bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cdc42 regulates cytokine expression and trafficking in bronchial epithelial cells
Authors: Shouib Rowayna , Eitzen Gary 
Published: November 2022

ABSTRACTAirway epithelial cells can respond to incoming pathogens, allergens and stimulants through the secretion of cytokines and chemokines. These pro-inflammatory mediators activate inflammatory signaling cascades that allow a robust immune response to be mounted. However, uncontrolled production and release of cytokines and chemokines can result in chronic inflammation and appears to be an underlying mechanism for the pathogenesis of pulmonary disorders such as asthma and COPD. The Rho GTPase, Cdc42, is an important signaling molecule that we hypothesize can regulate cytokine production and release from epithelial cells. We treated BEAS-2B lung epithelial cells with a set of stimulants to activate inflammatory pathways and cytokine release. The production, trafficking and secretion of cytokines were assessed when Cdc42 was pharmacologically inhibited with ML141 drug or silenced with lentiviral-mediated shRNA knockdown. We found that Cdc42 inhibition with ML141 differentially affected gene expression of a subset of cytokines; transcription of IL-6 and IL-8 were increased while MCP-1 was decreased. However, Cdc42 inhibition or depletion disrupted IL-8 trafficking and reduced its secretion even though transcription was increased. Cytokines transiting through the Golgi were particularly affected by Cdc42 disruption. Our results define a role for Cdc42 in the regulation of cytokine production and release in airway epithelial cells. This underscores the role of Cdc42 in coupling receptor activation to downstream gene expression and also as a regulator of cytokine secretory pathways.Short SummaryCytokine secretion from airway epithelial cells contributes to the pathogenesis of disease. We show that Cdc42 regulates cytokine gene expression and is required for cytokine secretion via control of transport through the Golgi complex.
Flagellar genes are associated with the colonization persistence phenotype of theDrosophila melanogastermicrobiota
Authors: Morgan Sarah J. , Chaston John M. 
Published: November 2022

ABSTRACTIn this work we useDrosophila melanogasteras a model to identify bacterial genes necessary for bacteria to colonize their hosts independent of the bulk flow of diet. Early work on this model system established that dietary replenishment drives the composition of theD. melanogastergut microbiota, and subsequent research has shown that some bacterial strains can stably colonize, or persist with, the fly independent of dietary replenishment. Here we reveal transposon insertions in specific bacterial genes that influence the bacterial colonization persistence phenotype by using a gene association approach. We initially established that different bacterial strains persist at varying levels, independent of dietary replenishment. We then repeated the analysis with an expanded panel of bacterial strains and performed a metagenome wide association (MGWA) to identify distinct bacterial genes that are significantly correlated with the colonization level of persistent bacterial strains. Based on the MGWA, we tested if 44 bacterial transposon insertion mutants from 6 gene categories affect bacterial persistence with the flies. We identified that transposon insertions in four flagellar genes, one urea carboxylase gene, one phosphatidyl inositol gene, one bacterial secretion gene, and one antimicrobial peptide (AMP) resistance gene each significantly influenced the colonization of anAcetobacter fabarumstrain withD. melanogaster. Follow-up experiments revealed that each flagellar mutant was non-motile, even though the wild-type strain was motile. Taken together, these results reveal transposon insertions in specific bacterial genes, including motility genes, are necessary for at least one member of the fly microbiota to persistently colonize the fly.IMPORTANCEDespite the growing body of research on the microbiota, the mechanisms by which the microbiota colonizes a host can still be further elucidated. This study identifies bacterial genes that are associated with colonization persistence phenotype of the microbiota inDrosophila melanogaster, which reveals specific bacterial factors that influence establishment of the microbiota with its host. Identification of specific genes that affect persistence can help inform how the microbiota colonizes a host. Furthermore, a deeper understanding of the genetic mechanisms of the establishment of the microbiota could aid in further developing theDrosophilamicrobiota as a model for microbiome research.
Rescue of neuropsychiatric phenotypes in a mouse model of 16p11.2 duplication syndrome by genetic correction of an epilepsy network hub
Authors: Forrest Marc P. , Santos Marc Dos , Piguel Nicolas H. , Wang Yi-Zhi , Hawkins Nicole A. , Bagchi Vikram A. , Dionisio Leonardo E. , Yoon Sehyoun , Simkin Dina , Martin-de-Saavedra Maria Dolores , Gao Ruoqi , Horan Katherine E. , George Alfred L. , LeDoux Mark S. , Kearney Jennifer A. , Savas Jeffrey N. , Penzes Peter 
Published: November 2022

AbstractNeuropsychiatric disorders (NPDs) share genetic etiology and are frequently co-morbid with epilepsy, but the biological basis of this shared risk remains poorly understood. The 16p11.2 microduplication (16p11.2dup/+) is a highly pleiotropic copy number variant (CNV) conferring risk for multiple NPDs including autism spectrum disorder, schizophrenia and intellectual disability, and is associated with a high prevalence of seizures. We used a mouse model of the16p11.2duplication (16p11.2dup/+) to uncover molecular and circuit properties associated with this broad phenotypic spectrum, and examined genes within the locus capable of phenotype reversal. Quantitative proteomics of cortical membranes revealed alterations to synaptic protein networks and products of diverse NPD risk genes in16p11.2dup/+mice. Network analysis identified an epilepsy-associated protein subnetwork, which was dysregulated in16p11.2dup/+mice and proteomic datasets from human NPDs. We investigated circuit properties in16p11.2dup/+mice and found they exhibited hypersynchronous activity and enhanced network glutamate release, which increased susceptibility to seizures. We hypothesized that a regulator of the synaptic and epilepsy-associated protein network could have an important impact on pathophysiology. Human brain co-expression and interactome analysis revealed PRRT2 as a major hub in the dysregulated epilepsy subnetwork. Remarkably, restoringPrrt2copy number to wild-type levels rescued aberrant circuit properties, seizure susceptibility and social interaction deficits in16p11.2dup/+mice. We show that proteomics and network biology can identify important disease hubs in multigenic CNVs, and reveal molecular and circuit phenotypes which may be relevant to the complex symptomatology of 16p11.2 duplication carriers.
Diversity of the woodland strawberry inflorescences results from heterochrony antagonistically regulated byFvTFL1andFvFT1
Authors: Lembinen Sergei , Cieslak Mikolaj , Zhang Teng , Mackenzie Kathryn , Elomaa Paula , Prusinkiewicz Przemyslaw , Hytönen Timo 
Published: November 2022

AbstractA vast variety of inflorescence architectures have formed during angiosperm evolution. Here we analyze the diversity and development of the woodland strawberry inflorescence. We show that it is a thyrse: a compound inflorescence in which the primary monopodial axis supports lateral sympodial branches, thus combining features of racemes and cymes. We demonstrate that this architecture is related to differences in the size and shape of the primary and lateral inflorescence meristems. We further show that woodland strawberry homologs of TERMINAL FLOWER 1 (TFL1) and FLOWERING LOCUS T (FT) antagonistically regulate the development of both the racemose and cymose components of the strawberry thyrse: the loss of functionalFvTFL1and overexpression ofFvFT1reduce the number and complexity of the cymose components, whereas silencing ofFvFT1has the opposite effect and can partially rescue thefvtfl1mutation. We complement our experimental findings with a computational model, which captures the development of the woodland strawberry inflorescence using a small set of rules, and shows that its phenotypic diversity can be explained in terms of heterochrony resulting from the opposite action of FvTFL1 and FvFT1 on the progression from the branching to flowering state.
Large-area electrical imaging having single neuron resolution using 236,880 electrodes CMOS-MEA technology
Authors: Suzuki I. , Matsuda N. , Han X. , Noji S. , Shibata M. , Nagafuku N. , Ishibashi Y. 
Published: November 2022

AbstractThe electrophysiological technology having a high spatio-temporal resolution at the single-cell level, and noninvasive measurements of large areas provides insights on underlying neuronal function. Here, we used a complementary metal-oxide semiconductor (CMOS)-microelectrode array (MEA) that uses 236,880 electrodes each with an electrode size of 11.22 × 11.22 µm and 236,880 covering a wide area of 5.5 × 5.7 mm in presenting a detailed and single-cell-level neural activity analysis platform for brain slices, human iPS cell-derived cortical networks, peripheral neurons, and human brain organoids. Propagation pattern characteristics between brain regions changes the synaptic strength into compounds based on single-cell time-series patterns, classification based on single DRG neuron firing patterns and compound responses, axonal conduction characteristics and changes to anticancer drugs, and network activities and transition to compounds in brain organoids were extracted. This detailed analysis of neural activity at the single-cell level using our CMOS-MEA provides a new understanding the basic mechanisms of brain circuitsin vitroandex vivo, on human neurological diseases for drug discovery, and compound toxicity assessment.
Inhibiting ribosome assembly and ribosome translation have distinctly different effects on the abundance and paralogue composition of ribosomal protein mRNAs inSaccharomyces cerevisiae
Authors: Shamsuzzaman Md , Rahman Nusrat , Gregory Brian , Bommakanti Ananth , Zengel Janice M , Bruno Vincent M , Lindahl Lasse 
Published: November 2022

AbstractMany mutations in genes for ribosomal proteins and assembly factors cause cell stress and altered cell fate resulting in congenital diseases, collectively called ribosomopathies. Even though all such mutations depress the cell’s protein synthesis capacity, they generate many different phenotypes, suggesting that the diseases are not due simply to insufficient protein synthesis capacity. To learn more, we have investigated how the global transcriptome inSaccharomyces cerevisiaeresponds to reduced protein synthesis generated in two different ways: abolishing the assembly of new ribosomes or inhibiting ribosomal function. Our results show that the mechanism by which protein synthesis is obstructed affects the ribosomal protein transcriptome differentially: ribosomal protein mRNA abundance increases during the abolition of ribosome formation but decreases during the inhibition of ribosome function. Interestingly, the ratio between mRNAs from some, but not all, paralogous genes encoding slightly different versions of a given r-protein change differently during the two types of stress, suggesting that specific ribosomal protein paralogues may contribute to the stress response. Unexpectedly, the abundance of transcripts for ribosome assembly factors and translation factors remains relatively unaffected by the stresses. On the other hand, the state of the translation apparatus does affect cell physiology: mRNA levels for some other proteins not directly related to the translation apparatus also change differentially, though not coordinately with the r-protein genes, in response to the stresses.ImportanceMutations in genes for ribosomal proteins or assembly factors cause a variety of diseases called ribosomopathies. These diseases are typically ascribed to a reduction in the cell’s capacity for protein synthesis. Paradoxically, ribosomal mutations result in a wide variety of disease phenotypes, even though they all reduce protein synthesis. Here we show that the transcriptome changes differently depending on how the protein synthesis capacity is reduced. Most strikingly, inhibiting ribosome formation and ribosome function have opposite effects on the abundance of mRNA for ribosomal proteins, while genes for ribosome translation and assembly factors show no systematic responses. Thus, the process by which the protein synthesis capacity is reduced contributes decisively to global mRNA composition. This emphasis on process is a new concept in understanding ribosomopathies and other stress responses.
Analysis of clinical manifestations and risk factors of HIV-1 associated thrombocytopenia in a general teaching hospital in western China
Authors: Tang Zhuoyun , Wang Zhonghao , Wang Tingting , Li Jingyi , Liu Chaonan , Tao Chuanmin 
Published: November 2022

AbstractBackgroundThrombocytopenia is one of the hematologic disorders that frequently accompany HIV-1 infection. The interaction of HIV-1 and platelets is crucial in the Blood-Brain Barrier’s (BBB) degeneration and causes neuroinflammation. The research aims to evaluate the prevalence and risk factors for HAT (HIV-1 associated thrombocytopenia) and summary the features of HAT-related neuroinflammation.MethodA retrospective study including 221 HAT patients was conducted in West China Hospital from 2017 to 2021. Clinical and laboratory data was analyzed the prevalence and risk factors for HAT and HAT-related neuroinflammation.ResultsThe prevalence of HAT was 11.06% and most patients were men (76.92%), elderly (≥50, 55.21%) and 63.80% patients were mild thrombocytopenia. CD4+T cell count, platelet crit (PCT) and the rate of large platelets (P-LCR) were significantly different between HAT group and control group (P< 0.001,P0.001,P=0.002). CD4+T cell count <200 cell/μL (P=0.001) was an important risk factor in the occurrence of HAT while advanced age and high viral load were closely related to the occurrence of HAT. HAT-related neuroinflammation patients were mostly distributed in male (X2=10.066,P=0.007), with higher viral load (X2=12.297,P=0.006) and advanced age (X2=11.721,P=0.02) with neuropsychiatric symptoms and rising level of inflammatory factors like IL-6 and proteins in CSF.ConclusionHAT and HAT with neuroinflammation cannot be ignored in HIV-1 infection because of the activation of monocytes, macrophages and microglia, further causing thrombocytopenia and neuroinflammation. Advanced age, lower CD4+T cell count and high viral load were closely related to the occurrence of HAT and HAT-related neuroinflammation.
Image restoration of degraded time-lapse microscopy data mediated by infrared-imaging
Authors: Gritti Nicola , Power Rory M. , Graves Alyssa , Huisken Jan 
Published: November 2022

ABSTRACTTime-lapse fluorescence microscopy is key to unraveling the processes underpinning biological development and function. However, living systems, by their nature, permit only a limited toolbox for interrogation. Consequently, following time-lapses, expended samples contain untapped information that is typically discarded. Herein we employ convolutional neural networks (CNNs) to augment the live imaging data using this complementary information. In particular, live, deep tissue imaging is limited by the spectral range of live-cell compatible probes/fluorescent proteins. We demonstrate that CNNs may be used to restore deep-tissue contrast in GFP-based time-lapse imaging using paired final-state datasets acquired using infrared dyes and improve information content accordingly. Surprisingly, the networks are remarkably robust over a wide range of developmental times. We employ said network to GFP time-lapse images captured during zebrafish and drosophila embryo/larval development and demonstrate live, deep tissue image contrast.
Human–bot co-working: job outcomes and employee responses
Authors: Zhu Yu-Qian , Kanjanamekanant Kritsapas 
Published: November 2022

PurposeRobotic process automation (RPA) has been widely implemented to automate digital tasks. The resulting new type of human–bot co-working environment, however, has been understudied. This paper investigated how the depth and breadth of RPA deployment impact employees' job autonomy and work intensification, as well as perceived RPA performance. It further examined how job autonomy, work intensification, and perceived RPA performance predict burnout and continuance intention to use RPA.Design/methodology/approachUsing data collected from online survey of 128 RPA users, whose organizations have already gone live on RPA, partial least squares is used in the validation of the conceptual model and analysis.FindingsThe analytical results indicate that RPA deployment breadth and depth affect work intensification differently, and RPA deployment breadth and depth significantly predict perceived RPA performance. While work intensification increases burnout, job autonomy alleviates the burnout of employees. Finally, job autonomy and perceived RPA performance are both positive predictors of continuance intention to use RPA.Originality/valueThis study contributes to the literature by investigating how co-working affects employees' autonomy and quality of work. It also advances the research on technology deployment by showing how deployment breadth and depth differently affect employees' evaluations of work-related aspects. Third, it extends the applicability of job demand-resource model into technology deployment and continuance technology use literature, by illustrating the importance of a job resource such as job autonomy. Finally, it provides firms with RPA implementation strategies.
Job pursuit intentions of undergraduates towards green job positions and descriptions, green performance management, green employee relations with employers' prestige as the mediator
Authors: Fernandez Diane Christine , Ganesan Jaya 
Published: November 2022

PurposeThe aim of this research is to explore the relationship between green job positions and descriptions, green performance management, green employee relations with job pursuit intentions and the role of employers’ prestige as the mediator.Design/methodology/approachA survey research design with a sample of 216 undergraduate specialising in the business fields from Malaysian private higher education institutions responded to the questionnaire, while purposive sampling and snowball sampling techniques were used in order to determine the research sample. Data for the research were collected from the target participants via questionnaires and Statistical Package for Social Science (SPSS), while partial least square structural equation modelling (PLS-SEM) via Smart-PLS was utilized to test the developed hypotheses of the research.FindingsThe results showed that only green employee relations has a significant relationship with job pursuit intentions out of the three direct hypotheses. As a result of assessing the mediating hypotheses, employers’ prestige mediates the effect of green job positions and descriptions and green employee relations on job pursuit intentions. Conversely, green performance management did not support the mediating association.Practical implicationsThis research recommended practitioners to adopt green HRM fundamentals to enhance EP, which results in JPI. Also, the research aids managers and practitioners by providing the outlook of green HRM from a job seeker’s perspective, which can embolden the managers and practitioners in planning a systematic human resource.Originality/valueThe study contributes by enriching the literature concerning the dimensions of green HRM, which is an emergent topic in the human resource field. Furthermore, the study advances by proposing GER in the research framework.
The influence of immersion on tourists’ satisfaction via perceived attractiveness and happiness
Authors: Li Fangxuan (Sam) , Shang Yuanyuan , Su Qianqian 
Published: November 2022

Purpose
The purpose of this study is to propose and test a model that is composed of immersion, perceived attractiveness, happiness, satisfaction and behavioral intention in light of the extended cognitive-affective-conative model.

Design/methodology/approach
To test the suggested research model, 271 genuine on-site questionnaires were gathered.

Findings
Immersion was found to positively affect perceived attractiveness and happiness. It is also suggested that perceived attractiveness and happiness mediate the association between immersion and tourist satisfaction.

Research limitations/implications
This study also has advantageous marketing and management implications for destination managers and marketers to improve tourist satisfaction.

Originality/value
As per the authors’ knowledge, this is the very first study that inspects the mechanism by which how immersion influences tourist satisfaction.
Weapon performance and contest assessment strategies of the cavitating snaps in snapping shrimp
Authors: Dinh Jason P. , Patek S. N. 
Published: November 2022

Abstract

Animals compete in contests over limited resources. Contestants forfeit once they ascertain that their opponent has greater resource‐holding potential (RHP; mutual assessment) or once they reach a threshold of costs (self‐assessment). Functional scaling studies of contest behaviour performance can inform how assessment signals, offensive capacity and endurance scale with RHP and thereby elucidate the mechanisms through which each of these assessment types operates.

Here, we performed behavioural contest analyses to determine the assessment strategies used in snapping shrimp (Alpheus heterochaelis) contests. Then, we used biomechanical measurements of a common contest behaviour to inform how assessment might operate. We were specifically interested in the snapping behaviour during which snapping shrimp fire imploding cavitation bubbles—hereafter, ‘snaps’—at their opponents.

We showed that A. heterochaelis use mutual assessment early in contests. Then, when they fire snaps, they switch to cumulative assessment—a type of self‐assessment where contestants endure costs from their own behaviours (e.g. energy) and their opponent's (e.g. injury).

Because larger individuals tend to win contests, we then tested how the maximum performance and endurance of snaps scaled with size. We measured the average angular velocity of the snapping dactyl, cavitation bubble duration and pressure of snaps as metrics of performance. We measured 10 snaps per individual (n = 76 individuals). From this series of 10 snaps, we calculated the maximum of each metric as the maximum performance and the attrition of each metric over the course of 10 snaps as a measure of endurance. Maximum performance increased with size, but endurance did not.

This suggests that cumulative assessment in snapping shrimp is driven by opponent‐imposed costs. Our results are not consistent with self‐assessment based on endurance; however, the experiment could not fully replicate the quick succession of snaps fired in real contests. Future experiments should better replicate the rapid firing of snaps to test if endurance matters in a more ecologically relevant context.

Our framework of integrating biomechanics and behavioural ecology provides a pathway to identify precise mechanisms of contest assessment and animal behaviour more broadly.

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