bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sound-evoked responses of distinct neuron classes from the tail of the striatum
Authors: Nardoci Matthew B. , Lakunina Anna A. , Henderling Devin C. , Pedregon Jewlyssa C. , Jaramillo Santiago 
Published: February 2022

AbstractGiven its inputs from auditory structures and neuromodulatory systems, the posterior tail of the striatum is ideally positioned to influence behavioral responses to acoustic stimuli according to context and previous rewards. Results from previous studies indicate that neurons in this striatal region display selective responses to sounds. However, it is not clear whether different striatal cell classes code for distinct features of sounds, nor how different striatal output pathways may use acoustic information to guide behavior. Here we compared the sound-evoked responses of posterior striatal neurons that form the striatal direct pathway (and express the dopamine receptor D1) to the responses of neighboring neurons in naive mice. We achieved this via optogenetic photo-identification of D1-expressing neurons during extracellular electrophysiological recordings in awake head-fixed mice of both sexes. We found that the frequency tuning of sound-responsive direct-pathway striatal neurons is comparable to that of their sound-responsive neighbors. Moreover, we found that both populations encode amplitude modulated sounds in a similar fashion. These results suggest that different classes of neurons in the posterior striatum of naive animals have similar access to acoustic features conveyed by the auditory system even outside the context of an auditory task.
The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization
Authors: Karger Amy B. , Brien James D. , Christen Jayne M. , Dhakal Santosh , Kemp Troy J. , Klein Sabra L. , Pinto Ligia A. , Premkumar Lakshmanane , Roback John D. , Binder Raquel A. , Boehme Karl W. , Boppana Suresh , Cordon-Cardo Carlos , Crawford James M. , Daiss John L. , Dupuis Alan P. , Espino Ana M. , Firpo-Betancourt Adolfo , Forconi Catherine , Forrest J. Craig , Girardin Roxie C. , Granger Douglas A. , Granger Steve W. , Haddad Natalie S. , Heaney Christopher D. , Hunt Danielle T. , Kennedy Joshua L. , King Christopher L. , Krammer Florian , Kruczynski Kate , LaBaer Joshua , Lee F. Eun-Hyung , Lee William T. , Liu Shan-Lu , Lozanski Gerard , Lucas Todd , Mendu Damodara Rao , Moormann Ann M. , Murugan Vel , Okoye Nkemakonam C. , Pantoja Petraleigh , Payne Anne F. , Park Jin , Pinninti Swetha , Pinto Amelia K. , Pisanic Nora , Qiu Ji , Sariol Carlos A. , Simon Viviana , Song Lusheng , Steffen Tara L. , Stone E. Taylor , Styer Linda M. , Suthar Mehul S. , Thomas Stefani N. , Thyagarajan Bharat , Wajnberg Ania , Yates Jennifer L. , Sobhani Kimia 
Published: March 2022

AbstractBackgroundIn October 2020, the National Cancer Institute (NCI) Serological Sciences Network (SeroNet) was established to study the immune response to COVID-19, and “to develop, validate, improve, and implement serological testing and associated technologies.” SeroNet is comprised of 25 participating research institutions partnering with the Frederick National Laboratory for Cancer Research (FNLCR) and the SeroNet Coordinating Center. Since its inception, SeroNet has supported collaborative development and sharing of COVID-19 serological assay procedures and has set forth plans for assay harmonization.MethodsTo facilitate collaboration and procedure sharing, a detailed survey was sent to collate comprehensive assay details and performance metrics on COVID-19 serological assays within SeroNet. In addition, FNLCR established a protocol to calibrate SeroNet serological assays to reference standards, such as the U.S. SARS-CoV-2 serology standard reference material and First WHO International Standard (IS) for anti-SARS-CoV-2 immunoglobulin (20/136), to facilitate harmonization of assay reporting units and cross-comparison of study data.ResultsSeroNet institutions reported development of a total of 27 ELISA methods, 13 multiplex assays, 9 neutralization assays, and use of 12 different commercial serological methods. FNLCR developed a standardized protocol for SeroNet institutions to calibrate these diverse serological assays to reference standards.ConclusionsSeroNet institutions have established a diverse array of COVID-19 serological assays to study the immune response to SARS-CoV-2 virus and vaccines. Calibration of SeroNet serological assays to harmonize results reporting will facilitate future pooled data analyses and study cross-comparisons.
Clinically oriented prediction of patient response to targeted and immunotherapies from the tumor transcriptome
Authors: Dinstag Gal , Shulman Eldad D. , Elis Efrat , Ben-Zvi Doreen S. , Tirosh Omer , Maimon Eden , Meilijson Isaac , Elalouf Emmanuel , Temkin Boris , Vitkovsky Philipp , Schiff Eyal , Hoang Danh-Tai , Sinha Sanju , Nair Nishanth Ulhas , Sang Lee Joo , Schäffer Alejandro A. , Ronai Ze’ev , Juric Dejan , Apolo Andrea B. , Dahut William L. , Lipkowitz Stanley , Berger Raanan , Kurzrock Razelle , Papanicolau-Sengos Antonios , Karzai Fatima , Gilbert Mark R. , Aldape Kenneth , Rajagopal Padma S. , Beker Tuvik , Ruppin Eytan , Aharonov Ranit 
Published: March 2022

AbstractBackgroundPrecision oncology is gradually advancing into mainstream clinical practice, demonstrating significant survival benefits. However, eligibility and response rates remain limited in many cases, calling for better predictive biomarkers.MethodsWe present ENLIGHT, a transcriptomics-based computational approach that identifies clinically relevant genetic interactions and uses them to predict a patient’s response to a variety of therapies in multiple cancer types, without training on previous treatment response data. We study ENLIGHT in two translationally oriented scenarios:Personalized Oncology (PO), aimed at prioritizing treatments for a single patient, andClinical Trial Design (CTD), selecting the most likely responders in a patient cohort.FindingsEvaluating ENLIGHT’s performance on 21 blinded clinical trial datasets in the PO setting, we show that it can effectively predict a patient’s treatment response across multiple therapies and cancer types. Its prediction accuracy is better than previously published transcriptomics-based signatures and is comparable to that of supervised predictors developed for specific indications and drugs. In combination with the IFN-γsignature, ENLIGHT achieves an odds ratio larger than 4 in predicting response to immune checkpoint therapy. In the CTD scenario, ENLIGHT can potentially enhance clinical trial success for immunotherapies and other monoclonal antibodies by excluding non-responders, while overall achieving more than 90% of the response rate attainable under an optimal exclusion strategy.ConclusionENLIGHT demonstrably enhances the ability to predict therapeutic response across multiple cancer types from the bulk tumor transcriptome.FundingThis research was supported in part by the Intramural Research Program, NIH and by the Israeli Innovation Authority.
Aging-regulated TUG1 is dispensable for endothelial cell function
Authors: Gimbel Anna Theresa , Koziarek Susanne , Theodorou Kosta , Schulz Jana Felicitas , Stanicek Laura , Ali Tamer , Günther Stefan , Kumar Sandeep , Jo Hanjoong , Hübner Norbert , Maegdefessel Lars , Dimmeler Stefanie , van Heesch Sebastiaan , Boon Reinier A. 
Published: March 2022

AbstractThe evolutionary conserved Taurine Upregulated Gene 1 (TUG1) is a ubiquitously expressed gene that is one of the highest expressed genes in human and rodent endothelial cells (ECs). We here show that TUG1 expression decreases significantly in aging mouse carotid artery ECs and human ECs in vitro, indicating a potential role in the aging endothelial vasculature system. We therefore investigated if, and how, TUG1 might function in aging ECs, but despite extensive phenotyping found no alterations in basal EC proliferation, apoptosis, barrier function, migration, mitochondrial function, or monocyte adhesion upon TUG1 silencing in vitro. TUG1 knockdown did slightly and significantly decrease cumulative sprout length upon vascular endothelial growth factor A stimulation in human umbilical vein endothelial cells (HUVECs), though TUG1-silenced HUVECs displayed no transcriptome-wide mRNA expression changes explaining this effect. Further, ectopic expression of the highly conserved and recently discovered 153 amino acid protein translated from certain TUG1 transcript isoforms did not alter angiogenic sprouting in vitro. Our data show that, despite a high expression and strong evolutionary conservation of both the TUG1 locus and the protein sequence it encodes, TUG1 does not seem to play a major role in basic endothelial cell function.
Genetic Examination of Hematological Parameters in SARS-CoV-2 Infection and COVID-19
Authors: Rowland Bryce , Sun Quan , Wang Wanjiang , Miller-Fleming Tyne , Cox Nancy , Graff Misa , Faucon Annika , Shuey Megan M. , Blue Elizabeth E. , Auer Paul , Li Yun , Sankaran Vijay G. , Reiner Alexander P. , Raffield Laura M. 
Published: March 2022

AbstractBackgroundPeople hospitalized with COVID-19 often exhibit hematological alterations, such as lower lymphocyte and platelet counts, which have been reported to associate with disease prognosis. It is unclear whether inter-individual variability in baseline hematological parameters prior to acute infection influences risk of SARS-CoV-2 infection and progression to severe COVID-19.MethodsWe assessed the association of blood cell counts and indices with incident SARS-CoV-2 infection and severe COVID-19 in UK Biobank and the Vanderbilt University Medical Center Synthetic Derivative (VUMC SD). Since genetically determined blood cell measures better represent cell abundance across the lifecourse, we used summary statistics from genome-wide association studies to assess the shared genetic architecture of baseline blood cell counts and indices on COVID-19 outcomes.ResultsWe observed inconsistent associations between measured blood cell indices and both SARS-CoV-2 infection and COVID-19 hospitalization in UK Biobank and VUMC SD. In Mendelian randomization analyses using genetic summary statistics, no putative causal relationships were identified between COVID-19 related outcomes and hematological indices after adjusting for multiple testing. We observed overlapping genetic association signals between hematological parameters and COVID-19 traits. For example, we observed overlap between infection susceptibility-associated variants atPPP1R15Aand red blood cell parameters, and between disease severity-associated variants atTYK2and lymphocyte and platelet phenotypes.ConclusionsWe did not find convincing evidence of a relationship between baseline hematological parameters and susceptibility to SARS-CoV-2 infection or COVID-19 severity, though this relationship should be re-examined as larger and better-powered genetic analyses of SARS-CoV-2 infection and severe COVID-19 become available.
Impact of the representation of contact data on the evaluation of interventions in infectious diseases simulations
Authors: Contreras Diego Andrés , Colosi Elisabetta , Bassignana Giulia , Colizza Vittoria , Barrat Alain 
Published: March 2022

AbstractComputational models offer a unique setting to test strategies to mitigate infectious diseases’ spread, providing useful insights to applied public health. To be actionable, models need to be informed by data, which can be available at different levels of detail. While high resolution data describing contacts between individuals are increasingly available, data gathering remains challenging, especially during a health emergency: many models thus use synthetic data or coarse information to evaluate intervention protocols. Here, we evaluate how the representation of contact data might affect the impact of various strategies in models, in the realm of COVID-19 transmission in educational and work contexts. Starting from high resolution contact data, we use data representations ranging from very detailed to very coarse to inform a model for the spread of SARS-CoV-2 and simulate several mitigation strategies. We find that coarse data representations underestimate the risk of super-spreading events. However, the rankings of protocols according to their efficiency or cost remain coherent across representations, ensuring the consistency of model findings to inform public health advice. Caution should be taken, however, on the quantitative estimations of those benefits and costs that may trigger the adoption of protocols, as these may depend on data representation.
Extracellular vesicles and high-density lipoproteins: Exercise and estrogen-responsive small RNA carriers
Authors: Karvinen Sira , Korhonen Tia-Marje , Sievänen Tero , Karppinen Jari E. , Juppi Hanna-Kaarina , Jakoaho Veera , Kujala Urho M. , Laukkanen Jari A. , Lehti Maarit , Laakkonen Eija K. 
Published: March 2022

SUMMARYDecreased systemic estrogen levels (i.e., menopause) affect metabolic health. However, the detailed mechanisms underlying this process remain unclear. Both estrogens and exercise have been shown to improve metabolic health, which may be partly mediated by circulating microRNA (c-miR) signaling. In recent years, extracellular vesicles (EV) have increased interest in the field of tissue crosstalk. However, in many studies on EV-carried miRs, the co-isolation of high-density lipoprotein (HDL) particles with EVs has not been considered, potentially affecting the results. Here, we demonstrate that EV and HDL particles have distinct small RNA (sRNA) content, including both host and nonhost sRNAs. Exercise caused an acute increase in relative miR abundancy in EVs, whereas in HDL particles, it caused an increase in transfer RNA-derived sRNA. Furthermore, we demonstrate that estrogen deficiency caused by menopause blunts acute exercise-induced systemic miR-response in both EV and HDL particles.HIGHLIGHTSExtracellular vesicles and HDL particles have a distinct sRNA contentExtracellular vesicles and HDL particles carry both host and nonhost sRNA cargoEstrogen deficiency blunts the c-miR-response induced by acute exerciseExercise responsive miRs in HT users may regulate the choice of energy substrate
Stress induced TDP-43 mobility loss independent of stress granules
Authors: Streit Lisa , Kuhn Timo , Vomhof Thomas , Ludolph Albert C. , Weishaupt Jochen H. , Gebhardt J. Christof M. , Michaelis Jens , Danzer Karin M. 
Published: March 2022

AbstractTAR DNA binding protein 43 (TDP-43) is closely related to the pathogenesis of amyotrophic lateral sclerosis (ALS) and translocates to stress granules (SGs). The role of SGs as aggregation-promoting “bioreactors” for TDP-43, however, is still under debate. We analyzed TDP-43 mobility and localization under different stress and recovery conditions using live cell single-molecule tracking and super-resolution microscopy. Besides reduced mobility within SGs, a stress induced decrease of TDP-43 mobility in the cytoplasm and the nucleus was observed. Stress removal led to a recovery of TDP-43 mobility, which strongly depended on the stress duration. ‘Stimulated-emission depletion microscopy’ (STED) and ‘tracking and localization microscopy’ (TALM) revealed not only TDP-43 substructures within stress granules but also numerous patches of slow TDP-43 species throughout the cytoplasm. The data provide new insights into the aggregation of TDP-43 in living cells and provide evidence suggesting that TDP-43 oligomerization takes place in the cytoplasm separate from SGs.
Architecture of the yeast Pol III pre-termination complex and pausing mechanism on poly-dT termination signals
Authors: Girbig Mathias , Xie Juanjuan , Grötsch Helga , Libri Domenico , Porrua Odil , Müller Christoph W. 
Published: March 2022

ABSTRACTRNA polymerase (Pol) III is specialized to transcribe short, abundant RNAs, for which it terminates transcription on poly-thymine (dT) stretches on the non-template (NT) strand. When Pol III reaches the termination signal, it pauses and forms the pre-termination complex (PTC). Here, we report cryo-EM structures of the yeast Pol III PTC and complementary functional states at 2.7-3.9 Å resolution. Pol III recognizes the poly-dT termination signal with subunit C128 that forms a hydrogen-bond network with the NT-strand and, thereby, induces pausing. Mutating key interacting residues interferes with transcription termination in vitro, impairs yeast growth, and causes global termination defects in vivo confirming our structural results. Additional cryo-EM analysis reveals that C53-C37, a Pol III subcomplex and key termination factor, participates indirectly in Pol III termination. We propose a mechanistic model of Pol III transcription termination and rationalize why Pol III, unlike Pol I and Pol II, terminates on poly-dT signals.
Hominoid-specific sulcal variability is related to face perception ability
Authors: Parker Benjamin J. , Voorhies Willa I. , Jiahui Guo , Miller Jacob A. , Willbrand Ethan , Hallock Tyler , Furl Nicholas , Garrido Lúcia , Duchaine Brad , Weiner Kevin S. 
Published: March 2022

ABSTRACTHuman perception requires complex cortical networks that function at neuroanatomical scales of microns and temporal scales of milliseconds. Despite this complexity, what if just one morphological feature of the brain could predict perceptual ability? Here, we tested this hypothesis with pre-registered analyses of neuroanatomy and face perception in neurotypical controls (NTs) and individuals with developmental prosopagnosia (DPs). Results show that the length of the mid-fusiform sulcus (MFS), a hominoid-specific tertiary sulcus in ventral temporal cortex (VTC), was shorter in DPs than NTs. Furthermore, individual differences in MFS length in the right, but not left, hemisphere predicted individual differences in face perception. These results support theories linking brain structure and function to perception, as well as indicate that one feature – variability in MFS length – can predict face perception. Finally, these findings add to growing evidence supporting a role of morphological variability of late developing, tertiary sulci and individual differences in cognition.
Integrative analysis of transcriptomics in human craniofacial development reveals novel candidate disease genes
Authors: Yankee Tara N. , Wilderman Andrea , Winchester Emma Wentworth , VanOudenhove Jennifer , Cotney Justin 
Published: March 2022

SummaryCraniofacial disorders are among the most common of all congenital defects. A majority of craniofacial development occurs early in pregnancy and to fully understand how craniofacial defects arise, it is essential to observe gene expression during this critical time period. To address this we performed bulk and single-cell RNA-seq on human craniofacial tissue from embryonic development 4 to 8 weeks post conception. This data comprises the most comprehensive profiling of the transcriptome in the early developing human face to date. We identified 239 genes that were specifically expressed in craniofacial tissues relative to dozens of other human tissues and stages. We found that craniofacial specific enhancers are enriched within 400kb of these genes establishing putative regulatory interactions. To further understand how genes are organized in this program we constructed coexpression networks. Strong disease candidates are likely genes that are coexpressed with many other genes, serving as regulatory hubs within these networks. We leveraged large functional genomics databases including GTEx and GnomAD to reveal hub genes that are specifically expressed in craniofacial tissue and genes which are resistant to mutation in the normal healthy population. Our unbiased method revealed dozens of novel disease candidate genes that warrant further study.
Complex extracellular biology drives surface competition inBacillus subtilis
Authors: Jautzus Theresa , van Gestel Jordi , Kovács Ákos T. 
Published: March 2022

AbstractIn nature, many bacteria grow on surfaces, where they form cell collectives that compete for space. Within these collectives, cells often secrete molecules that benefit surface spreading by, for example, reducing surface tension or promoting filamentous growth. Although we have a detailed understanding of how these molecules are produced, much remains unknown about their role in surface competition. Here, we examine sliding motility inBacillus subtilisand compare how secreted molecules, essential for sliding, affect cooperation and competition on the surface. We specifically examine (i) the lipopeptide surfactin, (ii) the hydrophobin protein BslA and (iii) exopolysaccharides (EPS). We find that these molecules have a remarkably different effect on competition: whereas surfactin acts like a common good, which is costly to produce and benefits cells throughout the surface, BslA and EPS are cost-free and act locally. Accordingly, surfactin deficient mutants can exploit the wild-type strain in competition for space, while BslA and EPS mutants cannot. Using a mathematical model, we show that three factors are important in predicting the outcome of surface competition: the costs of molecule synthesis, the private benefits of molecule production, and the diffusion rate. Our results underscore the intricate extracellular biology that can drive bacterial surface competition.
The trait specific timing of accelerated genomic change in the human lineage
Authors: Kun Eucharist , Sohail Mashaal , Narasimhan Vagheesh M. 
Published: March 2022

SummaryHumans exhibit distinct characteristics compared to our primate and ancient hominin ancestors including bipedal locomotion and enhanced neurocognitive ability, but the timing of accelerated changes in these traits is uncertain. To investigate if specific trait-associated variation show enrichment during particular periods of human evolution, we combine genome wide association study (GWAS) data from 70 traits, spanning multiple categories including AI-based image-derived morphological phenotypes of the brain, heart, and skeletal tissues with data from 12 different evolutionary regions obtained from comparative functional genomics, multi-species alignments from long read sequencing, and ancient DNA reflecting 4 different major evolutionary divergence points. These regions cover epigenetic differences in the brain between humans and rhesus macaques, various human accelerated regions (HARs) including regions from the Zoonomia Project, ancient selective sweeps, and Neanderthal introgressed alleles. Using two complementary approaches to examine enrichment between GWAS loci and genomic regions, we show that more phenotypes are enriched in earlier periods of divergence of humans with macaques and chimps, and less so during the divergence with Neanderthals. These traits span respiratory, dermatological, reproductive, metabolic, and psychiatric domains along with skeletal and brain imaging traits, consistent with striking morphological changes between humans and other primates. Among brain imaging traits, we observe an enrichment of SNPs associated with the longitudinal fasciculus in human-gained epigenetic elements since macaques, the visual cortex in HARs, and the thalamus proper in Neanderthal introgressed alleles, implying associated functions such as language processing, decision making, relay of sensory signals, and motor control are enriched at different evolutionary depths.