bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bmper is required for morphogenesis of the anterior and posterior semicircular canal ducts in the developing zebrafish inner ear
Authors: Baxendale Sarah , Maier Esther C. , Obholzer Nikolaus D. , Burbridge Sarah , Zinski Joseph , Tuazon Francesca B. , van Hateren Nicholas J. , Romero M. Montserrat Garcia , Marzo Mar , Yokoya Kazutomo , Knight Robert D. , Megason Sean G. , Mullins Mary C. , Whitfield Tanya T. 
Published: June 2021

SummaryBMP signalling is known to have a conserved function in development of the semicircular canal system of the vertebrate inner ear, but its regulation, target genes and effects on cell behaviour during otic morphogenesis are not fully understood. We have characterised the effects of mutations in the zebrafish gene bmper, which codes for a regulator of BMP signalling with both pro- and anti-BMP roles in different developmental contexts. The inner ears of bmper mutant embryos develop with truncations of the anterior and posterior semicircular canal ducts. To image the developing ear in live embryos, we have exploited a new transgenic line, Tg(smad6b:EGFP), which exhibits strong GFP expression in the otic epithelium. Morphometric analysis indicates defects in the bmper mutant ear from early stages of semicircular canal formation, correlating with a specific reduction in BMP signalling activity and specific loss of dlx5a expression in dorsal otic epithelium. Subsequent changes to cell shape occur at the truncation site and the dorsolateral septum. The bmper mutations that we describe are adult viable; truncation of the anterior and posterior semicircular canal ducts persists into adulthood. Our results argue against a major role for Bmper in specification of the pre-placodal region, induction of the otic placode, or development of the neural crest, processes in which Bmper function has previously been implicated. Instead, we conclude that a key requirement for Bmper function in the zebrafish is to promote BMP signalling during patterning and morphogenesis of the semicircular canal system.
Attention cueing in rivalry: insights from pupillometry
Authors: Acquafredda Miriam , Binda Paola , Lunghi Claudia 
Published: June 2021

AbstractWe used pupillometry to evaluate the effects of attention cueing on perceptual bi-stability, as reported by adult human observers. Perceptual alternations and pupil diameter were measured during two forms of rivalry, generated by presenting a white and a black disk to the two eyes (binocular rivalry) or splitting the disks between eyes (interocular grouping rivalry). In line with previous studies, we found that subtle pupil size oscillations (about 0.05 mm) tracked alternations between exclusive dominance phases of the black or white disk. These oscillations were larger for perceptually stronger stimuli: presented to the dominant eye or with physically higher luminance contrast. However, cueing of endogenous attention to one of the rivaling percepts did not affect pupil oscillations during exclusive dominance phases. This was in spite of the reliable effects of endogenous attention on perceptual dominance, which shifted in favor of the cued percept by about 10%. The results were comparable for binocular and interocular grouping rivalry. Cueing only had a marginal modulatory effect on pupil size during mixed percepts in binocular rivalry. This may suggest that, rather than acting by modulating perceptual strength, endogenous attention primarily acts during periods of unresolved competition, which is compatible with attention being automatically directed to the rivaling stimuli during periods of exclusive dominance and thereby sustaining perceptual alternations.Significance StatementBinocular rivalry depends on attention. When it is diverted away from the stimuli, perceptual alternations slow down; when it is preferentially directed to one stimulus, perception lingers more on it, consistent with attention enhancing the effective strength of the rivaling stimuli. Here we introduce pupillometry as a means to indirectly track changes in effective stimulus strength. We find that pupil size oscillates, accurately tracking perceived luminance during two forms of rivalry: binocular rivalry and interocular grouping rivalry. Both show robust effects of attention cueing on perceptual dominance, but pupil oscillations during exclusive dominance are unaffected by cueing. This suggests that endogenous attention does not affect perceptual strength during exclusive dominance, though it might do so during transition phases.
Gut microbiota of ring-tailed lemurs (Lemur catta) vary across natural and captive populations and correlate with environmental microbiota
Authors: Bornbusch Sally L. , Greene Lydia K. , Rahobilalaina Sylvia , Calkins Samantha , Rothman Ryan S. , Clarke Tara A. , LaFleur Marni , Drea Christine M. 
Published: June 2021

AbstractBackgroundInter-population variation in host-associated microbiota reflects differences in the hosts’ environments, but this characterization is typically based on studies comparing few populations. The diversity of natural habitats and captivity conditions occupied by any given host species has not been captured in these comparisons. Moreover, intraspecific variation in gut microbiota, generally attributed to diet, may also stem from differential acquisition of environmental microbes – an understudied mechanism by which host microbiomes are directly shaped by environmental microbes. To more comprehensively characterize gut microbiota in an ecologically flexible host, the ring-tailed lemur (Lemur catta; n = 209), while also investigating the role of environmental acquisition, we used 16S rRNA sequencing of lemur gut and soil microbiota sampled from up to 13 settings, eight in the wilderness of Madagascar and five in captivity in Madagascar or the U.S. Based on matched fecal and soil samples, we used source-sink ecological theory to examine covariation between the two types of consortia.ResultsThe diversity of lemur gut microbes varied markedly within and between settings. Microbial diversity was not consistently greater in wild than in captive lemurs, indicating that this metric is not necessarily an indicator of host habitat or condition. Variation in microbial composition was inconsistent with either a single, representative gut community for wild conspecifics or a universal ‘signal of captivity’ that homogenizes the gut consortia of captive animals. Despite the similar, commercial diets of captive lemurs on both continents, lemurs within Madagascar were compositionally most similar, suggesting that non-dietary factors govern some of the variability. In particular, soil microbial communities were most distinct between the two continents, and there was significant and context-specific covariation between lemur gut and soil microbiota.ConclusionsAs one of the broadest, single-species investigations of primate microbiota, our study highlights that gut consortia are sensitive to multiple scales of environmental differences. This finding begs a reevaluation of the simple ‘captive vs. wild’ dichotomy. Beyond the important implications for animal care, health, and conservation, our finding that environmental acquisition may mediate aspects of host-associated consortia further expands the framework for how host-associated and environmental microbes interact across different microbial landscapes.
Damaged goods? Evaluating the impact of X-ray damage on conformational heterogeneity in room temperature and cryo-cooled protein crystals
Authors: Yabukarski Filip , Doukov Tzanko , Mokhtari Daniel A , Du Siyuan , Herschlag Daniel 
Published: June 2021

AbstractX-ray crystallography is a cornerstone of biochemistry. Traditional freezing of protein crystals to cryo-temperatures mitigates X-ray damage and facilitates crystal handling but provides an incomplete window into the ensemble of conformations at the heart of protein function and energetics. Room temperature (RT) X-ray crystallography provides more extensive ensemble information, and recent developments allow conformational heterogeneity, the experimental manifestation of ensembles, to be extracted from single crystal data. However, high sensitivity to X-ray damage at RT raises concerns about data reliability. To systematically address this critical question, we obtained increasingly X-ray-damaged high-resolution datasets (1.02–1.52 Å) from single thaumatin, proteinase K, and lysozyme crystals. Heterogeneity analyses indicated a modest increase in conformational disorder with X-ray damage. Nevertheless, these effects do not alter overall conclusions and can be minimized by limiting the extent of X-ray damage or eliminated by extrapolation to obtain heterogeneity information free from X-ray damage effects. To compare these effects to damage at cryo temperature and to learn more about damage and heterogeneity in cryo-cooled crystals, we carried out an analogous analysis of increasingly damaged proteinase K cryo datasets (0.9–1.16 Å). We found X-ray damage-associated heterogeneity changes that were not observed at RT. This observation and the scarcity of reported X-ray doses and damage extent render it difficult to distinguish real from artifactual conformations, including those occurring as a function of temperature. The ability to aquire reliable heterogeneity information from single crystals at RT provides strong motivation for further development and routine implementation of RT X-ray crystallography to obtain conformational ensemble information.SignificanceX-ray crystallography has allowed biologists to visualize the proteins that carry out complex biological processes and has provided powerful insights into how these molecules function. Our next level of understanding requires information about the ensemble of conformations that is at the heart of protein function and energetics. Prior results have shown that room temperature (RT) X-ray crystallography provides extensive ensemble information, but are subject to extenstive X-ray damage. We found that ensemble information with little or no effects from X-ray damage can be collected at RT. We also found that damage effects may be more prevalent than recognized in structures obtained under current standard cryogenic conditions. RT X-ray crystallography can be routinely implemented to obtain needed information about conformational ensembles.
Computational mechanisms for neural representation of words
Authors: Fu Ze , Wang Xiaosha , Wang Xiaoying , Yang Huichao , Wang Jiahuan , Wei Tao , Liao Xuhong , Liu Zhiyuan , Chen Huimin , Bi Yanchao 
Published: June 2021

AbstractA critical way for humans to acquire, represent and communicate information is through language, yet the underlying computation mechanisms through which language contributes to our word meaning representations are poorly understood. We compared three major types of word computation mechanisms from large language corpus (simple co-occurrence, graph-space relations and neural-network-vector-embedding relations) in terms of the association of words’ brain activity patterns, measured by two functional magnetic resonance imaging (fMRI) experiments. Word relations derived from a graph-space representation, and not neural-network-vector-embedding, had unique explanatory power for the neural activity patterns in brain regions that have been shown to be particularly sensitive to language processes, including the anterior temporal lobe (capturing graph-common-neighbors), inferior frontal gyrus, and posterior middle/inferior temporal gyrus (capturing graph-shortest-path). These results were robust across different window sizes and graph sizes and were relatively specific to language inputs. These findings highlight the role of cumulative language inputs in organizing word meaning neural representations and provide a mathematical model to explain how different brain regions capture different types of language-derived information.
CTCF and transcription influence chromatin structure re-configuration after mitosis
Authors: Zhang Haoyue , Lam Jessica , Zhang Di , Lan Yemin , Vermunt Marit W. , Keller Cheryl A. , Giardine Belinda , Hardison Ross C. , Blobel Gerd A. 
Published: June 2021

AbstractDuring mitosis, transcription is globally attenuated and chromatin architecture is dramatically reconfigured. Here we exploited the M- to G1-phase progression to interrogate the contributions of the architectural factor CTCF and the process of transcription to re-sculpting the genome in newborn nuclei. Depletion of CTCF specifically during the M- to G1-phase transition altered the re-establishment of local short-range compartmentalization after mitosis. Chromatin domain boundary reformation was impaired upon CTCF loss, but a subset (∼27%) of boundaries, characterized by transitions in chromatin states, was established normally. Without CTCF, structural loops failed to form, leading to illegitimate contacts betweencis-regulatory elements (CREs). Transient CRE contacts that are normally resolved after telophase persisted deeply into G1-phase in CTCF depleted cells. CTCF loss-associated gains in transcription were often linked to increased, normally illegitimate enhancer-promoter contacts. In contrast, at genes whose expression declined upon CTCF loss, CTCF seems to function as a conventional transcription activator, independent of its architectural role. CTCF-anchored structural loops facilitated formation CRE loops nested within them, especially those involving weak CREs. Transcription inhibition did not elicit global architectural changes and left transcription start site-associated boundaries intact. However, ongoing transcription contributed considerably to the formation of gene domains, regions of enriched contacts spanning the length of gene bodies. Notably, gene domains formed rapidly in ana/telophase prior to the completion of the first round of transcription, suggesting that epigenetic features in gene bodies contribute to genome reconfiguration prior to transcription. The focus on the de novo formation of nuclear architecture during G1 entry yielded novel insights into how CTCF and transcription contribute to the dynamic re-configuration of chromatin architecture during the mitosis to G1 phase progression.
Caspase-1-driven neutrophil pyroptosis promotes an incomplete NETosis upon Pseudomonas aeruginosa infection
Authors: Santoni Karin , Pericat David , Pinilla Miriam , Bagayoko Salimata , Hessel Audrey , Leon-Icaza Stephen-Adonai , Bellard Elisabeth , Mazères Serge , Doz-Deblauwe Emilie , Winter Nathalie , Paget Christophe , Girard Jean-Philippe , Cougoule Céline , Poincloux Renaud , Lamkanfi Mohamed , Lefrançais Emma , Meunier Etienne , Planès Rémi 
Published: June 2021

AbstractMultiple neutrophil death programs contribute to host defense against infections. Although expressing all necessary components, neutrophils specifically fail to undergo pyroptosis, a lytic form of cell death triggered by the activation of the pro-inflammatory complex inflammasome. In the light of the arm race, we hypothesized that intrinsic neutrophil pyroptosis resistance might be bypassed in response to specific microbial species. We show that Pseudomonas aeruginosa (P. aeruginosa) stimulates Caspase-1-dependent pyroptosis in human and murine neutrophils. Mechanistically, activated NLRC4 inflammasome supports Caspase-1-driven Gasdermin-D (GSDMD) activation, IL-1β cytokine release and neutrophil pyroptosis. Furthermore, GSDMD activates Peptidyl Arginine Deaminase-4 which drives an “incomplete NETosis” where neutrophil DNA fills the cell cytosol but fails crossing plasma membrane. Finally, we show that neutrophil Caspase-1 account for IL-1β production and contributes to various P. aeruginosa strains spread in mice. Overall, we demonstrate that neutrophils are fully competent for Caspase-1-dependent pyroptosis, which drives an unsuspected “incomplete NETosis”.SummaryNeutrophils play an essential roles against infections. Although multiple neutrophil death programs contribute to host defense against infections, they fail to undergo pyroptosis, a pro-inflammatory form of cell death. Upon Infections, pyroptosis can be induced in macrophages or epithelial cells upon activation of pro-inflammatory complexes, inflammasomes that trigger Caspase-1-driven Gasdermin dependent plasma membrane lysis. In the light of host-microbe interactions, we hypothesized that yet to find microbial species might hold the capacity to overcome neutrophil resistance to inflammasome-driven pyroptosis. Among several bacterial species, we describe that the bacterium Pseudomonas aeruginosa specifically engages the NLRC4 inflammasome, which promotes Caspase-1-dependent Gasdermin-D activation and subsequent neutrophil pyroptosis. Furthermore, inflammasome-driven pyroptosis leads to DNA decondensation and expansion into the host cell cytosol but not to the so called Neutrophil Extracellular Trap (NET) release as DNA fails breaching the plasma membrane. Finally, in vivo P. aeruginosa infections highlight that Caspase-1-driven neutrophil pyroptosis is functional and is detrimental upon P. aeruginosa infection. Altogether, our results unexpectedly underline neutrophil competence for Caspase-1-dependent pyroptosis, a process that contributes to host susceptibility to P. aeruginosa infection.
Cell-autonomous differentiation of human primed embryonic stem cells into trophoblastic syncytia through the nascent amnion-like cell state
Authors: Ohgushi Masatoshi , Eiraku Mototsugu 
Published: June 2021

SummeryHuman primed embryonic stem cells (pESCs) are known to be converted to cells with several trophoblast properties, but it has remained controversial whether this phenomenon represents the inherent differentiation competence of human pESCs to trophoblast lineages. In this study, we report that chemical blockage of ACTIVIN/NODAL and FGF signals is sufficient to steer human pESCs into GATA3-expressing cells that give rise to hormone-producing syncytia analogous to syncytiotrophoblasts of the post-implantation stage of the human embryo. Taking advantage of this system, we identified two distinct modes of cell-autonomous genetic programs and their coordinated actions to initiate the differentiation. We also found a transient population reminiscent of nascent amnion and then a spontaneous branch of differentiation trajectory leading to syncytiotrophoblast-like syncytial cells. These results provide insights into the possible extraembryonic differentiation pathway that is unique in primate embryogenesis and is relevant to the trophoblast competence of human primed pluripotent stem cells.
Embedded control of cell growth using tunable genetic systems
Authors: Fusco Virginia , Salzano Davide , Fiore Davide , di Bernardo Mario 
Published: June 2021

AbstractWe present an embedded feedback control strategy to control the density of a bacterial population, allowing cells to self-regulate their growth rate so as to reach a desired density at steady state. We consider a static culture condition, where cells are provided with a limited amount of space and nutrients. The control strategy is built using a tunable expression system (TES), which controls the production of a growth inhibitor protein, complemented with a quorum sensing mechanism for the sensing of the population density. We show on a simplified population-level model that the TES endows the control system with additional flexibility by allowing the set-point to be changed online. Finally, we validate the effectiveness of the proposed control strategy by means of realistic in silico experiments conducted in BSim, an agent-based simulator explicitly designed to simulate bacterial populations, and we test the robustness of our design to disturbances and parameters’ variations due, for instance, to cell-to-cell variability.
Early-stage cost estimation model for power generation project with limited historical data
Authors: Lee Jin Gang , Lee Hyun-Soo , Park Moonseo , Seo JoonOh 
Published: June 2021

PurposeReliable conceptual cost estimation of large-scale construction projects is critical for successful project planning and execution. For addressing the limited data availability in conceptual cost estimation, this study proposes an enhanced ANN-based cost estimating model that incorporates artificial neural networks, ensemble modeling and a factor analysis approach.Design/methodology/approachIn the ANN-based conceptual cost estimating model, the ensemble modeling component enhances training, and thus, improves its predictive accuracy and stability when project data quantity is low; and the factor analysis component finds the optimal input for an estimating model, rendering explanations of project data more descriptive.FindingsOn the basis of the results of experiments, it can be concluded that ensemble modeling and FAMD (Factor Analysis of Mixed Data) are both conjointly capable of improving the accuracy of conceptual cost estimates. The ANN model version combining bootstrap aggregation and FAMD improved estimation accuracy and reliability despite these very low project sample sizes.Research limitations/implicationsThe generalizability of the findings is hard to justify since it is difficult to collect cost data of construction projects comprehensively. But this difficulty means that our proposed approaches and findings can provide more accurate and stable conceptual cost forecasting in the early stages of project development.Originality/valueFrom the perspective of this research, previous uses of past-project data can be deemed to have underutilized that information, and this study has highlighted that — even when limited in quantity — past-project data can and should be utilized effectively in the generation of conceptual cost estimates.
Workplace bullying and organizational citizenship behavior: the parallel mediating effects of job satisfaction and resilience
Authors: Mendiratta Aparna , Srivastava Shalini 
Published: June 2021

PurposeUpholding congruency with conservation of resources (COR) theory, the study intends to analyze the impact of workplace bullying on organizational citizenship behavior (OCB) via job satisfaction and resilience as parallel mediators in the Indian hospitality sector.Design/methodology/approachThe study used a data of 240 respondents working in the hospitality sector in India. Direct and indirect effects were assessed through statistical techniques such as structural equation modeling and mediation analysis (Preacher and Hayes, 2004) for hypotheses testing using SPSS and AMOS tools.FindingsThe findings of the study suggest the negative correlation between workplace bullying and OCB. This study demonstrates the role of job satisfaction and resilience as parallel mediators in combating the cascading ill effect of workplace bullying on OCB.Research limitations/implicationsThe results help India's hospitality sector to understand the intensity and impact of workplace bullying on job satisfaction and OCB.Originality/valueThis is the original and first study examining the role of workplace bullying on OCB via job satisfaction and resilience as parallel mediators in the non-Western context.