bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global BioID-based SARS-CoV-2 proteins proximal interactome unveils novel ties between viral polypeptides and host factors involved in multiple COVID19-associated mechanisms
Authors: Laurent Estelle M.N. , Sofianatos Yorgos , Komarova Anastassia , Gimeno Jean-Pascal , Tehrani Payman Samavarchi , Kim Dae-Kyum , Abdouni Hala , Duhamel Marie , Cassonnet Patricia , Knapp Jennifer J. , Kuang Da , Chawla Aditya , Sheykhkarimli Dayag , Rayhan Ashyad , Li Roujia , Pogoutse Oxana , Hill David E. , Calderwood Michael A. , Falter-Braun Pascal , Aloy Patrick , Stelzl Ulrich , Vidal Marc , Gingras Anne-Claude , Pavlopoulos Georgios A. , Van Der Werf Sylvie , Fournier Isabelle , Roth Frederick P. , Salzet Michel , Demeret Caroline , Jacob Yves , Coyaud Etienne 
Published: August 2020

AbstractThe worldwide SARS-CoV-2 outbreak poses a serious challenge to human societies and economies. SARS-CoV-2 proteins orchestrate complex pathogenic mechanisms that underlie COVID-19 disease. Thus, understanding how viral polypeptides rewire host protein networks enables better-founded therapeutic research. In complement to existing proteomic studies, in this study we define the first proximal interaction network of SARS-CoV-2 proteins, at the whole proteome level in human cells. Applying a proximity-dependent biotinylation (BioID)-based approach greatly expanded the current knowledge by detecting interactions within poorly soluble compartments, transient, and/or of weak affinity in living cells. Our BioID study was complemented by a stringent filtering and uncovered 2,128 unique cellular targets (1,717 not previously associated with SARS-CoV-1 or 2 proteins) connected to the N- and C-ter BioID-tagged 28 SARS-CoV-2 proteins by a total of 5,415 (5,236 new) proximal interactions. In order to facilitate data exploitation, an innovative interactive 3D web interface was developed to allow customized analysis and exploration of the landscape of interactions (accessible athttp://www.sars-cov-2-interactome.org/). Interestingly, 342 membrane proteins including interferon and interleukin pathways factors, were associated with specific viral proteins. We uncovered ORF7a and ORF7b protein proximal partners that could be related to anosmia and ageusia symptoms. Moreover, comparing proximal interactomes in basal and infection-mimicking conditions (poly(I:C) treatment) allowed us to detect novel links with major antiviral response pathway components, such as ORF9b with MAVS and ISG20; N with PKR and TARB2; NSP2 with RIG-I and STAT1; NSP16 with PARP9-DTX3L. Altogether, our study provides an unprecedented comprehensive resource for understanding how SARS-CoV-2 proteins orchestrate host proteome remodeling and innate immune response evasion, which can inform development of targeted therapeutic strategies.
Non-Refoldability is Pervasive Across theE. coliProteome
Authors: To Philip , Whitehead Briana , Tarbox Haley E. , Fried Stephen D. 
Published: August 2020

AbstractThe foundational paradigm of protein folding is that the primary sequence of a protein contains all the information needed for it to adopt a specific native structure1,2. This remarkable property is explained by Anfinsen’s thermodynamic hypothesis3,4, which asserts that because native states minimize the Gibbs free energy of a protein molecule under physiological conditions, proteins can reliably navigate to their native structures and remain in those states by ergodically sampling their free energy landscapes5. Most experiments of protein folding – conducted on purified, small, single-domain soluble proteins – follow the proportion of protein molecules that are folded as a function of time, temperature, denaturant concentration, or sequence6–8, and have yielded immense insight into the molecular determinants that underpin stable globular folds9,10. However, our reliance on the thermodynamic hypothesis as a ground truth to interpret these experiments has limited our ability to study the folding of complex proteins or to consider alternative non-thermodynamic scenarios11,12. Here, we introduce an experimental approach to probe protein refolding for whole proteomes. We accomplish this by first unfolding and refoldingE. colilysates, and then interrogating the resulting protein structures using a permissive protease that preferentially cleaves at flexible regions. Using mass spectrometry, we analyze the digestion patterns to globally assess structural differences between native and ‘refolded’ proteins. These studies reveal that following denaturation, many proteins are incapable of navigating back to their native structures. Our results signal a pervasive role for co-translational folding in shaping protein biogenesis, and suggest that the apparent stability of many native states derive fromkinetic persistencerather than thermodynamic stability.
The SARS-CoV-2 ORF10 is not essentialin vitroorin vivoin humans
Authors: Pancer Katarzyna , Milewska Aleksandra , Owczarek Katarzyna , Dabrowska Agnieszka , Branicki Wojciech , Sanak Marek , Pyrc Krzysztof 
Published: August 2020

AbstractSARS-CoV-2 genome annotation revealed the presence of 10 open reading frames (ORFs), of which the last one (ORF10) is positioned downstream the N gene. It is a hypothetical gene, which was speculated to encode a 38 aa protein. This hypothetical protein does not share sequence similarity with any other known protein and cannot be associated with a function. While the role of this ORF10 was proposed, there is a growing evidence showing that the ORF10 is not a coding region.Here, we identified SARS-CoV-2 variants in which the ORF10 gene was prematurely terminated. The disease was not attenuated, and the transmissibility between humans was not hampered. Alsoin vitro, the strains replicated similarly, as the related viruses with the intact ORF10. Altogether, based on clinical observation and laboratory analyses, it appears that the ORF10 protein is not essential in humans. This observation further proves that the ORF10 should not be treated as the protein-coding gene, and the genome annotations should be amended.
Shared heritability of face and brain shape distinct from cognitive traits
Authors: Naqvi Sahin , Sleyp Yoeri , Hoskens Hanne , Indencleef Karlijne , Spence Jeffrey P. , Bruffaerts Rose , Radwan Ahmed , Eller Ryan J. , Richmond Stephen , Shriver Mark D. , Shaffer John R. , Weinberg Seth M. , Walsh Susan , Thompson James , Pritchard Jonathan K. , Sunaert Stefan , Peeters Hilde , Wysocka Joanna , Claes Peter 
Published: August 2020

ABSTRACTEvidence from both model organisms and clinical genetics suggests close coordination between the developing brain and face1–8, but it remains unknown whether this developmental link extends to genetic variation that drives normal-range diversity of face and brain shape. Here, we performed a multivariate genome-wide association study of cortical surface morphology in 19,644 European-ancestry individuals and identified 472 genomic loci influencing brain shape at multiple levels. We discovered a substantial overlap of these brain shape association signals with those linked to facial shape variation, with 76 common to both. These shared loci include transcription factors with cell-intrinsic roles in craniofacial development, as well as members of signaling pathways involved in brain-face crosstalk. Brain shape heritability is equivalently enriched near regulatory regions active in either brain organoids or in facial progenitor cells. However, brain shape association signals shared with face shape are distinct from those shared with behavioral-cognitive traits or neuropsychiatric disorder risk. Together, we uncover common genetic variants and candidate molecular players underlying brain-face interactions. We propose that early in embryogenesis, the face and the brain mutually shape each other through a combination of structural effects and paracrine signaling, but this interplay may have little impact on later brain development associated with cognitive function.
Silicon Nitride Inactivates SARS-CoV-2in vitro
Authors: Lehman Caitlin W. , Flur Rafaela , Kehn-Hall Kylene , McEntire Bryan J. , Bal B. Sonny , Bock Ryan M. 
Published: August 2020

ABSTRACTIntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, remains viable and therefore potentially infectious on several materials. One strategy to discourage the fomite-mediated spread of COVID-19 is the development of materials whose surface chemistry can spontaneously inactivate SARS-CoV-2. Silicon nitride (Si3N4), a material used in spine fusion surgery, is one such candidate because it has been shown to inactivate several bacterial species and viral strains. This study hypothesized that contact with Si3N4would inactivate SARS-CoV-2, while mammalian cells would remain unaffected.MaterialsSARS-CoV-2 virions (2×104PFU/mL diluted in growth media) were exposed to 5, 10, 15, and 20% (w/v) of an aqueous suspension of sintered Si3N4particles for durations of 1, 5, and 10 minutes, respectively. Before exposure to the virus, cytotoxicity testing of Si3N4alone was assessed in Vero cells at 24 and 48 hour post-exposure times. Following each exposure to Si3N4, the remaining infectious virus was quantitated by plaque assay.ResultsVero cell viability increased at 5% and 10% (w/v) concentrations of Si3N4at exposure times up to 10 minutes, and there was only minimal impact on cell health and viability up to 20% (w/v). However, the SARS-CoV-2 titers were markedly reduced when exposed to all concentrations of Si3N4; the reduction in viral titers was between 85% - 99.6%, depending on the dose and duration of exposure.ConclusionsSi3N4was non-toxic to the Vero cells while showing strong antiviral activity against SARS-CoV-2. The viricidal effect increased with increasing concentrations of Si3N4and longer duration of exposure. Surface treatment strategies based on Si3N4may offer novel methods to discourage SARS-CoV-2 persistence and infectivity on surfaces and discourage the spread of COVID-19.
Proximity labeling at non-centrosomal microtubule-organizing centers reveals VAB-10B and WDR-62 as distinct microtubule regulators
Authors: Sanchez Ariana D. , Branon Tess C. , Cote Lauren E. , Papagiannakis Alexandros , Liang Xing , Pickett Melissa A. , Shen Kang , Jacobs-Wagner Christine , Ting Alice Y. , Feldman Jessica L. 
Published: August 2020

SummaryReorganization of microtubules from the centrosome to non-centrosomal subcellular sites is central to cell differentiation. To identify components of non-centrosomal microtubule organizing centers in differentiated cells of a living organism, we developed the biotin ligase-based proximity labeling approach TurboID for use inC. elegans. We identified proteins proximal to the non-centrosomal microtubule minus end protein PTRN-1/Patronin at the apical membrane of epithelial cells, focusing on two conserved proteins: spectraplakin protein VAB-10B and WDR-62, a protein we identify as homologous to vertebrate primary microcephaly disease gene WDR62. We found that WDR-62 and VAB-10B independently regulate the growth and localization of non-centrosomal microtubules and the apical targeting of microtubule minus end proteins. This regulation occurs downstream of cell polarity and in conjunction with actin. Our data suggest a division of labor where microtubule growth and anchoring are regulated by distinct complexes and uncover novel functions of spectraplakins and WDR62 family proteins.
Endoderm Nitric Oxide Signals to Regulate Nascent Development of Cardiac Progenitors in Chicken Embryos
Authors: Shah Devan H. , Biswas Sujoy K. , Martin Adrian M. , Bianco Simone , Denetclaw Wilfred F. 
Published: August 2020

AbstractHeart development in the chicken embryo is regulated by a concert of cardiogenic morphogens and signaling molecules, but the physiological signal molecule nitric oxide(NO) has not been studied in the context of heart formation. A dynamic investigation of endoderm NO formation demonstrates for the first time a correlation with the established development events of the cardiac heart fields and heart tube. Manipulation of endoderm NO signaling demonstrate a role of NO signaling in the differentiation and proliferation of cardiac progenitors for heart tube formation and cardiac heart field development. To investigate NO in the proliferation of myocardial cells in the heart tube embryos, a computer vision based artificial intelligence approach is followed to automate the long and tedious job of counting cells in a large image dataset. We document NO as an important signaling molecule in the regulation of nascent embryonic cardiogenesis whose effects on other early cardiogenic morphogens is unknown.
Microbial bioprospecting for lignocellulose degradation at a unique Greek environment
Authors: Georgiadou Daphne N. , Avramidis Pavlos , Ioannou Efstathia , Hatzinikolaou Dimitris G. 
Published: August 2020

AbstractBacterial systems have gained wide attention for depolymerization of lignocellulosic biomass, due to their high functional diversity and adaptability. To achieve the full microbial exploitation of lignocellulosic residues and the cost-effective production of bioproducts within a biorefinery, multiple metabolic pathways and enzymes of various specificities are required. In this work, highly diverse aerobic, mesophilic bacteria enriched from Keri Lake, a pristine marsh of increased biomass degradation and natural underground oil leaks, were explored for their metabolic versatility and enzymatic potential towards lignocellulosic substrates. A wide diversity ofPseudomonasspecies were obtained from enrichment cultures where organosolv lignin served as the sole carbon and energy source and were able to assimilate a range of lignin-associated aromatic compounds. Highly complex bacterial consortia were also enriched in cultures with xylan or carboxymethyl cellulose as sole carbon sources, belonging to Actinobacteria, Proteobacteria, Bacilli, Sphingobacteriia, and Flavobacteria. Numerous individual isolates could target diverse structural lignocellulose polysaccharides by expressing hydrolytic activities on crystalline or amorphous cellulose and xylan. Specific isolates showed increased potential for growth in lignin hydrolysates prepared from alkali pretreated agricultural wastes. The results suggest that Keri isolates represent a pool of effective lignocellulose degraders with significant potential for industrial applications in a lignocellulose biorefinery.
Release probability increases towards distal dendrites boosting high-frequency signal transfer
Authors: Jensen Thomas P. , Kopach Olga , Savchenko Leonid P. , Reynolds James P. , Rusakov Dmitri A. 
Published: August 2020

ABSTRACTDendritic integration of synaptic inputs entangles their increased electrotonic attenuation at distal dendrites, which can be counterbalanced by the increased synaptic receptor density. However, during sustained network activity the influence of individual synapses depends on their release properties. How these properties are distributed along dendrites remains poorly understood. Here, we employed classical optical quantal analyses and a genetically encoded optical glutamate sensor in acute hippocampal slices to monitor release at CA3-CA1 synapses. We find that their release probability increases with greater distances from the soma. Similar-fidelity synapses tend to group together whereas release probability shows no trends regarding the within-branch position. Simulations with a realistic CA1 pyramidal cell hosting stochastic synapses suggest that the observed trends boost signal transfer fidelity, particularly at higher input frequencies. Because high-frequency bursting has been associated with learning, the release probability pattern we have found may play a key role in memory trace formation.
The connectome of the adultDrosophilamushroom body: implications for function
Authors: Li Feng , Lindsey Jack , Marin Elizabeth C. , Otto Nils , Dreher Marisa , Dempsey Georgia , Stark Ildiko , Bates Alexander Shakeel , Pleijzier Markus William , Schlegel Philipp , Nern Aljoscha , Takemura Shinya , Yang Tansy , Francis Audrey , Braun Amalia , Parekh Ruchi , Costa Marta , Scheffer Louis , Aso Yoshinori , Jefferis Gregory S. X. E. , Abbott L.F. , Litwin-Kumar Ashok , Waddell Scott , Rubin Gerald M. 
Published: August 2020

AbstractMaking inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) is well positioned for developing and testing such an approach due to its conserved neuronal architecture, recently completed dense connectome, and extensive prior experimental studies of its roles in learning, memory and activity regulation. Here we identify new components of the MB circuit inDrosophila, including extensive visual input and MB output neurons (MBONs) with direct connections to descending neurons. We find unexpected structure in sensory inputs, in the transfer of information about different sensory modalities to MBONs, and in the modulation of that transfer by dopaminergic neurons (DANs). We provide insights into the circuitry used to integrate MB outputs, connectivity between the MB and the central complex and inputs to DANs, including feedback from MBONs. Our results provide a foundation for further theoretical and experimental work.
A single cell trajectory of human archetypal pluripotent stem cell differentiation to trophoblast stem cells reveals induction of endogenous BMP5/7 and GATA3 without transitioning through a naive state
Authors: Tietze Ethan , Barbosa Andre Rocha , Silva Araujo Bruno Henrique , Euclydes Veronica , Cho Hyeon Jin , Lee Yong Kyu , Feltrin Arthur , Spiegelberg Bailey , Lorenzetti Alan , Leemput Joyce van de , Carlo Pasquale Di , Sawada Tomoyo , Ursini Gianluca , Benjamin Kynon J. , Brentani Helena , Kleinman Joel E. , Hyde Thomas M. , Weinberger Daniel R. , McKay Ronald , Shin Joo Heon , Paquola Apua C.M. , Erwin Jennifer A. 
Published: August 2020

AbstractThe human placenta is increasingly a focus of research related to early child development and the impact of maternal hyperimmune states. Primary human trophoblast stem cells (hTSC) and human pluripotent stem cells (hPSC) differentiated to hTSC can potentially model placental processesin vitro. Yet, it remains controversial how the differentiation of human pluripotent stem cells to trophectoderm relates toin vivodevelopment and the factors required for this differentiation. Here, we demonstrate that the primed pluripotent state retains potency to generate trophoblast stem cells by activating EGF and WNT and inhibiting TGFb, HDAC and ROCK signaling without exogenous BMP4 (named TS). We map this specification by temporal single cell RNAseq compared to activating BMP4 or activating BMP4 and inhibiting WNT. TS conditions generate a stable proliferating cell type that is highly similar to six-week placental cytotrophoblasts with activation of endogenous retroviral genes and without amnion expression. Multiple primed iPSC and ES lines differentiate to iPS-derived-TSCs that can be passaged for at least 30 passages and differentiate to pure populations of multinucleated syncytiotrophoblasts and extravillous trophoblast cells. Our findings establish that primed iPS cell specification to hTSC with TS conditions involves induction ofTMSB4X,BMP5/7, GATA3 andTFAP2Awithout transitioning through a naive state. Collectively, our results suggest that the primed state is on a continuum of potency and can differentiate to trophoblast stem cells via multiple paths.Significance StatementIn the present study, we map the specification of primed induced pluripotent stem cells to trophoblast stem cells (TSC). Primed iPS-derived-TSC share transcriptional, morphological and functional characteristics with humanex vivocytotrophoblasts including capacity of self-renewal and the ability to differentiate to pure extravillous and syncytiotrophoblasts. iPS-derived TSC display a uniquely active transcriptional network of human endogenous retroviruses similar toin vivotrophoblast. In addition, the fast conversion of primed iPSC to TSC allows for modeling placental diseases from large pluripotent stem cell cohorts which are traditionally banked at the primed state. Collectively, our results suggest that the primed state is on a continuum of potency which can differentiate to trophoblast stem cells via multiple paths.
Determinants of oversubscription of SME IPOs in India: evidence from quantile regression
Authors: Arora Nischay , Singh Balwinder 
Published: August 2020

PurposeThe study aims to measure the subscription level and examine the determinants of oversubscription of small and medium enterprise (SME) initial public offerings (IPOs) in India.Design/methodology/approachThe study employs cross sectional data to analyze 403 SME IPOs issued from Feb 2012 to May 2018 and listed on Bombay Stock Exchange's small and medium enterprise (BSE SME) platform and National Stock Exchange (NSE) EMERGE to investigate the determinants of oversubscription of SME IPOs. Hence, the study makes use of ordinary least square regression and quantile regression to test the hypotheses formulated for the determinants of oversubscription.FindingsThe main findings unveil that while issue price, pricing mechanism, listing delay negatively influence oversubscription; firm size, underwriter reputation, hot market and underpricing have been divulged to positively influence oversubscription. However, issue size emerged out to be significant in quantile regression at 25th, 50th and 75th quantiles.Research limitations/implicationsThe present study is confined to limited number of variables in understanding the factors impacting oversubscription. Future studies could include macroeconomic variables like gross domestic product (GDP), inflation rate, industry specific variable, i.e. technology/nontechnology industry, financial/nonfinancial industry for better understanding. Cross country analysis is suggested in future studies to validate the findings of current study. Future studies are advised to conduct the study examining the factors affecting oversubscription in light of COVID-19 pandemic.Practical implicationsThe findings of the present study offer implications to academicians, investors, investment advisors and regulators. It provides useful insights to researchers by listing the factors that contribute to variation in subscription levels in emerging economy like India thereby, paving the way for future researches in SME IPOs in countries with different institutional settings. For investors, the study provides additional and novel information useful for IPO valuation and informed investment decisions. In addition, the findings put investment advisors in better place to guide potential investors regarding investment in good quality SME stocks (i.e. highly subscribed stocks) in more informative manner. Last but not the least, as this study would assist the regulators in handling future IPOs in a way that augments the chances of success of SME IPOs.Originality/valueThis study is a novel contribution in widening the IPO literature by examining the relationship between pre-IPO firm actions like issue price, pricing mechanism, issue size, firm size, listing delay, underwriter reputation, hot market, underpricing and oversubscription in unexplored settings of Indian SME IPOs.