultured bacteria. In particular, scALA generated cSAGs from nanopore long-read sequencing data of SAGs by producing contiguous sequences with repeated bias reduction and assembly processes. From 12 human fecal samples, scALA generated 16 cSAGs of three specifically targeted bacterial species, Anaerostipes hadrus, Agathobacter rectalis, and Ruminococcus gnavus. A. hadrus cSAGs exhibited large, ten kbp-long, phage insertions, saccharide metabolic capacity, and frequent genomic recombination with related strains from cohabitant hosts. Noteworthy, cSAGs constructed using this method could expand bacterial genome databases and our understanding of within-species diversities in uncultured bacteria.
Recognition of copy-back defective interfering rabies virus genomes by RIG-I triggers the antiviral response against vaccine strains
Authors: Aouadi Wahiba , Najburg Valérie , Legendre Rachel , Varet Hugo , Kergoat Lauriane , Tangy Frédéric , Larrous Florence , Komarova Anastassia V. , Bourhy Hervé 
Published: March 2022

AbstractRabies virus (RABV) is a lethal neurotropic virus that causes 60,000 human deaths every year around the world. A typical feature of RABV infection is the suppression of type I and III interferon (IFN)-mediated antiviral response. However, molecular mechanisms leading to RABV sensing by RIG-I-like receptors (RLR) to initiate IFN signaling remain elusive. Here, we showed that RABV RNAs are recognized by RIG-I (retinoic acid-inducible gene I) sensor resulting in an IFN response of the infected cells but that this global feature was differently modulated according to the type of RABV used. RNAs from pathogenic RABV strain, THA, were poorly detected in the cytosol by RIG-I and therefore mediated a weak antiviral response. On the opposite, we revealed a strong interferon activity triggered by the RNAs of the attenuated RABV vaccine SAD strain mediated by RIG-I. Using next-generation sequencing (NGS) combined with bioinformatics tools, we characterized two major 5’copy-back defective interfering (5’cb DI) genomes generated during SAD replication. Furthermore, we identified a specific interaction of 5’cb DI genomes and RIG-I that correlated with a high stimulation of the type I IFN signaling. This study indicates that RNAs from a wild-type RABV poorly activate the RIG-I pathway, while the presence of 5’cb DIs in vaccine SAD strain serves as an intrinsic adjuvant that strengthens its efficiency by enhancing RIG-I detection and therefore strongly stimulates the IFN response.HighlightsRABV pathogenic strain replication in vitro is characterized by the absence of defective interfering genomes thus induces a weak RLR-mediated innate immunity antiviral response.RABV vaccine attenuated strain shows a high release of 5’ copy-back defective interfering genomes during replication in vitro and therefore enhances a strong antiviral response upon infection.RIG-I is the main sensor for RABV RNA detection within cells.
Improved And Optimized Drug Repurposing For The SARS-CoV-2 Pandemic
Authors: Cohen Sarel , Hershcovitch Moshik , Taraz Martin , Kißig Otto , Issac Davis , Wood Andrew , Waddington Daniel , Chin Peter , Friedrich Tobias 
Published: March 2022

AbstractThe active global SARS-CoV-2 pandemic caused more than 426 million cases and 5.8 million deaths worldwide. The development of completely new drugs for such a novel disease is a challenging, time intensive process. Despite researchers around the world working on this task, no effective treatments have been developed yet. This emphasizes the importance of drug repurposing, where treatments are found among existing drugs that are meant for different diseases. A common approach to this is based on knowledge graphs, that condense relationships between entities like drugs, diseases and genes. Graph neural networks (GNNs) can then be used for the task at hand by predicting links in such knowledge graphs. Expanding on state-of-the-art GNN research, Doshi et al. recently developed the Dr-COVID model. We further extend their work using additional output interpretation strategies. The best aggregation strategy derives a top-100 ranking of 8,070 candidate drugs, 32 of which are currently being tested in COVID-19-related clinical trials. Moreover, we present an alternative application for the model, the generation of additional candidates based on a given pre-selection of drug candidates using collaborative filtering. In addition, we improved the implementation of the Dr-COVID model by significantly shortening the inference and pre-processing time by exploiting data-parallelism. As drug repurposing is a task that requires high computation and memory resources, we further accelerate the post-processing phase using a new emerging hardware — we propose a new approach to leverage the use of high-capacity Non-Volatile Memory for aggregate drug ranking.
The anti-fibrotic effects of RLN3 aggravated the pathogenesis of adolescent idiopathic scoliosis-a preliminary study
Authors: Zhang Hao , Luo Beier , Sun Fengyuan , Xu Bing , Li Ming , Wang Guokun , Yang Zongde 
Published: March 2022

AbstractPrevious research proposed that ligament laxity is a clinical feature that can be easily overlooked in patients with adolescent idiopathic scoliosis (AIS). Relaxin and relaxin-related peptides, which have anti-fibrosis roles in the vascular and kidney system and relax the pubic symphysis during pregnancy, may contribute to ligament laxity. The goal of this research was to evaluate the role of in AIS. We found significantly increased relaxin-3 plasma in patients with AIS, as well as a significant correlation between joint hypermobility and relaxin 3 plasma levels. In a classic mouse model (C57BL/6J) of scoliosis, which was established according to the literature, showed significantly higher relaxin-3 plasma levels compared to normal group. In the relaxin-3 knockout C57BL/6J mice model the prevalence of scoliosis was significantly decreased. An in vitro experiment showed that relaxin 3 has anti-fibrotic effects on spinal ligament fibroblasts in both humans and mice by inhibiting TGF-β via relaxin family peptide receptor 3 (RXFP3) and increasing expression of matrix metalloproteinase 2 and matrix metalloproteinase 9 via the TGF-β/Smad2 and MAPK-ERK1/2 pathway. Blocking RXFP3 function with R3(B1-22)R significantly decreased the prevalence of scoliosis in C57BL/6J mice. In summary, the anti-fibrotic effects of relaxin-3 and RXFP3 activation may aggravate the pathogenesis of AIS.
Transcriptome-wide Analyses of Adipose Tissue in Outbred Rats Reveal Genetic Regulatory Mechanisms Relevant for Human Obesity
Authors: Crouse Wesley L. , Das Swapan K , Le Thu , Keele Greg , Holl Katie , Seshie Osborne , Craddock Ann L , Sharma Neeraj K. , Comeau Mary , Langefeld Carl D , Hawkins Greg , Mott Richard , Valdar William , Solberg Woods Leah C 
Published: March 2022

ABSTRACTTranscriptomic analysis in metabolically active tissues allows a systems genetics approach to identify causal genes and networks involved in metabolic disease. Outbred heterogeneous stock (HS) rats are used for genetic mapping of complex traits, but to-date, a systems genetics analysis of metabolic tissues has not been done. We investigated whether adiposity-associated genes and gene co-expression networks in outbred heterogeneous stock (HS) rats overlap those found in humans. We analyzed RNAseq data from adipose tissue of 415 male HS rats, correlated these transcripts with body weight (BW) and compared transcriptome signatures to two human cohorts: the African American Genetics of Metabolism and Expression and Metabolic Syndrome in Men. We used weighted gene co-expression network analysis to identify adiposity-associated gene networks and mediation analysis to identify genes under genetic control whose expression drives adiposity. We identified 554 orthologous “consensus genes” whose expression correlates with BW in the rat and with body mass index (BMI) in both human cohorts. Consensus genes fell within eight co-expressed networks and were enriched for genes involved in immune system function, cell growth, extracellular matrix organization and lipid metabolic processes. We identified 19 consensus genes for which genetic variation may influence BW via their expression, including those involved in lipolysis (e.g.,Hcar1), inflammation (e.g.,Rgs1), adipogenesis (e.g.,Tmem120b) or no previously known role in obesity (e.g.,St14, Msa4a6). Strong concordance between HS rat and human BW/BMI associated transcripts demonstrates translational utility of the rat model, while identification of novel genes expands our knowledge of the genetics underlying obesity.