bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection
Authors: Gupta Rishi K. , Rosenheim Joshua , Bell Lucy C. , Chandran Aneesh , Guerra-Assuncao Jose A. , Pollara Gabriele , Whelan Matthew , Artico Jessica , Joy George , Kurdi Hibba , Altmann Daniel M. , Boyton Rosemary , Maini Mala , McKnight Aine , Lambourne Jonathan , Cutino-moguel Teresa , Manisty Charlotte , Treibel Thomas A. , Moon James C , Chain Benjamin , Noursadeghi Mahdad 
Published: January 2021

AbstractWe hypothesised that host-response biomarkers of viral infections may contribute to early identification of SARS-CoV-2 infected individuals, critical to breaking chains of transmission. We identified 20 candidate blood transcriptomic signatures of viral infection by systematic review and evaluated their ability to detect SARS-CoV-2 infection, compared to the gold-standard of virus PCR tests, among a prospective cohort of 400 hospital staff subjected to weekly testing when fit to attend work. The transcriptional signatures had limited overlap, but were mostly co-correlated as components of type 1 interferon responses. We reconstructed each signature score in blood RNA sequencing data from 41 individuals over sequential weeks spanning a first positive SARS-CoV-2 PCR, and after 6-month convalescence. A single blood transcript for IFI27 provided the highest accuracy for discriminating individuals at the time of their first positive viral PCR result from uninfected controls, with area under the receiver operating characteristic curve (AUROC) of 0.95 (95% confidence interval 0.91–0.99), sensitivity 0.84 (0.7–0.93) and specificity 0.95 (0.85–0.98) at a predefined test threshold. The test performed equally well in individuals with and without symptoms, correlated with viral load, and identified incident infections one week before the first positive viral PCR with sensitivity 0.4 (0.17–0.69) and specificity 0.95 (0.85–0.98). Our findings strongly support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection, for screening individuals such as contacts of index cases, in order to facilitate early case isolation and early antiviral treatments as they emerge.
Forecasting the Spread of the COVID-19 Epidemic in Lombardy: A Dynamic Model Averaging Approach
Authors: Gianmoena Lisa , Rios Vicente 
Published: January 2021

AbstractForecasting with accuracy the evolution of COVID-19 daily incidence curves is one of the most important exercises in the field of epidemic modeling. We examine the forecastability of daily COVID-19 cases in the Italian region of Lombardy using Dynamic Model Averaging and Dynamic Model Selection methods. To investigate the predictive accuracy of this approach, we compute forecast performance metrics of sequential out-of-sample real-time forecasts in a back-testing exercise ranging from March 1 to December 10 of 2020. We find that (i) Dynamic Model Averaging leads to a consistent and substantial predictive improvements over alternative epidemiological models and machine learning approaches when producing short-run forecasts. Using estimated posterior inclusion probabilities we also provide evidence on which set of predictors are relevant for forecasting in each period. Our findings also suggest that (ii) future incidences can be forecasted by exploiting information on the epidemic dynamics of neighboring regions, human mobility patterns, pollution and temperatures levels.
Learning from pandemics: using extraordinary events can improve disease now-casting models
Authors: Mesquita Sara , Vieira Cláudio Haupt , Perfeito Lília , Gonçalves-Sá Joana 
Published: January 2021

ABSTRACTOnline searches have been used to study different health-related behaviours, including monitoring disease outbreaks. An obvious caveat is that several reasons can motivate individuals to seek online information and models that are blind to people’s motivations are of limited use and can even mislead. This is particularly true during extraordinary public health crisis, such as the ongoing pandemic, when fear, curiosity and many other reasons can lead individuals to search for health-related information, masking the disease-driven searches. However, health crisis can also offer an opportunity to disentangle between different drivers and learn about human behavior. Here, we focus on the two pandemics of the 21st century (2009-H1N1 flu and Covid-19) and propose a methodology to discriminate between search patterns linked to general information seeking (media driven) and search patterns possibly more associated with actual infection (disease driven). We show that by learning from such pandemic periods, with high anxiety and media hype, it is possible to select online searches and improve model performance both in pandemic and seasonal settings. Moreover, and despite the common claim that more data is always better, our results indicate that lower volume of the right data can be better than including large volumes of apparently similar data, especially in the long run. Our work provides a general framework that can be applied beyond specific events and diseases, and argues that algorithms can be improved simply by using less (better) data. This has important consequences, for example, to solve the accuracy-explainability trade-off in machine-learning.
RhoA within myofibers controls satellite cell microenvironment to allow hypertrophic growth
Authors: Noviello Chiara , Kobon Kassandra , Delivry Léa , Guilbert Thomas , Julienne Francis , Maire Pascal , Randrianarison-Huetz Voahangy , Sotiropoulos Athanassia 
Published: January 2021

SummaryAdult skeletal muscle is a plastic tissue that can adapt its size to workload. Here, we show that RhoA within myofibers is needed for overload-induced hypertrophy by controlling satellite cell fusion to the growing myofibers without affecting protein synthesis. At the molecular level, we demonstrate that, in response to increased workload, RhoA controls in a cell autonomous manner Erk1/2 activation and the expressions of extracellular matrix (ECM) regulators such asMmp9/Mmp13/Adam8and of macrophage chemo-attractants such asCcl3/Cx3cl1.Their decreased expression in RhoA mutant is associated with ECM and fibrillar collagen disorganization and lower macrophage infiltration. Moreover, Mmps inhibition and macrophage depletion in controls phenocopied the lack of growth of RhoA mutants. These findings unravel the implication of RhoA within myofibers, in response to increase load, in the building of a permissive microenvironment for muscle growth and for satellite cell accretion through ECM remodeling and inflammatory cell recruitment.
Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera
Authors: Muik Alexander , Wallisch Ann-Kathrin , Sänger Bianca , Swanson Kena A. , Mühl Julia , Chen Wei , Cai Hui , Sarkar Ritu , Türeci Özlem , Dormitzer Philip R. , Sahin Ugur 
Published: January 2021

AbstractRecently, a new SARS-CoV-2 lineage called B.1.1.7 has emerged in the United Kingdom that was reported to spread more efficiently than other strains. This variant has an unusually large number of mutations with 10 amino acid changes in the spike protein, raising concerns that its recognition by neutralizing antibodies may be affected. Here, we investigated SARS-CoV-2-S pseudoviruses bearing either the Wuhan reference strain or the B.1.1.7 lineage spike protein with sera of 16 participants in a previously reported trial with the mRNA-based COVID-19 vaccine BNT162b2. The immune sera had equivalent neutralizing titers to both variants. These data, together with the combined immunity involving humoral and cellular effectors induced by this vaccine, make it unlikely that the B.1.1.7 lineage will escape BNT162b2-mediated protection.
Primer biases in the molecular assessment of diet in multiple insectivorous mammals
Authors: Browett Samuel S. , Curran Thomas G. , O’Meara Denise B. , Harrington Andrew P. , Sales Naiara Guimarães , Antwis Rachael E. , O’Neill David , McDevitt Allan D. 
Published: January 2021

AbstractOur understanding of trophic interactions of small insectivorous mammals has been drastically improved with the advent of DNA metabarcoding. The technique has continued to be optimised over the years, with primer choice repeatedly being a vital factor for dietary inferences. However, the majority of dietary studies examining the effect of primer choice often rely onin silicoanalyses or comparing single-niche species. Here we apply DNA metabarcoding to empirically compare the prey detection capabilities of two widely used primer sets when assessing the diets of a flying (lesser horseshoe bat;Rhinolophus hipposideros) and two ground dwelling insectivores (greater white-toothed shrew;Crocidura russulaand pygmy shrew;Sorex minutus). AlthoughR. hipposiderosprimarily rely on two prey orders (Lepidoptera and Diptera), the unique taxa detected by each primer shows that a combination of primers may be the best approach to fully describe bat trophic ecology. However, random forest classifier analysis suggest that one highly degenerate primer set detected the majority of both shrews’ diet despite higher levels of host amplification. The wide range of prey consumed by ground-dwelling insectivores can therefore be accurately documented from using a single broad-range primer set, which can decrease cost and labour. The results presented here show that dietary inferences will differ depending on the primer or primer combination used for insectivores occupying different niches (i.e. hunting in the air or ground) and demonstrate the importance of performing empirical pilot studies for novel study systems.
Conserved Architecture of Brain Transcriptome Changes between Alzheimer’s Disease and Progressive Supranuclear Palsy in Pathologically Affected and Unaffected Regions
Authors: Wang Xue , Allen Mariet , Reddy Joseph S. , Carrasquillo Minerva M. , Asmann Yan W. , Funk Cory , Nguyen Thuy T. , Malphrus Kimberly G. , Younkin Steven G. , Dickson Dennis W. , Price Nathan D. , Golde Todd E. , Ertekin-Taner Nilüfer 
Published: January 2021

AbstractWe identify a striking correlation in the directionality and magnitude of gene expression changes in brain transcriptomes between Alzheimer’s disease (AD) and Progressive Supranuclear Palsy (PSP). Further, the transcriptome architecture in AD and PSP is highly conserved between the temporal and cerebellar cortices, indicating highly similar transcriptional changes occur in pathologically affected and “unaffected” areas of the brain. These data have broad implications for interpreting transcriptomic data in neurodegenerative disorders.
Interaction Between Phosphoinositide 3-Kinase and the VDAC2 Channel Tethers Endosomes to Mitochondria and Promotes Endosome Maturation
Authors: Satoh Aya O. , Fujioka Yoichiro , Kashiwagi Sayaka , Yoshida Aiko , Fujioka Mari , Sasajima Hitoshi , Nanbo Asuka , Amano Maho , Ohba Yusuke 
Published: January 2021

SUMMARYIntracellular organelles of mammalian cells communicate with each other during various cellular processes. The functions and molecular mechanisms of such interorganelle association remain largely unclear, however. We here identified voltage-dependent anion channel 2 (VDAC2), a mitochondrial outer membrane protein, as a binding partner of phosphoinositide 3-kinase (PI3K), a regulator of clathrin-independent endocytosis downstream of the small GTPase Ras. VDAC2 was found to tether endosomes positive for the Ras-PI3K complex to mitochondria in response to cell stimulation with epidermal growth factor and to promote clathrin-independent endocytosis as well as endosome maturation at membrane contact sites. With a newly developed optogenetics system to induce mitochondrion-endosome association, we found that, in addition to its structural role in such association, the pore function of VDAC2 is also required for the promotion of endosome maturation. Our findings thus uncover a previously unappreciated role of mitochondrion-endosome association in the regulation of endocytosis and endosome maturation.HighlightsThe mitochondrial protein VDAC2 binds PI3K and tethers endosomes to mitochondriaVDAC2 promotes clathrin-independent endocytosisVDAC2-PI3K interaction induces acidification of endosomes associated with mitochondriaThe pore function of VDAC2 also contributes to endosome maturation at contact sites
A nexus of intrinsic dynamics underlies translocase priming
Authors: Krishnamurthy Srinath , Eleftheriadis Nikolaos , Karathanou Konstantina , Smit Jochem H. , Portaliou Athina G. , Chatzi Katerina E. , Karamanou Spyridoula , Bondar Ana-Nicoleta , Gouridis Giorgos , Economou Anastassios 
Published: January 2021

SummaryThe cytoplasmic ATPase SecA and the membrane-embedded SecYEG channel assemble to form the functional Sec translocase. How this interaction primes and catalytically activates the translocase remains unclear. We now show that priming exploits a sophisticated nexus of intrinsic dynamics in SecA. Using atomistic simulations, single molecule FRET and hydrogen/deuterium exchange mass spectrometry we reveal multiple distributed dynamic islands that cross-talk with domain and quaternary motions. These dynamic elements are highly conserved and essential for function. Central to the nexus is a slender Stem through which, motions in the helicase ATPase domain of SecA biases how the preprotein binding domain rotates between open-closed clamping states. Multi-tier dynamics are enabled by an H-bonded framework covering most of the SecA structure and allowing conformational alterations with minimal energy inputs. As a result, dimerization, the channel and nucleotides select pre-existing conformations, and alter local dynamics to restrict or promote catalytic activity and clamp motions. These events prime the translocase for high affinity reception of non-folded preprotein clients. Such dynamics nexuses are likely universal and essential in multi-liganded protein machines.
A Chromosome-scale draft genome sequence of horsegram (Macrotyloma uniflorum)
Authors: Shirasawa Kenta , Chahota Rakesh , Hirakawa Hideki , Nagano Soichiro , Nagasaki Hideki , Sharma Tilak , Isobe Sachiko 
Published: January 2021

SummaryHorsegram [Macrotyloma uniflorum(Lam.) Verdc.] is an underutilized warm season diploid legume (2n=20, 22), It is consumed as a food legume in India, and animal feed and fodder in Africa and Australia. Because of its ability to grow under water-deficient and marginal soil conditions, horsegram is a preferred choice in the era of the global climatic change. In recognition of its potential as a crop species, we generated and analyzed a draft genome sequence for HPK-4. The genome sequences of HPK-4 were generated by Illumina platform. Ten chromosome-scale pseudomolecules were created by aligning scaffold sequences onto a linkage map. The total length of the ten pseudomolecules were 259.2 Mb, covering 89% of the total length of the assembled sequences. A total of 36,105 genes were predicted on the assembled sequences, and 14,736 were considered to be horsegram specific genes by comparative analysis withPhaseolus. vulgaris,Vigna. angularis,Lotus. japonicusandArabidopsis. thaliana. The results of macrosynteny analysis suggested that the genome structure ofV. angularisis more similar to horsegram than that ofP. vulgaris.Diversity analysis in the 91 accessions of horsegram with dd-RAD-Seq analysis indicated narrow genetic diversity among the horsegram accessions. This is the first attempt to generate a draft genome sequence in horsegram and will provide a reference for sequence-based analysis of the horsegram germplasm to elucidate the genetic basis of important traits.
Human Neural Stem Cells Differentiate and Integrate, Innervating Implanted zQ175 Huntington’s Disease Mouse Striatum
Authors: Holley Sandra M. , Reidling Jack C. , Cepeda Carlos , Lau Alice , Moore Cindy , Orellana Iliana , Fury Brian , Kopan Lexi , Yeung Sylvia , Neel Michael , Coleal-Bergum Dane , Monuki Edwin S. , Meshul Charles K. , Bauer Gerhard , Levine Michael S. , Thompson Leslie M. 
Published: January 2021

AbstractHuntington’s disease (HD), a genetic neurodegenerative disorder, primarily impacts the striatum and cortex with progressive loss of medium-sized spiny neurons (MSNs) and pyramidal neurons, disrupting cortico-striatal circuitry. A promising regenerative therapeutic strategy of transplanting human neural stem cells (hNSCs) is challenged by the need for long-term functional integration. We previously described that hNSCs transplanted into the striatum of HD mouse models differentiated into electrophysiologically active immature neurons, improving behavior and biochemical deficits. Here we show that 8-month implantation of hNSCs into the striatum of zQ175 HD mice ameliorates behavioral deficits, increases brain-derived neurotrophic factor (BDNF) and reduces mutant Huntingtin (mHTT) accumulation. Patch clamp recordings, immunohistochemistry and electron microscopy demonstrates that hNSCs differentiate into diverse neuronal populations, including MSN- and interneuron-like cells. Remarkably, hNSCs receive synaptic inputs, innervate host neurons, and improve membrane and synaptic properties. Overall, the findings support hNSC transplantation for further evaluation and clinical development for HD.
ACVR1R206Hincreases osteogenic/ECM gene expression and impairs myofiber formation in human skeletal muscle stem cells
Authors: Barruet Emilie , Garcia Steven M. , Wu Jake , Morales Blanca M. , Tamaki Stanley , Moody Tania , Pomerantz Jason H. , Hsiao Edward C. 
Published: January 2021

AbstractAbnormalities in skeletal muscle repair lead to poor function and complications such as scarring or heterotopic ossification (HO). Here, we use fibrodysplasia ossificans progressiva (FOP), a disease of progressive HO caused by ACVR1R206H(Activin receptor type-1 receptor) mutation, to elucidate how ACVR1 affects skeletal muscle repair. Rare and unique primary FOP human muscle stem cells (Hu-MuSCs) isolated from cadaveric skeletal muscle demonstrated increased ECM marker expression, and showed skeletal muscle-specific impaired engraftment and regeneration ability. Human induced pluripotent stem cell (iPSC)-derived muscle stem/progenitor cells (iMPCs) Single cell transcriptome analyses from FOP also revealed unusually increased ECM and osteogenic marker expression compared to control iMPCs. These results show that iMPCs can recapitulate many aspects of Hu-MuSCs for detailed in vitro study, that ACVR1 is a key regulator of Hu-MuSC function and skeletal muscle repair; and that ACVR1 activation in iMPCs or Hu-MuSCs contributes to HO by changing the local tissue environment.
Single-cell trajectory inference guided enhancement of thyroid maturationin vitrousing TGF-beta inhibition
Authors: Romitti Mírian , Eski Sema Elif , Fonseca Barbara Faria , Singh Sumeet Pal , Costagliola Sabine 
Published: January 2021

AbstractThe thyroid gland regulates metabolism and growth via secretion of thyroid hormones by thyroid follicular cells (TFCs). Loss of TFCs, by cellular dysfunction, autoimmune destruction or surgical resection, underlies hypothyroidism. Recovery of thyroid hormone levels by transplantation of mature TFCs derived from stem cellsin vitroholds great therapeutic promise. However, the utilization ofin vitroderived tissue for regenerative medicine is restricted by the efficiency of differentiation protocols to generate mature organoids. Here, to improve the differentiation efficiency for thyroid organoids, we utilized single-cell RNA-Seq to chart the molecular steps undertaken by individual cells during thein vitrotransformation of mouse embryonic stem cells to TFCs. Our single-cell atlas of mouse organoid systematically and comprehensively identifies, for the first time, the cell types generated during production of thyroid organoids. Using pseudotime analysis, we identify TGF-beta and planar-cell polarity (PCP) pathways as regulators of thyroid maturationin vitro. Using pharmacological manipulation of TGF-beta pathway, we improve the level of thyroid maturation, in particular the induction ofNisexpression. This in turn, leads to an enhancement of iodide organificationin vitro, suggesting functional improvement of the thyroid organoid. Our study highlights the potential of single-cell molecular characterization in understanding and improving thyroid maturation and paves the way for identification of therapeutic targets against thyroid disorders.
Computational and experimental approaches to controlling bacterial microcompartment assembly
Authors: Li Yaohua , Kennedy Nolan W. , Li Siyu , Mills Carolyn E. , Tullman-Ercek Danielle , de la Cruz Monica Olvera 
Published: January 2021

AbstractBacterial microcompartments compartmentalize the enzymes that aid chemical and energy production in many bacterial species. These protein organelles are found in various bacterial phyla and are postulated to help many of these organisms survive in hostile environments such as the gut of their hosts. Metabolic engineers are interested in repurposing these organelles for non-native functions. Here, we use computational, theoretical and experimental approaches to determine mechanisms that effectively control microcompartment self-assembly. As a model system, we find via multiscale modeling and mutagenesis studies, the interactions responsible for the binding of hexamer-forming proteins propanediol utilization bacterial microcompartments from Salmonella and establish conditions that form various morphologies. We determine how the changes in the microcompartment hexamer protein preferred angles and interaction strengths can modify the assembled morphologies including the naturally occurring polyhedral microcompartment shape, as well as other extended shapes or quasi-closed shapes. We demonstrate experimentally that such altered strengths and angles are achieved via amino acid mutations. A thermodynamic model that agrees with the coarse-grained simulations provides guidelines to design microcompartments. These findings yield insight in controlled protein assembly and provide principles for assembling microcompartments for biochemical or energy applications as nanoreactors.