bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic diversity and hotspot mutations in 30,983 SARS-CoV-2 genomes: moving toward a universal vaccine for the “confined virus”?
Authors: Alouane Tarek , Laamarti Meriem , Essabbar Abdelomunim , Hakmi Mohammed , Bouricha EL Mehdi , Chemao-Elfihri M.W. , Kartti Souad , Boumajdi Nasma , Bendani Houda , Laamarti Rokia , Ghrifi Fatima , Allam Loubna , Aanniz Tarik , Ouadghiri Mouna , El Hafidi Naima , Jaoudi Rachid EL , Benrahma Houda , Elattar Jalil , Mentag Rachid , Sbabou Laila , Nejjari Chakib , Amzazi Saaid , Belyamani Lahcen , Ibrahimi Azeddine 
Published: June 2020

AbstractThe COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially for the development of a universal vaccine covering all circulating strains. From this perspective, we analyzed 30,983 complete SARS-CoV-2 genomes from 79 countries located in the six continents and collected from December 24, 2019, to May 13, 2020, according to the GISAID database. Our analysis revealed the presence of 3,206 variant sites, with a uniform distribution of mutation types in different geographic areas. Remarkably, a low frequency of recurrent mutations has been observed; only 169 mutations (5.27%) had a prevalence greater than 1% of genomes. Nevertheless, fourteen non-synonymous hotspot mutations (> 10%) have been identified at different locations along the viral genome; eight in ORF1ab polyprotein (in nsp2, nsp3, transmembrane domain, RdRp, helicase, exonuclease, and endoribonuclease), three in nucleocapsid protein and one in each of three proteins: spike, ORF3a, and ORF8. Moreover, 36 non-synonymous mutations were identified in the RBD of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human ACE2 receptor. These results along with mutational frequency dissimilarity and intra-genomic divergence of SARS-CoV-2 could indicate that the SARS-CoV-2 is not yet adapted to its host. Unlike the influenza virus or HIV viruses, the low mutation rate of SARS-CoV-2 makes the development of an effective global vaccine very likely.
Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins
Authors: Singh Nilmani , Reyes-Ordoñez Adriana , Compagnone Michael A. , Moreno Castillo Jesus F. , Leslie Benjamin J. , Ha Taekjip , Chen Jie 
Published: June 2020

ABSTRACTPleckstrin homology (PH) domains are presumed to bind phosphoinositides (PIPs), but specific interaction with and regulation by PIPs for most PH domain-containing proteins are unclear. Here we employed a single-molecule pulldown assay to study interactions of lipid vesicles with full-length proteins in mammalian whole cell lysates. Of 67 human PH domaincontaining proteins examined, 36 (54%) were found to have affinity for PIPs with various specificity, the majority of which had not been reported before. Further investigation of ARHGEF3 revealed structural requirements and functional relevance of its newly discovered PI(4,5)P2binding. A recursive-learning algorithm based on the assay results of the 67 proteins was generated to analyze the sequences of 246 human PH domains, which predicted 48% of them to bind PIPs. A collection of the predicted PIP-binding proteins was assayed, with the vast majority found to bind PIPs. Collectively, our findings reveal unexpected lipid-binding specificity of PH domain-containing proteins.
Compartment-specific opioid receptor signaling is selectively modulated by Dynorphin subtypes
Authors: Kunselman Jennifer M. , Gupta Achla , Gomes Ivone , Devi Lakshmi A. , Puthenveedu Manoj A. 
Published: June 2020

AbstractMany signal transduction systems have an apparent redundancy built into them, where multiple physiological agonists activate the same receptors. Whether this is true redundancy, or whether this provides as-yet unrecognized specificity in downstream signaling, is not well understood. We address this question using the kappa opioid receptor (KOR), a physiologically relevant G protein-coupled receptor (GPCR) that is activated by multiple members of the Dynorphin family of opioid peptides. We show that, although highly related Dynorphins bind and activate KOR to similar extents on the cell surface, they localize KOR to distinct subcellular compartments, dictate different post-endocytic fates of the receptor, and differentially induce KOR signaling from the degradative pathway. Our results show that seemingly redundant endogenous opioid peptides that are often co-released can in fact fine-tune signaling by differentially regulating the subcellular spatial profile of GPCR localization and signaling.
ASpli2: Integrative analysis of splicing landscapes through RNA-Seq assays
Authors: Mancini Estefania , Rabinovich Andres , Iserte Javier , Yanovsky Marcelo , Chernomoretz Ariel 
Published: June 2020

AbstractGenome-wide analysis of alternative splicing has been a very active field of research since the early days of NGS (Next generation sequencing) technologies. Since then, ever-growing data availability and the development of increasingly sophisticated analysis methods have uncovered the complexity of the general splicing repertoire. However, independently of the considered quantification methodology, very often changes in variant concentration profiles can be hard to disentangle. In order to tackle this problem we present ASpli2, a computational suite implemented in R, that allows the identification of changes in both, annotated and novel alternative splicing events, and can deal with complex experimental designs.Our analysis workflow relies on the analysis of differential usage of subgenic features in combination with a junction-based description of local splicing changes. Analyzing simulated and real data we found that the consolidation of these signals resulted in a robust proxy of the occurrence of splicing alterations. While junction-based signals allowed us to uncover annotated as well and non-annotated events, bin-associated signals notably increased recall capabilities at a very competitive performance in terms of precision.
Iron limitation by transferrin promotes simultaneous cheating of pyoverdine and exoprotease inPseudomonas aeruginosa
Authors: Tostado-Islas Oswaldo , Mendoza-Ortiz Alberto , Ramírez-García Gabriel , Cabrera-Takane Isamu Daniel , Loarca Daniel , Pérez-González Caleb , Jasso-Chavez Ricardo , Jiménez-Cortés J Guillermo , Hoshiko Yuki , Maeda Toshinari , Cazares Adrian , García-Contreras Rodolfo 
Published: June 2020

AbstractPseudomonas aeruginosais the main bacterial model to study cooperative behaviors, since it yields exoproducts such as exoproteases and siderophores that act as public goods and can be exploited by selfish non-producers that behave as social cheaters. Non-producers of the siderophore pyoverdine are typically isolated in media with low free iron, mainly casamino acids medium supplemented with transferrin. Nevertheless, using a protein as the iron chelator could additionally select mutants unable to produce exoproteases that degrade the transferrin to facilitate iron release. Here, we investigated the dynamics of pyoverdine and exoprotease production in media in which iron was limited by using either transferrin or a cation chelating resin. Our experiments show that concomitant loss of pyoverdine and exoprotease production readily develops in media with transferrin whereas only lack of pyoverdine emerges in medium treated with the resin. Genomic characterization of the exoprotease- and pyoverdine-less mutants revealed large deletions (13 to 33 Kb) including Quorum Sensing (lasR, rsal and lasl) and flagellar genes. Complementation experiments, PCR and motility tests confirmed the deletions. Our work shows that using transferrin as an iron chelator imposes simultaneous selective pressure for the loss of pyoverdine and exoprotease production. The unintended effect of transferrin observed in our experiment settings can help revisiting or informing the design of similar studies.
A general role for ventral white matter pathways in morphological processing: going beyond reading
Authors: Yablonski Maya , Menashe Benjamin , Ben-Shachar Michal 
Published: June 2020

AbstractThe ability to recognize the structural components of words, known as morphological processing, was recently associated with the bilateral ventral white matter pathways, across different writing systems. However, it remains unclear whether these associations are specific to the context of reading. To shed light on this question, in the current study we investigated whether the ventral pathways are associated with morphological processing in an oral word production task that does not involve reading. Forty-five participants completed a morpheme-based fluency task in Hebrew, as well as diffusion MRI (dMRI) scans. We used probabilistic tractography to segment the major ventral and dorsal white matter pathways, and assessed the correlations between their microstructural properties and performance on the morpheme-based fluency task. We found significant correlations between morpheme-based fluency and properties of the bilateral ventral tracts, suggesting that the involvement of these tracts in morphological processing extends beyond the reading modality. In addition, significant correlations were found in the frontal aslant tract (FAT), a dorsal tract associated with oral fluency and speech production. Together, our findings emphasize that neurocognitive associations reflect both the cognitive construct under investigation as well as the task used for its assessment. Lastly, to elucidate the biological factors underlying these correlations, we incorporated the composite hindered and restricted model of diffusion (CHARMED) framework, measured in independent scans. We found that only some of our findings could be attributed to variation in a CHARMED-based estimate of fiber density. Further, we were able to uncover additional correlations that could not be detected using traditional dMRI indices. In sum, our results show that the involvement of the ventral tracts in morphological processing extends to the production domain, and demonstrate the added value of including sensitive structural measurements in neurocognitive investigations.
Baseline survey of the fish and invertebrate fauna of Hill Inlet, the northernmost estuary in south-western Australia
Authors: Tweedley James R. , Sama Ayme , Poh Brian , Lonergan Neil R. 
Published: June 2020

AbstractMicrotidal estuaries in Mediterranean climates are particularly vulnerable to the effects of anthropogenic degradation. This study provides the first data on the fish and benthic macroinvertebrate fauna of Hill Inlet, the northernmost estuary in south-western Australia. Sampling was conducted in June 2019 (Austral winter), when water levels were very high due to recent heavy rainfall and the bar at the mouth of the estuary was intact. Surface salinities were oligohaline and declined along the longitudinal axis, ranging from 12 to 3. A marked halocline was present at most sites, resulting in pronounced hypoxia. High water levels precluded the use of a seine net at some sites to sample the nearshore fish fauna, however, two species were recorded (Pseudogobius olorumandAcanthopagrus butcheri), both of which complete their life-cycle within the estuary. Deeper, offshore waters, sampled using gill nets, yielded only four species (Mugil cephalus, A. butcheri, Adrichetta forsteriandPomatomus saltatrix), due to the bar at the mouth of the estuary being closed prior to sampling thus limiting recruitment from marine species. Ten benthic macroinvertebrates species were collected, representing mainly polychaetes, molluscs and crustaceans. The low number of species was likely caused by the hypoxia present throughout most of the bottom waters. Although these data represent a benchmark against which future changes can be detected, it is recommended that additional sampling is conducted when water levels are lower and the bar has been open to provide a more holistic assessment of the fauna of Hill Inlet.
Characterizing transcriptional regulatory sequences in coronaviruses and their role in recombination
Authors: Yang Yiyan , Yan Wei , Hall A. Brantley , Jiang Xiaofang 
Published: June 2020

ABSTRACTNovel coronaviruses, including SARS-CoV-2, SARS, and MERS, often originate from recombination events. The mechanism of recombination in RNA viruses is template switching. Coronavirus transcription also involves template switching at specific regions, called transcriptional regulatory sequences (TRS). It is hypothesized but not yet verified that TRS sites are prone to recombination events. Here, we developed a tool called SuPER to systematically identify TRS in coronavirus genomes and then investigated whether recombination is more common at TRS. We ran SuPER on 506 coronavirus genomes and identified 465 TRS-L and 3509 TRS-B. We found that the TRS-L core sequence (CS) and the secondary structure of the leader sequence are generally conserved within coronavirus genera but different between genera. By examining the location of recombination breakpoints with respect to TRS-B CS, we observed that recombination hotspots are more frequently co-located with TRS-B sites than expected.
Characterization of 100 sequential SARS-CoV-2 convalescent plasma donations
Authors: Jungbauer Christof , Weseslindtner Lukas , Weidner Lisa , Gänsdorfer Simon , Farcet Maria R. , Gschaider-Reichhart Eva , Kreil Thomas R. 
Published: June 2020

AbstractTransfusion of SARS-CoV-2 convalescent plasma is a promising treatment for severe COVID-19 cases, with success of the intervention based on neutralizing antibody content. Measurement by serological correlates without biocontainment needs, and an understanding of donor characteristics that may allow for targeting of more potent donors would greatly facilitate effective collection.
Survival Analysis on Rare Events Using Group-Regularized Multi-Response Cox Regression
Authors: Li Ruilin , Tanigawa Yosuke , Justesen Johanne M. , Taylor Jonathan , Hastie Trevor , Tibshirani Robert , Rivas Manuel A. 
Published: June 2020

AbstractWe propose a Sparse-Group regularized Cox regression method to improve the prediction performance of large-scale and high-dimensional survival data with few observed events. Our approach is applicable when there is one or more other survival responses that 1. has a large number of observed events; 2. share a common set of associated predictors with the rare event response. This scenario is common in the UK Biobank (Sudlow et al. 2015) dataset where records for a large number of common and rare diseases of the same set of individuals are available. By analyzing these responses together, we hope to achieve higher prediction performance than when they are analyzed individually. To make this approach practical for large-scale data, we developed an accelerated proximal gradient optimization algorithm as well as a screening procedure inspired by Qian et al. (2019). We provide a software implementation of the proposed method and demonstrate its efficacy through simulations and applications to UK Biobank data.
Amyloid-beta mediates homeostatic synaptic plasticity
Authors: Galanis Christos , Fellenz Meike , Becker Denise , Bold Charlotte , Lichtenthaler Stefan F. , Müller Ulrike C. , Deller Thomas , Vlachos Andreas 
Published: June 2020

ABSTRACTThe physiological role of the amyloid-precursor protein (APP) is insufficiently understood. Recent work has implicated APP in the regulation of synaptic plasticity. Substantial evidence exists for a role of APP and its secreted ectodomain APPsα in Hebbian plasticity. Here, we addressed the relevance of APP in homeostatic synaptic plasticity using organotypic tissue cultures ofAPP−/−mice. In the absence of APP, dentate granule cells failed to strengthen their excitatory synapses homeostatically. Homeostatic plasticity is rescued by amyloid-β (Aβ) and not by APPsα, and it is neither observed inAPP+/+tissue treated with β- or γ-secretase inhibitors nor in synaptopodin-deficient cultures lacking the Ca2+-dependent molecular machinery of the spine apparatus. Together, these results suggest a role of APP processing via the amyloidogenic pathway in homeostatic synaptic plasticity, representing a function of relevance for brain physiology as well as for brain states associated with increased Aβ levels.
Activation of mitochondria is an acute Akt-dependent response during osteogenic differentiation
Authors: Smith C. Owen , Eliseev Roman 
Published: June 2020

AbstractOsteogenic differentiation, the process by which bone marrow mesenchymal stem/stromal (a.k.a. skeletal stem) cells and osteoprogenitors form osteoblasts, is a critical event for bone formation during development, fracture repair, and tissue maintenance. Extra- and intracellular signaling pathways triggering osteogenic differentiation are relatively well known; however, the ensuing change in cell energy metabolism is less clearly defined. Here we tested the effect of osteogenic media containing ascorbate and β-glycerol phosphate, or various osteogenic hormones and growth factors on energy metabolism in long bone (ST2)- and calvarial bone (MC3T3-E1)-derived osteoprogenitors. We show that osteogenic media, and differentiation factors, Wnt3a and BMP2, stimulate mitochondrial oxidative phosphorylation (OxPhos) with little effect on glycolysis. The activation of OxPhos occurs acutely, suggesting a metabolic signaling change rather than protein expression change. To this end, we found that the observed mitochondrial activation is Akt-dependent. Akt is activated by osteogenic media, Wnt3a, and BMP2, leading to increased phosphorylation of various mitochondrial Akt targets, a phenomenon known to stimulate OxPhos. In sum, our data provide comprehensive analysis of cellular bioenergetics during osteoinduction in cells of two different origins (mesenchyme vs neural crest) and identify Wnt3a and BMP2 as physiological stimulators of mitochondrial respiration via Akt activation.
Relational governance in supply chain: a systematic literature review
Authors: Bonatto Franciele , de Resende Luis Mauricio Martins , Pontes Joseane 
Published: June 2020

PurposeThe goal of this research is to establish which contextual factors influence the selection of relational governance instruments in supply chains (SCs) and how these factors impact the expected performance.Design/methodology/approachA systematic literature review (SLR) identified 103 conceptual, empirical and analytical studies between 2007 and 2017.FindingsA conceptual framework is developed from the categorization of contextual factors, relational governance instruments and expected SC performance. The conceptual framework provides three propositions: (1) The choice for relational governance instrument is influenced differently by the contextual factors; (2) the impact that the contextual factors have on the governance instruments and SC performance is mediated by trust; (3) The SC performance is affected differently by the instruments of flexibility, solidarity and information sharing.Practical implicationsThe findings of this research can help business managers better govern and know the contextual factors and use different relational governance instruments and trust dimensions to drive the expected results of the SC.Originality/valueThe synthesis reveals contingencies of relational governance instruments in SCs for performance expected in different contexts and proposes a standpoint for further research in the area.
Putting the entrepreneur back into entrepreneurial ecosystems
Authors: Lux Andrei Alexander , Macau Flávio Romero , Brown Kerry Ann 
Published: June 2020

PurposeThis paper extends entrepreneurial ecosystems theory by testing how aspects of the local business environment affect individual entrepreneurs' ability to translate their personal resources into firm performance.Design/methodology/approachData were collected from 223 business owners across Australia. Moderation hypotheses were tested using multiple hierarchical regression and confirmed with the Preacher and Hayes (2004) bootstrapping method.FindingsThe results show that business owners' psychological capital, social capital and entrepreneurial education directly affect their individual firm performance. These positive relations are moderated by specific aspects of the business environment, such that they are stronger when the environment is more favorable.Originality/valueThis study puts individual business owners back into entrepreneurial ecosystems theory and explains how they can make the most of their personal resources, suggesting a complex interplay where one size does not fit all. Far-reaching practical implications for policymakers are discussed.
Classical and Bayesian estimation of stress-strength reliability of a component having multiple states
Authors: K C Siju , Kumar Mahesh , Beer Michael 
Published: June 2020

PurposeThis article presents the multi-state stress-strength reliability computation of a component having three states namely, working, deteriorating and failed state.Design/methodology/approachThe probabilistic approach is used to obtain the reliability expression by considering the difference between the values of stress and strength of a component, say, for example, the stress (load) and strength of a power generating unit is in terms of megawatt. The range of values taken by the difference variable determines the various states of the component. The method of maximum likelihood and Bayesian estimation is used to obtain the estimators of the parameters and system reliability.FindingsThe maximum likelihood and Bayesian estimates of the reliability approach the actual reliability for increasing sample size.Originality/valueObtained a new expression for the multi-state stress-strength reliability of a component and the findings are positively supported by presenting the general trend of estimated values of reliability approaching the actual value of reliability.
Antihypertensive effect of carvacrol is improved after incorporation in β‐cyclodextrin as a drug delivery system
Authors: Barreto da Silva Liliane , Camargo Samuel Barbosa , Moraes Raiana dos Anjos , Medeiros Carla Fiama , Jesus Anderson de Melo , Evangelista Afrânio , Villarreal Cristiane Flora , Quintans‐Júnior Lucindo José , Silva Darízy Flávia 
Published: June 2020

AbstractCarvacrol (CARV), has been shown to possess various pharmacological properties, especially in the treatment of cardiovascular diseases. We evaluated the antihypertensive effect of the CARV free and encapsulation of CARV in β‐cyclodextrin (CARV/β‐CD), and whether CARV/β‐CD is able to improve the antihypertensive effects of CARV free in spontaneously hypertensive rats (SHR). The rats were randomly divided into four groups, each treated daily for 21 days and the mean arterial pressure and heart rate was measured every 5 days: group 1, Wistar‐vehicle solution; group 2, SHR‐vehicle; group 3, SHR‐CARV 50 mg/kg/d; and group 4, CARV/β‐CD 50 mg/kg/d. After 21 days of treatment, the mesenteric artery from treated animals was tested for phenylephrine (Phe) and sodium nitroprusside (SNP) sensitivity. In addition, administration of CARV/β‐CD induced important antihypertensive activity when compared with the uncomplexed form, reducing the progression of arterial hypertension in SHR. Moreover, pharmacological potency to Phe in the SHR‐CARV and CARV/β‐CD groups was increased, approaching values expressed in the Wistar‐vehicle. Furthermore, CARV/β‐CD reduced the production of the pro‐inflammatory mediator, IL‐1β, and increased anti‐inflammatory cytokine, IL‐10. Together, these results produced evidence that the encapsulation of CARV in β‐CD can improve cardiovascular activity, showing potential anti‐inflammatory and antihypertensive effects.