bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solution structures of theShewanella woodyiH-NOX protein in the presence and absence of soluble guanylyl cyclase stimulator IWP-051
Authors: Chen Cheng-Yu , Lee Woonghee , Montfort William R. 
Published: August 2020

AbstractHeme-nitric oxide/oxygen binding (H-NOX) domains bind gaseous ligands for signal transduction in organisms spanning prokaryotic and eukaryotic kingdoms. In the bioluminescent marine bacteriumShewanella woodyi(Sw), H-NOX proteins regulate quorum sensing and biofilm formation. In higher animals, soluble guanylyl cyclase (sGC) binds nitric oxide with an H-NOX domain to induce cyclase activity and regulate vascular tone, wound healing and memory formation. sGC also binds stimulator compounds targeting cardiovascular disease. The molecular details of stimulator binding to sGC remain obscure but involve a binding pocket near an interface between H-NOX and coiled-coil domains. Here, we report the full NMR structure for CO-ligatedSwH-NOX in the presence and absence of stimulator compound IWP-051, and its backbone dynamics. Non-planar heme geometry was retained using a semi-empirical quantum potential energy approach. Although IWP-051 binding is weak, a single binding conformation was found at the interface of the two H-NOX subdomains. Binding lead to rotation of the subdomains and closure of the binding pocket. Backbone dynamics for the protein are similar across both domains except for two helix-connecting loops, which display increased dynamics that are further enhanced by compound binding. Structure-based sequence analyses indicate high sequence diversity in the binding pocket, but the pocket itself appears conserved among H-NOX proteins. The largest dynamical loop lies at the interface betweenSwH-NOX and its binding partner as well as in the interface with the coiled coil in sGC, suggesting a critical role for the loop in signal transduction.
Recombinant SARS-CoV-2 RBD molecule with a T helper epitope as a built in adjuvant induces strong neutralization antibody response
Authors: Su Qiudong , Zou Yening , Yi Yao , Shen Liping , Ye Xiangzhong , Zhang Yang , Wang Hui , Ke Hong , Song Jingdong , Hu Keping , Cheng Bolin , Qiu Feng , Yu Pengcheng , Zhou Wenting , Cao Lei , Bi Shengli , Wu Guizhen , Gao George Fu , Zheng Jerry 
Published: August 2020

AbstractWithout approved vaccines and specific treatment, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading around the world with above 20 million COVID-19 cases and approximately 700 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 – Gly548 of Spike protein of SARS-CoV-2 linked with Gln830 – Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5), and prokaryotic expression, chromatography purification and the rational renaturation of the protein were performed. The antigenicity and immunogenicity of S1-4 protein was evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency of it was measured by virus neutralization test in Vero E6 cells with SARS-CoV-2. S1-4 protein was prepared to high homogeneity and purity by prokaryotic expression and chromatography purification. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity compared with S1-5 protein. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralization antibody GMT 256. The candidate subunit vaccine molecule could stimulate strong humoral and Th1 and Th2-type cellular immune response in mice, giving us solid evidence that S1-4 protein could be a promising subunit vaccine candidate.
Mutually Beneficial Symbiosis Between Human and Gut-DominantBacteroidesSpecies Through Bacterial Assimilation of Host Mucosubstances
Authors: Sato Masahiro , Kajikawa Kanta , Kumon Tomoya , Watanabe Daisuke , Takase Ryuichi , Hashimoto Wataru 
Published: August 2020

AbstractThe composition of gut microbiota is influenced by the quantity and type of nutrients in host. Even with someBacteroidesspecies being categorized as pathogens,Bacteroidesis one of the most dominant gut bacteria. Here we indicate the physiological determinants of the species ofBacteroidesfor being dominant in human gut microbiota. Each of the host extracellular mucosubstances including glycosaminoglycans (GAGs) and mucin has grown human gut microbiota. In spite of the differences among initial microbiota profiles,Bacteroidesspecies dominated the community when GAG (e.g., chondroitin sulfate or hyaluronan) was used as a sole carbon source. In fact, GAGs and theBacteroidesgenes which are vital for the degradation of GAGs were commonly detected in human feces. Mucin has encouraged the growth ofBacteroidesand several other genera. A comprehensive analysis on the degradation and assimilation of mucosubstances by the genusBacteroidesusing around 30 species has shown that most species degrade and assimilate GAGs and mucin, showing thatBacteroidesspecies can survive even in the undernutrition condition including the fasting state. In the assimilation of GAG or mucin,Bacteroidesspecies significantly secreted essential amino acids, γ-amino butyrate (GABA), and/or short-chain fatty acids which are needed for human health. This is the first report as regards mutually beneficial interaction between human andBacteroidesspecies via bacterial assimilation of host mucosubstances and secretion of metabolites for host health promotion.SignificanceThe genusBacteroidesis one of the most dominant gut bacteria, although its beneficial effects on human health have not been well understood. Here, we show modes of action in human-Bacteroidesinterrelationship. Mucosubstances including GAGs and mucin secreted by human host are abundant in gut for microbiota to grow well.Bacteroidesspecies are dominant in the community in the presence of GAGs, and provide human host with a considerable amount of essential amino acids, γ-amino butyrate, and short-chain fatty acids produced from mucosubstances. These results postulate mutually beneficial symbiosis system between human andBacteroidesthrough bacterial assimilation of host mucosubstances and secretion of metabolites for human body and mental health promotion even in the undernutrition condition including the fasting state.
Molecular basis for substrate recruitment to the PRMT5 methylosome
Authors: Mulvaney Kathleen M. , Blomquist Christa , Acharya Nischal , Li Ruitong , O’Keefe Meghan , Ranaghan Matthew , Stokes Matthew , Nelson Alissa J , Jain Sidharth S. , Columbus Josie , Bozal Fazli K. , Skepner Adam , Raymond Donald , McKinney David C. , Freyzon Yelena , Baidi Yossef , Porter Dale , Ianari Alessandra , McMillan Brian , Sellers William R. 
Published: August 2020

AbstractPRMT5 is an arginine methyltransferase and a therapeutic target inMTAPnull cancers. PRMT5 utilizes adaptor proteins for substrate recruitment through a previously undefined mechanism. Here, we identify an evolutionarily conserved peptide sequence shared among the three known substrate adaptors (pICln/CLNS1A, RIOK1 and COPR5) and show it is necessary and sufficient for interaction with PRMT5. We structurally resolve the interface with PRMT5 and show via genetic perturbation that it is required for methylation of adaptor-recruited substrates including the spliceosome, histones, and ribosome assembly complexes. Genetic disruption of the PRMT5-substrate adaptor interface leads to a hypomorphic decrease in growth ofMTAPnull tumor cells and is thus a novel site for development of therapeutic inhibitors of PRMT5.
Active Perception during Angiogenesis: Filopodia speed up Notch selection of tip cellsin silicoandin vivo
Authors: Zakirov Bahti , Charalambous Georgios , Aspalter Irene M. , Van-Vuuren Kelvin , Mead Thomas , Harrington Kyle , Thuret Raphael , Regan Erzsébet Ravasz , Herbert Shane Paul , Bentley Katie 
Published: August 2020

AbstractHow do cells make efficient collective decisions during tissue morphogenesis? Humans and other organisms utilize feedback between movement and sensing known as ‘sensorimotor coordination’ or ‘active perception’ to inform behaviour, but active perception has not before been investigated at a cellular level within organs. Here we provide the first proof of conceptin silico/in vivostudy demonstrating that filopodia (actin-rich, dynamic, finger like cell-membrane protrusions) play an unexpected role in speeding up collective endothelial decisions during the time-constrained process of ‘tip cell’ selection during blood vessel formation (angiogenesis).We first validate simulation predictionsin vivowith live imaging of zebrafish intersegmental vessel growth. Further simulation studies then indicate the effect is due to the coupled positive feedback between movement and sensing on filopodia conferring a bistable switch-like property to Notch lateral inhibition, ensuring tip selection is a rapid and robust process. We then employ measures from computational neuroscience to assess whether filopodia function as a primitive (‘basal’) form of active perception and find evidence in support. By viewing cell behaviour in tissues through the ‘basal cognitive lens’ we acquire a fresh perspective on not only the well-studied tip cell selection process, revealing a hidden, yet vital, time-keeping role for filopodia, but on how to interpret and understand cell behaviour in general, opening up a myriad of new and exciting research directions.
Live imaging of avian embryos revealing a new head precursor map and the role for the anterior mesendoderm in brain development
Authors: Yoshihi Koya , Kato Kagayaki , Iida Hideaki , Teramoto Machiko , Kawamura Akihito , Watanabe Yusaku , Nunome Mitsuo , Nakano Mikiharu , Matsuda Yoichi , Sato Yuki , Mizuno Hidenobu , Iwasato Takuji , Ishii Yasuo , Kondoh Hisato 
Published: August 2020

ABSTRACTWe investigated the initial stages of head development using a new method to randomly label chicken epiblast cells with enhanced green fluorescent protein, and tracking the labeled cells. This analysis was combined with grafting mCherry-expressing quail nodes, or node-derived anterior mesendoderm (AME). These live imagings provided a new conception of the cellular mechanisms regulating brain and head ectoderm development. Virtually all anterior epiblast cells are bipotent for the development into the brain or head ectoderm. Their fate depends on the positioning after converging to the AME. When two AME tissues exist following the ectopic node graft, the epiblast cells converge to the two AME positions and develop into two brain tissues. The anterior epiblast cells bear gross regionalities that already correspond to the forebrain, midbrain, and hindbrain axial levels shortly after the node is formed. Therefore, brain portions that develop with the graft-derived AME are dependent on graft positioning.
Age effects aggressive behavior: RNA-seq analysis in cattle with implications for studying neoteny under domestication
Authors: Eusebi Paulina G. , Sevane Natalia , O’Rourke Thomas , Pizarro Manuel , Boeckx Cedric , Dunner Susana 
Published: August 2020

AbstractAggressiveness is one of the most basic behaviors, characterized by targeted intentional actions oriented to cause harm. The reactive type of aggression is regulated mostly by the brain’s prefrontal cortex; however, the molecular changes underlying aggressiveness in adults have not been fully characterized. Here we used an RNA-seq approach to investigate differential gene expression in the prefrontal cortex of bovines from the aggressive Lidia breed at different age stages: young three-year old and adult four-year-old bulls. A total of 50 up and 193 down-regulated genes in the adult group were identified. Furthermore, a cross-species comparative analysis retrieved 29 genes in common with previous studies on aggressive behaviors, representing an above-chance overlap with the differentially expressed genes in adult bulls.Particularly, we detected changes in the regulation of networks such as synaptogenesis, involved in maintenance and refinement of synapses, and the glutamate receptor pathway, which acts as excitatory driver in aggressive responses. Our results provide insights into candidate genes and networks involved in the molecular mechanisms leading to the maturation of the brain. The reduced reactive aggression typical of domestication has been proposed to form part of a retention of juvenile traits as adults (neoteny). The significant age-associated differential expression of genes implicated in aggressive behaviors and concomitant increase in Lidia cattle aggression validates this species as a novel model comparator to explore the impact of behavioral neoteny under domestication.
Functional validation of a finding from a mouse genome-wide association study demonstrates that a mutant allele ofAzi2alters sensitivity to methamphetamine
Authors: Zhou Xinzhu , Barkley-Levenson Amanda , Montilla-Perez Patricia , Telese Francesca , Palmer Abraham A. 
Published: August 2020

AbstractMethamphetamine is a widely abused psychostimulant. In a previous genome-wide association study (GWAS), we identified a locus that influenced the stimulant response to methamphetamine. That locus was also an eQTL for the geneAzi2. Based on those findings, we hypothesized that heritable differences in the expression ofAzi2were causally related to the differential response to methamphetamine. In this study, we created a mutantAzi2allele that caused lowerAzi2expression and enhanced the locomotor response to methamphetamine; however, based on the GWAS findings, we had expected lowerAzi2to decrease rather than increase the stimulant response to methamphetamine. We then sought to explore the mechanism by whichAzi2influenced methamphetamine sensitivity. A recent publication had reported that the 3’UTR ofAzi2mRNA downregulates the expression ofSlc6a3, which encodes the dopamine transporter (DAT), which is a key target of methamphetamine. We evaluated the relationship betweenAzi2/Azi23’UTR andSlc6a3expression in the VTA in the mutantAzi2mice and in a new cohort of CFW mice. We did not observe any correlation betweenAzi2andSlc6a3in the VTA in either cohort. However, RNA sequencing confirmed that theAzi2mutation alteredAzi2expression and also revealed a number of potentially important genes and pathways that were regulated byAzi2, including the metabotropic glutamate receptor group III pathway and nicotinic acetylcholine receptor signaling pathway. Our results support a role forAzi2in methamphetamine sensitivity; however, the exact mechanism does not appear to involve regulation ofSlc6a3and thus remains unknown.
Leading edge maintenance in migrating cells is an emergent property of branched actin network growth
Authors: Garner Rikki M. , Theriot Julie A. 
Published: August 2020

AbstractAnimal cell migration is predominantly driven by the coordinated, yet stochastic, polymerization of thousands of nanometer-scale actin filaments across micron-scale cell leading edges. It remains unclear how such inherently noisy processes generate robust cellular behavior. We employed high-speed imaging of migrating neutrophil-like HL-60 cells to explore the fine-scale shape fluctuations that emerge and relax throughout the process of leading edge maintenance. We then developed a minimal stochastic model of the leading edge that reproduces this stable relaxation behavior. Remarkably, we find lamellipodial stabilitynaturally emergesfrom the interplay between branched actin network growth and leading edge shape – with no additional feedback required – based on a synergy between membrane-proximal branching and lateral spreading of filaments. These results thus demonstrate a novel biological noise-suppression mechanism based entirely on system geometry. Furthermore, our model suggests that the Arp2/3-mediated ~70-80° branching angle optimally smooths lamellipodial shape, addressing its long-mysterious conservation from protists to mammals.Significance StatementAll cellular functions are driven by the stochastic dynamics of macromolecules, and thus are subject to biological noise. Here, as a model system for noise-suppression in the context of cell migration, we investigate lamellipodial maintenance – where thousands of stochastically polymerizing filaments self-organize into a highly-stable, micron-scale leading edge. Combining experiment and computational modeling, we (1) establish lamellipodial stability is anemergent propertyof dendritically-branched actin network growth, (2) outline a noise-suppression mechanism based on thegeometryof lamellipodial actin, and (3) determine the evolutionarily-conserved Arp2/3-mediated ~70-80° branching angle optimally suppresses stochastic fluctuations. Our results not only explain the essential role of Arp2/3-mediated branching in lamellipodial formation, but also address the decades-old question ofwhythis specific geometry is so well-conserved.
Distinct temporal difference error signals in dopamine axons in three regions of the striatum in a decision-making task
Authors: Tsutsui-Kimura Iku , Matsumoto Hideyuki , Uchida Naoshige , Watabe-Uchida Mitsuko 
Published: August 2020

SUMMARYDifferent regions of the striatum regulate different types of behavior. However, how dopamine signals differ across striatal regions and how dopamine regulates different behaviors remain unclear. Here, we compared dopamine axon activity in the ventral, dorsomedial, and dorsolateral striatum, while mice performed in a perceptual and value-based decision task. Surprisingly, dopamine axon activity was similar across all three areas. At a glance, the activity multiplexed different variables such as stimulus-associated values, confidence and reward feedback at different phases of the task. Our modeling demonstrates, however, that these modulations can be inclusively explained by moment-by-momentchangesin the expected reward, i.e. the temporal difference error. A major difference between these areas was the overall activity level of reward responses: reward responses in dorsolateral striatum (DLS) were positively shifted, lacking inhibitory responses to negative prediction error. Tenets of habit and skill can be explained by this positively biased dopamine signal in DLS.
Business process modeling, implementation, analysis, and management: the case of business process management tools
Authors: Zuhaira Behjat , Ahmad Naveed 
Published: August 2020

PurposeSignificant numbers of business process management (BPM) projects fail. Their failure is attributed toward many factors. Among them, low quality of BPM is one reason. Some of the tasks in BPM have their roots in business process reengineering (BPR). The literature has cited many different critical success and failure factors for quality BPM and BPR. Lack of software tools is one of the technology-oriented factors that results in poor BPM and BPR. This paper aims to build a generic feature set offered by software tools for process modeling their analysis implementation and management. It presents an objective analysis in identifying weaknesses and strengths of these tools, primarily for BPM.Design/methodology/approachA method is proposed to evaluate the quality of process reengineering and management delivered by software tools. It consists of four phases: feature extraction, tool selection, data extraction and tool evaluation.FindingsThe data gathered is quantified to test research hypotheses, the results are statistically significant and highlight multiple areas for future improvements. Moreover, the cluster visualizations created also help to understand the strengths and weaknesses of BPM/BPR tools.Research limitations/implicationsDespite the research approach used, there is a chance of subjectivity when it comes to evaluating different tools.Practical implicationsThe paper includes implications for practitioners and researchers for choosing appropriate software tool for process modeling, analysis, implementation and management, matching their requirements with BPM and BPR. It also identifies features that are missing in these tools.Originality/valueThis paper provides a comprehensive analysis of BPM and supporting tools, relates them to key stages of BPM life cycle and BPR methodologies. It also identifies various areas for further development in these tools.
Are smallholder farmers’ perceptions of climate variability supported by climatological evidence? Case study of a semi-arid region in South Africa
Authors: Rapholo Maropene Tebello , Diko Makia Lawrence 
Published: August 2020

Purpose
Literature contends that not much is known about smallholder farmers’ perceptions of climate variability and the impacts thereof on agricultural practices in Sub-Saharan Africa and South Africa in particular. The purpose of this study is to examine the perceptions of smallholder farmers from Botlokwa (a semi-arid region in South Africa) on climate variability in relation to climatological evidence.

Design/methodology/approach
The study area is in proximity to a meteorological station and comprises mainly rural farmers, involved in rain-fed subsistence agriculture. Focus group discussions and closed-ended questionnaires covering demographics and perceptions were administered to 125 purposely sampled farmers. To assess farmers’ perceptions of climate variability, their responses were compared with linear trend and variability of historical temperature and rainfall data (1985-2015). Descriptive statistics were used to provide insights into respondents’ perceptions.

Findings
About 64% of the farmers perceived climate variability that was consistent with the meteorological data, whereas 36% either held contrary observations or were unable to discern. Age, level of education, farming experience and accessibility to information influenced the likelihood of farmers to correctly perceive climate variability. No significant differences in perception based on gender were observed. This study concludes that coping and adaption strategies of over one-third of the farmers could be negatively impacted by wrong perceptions of climate variability.

Originality/value
This study highlights discrepancies in perceptions among farmers with similar demographic characteristics. To guarantee sustainability of the sector, intervention by government and other key stakeholders to address underlying factors responsible for observed discrepancies is recommended.
Building the resilience of periurban communities to the impacts of climate change and urbanization
Authors: Narain Vishal 
Published: August 2020

Purpose
This paper aims to describe how social capital is mobilized in the mediation of periurban water insecurity induced by urbanization and climate change. Investing in social capital through the process of creating mechanisms for civic engagement is an important means of building resilience of periurban communities.

Design/methodology/approach
This paper draws on ethnographic and action research. The main sources of data were direct observation of water appropriation and access and semi-structured interviews. Convenience, snowball and theoretical sampling were used.

Findings
The residents of periurban Gurgaon have lost access to water on account of urbanization and climate change. In this context, they mobilize social relationships to collectively improve their access to water. Norms of cooperation and kinship play an important role in the mediation of water insecurity. Creating social capital by building platforms for civic engagement helped to improve their water security.

Originality/value
While there has been much interest in issues of periurban water insecurity, the role of social capital in the mediation of water insecurity has received scant attention. At the same time, while scholars have been interested in the role of social capital in adapting to the impacts of climate change, it has scarcely been studied in a periurban context. This paper seeks to bridge this research gap.