bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing cortex-wide gene expression patterns between species in a common reference frame
Authors: Englund Mackenzie , James Sebastian S. , Bottom Riley , Huffman Kelly J. , Wilson Stuart P. , Krubitzer Leah A. 
Published: July 2021

AbstractAdvances in sequencing techniques have made comparative studies of gene expression a current focus for understanding evolutionary and developmental processes. However, insights into the spatial expression of genes have been limited by a lack of robust methodology. We therefore developed a set of algorithms for quantifying and comparing tissue-wide spatial patterns of gene expression within and across species. Here we apply these algorithms to compare cortex-wide expression of Id2 and RZRβ mRNA in early postnatal mice and voles. We show that neocortical patterns of Id2 expression are moderately conserved between species, but that the degree of conservation varies by cortical layer and area. By comparison, patterns of RZRβ expression are highly conserved in somatosensory areas, and more variable between species in visual and auditory areas. We consider if these differences reflect independent evolution in the 35 million years since the last common ancestor.
Multi-tier mechanics control stromal adaptations in swelling lymph nodes
Authors: Assen Frank P. , Hons Miroslav , Hauschild Robert , Shamipour Shayan , Abe Jun , Kaufmann Walter A. , Costanzo Tommaso , Krens Gabriel , Brown Markus , Ludewig Burkhard , Hippenmeyer Simon , Stein Jens V. , Heisenberg Carl-Philipp , Hannezo Edouard , Luther Sanjiv A. , Sixt Michael 
Published: July 2021

AbstractLymph nodes (LNs) comprise two main structural elements: Fibroblastic reticular cells (FRCs) that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. While LNs are fairly stable in size during homeostatic conditions, immunological challenge causes more than 10-fold increase in size within only a few days. How a solid organ can accommodate such extreme volumetric changes is poorly understood. Here, we characterize the biomechanics of LN swelling on the cellular and organ scale. We identify lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing FRCs and their associated conduits to stretch. After an initial phase of relaxation, FRCs sense the resulting strain via cell matrix adhesions, which coordinates local growth and remodeling of the stromal network. While the expanded FRC network adopts its typical configuration, a massive fibrotic reaction of the organ capsule sets in and counters further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multi-tier fashion.
Machine Learning of Pseudomonas aeruginosa transcriptomes identifies independently modulated sets of genes associated with known transcriptional regulators
Authors: Rajput Akanksha , Tsunemoto Hannah , Sastry Anand V. , Szubin Richard , Rychel Kevin , Sugie Joseph , Pogliano Joe , Palsson Bernhard O. 
Published: July 2021

AbstractThe transcriptional regulatory network (TRN) of Pseudomonas aeruginosa plays a critical role in coordinating numerous cellular processes. We extracted and quality controlled all publicly available RNA-sequencing datasets for P. aeruginosa to find 281 high-quality transcriptomes. We produced 83 new RNAseq data sets under critical conditions to generate a comprehensive compendium of 364 transcriptomes. We used this compendium to reconstruct the TRN of P. aeruginosa using independent component analysis (ICA). We identified 104 independently modulated sets of genes (called iModulons), among which 81 (78%) reflect the effects of known transcriptional regulators. We show that iModulons: 1) play an important role in defining the genomic boundaries of biosynthetic gene clusters (BGCs); 2) show increased expression of the BGCs and associated secretion systems in conditions that emulate cystic fibrosis (CF); 3) show the presence of a novel BGC named RiPP (bacteriocin producer) which might have a role in worsening CF outcomes; 4) exhibit the interplay of amino acid metabolism regulation and central metabolism across carbon sources, and 5) clustered according to their activity changes to define iron and sulfur stimulons. Finally, we compare the iModulons of P. aeruginosa with those of E. coli to observe conserved regulons across two gram negative species. This comprehensive TRN framework covers almost every aspect of the transcriptional regulatory machinery in P. aeruginosa, and thus could prove foundational for future research of its physiological functions.
Exploratory extracellular vesicle-bound miRNA profiling to identify candidate biomarkers of chronic alcohol drinking in non-human primates
Authors: Lewis Sloan A. , Doratt Brianna , Sureshchandra Suhas , Pan Tianyu , Gonzalez Steven W. , Shen Weining , Grant Kathleen A. , Messaoudi Ilhem 
Published: July 2021

ABSTRACTBackgroundLong-term alcohol drinking is associated with numerous health complications including susceptibility to infection, cancer, and organ damage. However, due to the complex nature of human drinking behavior, it is challenging to determine whether alcohol use should be considered a risk factor during diagnosis and treatment. We lack reliable biomarkers of alcohol use that could be used to determine drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle-bound microRNA (EV-miRNA) have been discovered to be consistent biomarkers of conditions including cancer and liver disease.MethodsIn this study, we profiled the plasma EV-miRNA content by miRNA-Seq from 80 non-human primates after 12 months of voluntary ethanol drinking.ResultsWe identified a list of up- and downregulated EV-miRNA candidate biomarkers of both heavy drinking as well as those positively correlated with ethanol dose. We further overexpressed these candidate miRNA in control primary peripheral immune cells to assess potential functional mechanisms of these EV-miRNA. We identified that overexpression of miR-155, miR-154, miR-34c, miR-450a, and miR-204 led to increased inflammatory TNFα or IL-6 production in PBMC after stimulation.ConclusionThis exploratory study identified several EV-miRNA that could serve as biomarkers of long-term alcohol drinking as well as provided a mechanism for alcohol-induced peripheral inflammation.
The swine spatiotemporal H3K27ac spectrum provides novel resources for exploring gene regulation related to complex traits and fundamental biological process
Authors: Zhu Yaling , Zhou Zhimin , Huang Tao , Zhang Zhen , Li Wanbo , Ling Ziqi , Jiang Tao , Yang Jiawen , Yang Siyu , Xiao Yanyuan , Charlier Carole , Georges Michel , Yang Bin , Huang Lusheng 
Published: July 2021

AbstractThe limited knowledge of genomic non-coding and regulatory regions has limited our ability to decipher the genetic mechanisms underlying complex traits in pigs. In this study, we characterize the spatiotemporal landscape of putative enhancers and promoters and their target genes by combining H3K27ac targeted ChIP-Seq and RNA-Seq in fetal (day 74-75 pc) and adult (day 132-150 pn) tissues (brain, liver, heart, muscle and small intestine) sampled from Asian aboriginal Bamaxiang and European highly selected Large White pigs of both sexes. We identify 101,290 H3K27ac peaks marking 18,521 promoters and 82,769 enhancers, including peaks that are active across all tissues and developmental stages could indicate safe harbors for exogenous gene insertion, and tissue and developmental-stage specific peaks that regulate genes pathways matching tissue and developmental stage specific physiological functions. We found H3K27ac and DNA methylation in the promoter region of the XIST gene may involve in X chromosome inactivation, and demonstrate utility of the present resource to reveal regulatory patterns of known causal genes and to prioritize candidate causal variants for complex traits in pigs. We have developed a web browser to improve the accessibility of the results (http://39.108.231.116/browser/?genome=susScr11).
Outcome-selective reinstatement is predominantly context-independent, and associated with c-Fos activation in the posterior dorsomedial striatum
Authors: Abiero Arvie R. , Ali Zaid , Vissel Bryce , Bradfield Laura A. 
Published: July 2021

AbstractResearch from human and animal studies has found that responding that has been successfully reduced following treatment can return upon exposure to certain contexts. An individual in recovery from alcohol use disorder, for example, might relapse to drinking upon visiting their favourite bar. However, most of these data have been derived from experiments involving a single (active) response, and the context-dependence of returned responding in situations involving choice between multiple actions and outcomes is less well-understood. We thus investigated how outcome-selective reinstatement – a procedure involving choice between multiple actions – was affected by altering the physical context in rats. In Experiment 1, rats were trained over 6 days to press a left lever for one food outcome (pellets or sucrose) and a right lever for the other outcome. Then, rats received an extinction session in either the same context (A) as lever press training, or in a different context (B). Rats were tested immediately (5 minutes) after extinction in Context A or B such that there were four groups in total: AAA, ABB, ABA, and AAB. Reinstatement testing consisted of one food outcome being delivered ‘freely’ (i.e. unearned by lever pressing and unsignalled by cues) to the food magazine every 4 minutes in the following order: Sucrose, Pellet, Pellet, Sucrose. Selective reinstatement was considered intact if pellet delivery increased pressing selectively on the pellet lever, and sucrose delivery selectively increased pressing on the sucrose lever. This result (Reinstated > Nonreinstated) was observed for rats in group AAA and ABB, but not rats in groups ABA and AAB. Experiment 2 was conducted identically, except that rats received two extinction sessions over two days and tested one day later. This time, all groups demonstrated intact outcome-selective reinstatement regardless of context. Analysis of c-Fos expression in several brain regions revealed that only c-Fos expression in the posterior dorsomedial striatum (pDMS) was related to intact reinstatement performance. Overall, these results suggest that outcome-selective reinstatement is predominantly context-independent, and that intact reinstatement is related to neuronal activity in the pDMS.HighlightsOutcome-selective reinstatement is predominantly context-independentOutcome-selective reinstatement is entirely context-independent after multiple extinction sessionsOutcome-selective reinstatement increases c-Fos expression in dorsomedial striatumc-Fos expression in orbitofrontal cortex and dorsal hippocampus is unaffected by selective reinstatement.
Systems analysis of immune responses to attenuated P. falciparum malaria sporozoite vaccination reveals excessive inflammatory signatures correlating with impaired immunity
Authors: Du Ying , Hertoghs Nina , Duffy Fergal J. , Carnes Jason , McDermott Suzanne M. , Neal Maxwell L. , Schwedhelm Katharine V. , McElrath M. Juliana , De Rosa Stephen C. , Aitchison John D. , Stuart Kenneth D. 
Published: July 2021

AbstractImmunization with radiation-attenuated sporozoites (RAS) can confer sterilizing protection against malaria, although the mechanisms behind this protection are incompletely understood. We performed a systems biology analysis of samples from the Immunization by Mosquito with Radiation Attenuated Sporozoites IMRAS) trial, which comprised P. falciparum RAS-immunized (PfRAS), malaria-naive participants whose protection from malaria infection was subsequently assessed by controlled human malaria infection (CHMI). Blood samples collected after initial PfRAS immunization were analyzed to compare immune responses between protected and non-protected volunteers leveraging integrative analysis of whole blood RNA-seq, high parameter flow cytometry, and single cell CITEseq of PBMCs. This analysis revealed differences in early innate immune responses indicating divergent paths associated with protection. In particular, elevated levels of inflammatory responses early after the initial immunization were detrimental for the development of protective adaptive immunity. Specifically, non-classical monocytes and early type I interferon responses induced within 1 day of PfRAS vaccination correlated with impaired immunity. Non-protected individuals also showed an increase in Th2 polarized T cell responses whereas we observed a trend towards increased Th1 and T-bet+ CD8 T cell responses in protected individuals. Temporal differences in genes associated with natural killer cells suggest an important role in immune regulation by these cells. These findings give insight into the immune responses that confer protection against malaria and may guide further malaria vaccine development.
Competitive advantage of oral streptococci for colonization of the middle ear mucosa
Authors: Jacob Kristin M. , Reguera Gemma 
Published: July 2021

AbstractThe intermittent aeration of the middle ear seeds its mucosa with saliva aerosols and selects for a distinct community of commensals adapted to the otic microenvironment. We gained insights into the selective forces that enrich for specific groups of oral migrants in the middle ear mucosa by investigating the phylogeny and physiology of 19 strains enriched (Streptococcus) or transiently present (Staphylococcus, Neisseria and actinobacterial Micrococcus and Corynebacterium) in otic secretions. Phylogenetic analyses of full length 16S rRNA sequences resolved close relationships between the streptococcal strains and oral commensals as well as between the transient migrants and known nasal and oral species. Physiological functions that facilitate mucosal colonization (swarming motility, surfactant production) and nutrition (mucin and protein degradation) were widespread in all the otic cultivars, as was the ability of most of the isolates to grow both aerobically and anaerobically. However, streptococci stood out for their enhanced biofilm-forming abilities under oxic and anoxic conditions and for their efficient fermentation of mucosal substrates into lactate, a key metabolic intermediate in the otic trophic webs. Additionally, the otic streptococci inhibited the growth of common otopathogens, an antagonistic interaction that could exclude competitors and protect the middle ear mucosa from infections by transient pathobionts. These adaptive traits allow streptococcal migrants to colonize the otic mucosa and grow microcolonies with syntrophic anaerobic partners, establishing trophic webs with other commensals similar to those formed by the oral ancestors in buccal biofilms.ImportanceThe identification of a diverse microbiome in otic secretions from healthy young adults challenged the entrenched dogma of middle ear sterility and underscored previously unknown roles for oral commensals in the seeding of otic biofilms. By comparing the physiology of novel lineages of streptococci and transient (peri)oral species isolated from otic secretions, we identified adaptive behaviors that allow specific oral streptococcal species to successfully colonize the mucosa of the middle ear. We also describe antagonistic properties of the otic streptococci that help them outcompete transient nasal and oral migrants, including known otopathogens. This knowledge is important to predictively understand the functionality of the otic communities, their interactions with the host mucosa and the outcome of infections.
Construction of transcript regulation mechanism prediction models based on binding motif environment of transcription factor AoXlnR in Aspergillus oryzae
Authors: Oka Hiroya , Kojima Takaaki , Kato Ryuji , Ihara Kunio , Nakano Hideo 
Published: July 2021

AbstractRecent study revealed that there are thousands of genes that remain unaffected by increased AoXlnR expression, despite the presence of one or more AoXlnR-binding motifs in their promoter region. Given this knowledge, we designed this study to construct several predictive models for determining whether a gene can exhibit a differential response to changes in AoXlnR expression. These models were constructed using 3D DNA shape information determined using the sequence around the AoXlnR binding motifs with classification as functional or nonfunctional. These models were created using a support vector machine followed by the evaluations designed to determine whether these DNA shape-based models can correctly classify functional motifs in terms of area under the receiver operating characteristic curve. The results showed that the differential expression levels of genes located downstream of the AoXlnR motif are closely related to specific DNA shape information around the binding motifs. Furthermore, we found that the parameters contributing to differential expressions differed depending on the number of motifs in the promoter region by comparing the prediction models using regions with only one binding DNA motif and those with multiple binding DNA motifs.Author SummaryDNA-binding transcription factors (TFs) play a central role in transcriptional regulation mechanisms, mainly through their specific binding to target sites on the genome and regulation of the expression of downstream genes. Therefore, a comprehensive analysis of the function of these TFs will lead to the understanding of various biological mechanisms. However, the functions of TFs in vivo are diverse and complicated, and the identified binding sites on the genome are not necessarily involved in the regulation of downstream gene expression. In this study, we investigated whether DNA structural information around the binding site of transcription factors can be used to predict the involvement of the binding site in the regulation of the expression of genes located downstream of the binding site. Specifically, we calculated the structural parameters based on the DNA shape around the DNA binding motif located upstream of the gene whose expression is directly regulated by the transcription factor AoXlnR from Aspergillus oryzae, and showed that the presence or absence of expression regulation can be predicted from the sequence information with high accuracy by machine learning incorporating these parameters.
Social capital and the shadow economy: a Bayesian analysis of the BRICS
Authors: Duong Tien Ha My , Nguyen Thi Anh Nhu , Nguyen Van Diep 
Published: July 2021

PurposeThe paper aims to examine the impact of social capital on the size of the shadow economy in the BIRCS countries over the period 1995–2014.Design/methodology/approachThe authors employ the Bayesian linear regression method to uncover the relationship between social capital and the shadow economy. The method applies a normal distribution for the prior probability distribution while the posterior distribution is determined using the Markov chain Monte Carlo technique.FindingsThe results indicate that the unemployment rate and tax burden positively affect the size of the shadow economy. By contrast, corruption control and trade openness are negatively associated with the development of this informal sector. Moreover, the paper's primary finding is that social capital represented by social trust and tax morale can hinder the size of the shadow economy.Research limitations/implicationsThis study is limited to the case of the BRICS countries for the period 1995–2014. The determinants of the shadow economy in different groups of countries can be heterogeneous. Moreover, social capital is a multidimensional concept that may consist of various components. This difficulty of measuring the social capital calls for further research on the relationship between other dimensions of social capital and the shadow economy.Originality/valueMany studies investigate the effect of economic factors on the size of the shadow economy. This paper applies a new approach to discover the issue. Notably, the authors use the Bayesian linear regression method to analyze the relationship between social capital and the shadow economy in the BRICS countries.
Identifying tourist profiles to reduce overtourism: the case of a cultural destination
Authors: Martínez Suárez Rocío , Castañeda García José Alberto , Rodríguez Molina Miguel Ángel 
Published: July 2021

Purpose
Knowing the behavior of tourists visiting cultural destinations enables better management of tourist flows, a better understanding of areas with greater tourist density and an opportunity to decongest popular neighborhoods. The purpose of this study is to segment tourists according to their spatio-temporal behavior and identify the primary variables that characterize the resulting segments, which will help urban destinations prevent problems arising from the saturation of tourists in certain areas.

Design/methodology/approach
To do this, this paper analyzes the behavior of tourists visiting the southeastern Spanish city of Granada, one of the most highly visited cultural tourism destinations. The data analysis used the methodology of sequence alignment which is used to identify segments as a function of their contained elements and the order in which these appear.

Findings
The results demonstrate the existence of three segments with different behavioral patterns: the “explorer tourists” segment, the “non-traditional cultural tourists” segments and the “typical cultural tourists” segment. These segments show differences in the concentration of their visits. This study discovered that the segments that visit a greater number of destination areas are those with less cultural orientation, higher travel budgets and younger and more frequent visitors.

Originality/value
In the segmentation not only keep in mind the visited areas, but the order in which they were visited as well. In addition, one should consider the time that each tourist remains in each relevant zone of the destination, given that the visiting time is an important variable to assess the congestion of an area.
Digital civic learning in schools: Youth perspectives and experiences
Authors: DiGiacomo Daniela K. 
Published: July 2021

Purpose
While living in the information age is not new, the continued spread of dis/mis/information in tandem with rising partisanship has made clear the educational need for robust and critical information and media literacy education (Bulger and Davison, 2018; Garcia et al., 2021; Reich, 2018; Wineburg and McGrew, 2016). Given that most young people (and adults) today get their information and news about the world through online sources, including social media (Pew Research Center, 2018; Garcia et al., 2021), it is imperative for the health of the American democracy that students’ school-based civic learning opportunities include digital civic learning, too. This paper aims to offer a study into one such schooling landscape in a large and diverse public school district in the USA.

Design/methodology/approach
A mixed-method approach – including an online survey and face-to-face group interviews – was used to understand the opportunity landscape more broadly and glean insight into the texture and nuance of youth perspectives and experiences on digital civic learning.

Findings
Analysis of data reveals a dearth of consistent and routine opportunities for digital civic learning within the Rio Public School District context.

Originality/value
Empirical research that examines and makes visible students’ lived experiences and perspectives with digital civic information is essential if as educators and researchers, the authors are to successfully design for more and better of these experiences.