bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycobacterium tuberculosisESX-T7SS impacts the 3D architecture of tuberculous lesion in susceptible mice
Authors: Beltran Caroline G.G. , Kriel Jurgen , Botha Stefan M. , Nolan Margaret B. , Ciccarelli Alessandro , Loos Ben , Gutierrez Maximiliano G. , Walzl Gerhard 
Published: June 2024

AbstractTuberculosis (TB) is characterized by the formation of heterogenous, immune-rich granulomas present in various forms in the lungs. Both host and pathogen contribute to this heterogeneity however the molecular and cellular drivers of within-host granuloma heterogeneity remain to be fully elucidated. This knowledge gap is due to a lack of experimental approaches that can fully capture the complex dynamics of the lung architecture, dynamics of host-pathogen interplay and pathogenesis. Here, we developed an approach that combines PACT-based clearing with light sheet fluorescent microscopy for visualizing lesion architecture development and lung involvement inM. tuberculosis-infected C3HeB/FeJ susceptible mice. This 3D modelling of whole lung lobes approach revealed critical architectural features in lesion development and lung involvement that were not apparent using traditional thin section imaging. Wild typeM. tuberculosisinfection triggered a clear and well-organized granulomatous-like organization with substantial growth throughout the infection period that invaded a high percentage of the total lung volume. In contrast, infection with the avirulent ESX-1 deletion mutant strainMtbΔRD1 showed an altered growth pattern with diffuse and sparsely organized CD11b recruitment to sites of infection. Moreover, most of theMtbΔRD1-triggered lesions were present in the periphery of the lungs and did not display any formal organization. We further provide a novel way of interrogating PACT-cleared tissue for high ultrastructural content using volumetric correlative light and electron microscopy, allowing individual immune cell populations to be tracked and their fate within the granuloma captured. Ultimately, the combination of both modalities allowed an unprecedented view of the architectural distribution ofM. tuberculosisin the lungs and the progression of lesion development over time. Our data highlight that ESX-1 fromM. tuberculosisis required for lesion architecture progression in a susceptible mouse model of TB.
Using AlphaFold Multimer to discover interkingdom protein-protein interactions
Authors: Homma Felix , Lyu Joy , van der Hoorn Renier A. L. 
Published: June 2024

ABSTRACTStructural prediction by artificial intelligence (AI) can be powerful new instruments to discover novel protein-protein interactions, but the community still grapples with the implementation, opportunities and limitations. Here, we discuss and re-analyse our in-silico screen for novel pathogen-secreted inhibitors of immune hydrolases to illustrate the power and limitations of structural predictions. We discuss strategies of curating sequences, including controls, and reusing sequence alignments and highlight important limitations originating from platforms, sequence depth and computing times. We hope these experiences will support similar interactomic screens by the research community.
A larval zebrafish model of TBI: Optimizing the dose of neurotrauma for discovery of treatments and aetiology
Authors: Locskai Laszlo F. , Gill Taylor , Tan Samantha A.W. , Burton Alexander H. , Alyenbaawi Hadeel , Burton Edward A. , Allison W. Ted 
Published: June 2024

AbstractTraumatic brain injuries (TBI) are diverse with heterogeneous injury pathologies, which creates challenges for the clinical treatment and prevention of secondary pathologies such as post-traumatic epilepsy and subsequent dementias. To develop pharmacological strategies that treat TBI and prevent complications, animal models must capture the spectrum of TBI severity to better understand pathophysiological events that occur during and after injury. To address such issues, we improved upon our recent larval zebrafish TBI paradigm emphasizing titrating to different injury levels. We observed coordination between an increase in injury level and clinically relevant injury phenotypes including post-traumatic seizures (PTS) and tau aggregation. This preclinical TBI model is simple to implement, allows dosing of injury levels to model diverse pathologies, and can be scaled to medium- or high-throughput screening.
Potassium-selective channelrhodopsins can exert hyper- or depolarizing effects in excitable cells ofCaenorhabditis elegans, depending on experimental condition
Authors: Ruse Christiane , Seidenthal Marius , Tillert Linda , Vierock Johannes , Gottschalk Alexander 
Published: June 2024

AbstractOne of the most frequent applications of optogenetic tools is for depolarization and stimulation of excitable cells such as neurons and muscles. Equally important, but less frequently used, are inhibitory tools that suppress activity through cellular hyperpolarization. These tools often rely on chloride conductance. Yet,in vivo, re- and hyperpolarization is typically mediated by potassium. In recent years, light-gated ion channels with a high preference for potassium were identified (Kalium channelrhodopsins, KCRs), and their inhibitory potential described in different organisms. Here, we characterizedHcKCR1 and WiChR, in cholinergic neurons and muscles ofCaenorhabditis elegans. Hyperpolarization of these cell types both induces muscle relaxation and, consequently, an elongation of the animals. Thus, we analyzed body length before, during, and after illumination, to assess KCR effectiveness, and to benchmark stimulation parameters like light intensity and duration. ForHcKCR1 in cholinergic neurons, continuous illumination at high light intensities (1-4.5 mW/mm2) evoked only a transient elongation, while stimulation at 0.1 mW/mm2could maintain inhibition for the duration of the stimulus in some transgenic strains. For animals expressing WiChR in body wall muscle cells or cholinergic neurons, we again observed brief hyperpolarization during continuous illumination, however, still during the stimulus, this changed to body contraction, corresponding to depolarization. This effect was long lasting, and required dozens of seconds for reversion, but could be reduced by pulsed illumination and fully avoided by less efficient channel activation using green or orange light. Hence, KCRs can be applied to hyperpolarizeC. eleganscells, but require optimized illumination parameters.Article summaryTo inhibit excitable cells, light-gated, potassium-selective channels (KCRs) can be used. This study explores whether stimulation of KCRsHcKCR1 and WiChR in cholinergic neurons and muscle cells ofCaenorhabditis eleganscan induce inhibition during illumination. While inhibition could be achieved, depending on light conditions, the authors unexpectedly also observed excitation. These effects may occur due to a combination of high conductivity of KCRs, and partial conductance of other cations. These findings highlight the need for specific experimental conditions in future studies utilizing these tools. The authors also present conditions that can partially or fully avoid the unwanted depolarizing effects.
Transcriptomics-informed pharmacology identifies epigenetic and cell cycle regulators as enhancers of AAV production
Authors: Tworig Joshua , Grafton Francis , Hörer Markus , Reid Christopher A. , Mandegar Mohammad A. 
Published: June 2024

AbstractRecombinant adeno-associated virus (rAAV) is a widely used viral vector for gene therapy. Despite its clinical efficacy, the manufacturing of rAAV faces challenges in productivity and quality, leading to limited availability. To address the growing demand, next-generation process development should be informed by a mechanistic understanding of the cellular response to rAAV. In this study, we performed transcriptomic analysis of 5 cell lines with variable capacities for rAAV production. Using an intersectional approach, we assessed the transcriptional response to rAAV production and compared transcriptional profiles between high and baseline producers to identify possible targets for enhancing production. Modulation of cell cycle and nucleosome components suggested a reduction of proliferative capacity and a shift toward DNA replication to support rAAV production. During rAAV production, we observed upregulation of several core functions including transcription, stress response, and Golgi and endoplasmic reticulum organization. Conversely, inhibitors of DNA-binding proteins and mitochondrial components were consistently downregulated during rAAV production. We next performed a drug connectivity analysis of these results and identified 5 classes of drugs predicted to enhance rAAV production. Validation studies confirmed the efficacy of HDAC and microtubule inhibitors. Our data uncover novel and previously identified pathways that may enhance rAAV productivity, potentially enabling a path to engineer improved processes and cell lines for higher yields and better quality rAAV production.Graphical abstract
Rad51 determines pathway usage in post-replication repair
Authors: Meyer Damon , Ceballos Shannon J. , Gore Steven , Liu Jie , Reginato Giordano , Cano-Linares Maria I. , Maslowska Katarzyna H. , Villafañez Florencia , Ede Christopher , Pagès Vincent , Prado Felix , Cejka Petr , Heyer Wolf-Dietrich 
Published: June 2024

ABSTRACTStalled replication forks can be processed by several distinct mechanisms collectively called post-replication repair which includes homologous recombination, fork regression, and translesion DNA synthesis. However, the regulation of the usage between these pathways is not fully understood. The Rad51 protein plays a pivotal role in maintaining genomic stability through its roles in HR and in protecting stalled replication forks from degradation. We report the isolation of separation-of-function mutations inSaccharomyces cerevisiaeRad51 that retain their recombination function but display a defect in fork protection leading to a shift in post-replication repair pathway usage from HR to alternate pathways including mutagenic translesion synthesis. Rad51-E135D and Rad51-K305N show normalin vivoandin vitrorecombination despite changes in their DNA binding profiles, in particular to dsDNA, with a resulting effect on their ATPase activities. The mutants lead to a defect in Rad51 recruitment to stalled forksin vivoas well as a defect in the protection of dsDNA from degradation by Dna2-Sgs1 and Exo1in vitro. A high-resolution cryo-electron microscopy structure of the Rad51-ssDNA filament at 2.4 Å resolution provides a structural basis for a mechanistic understanding of the mutant phenotypes. Together, the evidence suggests a model in which Rad51 binding to duplex DNA is critical to control pathway usage at stalled replication forks.
Explicit finite element simulations of dynamic low adhesion behavior between wheel and rail in the presence of high-frequency vibrations
Authors: Liu Wen , Huang Shuangchao , Qi Hongfeng , Zhao Xin , Liang Shulin , Jin Xuesong 
Published: June 2024

PurposeDynamic low adhesion (DLA) has become an urgent problem for the high-speed wheel-rail system because of continuous decrease of adhesion redundancy in the past decades. This article aims to provide a simulation method to reveal the mechanism of DLA under high-frequency vibrations.Design/methodology/approachA transient wheel-rail rolling contact model is developed for a typical Chinese high-speed railway system using the explicit finite element (FE) method. Instantaneous adhesion exploitation levels are studied in the time domain, for which driving cases over corrugated rails are taken as an example. A speed up to 500 km/h is considered together with different traction coefficients and corrugation dimensions. DLA is expected when the instantaneous adhesion exploitation level reaches 1.0, that is adhesion saturates and full sliding contact occurs.FindingsThe instantaneous adhesion exploitation level can be very high in the presence of corrugation, even at low traction coefficients. DLA is found to occur as great vertical unloading takes place and causes a significant increase of creepage. An approach is further developed to determine the critical depth of corrugation over which DLA occurs.Originality/valueThis study employs the transient wheel-rail rolling contact model to predict the instantaneous adhesion exploitation level under high-frequency vibrations. The presented results reveal a mechanism of DLA being beneficial to guidelines for future railway practice.
The application of building information modeling (BIM) system in the smartification of green and sustainable buildings
Authors: Anjomshoa Erfan 
Published: June 2024

PurposeNowadays, designing environmentally compatible buildings with acceptable performance in terms of cost, materials, and energy efficiency is considered crucial for developing sustainable cities. This research aims to identify and rank the most influential factors in the application of Building Information Modeling (BIM) systems in the smartification of green and sustainable buildings.Design/methodology/approachThe present research is applied and descriptive. In this study, we identified the most influential factors in the application of Building Information Modeling (BIM) systems through library studies and expert opinions. Data were collected using a questionnaire, and a combination of the one-sample t-test method with a 95% confidence level and the fuzzy VIKOR method was employed for analysis.FindingsThe results show that the most influential factors in the application of Building Information Modeling (BIM) systems in the Smartification of green and sustainable buildings, in order, are: “Energy saving and consumption reduction,” “Increased productivity and efficiency,” “Life-cycle assessment (LCA),” “Eco-friendly design,” “Integration with IoT and other technologies.”Originality/valueIn this study, while addressing the intersection of BIM technology, green building principles, and smart building objectives to optimize the performance of buildings during their life cycle, the most influential factors in the use of this system were ranked based on the criteria of “impact level,” “importance level,” and “availability of necessary tools” for implementation in Kerman. Moreover, solutions for more effectively utilizing this system in the smartification of green and intelligent buildings were proposed.
Can work-family balance reduce the unsafe behavior of new generation of construction workers effectively in China? A moderated mediation model
Authors: Ni Guodong , Fang Yaqi , Miao Xinyue , Qiao Yaning , Wang Wenshun , Xuan Jian 
Published: June 2024

PurposeThis study aims to provide a new perspective and path to reduce the unsafe behavior of new generation of construction workers (NGCWs) in China. The purpose of this study is to explore the influencing mechanism of work-family balance on the unsafe behavior of NGCWs and test the mediating effect of job satisfaction and the moderating effect of group safety climate.Design/methodology/approachA theoretical model on the influencing mechanism of work-family balance on unsafe behavior of NGCWs was constructed through theoretical analysis. Research data were collected from 502 NGCWs via a questionnaire survey, and research hypotheses were testified with regression analysis.FindingsThe results show that work-family balance not only directly reduces NGCWs’ unsafe behavior but also indirectly reduces it through job satisfaction, which plays a partial mediating role. In addition to positively moderating the relationship between work-family balance and NGCWs’ unsafe behavior, group safety climate can also moderate the relationship between work-family balance and job satisfaction in a positive way.Practical implicationsThis study provides practical implications for construction companies to reduce the unsafe behaviors of NGCWs from the perspective of work-family balance. Specifically, construction companies should adopt more flexible work rules, such as flexible organization and rotation systems, to increase their work autonomy. Meanwhile, construction companies need to improve the work environment and basic conditions for NGCWs, establish a reasonable salary system and provide attractive promotion opportunities to increase their job satisfaction. In addition, construction companies should provide active safety lectures and training, and supervisors should improve safety communication and interaction levels. Co-workers should remind workers about their safety attitudes and behaviors promptly. A good group safety climate will be created through the efforts of construction companies, supervisors and co-workers.Originality/valueThis study clarifies the influencing mechanism of work-family balance on the NGCWs’ unsafe behavior and further tests the partial mediating role of job satisfaction and the positively moderating effect of group safety climate on the influence relationship of work-family balance on job satisfaction and NGCWs’ unsafe behavior, which defines the boundary conditions of the relationship between work-family balance and NGCWs’ unsafe behavior, and promotes the effective integration of social exchange theory and theoretical system of influencing mechanism of construction workers’ unsafe behavior.
Institutional configurations and social entrepreneurship: a country-based comparison using fuzzy-set qualitative comparative analysis
Authors: Yin Juelin , Zhao Jiaxin , Du Yunzhou 
Published: June 2024

PurposeIntegrating institutional logic theory with institutional configurational perspective, this study proposes a theoretical framework to explore the configurational effect of multiple institutional logics, including state, market, and social logics, on social entrepreneurship (SE) participation.Design/methodology/approachUsing data from the Global Entrepreneurship Monitor (GEM) survey combined with other international databases, this study applies a fuzzy-set qualitative comparative analysis (fsQCA) to identify the pathways that how state, market and social logics jointly promote or hinder high SE prevalence among 38 developing countries.FindingsResults show that high SE prevalence rates are achieved through the interaction of multiple institutional logics rather than by any single factor and identify three institutional configuration pathways leading to high SE participation. Further, the pathways impeding high SE participation are not simply the negation of conditions that lead to high SE prevalence.Research limitations/implicationsThis study not only extends the institutional logics perspective to SE, enriching the growing research stream on how institutional complexity shapes entrepreneurial activities globally, but also underscores the significance of asymmetric institutional conditions in determining the presence and absence of high SE prevalence. These results have implications for policymakers to improve entrepreneurial institutional configurations that foster social entrepreneurial activities.Originality/valueCompared with conventional statistical methods, which have limited effectiveness in exploring the synergies of multiple factors, the fsQCA method offers a more robust analysis of the causal complexity of institutional logics promoting or discouraging SE participation.
Pre-organization theory: an evolutionary approach integrating memetics, inducement-contribution theory and generalized darwinism
Authors: Powell Benjamin Caldwell 
Published: June 2024

PurposeOrganization theory seeks to explain how people coordinate their behaviors to achieve common objectives, but it has offered little insight into how organizations emerge from such coordination. Fully understanding entities requires knowing their origins. The purpose of this paper is to draw attention to and to suggest an approach for fortifying a foundational weakness in organization theory: pre-organization theory.Design/methodology/approachTo develop pre-organization theory, this paper employs an evolutionary approach that integrates three theories. This paper first employs memetics to articulate a unit of selection, the i-memeplex, and next introduces inducement-contribution theory to tailor the i-memeplex to pre-organization, yielding a founder’s mental map for exchanges of inducements and contributions. It then applies generalized Darwinism to complete its evolutionary theory of pre-organization.FindingsMemetics, inducement-contribution theory, and generalized Darwinism can be integrated to create a promising theoretical solution, but further investigation is needed to assess the empirical and practical value of pre-organization theory.Originality/valueThis paper contributes to organization theory by (1) explicating a foundational weakness in organization theory – its lack of pre-organization theory – and (2) integrating a novel set of theories to develop an evolutionary theory of pre-organization.
Don’t let them get stressed! HPWS mechanisms in improving psychological well-being in the workplace
Authors: Ardianto Heni , Rosari Reni 
Published: June 2024

PurposeThe growing literature does not highlight the impact of high-performance work systems (HPWSs) on employee psychological well-being. This study aimed to test this influence by exploring the mediation of psychosocial safety and the moderation of supervisor support to overcome knowledge gaps in optimizing productivity in an increasingly dynamic workplace.Design/methodology/approachThis study involved 395 service employees in Indonesia. Data were analyzed using the PROCESS macro approach.FindingsThe research findings indicate that while HPWS are perceived as organizational investments by employees, they do not directly impact employees’ psychological well-being in the service sector in Indonesia. Despite previous literature suggesting a positive relationship, this study emphasizes the importance of considering factors such as psychosocial safety and supervisor support in influencing employee perceptions.Research limitations/implicationsThis study extends the existing literature on the mechanisms of HPWS in promoting psychological well-being in the workplace. Furthermore, Psychological safety has also been identified as a strategic approach to reduce workplace bullying.Practical implicationsOrganizations should prioritize creating a work environment that considers psychosocial safety and provides adequate supervisor support to enhance employees’ psychological well-being. Understanding the unique needs and perceptions of employees, including factors such as age and gender, is crucial in designing effective HPWS that foster a positive workplace culture and mitigate potential negative impacts.Originality/valueThe authors seek to explore the not yet fully understood relationship between HPWS, psychosocial safety, and supervisor support in promoting employee psychological well-being. This research also provides a broader view of how to prevent employees from feeling pressured and stressed in the workplace.