bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHD4 is recruited by GATA4 and NKX2-5 silencers to repress non-cardiac gene programs in the developing heart
Authors: Robbe Zachary L. , Shi Wei , Wasson Lauren K. , Wilczewski Caralynn M. , Sheng Xinlei , Hepperla Austin J. , Akerberg Brynn N. , Pu William T. , Cristea Ileana M. , Davis Ian J. , Conlon Frank L. 
Published: October 2021

AbstractThe Nucleosome Remodeling and Deacetylase (NuRD) complex is one of the central chromatin remolding complexes that mediate gene repression. NuRD is essential for numerous developmental events, including heart development. Clinical and genetic studies have provided direct evidence for the role of chromodomain helicase DNA-binding protein 4 (CHD4), the catalytic component of NuRD, in congenital heart disease (CHD), including atrial and ventricular septal defects. Further, it has been demonstrated that CHD4 is essential for mammalian cardiomyocyte formation and function. A key unresolved question is how CHD4/NuRD is localized to specific cardiac targets genes, as neither CHD4 nor NuRD can directly bind DNA. Here, we coupled a bioinformatics-based approach with mass spectrometry analyses to demonstrate that CHD4 interacts with the core cardiac transcription factors GATA4, NKX2-5 and TBX5 during embryonic heart development. Using transcriptomics and genome-wide occupancy data, we have characterized the genomic landscape of GATA4, NKX2-5 and TBX5 repression and defined the direct cardiac gene targets of GATA4-CHD4, NKX2-5-CHD4 and TBX5-CHD4 complexes. These data were used to identify putative cis-regulatory elements regulated controlled by these complexes. We genetically interrogated two of these silencers in vivo,Acta1andMyh11. We show that deletion of these silencers leads to inappropriate skeletal and smooth muscle gene mis-expression, respectively, in the embryonic heart. These results delineate how CHD4/NuRD is localized to specific cardiac loci and explicates how mutations in the broadly expressed CHD4 protein lead to cardiac specific disease states.
Vagus nerve stimulation accelerates motor learning through cholinergic modulation
Authors: Bowles Spencer , Hickman Jordan , Peng Xiaoyu , Williamson W. Ryan , Huang Rongchen , Washington Kayden , Donegan Dane , Welle Cristin G 
Published: October 2021

AbstractVagus nerve stimulation (VNS) is a neuromodulation therapy for a broad and rapidly expanding set of neurologic conditions. Classically used to treat epilepsy and depression, VNS has recently received FDA approval for stroke rehabilitation and is under preclinical and clinical investigation for other neurologic indications. Despite benefits across a diverse range of neurological disorders, the mechanism through which VNS influences central nervous system circuitry is not well described, limiting therapeutic optimization. A deeper understanding of the influence of VNS on neural circuits and activity is needed to maximize the use of VNS therapy across a broad range of neurologic conditions.To investigate how VNS can influence the neurons and circuits that underlie behavior, we paired VNS with upper limb movement in mice learning a skilled motor task. We leveraged genetic tools to perform optogenetic circuit dissection, as well as longitudinal in vivo imaging of calcium activity in cortical neurons to understand the effect of VNS on neural function. We found that VNS robustly enhanced motor learning when temporally paired with successful movement outcome, while randomly applied VNS impaired learning. This suggests that temporally-precise VNS may act through augmenting outcome cues, such as reinforcement signals. Within motor cortex, VNS paired with movement outcome selectively modulates the neural population that represents outcome, but not other movement-related neurons, across both acute and behaviorally-relevant timescales. Phasic cholinergic signaling from basal forebrain is required both for VNS-driven improvements in motor learning and the effects on neural activity in M1. These results indicate that VNS enhances motor learning through precisely-timed phasic cholinergic signaling to reinforce outcome, resulting in the recruitment of specific, behaviorally-relevant cortical circuits. A deeper understanding of the mechanisms of VNS on neurons, circuits and behavior provides new opportunities to optimize VNS to treat neurologic conditions.
Coloring inside the lines: genomic architecture and evolution of a widespread color pattern in frogs
Authors: Goutte Sandra , Hariyani Imtiyaz , Utzinger Kole Deroy , Bourgeois Yann , Boissinot Stéphane 
Published: October 2021

SummaryTraits shared among distantly related lineages are indicators of common evolutionary constraints, at the ecological, physiological or molecular level. The vertebral stripe is a color pattern that is widespread across the anuran phylogeny. Despite its prevalence in the order, surprisingly little is known about the genetic basis and evolutionary dynamic of this color pattern. Here we combine histology, genome- and transcriptome-wide analyses with order-scale phylogenetic comparative analyses to investigate this common phenotype. We show that the vertebral stripe has evolved hundreds of times in the evolutionary history of anurans and is selected for in terrestrial habitats. Using the Ethiopian Ptychadena radiation as a model system, we demonstrate that variation at the ASIP gene is responsible for the different vertebral stripe phenotypes. Alleles associated to these phenotypes are younger than the split between closely related Ptychadena species, thus indicating that the vertebral stripe results from parallel evolution within the group. Our findings demonstrate that this widespread color pattern evolves rapidly and recurrently in terrestrial anurans, and therefore constitute an ideal system to study repeated evolution.
Allele frequency dynamics under sex-biased demography and sex-specific inheritance in a pedigreed jay population
Authors: Driscoll Rose M.H. , Beaudry Felix E.G. , Cosgrove Elissa J. , Fitzpatrick John W. , Schoech Stephan J. , Chen Nancy 
Published: October 2021

ABSTRACTSex-biased demography, including sex-biased survival or migration, can alter allele frequency changes across the genome. In particular, we can expect different patterns of genetic variation on autosomes and sex chromosomes due to sex-specific differences in life histories, as well as differences in effective population size, transmission modes, and the strength and mode of selection. Here, we demonstrate the role that sex differences in life history played in shaping short-term evolutionary dynamics across the genome. We used a 25-year pedigree and genomic dataset from a long-studied population of Florida Scrub-Jays (Aphelocoma coerulescens) to directly characterize the relative roles of sex-biased demography and inheritance in shaping genome-wide allele frequency trajectories. We used gene dropping simulations to estimate individual genetic contributions to future generations and to model drift and immigration on the known pedigree. We quantified differential expected genetic contributions of males and females over time, showing the impact of sex-biased dispersal in a monogamous system. Due to female-biased dispersal, more autosomal variation is introduced by female immigrants. However, due to male-biased transmission, more Z variation is introduced by male immigrants. Finally, we partitioned the proportion of variance in allele frequency change through time due to male and female contributions. Overall, most allele frequency change is due to variance in survival and births. Males and females make similar contributions to autosomal allele frequency change, but males make higher contributions to allele frequency change on the Z chromosome. Our work shows the importance of understanding sex-specific demographic processes in characterizing genome-wide allele frequency change in wild populations.
Deciphering the species-level structure of topologically associating domains
Authors: Singh Rohit , Berger Bonnie 
Published: October 2021

SummaryChromosome conformation capture technologies such as Hi-C have revealed a rich hierarchical structure of chromatin, with topologically associating domains (TADs) as a key organizational unit, but experimentally reported TAD architectures, currently determined separately for each cell type, are lacking for many cell/tissue types. A solution to address this issue is to integrate existing epigenetic data across cells and tissue types to develop a species-level consensus map relating genes to TADs. Here, we introduce the TAD Map, a bag-of-genes representation that we use to infer, or “impute,” TAD architectures for those cells/tissues with limited Hi-C experimental data. The TAD Map enables a systematic analysis of gene coexpression induced by chromatin structure. By overlaying transcriptional data from hundreds of bulk and single-cell assays onto the TAD Map, we assess gene coexpression in TADs and find that expressed genes cluster into fewer TADs than would be expected by chance, and show that time-course and RNA velocity studies further reveal this clustering to be strongest in the early stages of cell differentiation; it is also strong in tumor cells. We provide a probabilistic model to summarize any scRNA-seq transcriptome in terms of its TAD activation profile, which we term a TAD signature, and demonstrate its value for cell type inference, cell fate prediction, and multimodal synthesis. More broadly, our work indicates that the TAD Map’s comprehensive, quantitative integration of chromatin structure and scRNA-seq data should play a key role in epigenetic and transcriptomic analyses.Software availability: https://tadmap.csail.mit.eduGraphical Abstract
Genetic evidence for signal transduction within the Bacillus subtilis GerA germinant receptor
Authors: Amon Jeremy D. , Artzi Lior , Rudner David Z. 
Published: October 2021

AbstractBacterial spores can rapidly exit dormancy through the process of germination. This process begins with the activation of nutrient receptors embedded in the spore membrane. The prototypical germinant receptor in Bacillus subtilis responds to L-alanine and is thought to be a complex of proteins encoded by the genes in the gerA operon: gerAA, gerAB, and gerAC. The GerAB subunit has recently been shown to function as the nutrient sensor, but beyond contributing to complex stability, no additional functions have been attributed to the other two subunits. Here, we investigate the role of GerAA. We resurrect a previously characterized allele of gerA (termed gerA*) that carries a mutation in gerAA and show it constitutively activates germination even in the presence of a wild-type copy of gerA. Using an enrichment strategy to screen for suppressors of gerA*, we identified mutations in all three gerA genes that restore a functional receptor. Characterization of two distinct gerAB suppressors revealed that one (gerAB-E105K) reduces the GerA complex’s ability to respond to L-alanine, while another (gerAB-F259S) disrupts the germinant signal downstream of L-alanine recognition. These data argue against models in which GerAA is directly or indirectly involved in germinant sensing. Rather, our data suggest that GerAA is responsible for transducing the nutrient signal sensed by GerAB. While the steps downstream of gerAA have yet to be uncovered, these results validate the use of a dominant-negative genetic approach in elucidating the gerA signal transduction pathway.ImportanceEndospore formers are a broad group of bacteria that can enter dormancy upon starvation and exit dormancy upon sensing the return of nutrients. How dormant spores sense and respond to these nutrients is poorly understood. Here, we identify a key step in the signal transduction pathway that is activated after spores detect the amino acid L-alanine. We present a model that provides a more complete picture of this process that is critical for allowing dormant spores to germinate and resume growth.
UGC's responses to the pandemic: roles of Institutional Quality Assurance Cells in Bangladesh
Authors: Genilo Jude William Ramiro 
Published: October 2021

PurposeThe paper documents the roles played by the institutional quality assurance cells (IQACs) to implement the University Grants Commission (UGC) directive to shift to online education during the COVID-19 pandemic period in Bangladesh. It highlights the government's efforts to ensure quality education, particularly in utilizing IQACs in the various public and private universities. The paper starts with the pandemic situation in the country, followed by the overall responses of the government, including its directives regarding the conduct of higher education.Design/methodology/approachThe paper utilizes as framework the Sloan Consortium's Five Pillars of Quality Online Learning – learning effectiveness, student satisfaction, teacher satisfaction, scale and access. The paper then analyzes the oral reports of 26 IQACs, which were presented to government officials in two meetings.FindingsFrom the analysis, it is apparent that IQACs have contributed toward the shift to full online education during the pandemic period. Universities responded to the crisis mainly in the areas of governance, teaching and learning and student support services. To guide policy formulation, the IQACs (with the help of other university units) conducted surveys among their faculty and students regarding their access to Internet, financial difficulties and mental health situation. From here, they drafted academic policies (attendance, student assessment and online teaching), conducted capacity building activities, monitored faculty performance, formulated guidelines on student online behavior and encouraged stakeholders to trust the online system.Originality/valueThe study is original since (like many countries) the pandemic has forced education activities to go online. It looks at both the macro level (the concerns of the University Grants Commission or UGC concerning quality education in an online setting) and the micro level (what universities have undertaken to address the concerns of the UGC).
Multi-objective design optimisation of steel framed structures using three different methods
Authors: Alkhadashi Abdalhakem , Mohammad Fouad , Zubayr Rasheedah Olamide , Aoun Klalib Hynda , Balik Piotr 
Published: October 2021

PurposeThe optimality objectives are the structure weight and embodied energy as well as calculating the cost and embodied carbon of the resulting optimum options. Three optimality algorithms developed in MATLAB, namely, genetic algorithms (GA), particle swarm optimisation (PSO) and harmony search algorithm (HSA), were used for structural optimisation to compare the effectiveness of the algorithms. Two life-cycle stages were considered, production and construction stages, which include three boundaries: materials, transportation and erection. In the formulation of the optimum design problem, 107 universal steel beams (UKB) and 64 columns (UKC) sections were considered for the discrete design variables. The imposed behavioural constraints in the optimum design process were set according to the provision of Eurocode 3 (EC3). The study aims to find the optimum solution of 2D steel frames whilst considering weight and embodied energy, investigate the performance of the analysis integrated with MATLAB and provide three examples to which all these are applied to.Design/methodology/approachUndoubtedly, in structural engineering, the best design of any structure aims at the most economical and environmental option, without impairing the functional and its structural integrity. In the paper, multi-objective stochastic search methods are proposed for optimum design of three two-dimensional multi-story frames.FindingsResults showed that the optimised designs obtained by HSA are better than those found by the GA and PSO with an average difference of 16% from GA and PSO, where this difference increases at larger frame structures. It was, therefore, concluded that the integration of the analysis, design and optimisation methods employed in MATLAB can be effective in obtaining prompt optimum results during the decision-making stage.Research limitations/implicationsThere may be some possible limitations in the study. Due to the time constraints, only three meta-heuristic approaches were investigated, where more methods should be investigated to fully understand their effectiveness in multi-objective problems.Originality/valueInvestigating the performance of three optimisation methods in multi-objective problems developed in MATLAB. More importantly, developing optimisation models for evaluation of embodied energy, embodied carbon and cost for steel structures to assist designers, during the initial stages, to evaluate design decisions against their energy consumption and carbon impacts.
How to select good leaders in Asian countries: the case of China and Singapore
Authors: Choi Franky K.H. 
Published: October 2021

PurposeThe purpose of this paper is to bring out the possibility of selecting good leaders in Asian countries, i.e., China and Singapore.Design/methodology/approachSince comparative historical analysis enhances the objectivity for academic discussion, Deng Xiaoping’s and Lee Kuan Yew’s leadership successions have been chosen as the cases for studies by virtue of “method of agreement”. Incorporating “argument based on the contrary” into the context for macro-historical analysis, this paper characterises the duo’s successful (at least quite successful) leadership successions, thus offering an alternative paradigm beyond Western-style democracy.FindingsBoth cases of post-Mao China and the independent Singapore indicate that in quite a number of Asian countries, good leaders could still be selected beyond universal suffrage as practised among Western Electoral Democracies, mainly because of the elites-driven context. As to the duo’s succession results, Deng Xiaoping’s selection of leaders was somewhat successful, while Lee Kuan Yew’s was phenomenal.OriginalityThis paper offers readers a glance over the possibility of selecting good leaders in Asian countries not fully based on Western-style democracy. Learning from the duo’s leadership successions, the West may treat elite politics as the supplement under Western Electoral Democracies in order to avoid their countries falling into the trap of populism. The West could meanwhile consider the exceptional criteria prized by the duo for leadership successions. Considering such interactions among elites in the real-life context, it could serve as an alternative model to Western-style democracy.
The mechanism of process parameters influencing the AlSi10Mg side surface quality fabricated via laser powder bed fusion
Authors: Dai Shimin , Liao Hailong , Zhu Haihong , Zeng Xiaoyan 
Published: October 2021

Purpose
For the laser powder bed fusion (L-PBF) technology, the side surface quality is essentially important for industrial applicated parts, such as the inner flow parts. Contour is generally adopted at the parts’ outline to enhance the side surface quality. However, the side surface roughness (Ra) is still larger than 10 microns even with contour in previous studies. The purpose of this paper is to study the influence of contour process parameters, laser power and scanning velocity on the side surface quality of the AlSi10Mg sample.

Design/methodology/approach
Using L-PBF technology to manufacture AlSi10Mg samples under different contour process parameters, use a laser confocal microscope to capture the surface information of the samples, and obtain the surface roughness Ra and the maximum surface height Rz of each sample after analysis and processing.

Findings
The results show that the side surface roughness decreases with the increase of the laser power at the fixed scanning velocity of 1,000 mm/s, the side surface roughness Ra stays within the error range as the contour velocity increases. It is found that the Ra increases with the scanning velocity increasing and the greater the laser power with the greater Ra increases when the laser power of contour process parameters is 300 W, 350 W and 400 W. The Rz maintain growth with the contour scanning velocity increasing at constant laser power. The continuous uniform contour covers the pores in the molten pool of the sample edge and thus increase the density of the sample. Two mechanisms named “Active adhesion” and “Passive adhesion” cause sticky powder.

Originality/value
Formation of a uniform and even contour track is key to obtain the good side surface quality. The side surface quality is determined by the uniformity and stability of the contour track when the layer thickness is fixed. These research results can provide helpful guidance to improve the surface quality of L-PBF manufactured parts.
What makes urban parks good for California quail? Evaluating park suitability, species persistence, and the potential for reintroduction into a large urban national park
Authors: Iknayan Kelly J. , Wheeler Megan M. , Safran Samuel M. , Young Jonathan S. , Spotswood Erica N. 
Published: October 2021

Abstract

Preserving and restoring wildlife in urban areas benefits both urban ecosystems and the well‐being of urban residents. While urban wildlife conservation is a rapidly developing field, the majority of conservation research has been performed in wildland areas. Understanding the applicability of wildland science to urban populations and the relative importance of factors limiting species persistence are of critical importance to identifying prescriptive management strategies for restoring wildlife to urban parks.

We evaluated how habitat fragmentation, habitat quality and mortality threats influence species occupancy and persistence in urban parks. We chose California quail Callipepla californica as a representative species with potential to respond to urban conservation. We used publicly available eBird data to construct occupancy models of quail in urban parks across their native range, and present an application using focal parks interested in exploring quail reintroduction.

Urban parks had a 0.23 ± 0.02 probability of quail occupancy, with greater occupancy in larger parks that were less isolated from potential source populations, had higher shrub cover and had lower impervious cover. Less isolated parks had higher colonization rates, while larger parks had lower extinction rates. These results align with findings across urban ecology showing greater biodiversity in larger and more highly connected habitat patches.

A case study highlighted that interventions to increase effective park size and improve connectivity would be most influential for two highly urban focal parks, while changes to internal land cover would have a relatively small impact. Low joint extinction probability in the parks (0.010 ± 0.013) indicated reintroduced populations could persist for some time.

Synthesis and applications. We show how eBird data can be harnessed to evaluate the responsiveness of wildlife to urban parks of variable size, connectivity and habitat quality, highlighting what management actions are most needed. Using California quail as an example, we found park size, park isolation and presence of coyotes are all important drivers of whether quail can colonize and persist in parks. Our results suggest reintroducing quail to parks could be successful provided parks are large enough to support quail, and management actions are taken to enhance regional connectivity or periodic assisted colonization is used to supplement local populations.