bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Customizable Low-Cost System for Massively Parallel Zebrafish Behavior Phenotyping
Authors: Joo William , Vivian Michael D. , Graham Brett J. , Soucy Edward R. , Thyme Summer B. 
Published: September 2020

AbstractHigh-throughput behavioral phenotyping is critical to genetic or chemical screening approaches. Zebrafish larvae are amenable to high-throughput behavioral screening because of their rapid development, small size, and conserved vertebrate brain architecture. Existing commercial behavior phenotyping systems are expensive and not easily modified for new assays. Here, we describe a modular, highly adaptable, and low-cost behavior system. Along with detailed assembly and operation instructions, we provide data acquisition software and a robust, parallel analysis pipeline. We validate our approach by analyzing stimulus response profiles in larval zebrafish, confirming prepulse inhibition phenotypes of two previously isolated mutants, and highlighting best practices for growing larvae prior to behavioral testing. Our new design thus allows rapid construction and streamlined operation of many large-scale behavioral setups with minimal resources and fabrication expertise, with broad applications to other aquatic organisms.
Suberoyl bis-hydroxamic acid reactivates Kaposi’s sarcoma-associated herpesvirus through histone acetylation and induces apoptosis in lymphoma cells
Authors: Iida Shun , Mine Sohtaro , Ueda Keiji , Suzuki Tadaki , Hasegawa Hideki , Katano Harutaka 
Published: September 2020

AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) is an etiologic agent of Kaposi’s sarcoma as well as primary effusion lymphoma (PEL), an aggressive B-cell neoplasm which mostly arises in immunocompromised individuals. At present, there is no specific treatment available for PEL and its prognosis is poor. Lytic replication of KSHV is also associated with a subset of multicentric Castleman diseases. In this study, we found that the histone deacetylase inhibitor suberoyl bis-hydroxamic acid (SBHA) induced KSHV reactivation in PEL cells in a dose-dependent manner. Next-generation sequencing analysis showed that more than 40% of all transcripts expressed in SBHA-treated PEL cells originated from the KSHV genome compared with less than 1% in untreated cells. Chromatin immunoprecipitation assays demonstrated that SBHA induced histone acetylation targeting the promoter region of the KSHV replication and transcription activator gene. However, there was no significant change in methylation status of the promoter region of this gene. In addition to its effect of KSHV reactivation, this study revealed that SBHA induces apoptosis in PEL cells in a dose-dependent manner, inducing cleavage of caspases and expression of proapoptotic factors, including Bim and Bax. These findings suggest that SBHA reactivates KSHV from latency and induces apoptosis through the mitochondrial pathway in PEL cells. Therefore, SBHA can be considered a new tool for induction of KSHV reactivation, and could provide a novel therapeutic strategy against PEL.ImportanceKaposi’s sarcoma and primary effusion lymphoma cells are latently infected with Kaposi’s sarcoma-associated herpesvirus (KSHV), whereas KSHV replication is frequently observed in multicentric Castleman disease. Although KSHV replication can be induced by some chemical reagents (e.g. 12-O-tetradecanoylphorbol-13-acetate), the mechanism of KSHV replication is not fully understood. We found that the histone deacetylase inhibitor suberoyl bis-hydroxamic acid (SBHA) induced KSHV reactivation with high efficiency, through histone acetylation in the promoter of the replication and transcription activator gene, compared with 12-O-tetradecanoylphorbol-13-acetate. SBHA also induced apoptosis through the mitochondrial pathway in KSHV-infected cells, with a lower EC50than measured for viral reactivation. SBHA could be used in a highly efficient replication system for KSHVin vitro,and as a tool to reveal the mechanism of replication and pathogenesis of KSHV. The ability of SBHA to induce apoptosis at lower levels than needed to stimulate KSHV reactivation, indicates its therapeutic potential.
Influenza A virus-induced thymus atrophy differentially affects dynamics of conventional and regulatory T cell development
Authors: Elfaki Yassin , Robert Philippe A. , Binz Christoph , Falk Christine S. , Bruder Dunja , Prinz Immo , Floess Stefan , Meyer-Hermann Michael , Huehn Jochen 
Published: September 2020

ABSTRACTFoxp3+regulatory T (Treg) cells, which are crucial for maintenance of self-tolerance, mainly develop within the thymus, where they arise from CD25+Foxp3-or CD25-Foxp3+Treg cell precursors. Although it is known that infections can cause transient thymic involution, the impact of infection-induced thymus atrophy on thymic Treg (tTreg) cell development is unknown. Here, we infected mice with influenza A virus (IAV) and studied thymocyte population dynamics post infection. IAV infection caused a massive, but transient thymic involution, dominated by a loss of CD4+CD8+double-positive (DP) thymocytes, which was accompanied by a significant increase in the frequency of CD25+Foxp3+tTreg cells. Differential apoptosis susceptibility could be experimentally excluded as a reason for the relative tTreg cell increase, and mathematical modeling suggested that enhanced tTreg cell generation cannot explain the increased frequency of tTreg cells. Yet, an increased death of DP thymocytes and augmented exit of single-positive (SP) thymocytes was suggested to be causative. Interestingly, IAV-induced thymus atrophy resulted in a significantly reduced T cell receptor (TCR) repertoire diversity of newly produced tTreg cells. Taken together, IAV-induced thymus atrophy is substantially altering the dynamics of major thymocyte populations, finally resulting in a relative increase of tTreg cells with an altered TCR repertoire.
Interaction network of SARS-CoV-2 with host receptome through spike protein
Authors: Gu Yunqing , Cao Jun , Zhang Xinyu , Gao Hai , Wang Yuyan , Wang Jia , Zhang Jinlan , Shen Guanghui , Jiang Xiaoyi , Yang Jie , Zheng Xichen , Xu Jianqing , Zhang Cheng Cheng , Lan Fei , Qu Di , Zhao Yun , Xu Guoliang , Xie Youhua , Luo Min , Lu Zhigang 
Published: September 2020

SUMMARYHost cellular receptors are key determinants of virus tropism and pathogenesis. Virus utilizes multiple receptors for attachment, entry, or specific host responses. However, other than ACE2, little is known about SARS-CoV-2 receptors. Furthermore, ACE2 cannot easily interpret the multi-organ tropisms of SARS-CoV-2 nor the clinical differences between SARS-CoV-2 and SARS-CoV. To identify host cell receptors involved in SARS-CoV-2 interactions, we performed genomic receptor profiling to screen almost all human membrane proteins, with SARS-CoV-2 capsid spike (S) protein as the target. Twelve receptors were identified, including ACE2. Most receptors bind at least two domains on S protein, the receptor-binding-domain (RBD) and the N-terminal-domain (NTD), suggesting both are critical for virus-host interaction. Ectopic expression of ASGR1 or KREMEN1 is sufficient to enable entry of SARS-CoV-2, but not SARS-CoV and MERS-CoV. Analyzing single-cell transcriptome profiles from COVID-19 patients revealed that virus susceptibility in airway epithelial ciliated and secretory cells and immune macrophages highly correlates with expression of ACE2, KREMEN1 and ASGR1 respectively, andACE2/ASGR1/KREMEN1 (ASK) together displayed a much better correlation than any individual receptor. Based on modeling of systemic SARS-CoV-2 host interactions through S receptors, we revealed ASK correlation with SARS-CoV-2 multi-organ tropism and provided potential explanations for various COVID-19 symptoms. Our study identified a panel of SARS-CoV-2 receptors with diverse binding properties, biological functions, and clinical correlations or implications, including ASGR1 and KREMEN1 as the alternative entry receptors, providing insights into critical interactions of SARS-CoV-2 with host, as well as a useful resource and potential drug targets for COVID-19 investigation.
Ecological niche adaptation of a bacterial pathogen associated with reduced zoonotic potential
Authors: Kirkwood Mark , Vohra Prerna , Bawn Matt , Thilliez Gaëtan , Pye Hannah , Tanner Jennifer , Chintoan-Uta Cosmin , Branchu Priscilla , Petrovska Liljana , Dallman Timothy , Hall Neil , Stevens Mark P. , Kingsley Robert A. 
Published: September 2020

AbstractThe emergence of new bacterial pathogens is a continuing challenge for agriculture and food safety.Salmonella entericaserovar Typhimurium (S. Typhimurium) is a major cause of foodborne illness worldwide, with pigs a major zoonotic reservoir. Two variants,S. Typhimurium phage type U288 and monophasicS. Typhimurium (S. 4,[5],12:i:-) ST34 emerged and have accounted for the majority of isolates from pigs in the UK in the past two decades, but have distinct host range and risk to food safety. ST34 accounts for over 50% of allS. Typhimurium infections in people while U288 less than 2%. U288 and ST34 form distinct phylogenetic clusters withinS. Typhimurium, defined by approximately 600 SNPs within their 5 Mbp genomes. Evolution of the U288 clade from an LT2-like ancestor was characterised by the acquisition of AMR genes, insertions and deletions in the virulence plasmid pU288-1, and the accumulation of polymorphisms, some of which resulted in truncation of coding sequences. U288 isolates exhibited lower growth rate and viability following desiccation compared to ST34 isolates, characteristics that could affect transmission through the food chain. U288 and ST34 isolates exhibited distinct outcomes of infection in the murine model of colitis, and colonised pigs in a manner that affected the disease symptoms and distribution in organs. U288 infection was more disseminated in the lymph nodes while ST34 were recovered in greater numbers in the intestinal contents. These data are consistent with the evolution ofS. Typhimurium U288 adaptation to pigs that may determine their reduced zoonotic potential.ImportanceBacterial pathogens continually evolve to exploit new ecological niches as they emerge due to human activity including agricultural, medical or societal practice. The consequences of the emergence of new pathogens may affect outcome of infection and risk to human or animal health. Genome sequence can resolve the population structure, identify variants that are evolving as they enter a new niche, and pinpoint potential functional divergence. We report a variantS. Typhimurium that adapted to a unique niche distinct to that occupied by a secondS. Typhimurium variant circulating in the same pig populations. Adaptation was accompanied by phenotypic and genotypic changes consistent with a more invasive lifestyle and a decreased zoonotic potential observed in the epidemiological record. Our findings suggest that pathogen genotypic variation may be useful in estimating zoonotic potential and threat to livestock welfare.
Probing neuronal functions with precise and targeted laser ablation in the living cortex
Authors: Cheng Zongyue , Han Yiyong , Wei Bowen , Li Baoming , Cui Meng , Gan Wenbiao 
Published: September 2020

AbstractTargeted cell ablation is an important strategy for dissecting the function of individual cells within biological tissues. Here we developed an amplified femtosecond laser-coupled two-photon microscopy (AFL-TPM) system that allows instantaneous and targeted ablation of individual cells and real-time monitoring of neuronal network changes in the living mouse cortex. Through precise and iterative control of the laser power and position, individual cells could be ablated by a single femtosecond light pulse with minimum collateral damage. We further show that ablation of individual somatostatin-expressing interneuron increases the activity of nearby neurons in the primary motor cortex during motor learning. Through precise dendrotomy, we reveal that different dendritic branches of layer 5 pyramidal neurons are structurally and functionally independent. By ablating individual cells and their processes in a spatiotemporally specific manner, the AFL-TPM system could serve as an important means for understanding the functions of cells within the complicated neuronal network.
Spatial variation in population-density, movement and detectability of snow leopards in a multiple use landscape in Spiti Valley, Trans-Himalaya
Authors: Sharma Rishi Kumar , Sharma Koustubh , Borchers David , Bhatnagar Yash Veer , Suryawanshi Kulbhushan Singh , Mishra Charudutt 
Published: September 2020

AbstractThe endangered snow leopardPanthera unciaoccurs in human use landscapes in the mountains of South and Central Asia. Conservationists generally agree that snow leopards must be conserved through a land-sharing approach, rather than land-sparing in the form of strictly protected areas. Effective conservation through land-sharing requires a good understanding of how snow leopards respond to human use of the landscape. Snow leopard density is expected to show spatial variation within a landscape because of variation in the intensity of human use and the quality of habitat. However, snow leopards have been difficult to enumerate and monitor. Variation in the density of snow leopards remains undocumented, and the impact of human use on their populations is poorly understood. We examined spatial variation in snow leopard density in Spiti Valley, an important snow leopard landscape in India, via spatially explicit capture recapture analysis of camera trap data. We camera trapped an area encompassing a minimum convex polygon of 953 km2. We estimated an overall density of 0.49 (95% CI: 0.39-0.73) adult snow leopards per 100 km2. Using AIC, our best model showed the density of snow leopards to depend on wild prey density, movement about activity centres to depend on altitude, and the expected number of encounters at the activity centre to depend on topography. Models that also used livestock biomass as a density covariate ranked second, but the effect of livestock was weak. Our results highlight the importance of maintaining high density pockets of wild prey populations in multiple use landscapes to enhance snow leopard conservation.
Screening of candidate host cell membrane proteins involved in SARS-CoV-2 entry
Authors: Kotani Norihiro , Nakano Takanari , Kuwahara Ryusuke 
Published: September 2020

ABSTRACTCoronavirus disease (COVID-19) represents a real threat to the global population, and understanding the biological features of the causative virus, i.e., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is imperative for mitigating this threat. Analyses of proteins such as primary receptors and co-receptors (co-factors), which are involved in the entry of SARS-CoV-2 into host cells, will provide important clues to help control the virus. Here, we identified host cell membrane protein candidates present in proximity to the attachment sites of SARS-CoV-2 spike proteins, using proximity labeling and proteomic analysis. The identified proteins represent key candidate factors that may be required for viral entry. DPP4, Cadherin-17, and CD133 were found to co-localize with cell membrane-bound SARS-CoV-2 spike proteins in Caco-2 cells and thus showed potential as candidate factors. The experimental infection with a SARS-CoV-2 pseudovirus indicated a 2-fold enhanced infectivity in the CD133-ACE2-coexpressing HEK293T cells compared to that in HEK293T cells expressing ACE-2 alone. The information and resources regarding these co-receptor labeling and analysis techniques could be utilized for the development of antiviral agents against SARS-CoV-2 and other emerging viruses.
Long-read sequencing reveals rapid evolution of immunity- and cancer-related genes in bats
Authors: Scheben Armin , Mendivil Ramos Olivia , Kramer Melissa , Goodwin Sara , Oppenheim Sara , Becker Daniel J , Schatz Michael C , Simmons Nancy B , Siepel Adam , McCombie W Richard 
Published: September 2020

AbstractBats are exceptional among mammals for their powered flight, extended lifespans, and robust immune systems. To investigate the genomic underpinnings of unique bat adaptations, we sequenced the genomes of the Jamaican fruit bat (Artibeus jamaicensis) and the Mesoamerican mustached bat (Pteronotus mesoamericanus) and compared them to a diverse collection of 13 additional bat species together with other mammals. We used the Oxford Nanopore Technologies long-read platform to generate highly complete assemblies (N50: 28-29Mb) and facilitate analysis of complex genomic regions containing duplicated genes. Using gene family size analysis, we found that the type I interferon locus was contracted by eight genes in the most recent common ancestor (MRCA) of bats, shifting the proportion of interferon-ω to interferon-α and making interferon-ω the most common type I interferon in bats. Antiviral genes stimulated by type I interferons were also rapidly evolving, with interferon-induced transmembrane genes experiencing a lineage-specific duplication and strong positive selection in the gene IFIT2. Moreover, the lineage of phyllostomid bats showed an unprecedented expansion of PRDM9, a recombination-related gene also involved in infection responses, raising the possibility that this gene contributes to bat antiviral defenses. These modifications in the bat innate immune system may be important adaptations allowing them to harbor viruses asymptomatically. We additionally found evidence of positive selection on the branch leading to the MRCA of bats acting on 33 tumor suppressors and six DNA repair genes, which may contribute to the low cancer rates and longevity observed across bats. These new genomic resources enable insights into the extraordinary adaptations of bats, with implications for mammalian evolutionary studies and public health.
On theoretical engorgement and the myth of fair value accounting in China: a reply
Authors: Bewley Kathryn , Graham Cameron , Peng Songlan 
Published: September 2020

PurposeThis article is a reply to “On theoretical engorgement and the myth of fair value accounting in China” Nobes (2019) from the authors of “Adaptability to fair value accounting in an emerging economy: A case study of China's IRFS convergence” (Peng and Bewley, 2010) and “The Winding Road to Fair Value Accounting in China: A Social Movement Analysis” (Bewley et al., 2018).Design/methodology/approachThis article engages directly with the arguments of the criticism.FindingsThis article argues that the author of the commentary misunderstands the purpose, content and findings of both papers. By providing only a narrowly focused technical analysis of the new Chinese accounting standards, the author fails to see that their qualitative research approach reveals important, complex social and political factors at play in China's attempts to adopt modern international accounting principles. The commentary expresses a view that accounting is a neutral technology that needs only to be clearly defined and enumerated to be correctly implemented, whereas this research takes a much broader and deeper perspective. The authors seek to understand how China was able to successfully adopt fair value accounting standards in 2006, whereas an earlier attempt to introduce fair value in 1998 had led to abuse of fair value measurements and the eventual repeal of fair value regulations in 2001.Practical implicationsThis article helps clarify the purpose of qualitative accounting research, the role of theory in such research and the usefulness of theory in describing and explaining empirical case facts related to changes in accounting standards, particularly in an international context.Originality/valueThis article contributes to a better appreciation of qualitative accounting research.
Stakeholder-informed considerations for a food poverty definition
Authors: Beacom Emma , Furey Sinéad , Hollywood Lynsey Elizabeth , Humphreys Paul 
Published: September 2020

PurposeA number of food poverty definitions have been identified by academics and various government organisations globally; however, there exists no government-endorsed definition of food poverty in the United Kingdom (UK), and there remains a gap regarding how relevant current food poverty definitions are in the Northern Ireland (NI)/UK contexts.Design/methodology/approachInterviews (n = 19) with a range of stakeholders (e.g. policymakers, politicians, community advice centre workers, consumer sub-group representatives, food bank and food redistribution organisation representatives) were conducted to examine (1) the usefulness of a food poverty definition, (2) what a food poverty definition should include and (3) the applicability of an existing definition (Radimer et al., 1992) in the NI/UK context. Data was thematically analysed using QSR NVivo (v.12).FindingsDefinition was considered important to increase awareness and understanding. Any consideration of revising the Radimer et al. (1992) definition, or of establishing a new standardised definition, should seek to reduce/remove ambiguity and subjectivity of terminology used (i.e. more clearly defining what the terms “adequate”, “sufficient”, “quality” and “socially acceptable ways” mean in this context).Practical implicationsThis research emphasises the importance of appropriately conceptually defining social phenomena such as food poverty, as a first step to constructing and reviewing measurement approaches and ultimately assessing predictors and recommending solutions.Originality/valueThis research addresses the gap relating to stakeholders’ opinion on food poverty definition and contributes recommendations for modifying the Radimer et al. (1992) definition in the NI/UK and present-day contexts.
A global sensitivity analysis approach for multiple failure modes based on convex-probability hybrid uncertainty
Authors: Zhang Yidu , Liu Yongshou , Guo Qing 
Published: September 2020

Purpose
This paper aims to develop a method for evaluating the failure probability and global sensitivity of multiple failure modes based on convex-probability hybrid uncertainty.

Design/methodology/approach
The uncertainty information of the input variable is considered as convex-probability hybrid uncertainty. Moment-independent variable global sensitivity index based on the system failure probability is proposed to quantify the effect of the input variable on the system failure probability. Two-mode sensitivity indices are adopted to characterize the effect of each failure mode on the system failure probability. The method based on active learning Kriging (ALK) model with a truncated candidate regions (TCR) is adopted to evaluate the systems failure probability, as well as sensitivity index and this method is termed as ALK-TCR.

Findings
The results of five examples demonstrate the effectiveness of the sensitivity index and the efficiency of the ALK-TCR method in solving the problem of multiple failure modes based on the convex-probability hybrid uncertainty.

Originality/value
Convex-probability hybrid uncertainty is considered on system reliability analysis. Moment-independent variable sensitivity index based on the system failure probability is proposed. Mode sensitivity indices are extended to hybrid uncertain reliability model. An effective global sensitivity analysis approach is developed for the multiple failure modes based on convex-probability hybrid uncertainty.