bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hand-selective visual regions represent how to grasp 3D tools: brain decoding during real actions
Authors: Knights Ethan , Mansfield Courtney , Tonin Diana , Saada Janak , Smith Fraser W. , Rossit Stéphanie 
Published: October 2020

AbstractMost neuroimaging experiments that investigate how tools and their actions are represented in the brain use visual paradigms where tools or hands are displayed as 2D images and no real movements are performed. These studies discovered selective visual responses in occipito-temporal and parietal cortices for viewing pictures of hands or tools, which are assumed to reflect action processing, but this has rarely been directly investigated. Here, we examined the responses of independently visually defined category-selective brain areas when participants grasped 3D tools. Using real action fMRI and multi-voxel pattern analysis, we found that grasp typicality representations (i.e., whether a tool is being grasped appropriately for use) were decodable from hand-selective areas in occipito-temporal and parietal cortices, but not from tool-, object-, or body-selective areas, even if partially overlapping. Importantly, these effects were exclusive for actions with tools, but not for biomechanically matched actions with control nontools. In addition, decoding of grasp typicality was significantly higher in hand than tool-selective parietal regions. Notably, grasp typicality representations were automatically evoked even when there was no requirement for tool use and participants were naïve to object category (tool vs non-tools). Finding a specificity for typical tool grasping in hand-, rather than tool-, selective regions challenges the long-standing assumption that brain activation for viewing tool images reflects sensorimotor processing linked to tool manipulation. Instead our results show that typicality representations for tool grasping are automatically evoked in visual regions specialised for representing the human hand, the brain’s primarytoolfor interacting with the world.Significance StatementThe unique ability of humans to manufacture and use tools is unsurpassed across the animal kingdom, with tool use considered a defining feature of our species. Most neuroscientific studies that investigate the brain mechanisms that support tool use, record brain activity while people simply view images of tools or hands and not when people perform actual hand movements with tools. Here we show that specific areas of the human visual system that preferentially process hands automatically encode how to appropriately grasp 3D tools, even when no actual tool use is required. These findings suggest that visual areas optimized for processing hands represent fundamental aspects of tool grasping in humans, such as which side they should be grasped for correct manipulation.
Ensemble epistasis: thermodynamic origins of non-additivity between mutations
Authors: Morrison Anneliese J. , Wonderlick Daria R. , Harms Michael J. 
Published: October 2020

AbstractNon-additivity between mutations—epistasis—profoundly shapes evolution. It can be difficult to understand its mechanistic origins. Here we show that “ensemble epistasis” is likely a universal feature of macromolecules. Using a simple analytical model, we found that epistasis arises when two conditions are met: 1) a macro-molecule populates at least three structures and 2) mutations have differential effects on a least two of the inactive structures. To explore the relative magnitude of ensemble epistasis, we performed a virtual deep-mutational scan of the allostericCa2+signaling protein S100A4. We found that 27% of mutation pairs gave ensemble epistasis with a magnitude on the order of thermal fluctuations, 1 kT. We observed many forms of epistasis: magnitude, sign, and reciprocal sign epistasis. Depending on the effector concentration, the same mutation pair could even exhibit different forms of epistasis. The ubiquity of ensembles in biology and its pervasiveness in our dataset suggests that ensemble epistasis may be a universal mechanism of epistasis.Significance statementAddressing the mechanistic origins of evolutionary unpredictability is critical to understanding how mutations combine to determine phenotype. Here we lay the theoretical foundations and investigate the plausibility of a potentially universal mechanism of unpredictability in macromolecules. Macromolecules often adopt a set of interchanging structures, called a thermodynamic ensemble. Mutations can change the relative population of each structure, introducing unpredictability in the mapping between genotype and phenotype. The conditions under which we expect this to arise are common in macromolecules, suggesting that this form of unpredictability may be pervasive in evolution. We conclude that the thermodynamic ensemble bakes unpredictability into biology and that future attempts to address it might incorporate this mechanistic insight.
COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding
Authors: Abitogun Folagbade , Srivastava R. , Sharma S. , Komarysta V. , Akurut E. , Munir N. , Macalalad L. , Olawale O. , Owolabi O. , Abayomi G. , Debnath S. 
Published: October 2020

AbstractThe COVID19 pandemic has resulted in 1,092,342 deaths as of 14thOctober 2020, indicating the urgent need for a vaccine. This study highlights novel protein sequences generated by shot gun sequencing protocols that could serve as potential antigens in the development of novel subunit vaccines and through a stringent inclusion criterion, we characterized these protein sequences and predicted their 3D structures. We found distinctly antigenic sequences from the SARS-CoV-2 that have led to identification of 4 proteins that demonstrate an advantageous binding with Human leukocyte antigen-1 molecules. Results show how previously unexplored proteins may serve as better candidates for subunit vaccine development due to their high stability and immunogenicity, reinforce by their HLA-1 binding propensities and low global binding energies. This study thus takes a unique approach towards furthering the development of vaccines by employing multiple consensus strategies involved in immuno-informatics technique.
Selective connectivity limits functional binocularity in the retinogeniculate pathway of the mouse
Authors: Bauer Joel , Weiler Simon , Fernholz Martin , Laubender David , Scheuss Volker , Hübener Mark , Bonhoeffer Tobias , Rose Tobias 
Published: October 2020

AbstractEye-specific segregation of retinal ganglion cell (RGC) axons in the dorsal lateral geniculate nucleus (dLGN) is considered a hallmark of visual system development. However, a recent anatomical study showed that nearly half of the neurons in dLGN of adult mice still receive input from both retinae, but functional data about binocularity in mature dLGN is conflicting. Here, we found that a variable but small fraction of thalamocortical neurons is binocularin vivo. Using dual-channel optogeneticsin vitrowe correspondingly found that dLGN neurons are dominated by retinogeniculate input from one eye only, although most neurons also received small but detectable input from the non-dominant eye. Anatomical overlap between RGC axons and dLGN neuron dendrites did not explain this strong bias towards monocularity. Our data rather suggest that functional input selection and refinement, leaving the remaining non-dominant eye inputs in a juvenile-like state, underlies the prevalent monocularity of neurons in dLGN.
Vaginal Isolates ofCandida glabrataare Uniquely Susceptible to Ionophoric Killer Toxins Produced bySaccharomyces cerevisiae
Authors: Fredericks Lance R. , Lee Mark D. , Eckert Hannah R. , Li Shunji , Shipley Mason A. , Roslund Cooper R. , Boikov Dina A. , Kizer Emily A. , Sobel Jack D. , Rowley Paul A. 
Published: October 2020

ABSTRACTCompared to other species ofCandidayeasts, the growth ofCandida glabratawas inhibited by many different strains ofSaccharomyceskiller yeasts. The ionophoric K1 and K2 killer toxins were broadly inhibitory to all clinical isolates ofC. glabratafrom patients with recurrent vulvovaginal candidiasis, despite high levels of resistance to clinically relevant antifungal therapeutics.
Temporal stability of human sperm mosaic mutations results in life-long threat of transmission to offspring
Authors: Yang Xiaoxu , Breuss Martin W. , Xu Xin , Antaki Danny , James Kiely N. , Stanley Valentina , Ball Laurel L. , George Renee D. , Wirth Sara A. , Cao Beibei , Nguyen An , McEvoy-Venneri Jennifer , Chai Guoliang , Nahas Shareef , Van Der Kraan Lucitia , Ding Yan , Sebat Jonathan , Gleeson Joseph G. 
Published: October 2020

SummaryEvery newborn harbors scores of new single nucleotide variants (SNVs) that may impact health and disease1–4; the majority of these are contributed by the paternal germ cells5. In some cases, these mutations are identifiable in a subset of the parents’ cells—a phenomenon called mosaicism, which is capable of producing disease recurrence6–8. Here, we provide a comprehensive analysis of male gonadal mosaic mutations, employing 300× whole genome sequencing (WGS) of blood and sperm in 17 healthy individuals, including assessment across multiple samples and age groups. Approximately 1 in 15 healthy males is predicted to harbor a transmissible, likely pathogenic exonic variant that is mosaic in his sperm. In general, only a third of sperm mosaic mutations were detectable in blood cells, all were remarkably stable over the course of months to years, and 23% were present in 5% or more of sperm cells. There was no evidence of age-dependent clonal expansion or collapse, as seen in hematopoiesis. Thus, despite the observed increase of mutations in offspring of men with advanced paternal age, detectable sperm mosaicism remains stable, represents a life-long transmission risk to offspring, and suggests a testis stem cell niche that prevents widespread clonality.
Convergence of a common solution to broad ebolavirus neutralization by glycan cap directed human antibodies
Authors: Murin Charles D. , Gilchuk Pavlo , Ilinykh Philipp A. , Huang Kai , Kuzmina Natalia , Shen Xiaoli , Bruhn Jessica F. , Bryan Aubrey L. , Davidson Edgar , Doranz Benjamin J. , Williamson Lauren E. , Copps Jeffrey , Alkutkar Tanwee , Flyak Andrew I. , Bukreyev Alexander , Crowe James E. , Ward Andrew B. 
Published: October 2020

SummaryAntibodies that target the glycan cap epitope on ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of their epitopes and basis for neutralization is not well-understood. Here we present cryo-electron microscopy (cryo-EM) structures of several glycan cap antibodies that variably synergize with GP base-binding antibodies. These structures describe a conserved site of vulnerability that anchors the mucin-like domains (MLD) to the glycan cap, which we name the MLD-anchor and cradle. Antibodies that bind to the MLD-cradle share common features, including the use ofIGHV1-69andIGHJ6germline genes, which exploit hydrophobic residues and form beta-hairpin structures to mimic the MLD-anchor, disrupt MLD attachment, destabilize GP quaternary structure and block cleavage events required for receptor binding. Our results collectively provide a molecular basis for ebolavirus neutralization by broadly reactive glycan cap antibodies.
Reinvestigation of grain weight genesTaTGW6andOsTGW6casts doubt on their role in auxin regulation in developing grains
Authors: Kabir Muhammed Rezwan , Nonhebel Heather M. 
Published: October 2020

AbstractTheTHOUSAND-GRAIN WEIGHT 6genes (TaTGW6andOsTGW6) are reported to result in larger grains of wheat and rice by reducing production of indole-3-acetic acid (IAA) in developing grains. However, a critical comparison of data onTaTGW6andOsTGW6with other reports on IAA synthesis in cereal grains requires that this hypothesis be reinvestigated. Here, we show thatTaTGW6andOsTGW6are members of a large gene family that has undergone major, lineage-specific gene expansion. Wheat has nine genes, and rice three genes encoding proteins with more than 80% amino acid identity with TGW6 making it difficult to envisage how a single inactive allele could have a major effect on IAA levels. TGW6 is proposed to affect auxin levels by catalysing the hydrolysis of IAA-glucose (IAA-Glc). However, we show that developing wheat grains contain undetectable levels of ester IAA in comparison to free IAA and do not express an IAA-glucose synthase. Previous work onTGW6, reported maximal expression at 20 days after anthesis (DAA) in wheat and 2 DAA in rice. However, we show that neither gene is expressed in developing grains. Instead,TaTGW6, OsTGW6and their close homologues are exclusively expressed in pre-emergence inflorescences;TaTGW6is expressed particularly in microspores prior to mitosis. This combined with evidence for high levels of IAA production from tryptophan in developing grains demonstratesTaTGW6andOsTGW6cannot regulate grain size via the hydrolysis of IAA-Glc. Instead, their similarity to rice strictosidine synthase-like (OsSTRL2) suggests they play a key role in pollen development.
Use of convalescent serum reduces severity of COVID-19 in nonhuman primates
Authors: Cross Robert W. , Prasad Abhishek N. , Borisevich Viktoriya , Woolsey Courtney , Agans Krystle N. , Deer Daniel J. , Dobias Natalie S. , Geisbert Joan B. , Fenton Karla A. , Geisbert Thomas W. 
Published: October 2020

AbstractPassive transfer of convalescent plasma or serum is a time-honored strategy for treating infectious diseases. Human convalescent plasma containing antibodies against SARS-CoV-2 is currently being used to treat COVID-19 patients. However, most patients have been treated outside of randomized clinical trials making it difficult to determine the efficacy of this approach. Here, we assessed the efficacy of convalescent sera in a newly developed African green monkey model of COVID-19. Groups of SARS-CoV-2-infected animals were treated with pooled convalescent sera containing either high or low to moderate anti-SARS-CoV-2 neutralizing antibody titers. Differences in viral load and disease pathology were minimal between monkeys that received the lower titer convalescent sera and untreated controls. However, and importantly, lower levels of SARS-CoV-2 in respiratory compartments, reduced gross and histopathological lesion severity in the lungs, and reductions in several parameters associated with coagulation and inflammatory processes were observed in monkeys that received convalescent sera versus untreated controls. Our data support human studies suggesting that convalescent plasma therapy is an effective strategy if donors with high level of antibodies against SARS-CoV-2 are employed and if recipients are at an early stage of disease.
Experimental phasing with vanadium and application to nucleotide-binding membrane proteins
Authors: El Omari Kamel , Mohamad Nada , Bountra Kiran , Duman Ramona , Romano Maria , Schlegel Katja , Kwong Hok-Sau , Mykhaylyk Vitaliy , Olesen Claus , Moller Jesper Vuust , Bublitz Maike , Beis Konstantinos , Wagner Armin 
Published: October 2020

The structure determination of soluble and membrane proteins can be hindered by the crystallographic phase problem, especially in the absence of a suitable homologous structure. Experimental phasing is the method of choice for novel structures; however, it often requires heavy-atom derivatization, which can be difficult and time-consuming. Here, a novel and rapid method to obtain experimental phases for protein structure determination by vanadium phasing is reported. Vanadate is a transition-state mimic of phosphoryl-transfer reactions and it has the advantage of binding specifically to the active site of numerous enzymes catalyzing this reaction. The applicability of vanadium phasing has been validated by determining the structures of three different protein–vanadium complexes, two of which are integral membrane proteins: the rabbit sarcoplasmic reticulum Ca2+-ATPase, the antibacterial peptide ATP-binding cassette transporter McjD from Escherichia coli and the soluble enzyme RNAse A from Bos taurus. Vanadium phasing was successful even at low resolution and despite severe anisotropy in the data. This method is principally applicable to a large number of proteins, representing six of the seven Enzyme Commission classes. It relies exclusively on the specific chemistry of the protein and it does not require any modifications, making it a very powerful addition to the phasing toolkit. In addition to the phasing power of this technique, the protein–vanadium complexes also provide detailed insights into the reaction mechanisms of the studied proteins.
A moderated mediation model for the relationship between inclusive leadership and job embeddedness
Authors: Elsaied Mervat Mohamed 
Published: October 2020

PurposeThis study aimed to examine the effect of inclusive leadership (IL) on job embeddedness (JE) by developing a moderated mediation model. The model focuses on the mediating role of the organizational identification (OID) that underpins the relationship between IL and JE, as well as the moderating influence of person–supervisor fit (P–S fit) on the mediation.Design/methodology/approachData were collected from 364 employees working in 25 five-star hotels in Hurghada, Egypt. Statistical methods such as hierarchical regression, correlation analysis and a bootstrapping test were used to analyze the data.FindingsThe results indicated that OID fully mediated the positive relationship between IL and JE. It also found that P–S fit moderated the mediated relationship between IL and JE via OID. This resulted in the mediated relationship becoming stronger for employees who perceive higher P–S fit rather than who perceive lower P–S fit with their leaders.Originality/valueThis study is the first to consider the effect of OID (a mediator) on the relationship between IL and JE. It also extends our understanding of the mechanism linking IL and JE by testing the mediating influence of OID and the moderating influence of P–S fit.
The influence of showrooming on Millennial generational cohorts online shopping behaviour
Authors: Johnson Olivia , Ramirez Stefanie Ann 
Published: October 2020

PurposeOmnichannel retailing has changed the behaviour of consumers by empowering activities like showrooming which is the process of collecting product information in store then making the purchase online. Since individuals, particularly Millennials, interact with multiple touchpoints throughout their shopping journey, retailers must consider how these experiences influence purchasing behaviour. Literature regarding showrooming has focussed primarily on antecedents to the phenomenon and the negative effects to brick and mortar retailers, however limited studies have investigated the quantitative influence of showrooming from the consumers' perspective. While data show that interest in online shopping is spiking, a vast majority of retail sales are made in-store suggesting barriers to online shopping still exist. Thus, the purpose of this research is to identify the role of showrooming in decreasing risk in an online shopping context. Additionally, Millennial generational cohorts (MGCs) were proposed as moderators in exploring the differences between the dimensions of perceived risk and online shopping intention.Design/methodology/approachTo explore the relationship between showrooming and MGCs online shopping behaviour an online survey was administered. Data were collected from 480 Millennial consumers at a large southwestern university. Multiple linear regression was used to determine the direction, magnitude and significance of relationships within the models.FindingsResults from the analysis revealed showrooming and MGCs influence online shopping behaviour as it relates to dimensions of risk. Moreover, showrooming increased online shopping intention specifically in relation to product and financial risk.Originality/valueThis paper contributes to the relevant literature by proposing a relationship between showrooming and online shopping behaviour. This research provides evidence that Millennials are not a monolithic generation and consume differently.
Does institutional quality affect tourism demand? Evidence from India
Authors: Mushtaq Reffat , Thoker Aijaz Abdullah , Bhat Aaqib Ahmad 
Published: October 2020

PurposeThe purpose of this paper is to empirically examine the impact of institutional quality on the international tourism demand of India. To carry out the analysis, the study first analyses the impact of composite institutional quality index and then proceeds to examine the impact of each of the individual components of institutional quality on the international tourism demand of India. The impact of income of the tourist originating countries, tourism price, trade openness and Human Development Index (HDI) on tourism demand has also been examined.Design/methodology/approachThe study employed panel autoregressive distributed lag (ARDL) model, with data from top 30 tourist originating countries for India for the period of 1995–2016.FindingsThe results indicated that an increase in the income of the tourist originating countries has spillover effects on the development of tourism sector of India. The impact of cost of travel proxied by relative prices between the destination and origin country is found to be negative, however, statistically insignificant. The impact of trade openness and development level of the host country (proxied by HDI) is found to have positive association with the tourism demand. Institutional quality is found to have positive association with international tourism demand of India. Among the individual components of institutional quality, rule of law, regulatory quality, control of corruption and voice and accountability are found to promote the tourism sector development in the economy. Contrarily, the impact of government effectiveness is found to be negative. In the short run, most of the variables were found to support their counterpart results in long run.Practical implicationsThis study has practical implication not only in formulating tourism sector policies of the host countries but also for issuing tourist advisories in tourist originating countries. The study holds that policymakers should work for improving institutional environment of the country such as bureaucracy, legislature, regulatory quality, rule of law and for reducing corruption at all levels so as to ensure a sustained rise in tourist inflows to India.Originality/valueThis study validates the link between institutional quality of a country and international demand for its tourism. To the best of the authors' knowledge, the study is the first attempt that has comprehensively analysed the impact of institutional quality on tourism demand in Indian context which has been generally ignored in the tourism literature.