bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamical model of antibiotic responses linking expression of resistance to metabolism explains emergence of heterogeneity during drug exposures
Authors: Stevanovic Mirjana , Teuber Carvalho João Pedro , Bittihn Philip , Schultz Daniel 
Published: September 2023

AbstractAntibiotic responses in bacteria are highly dynamic and heterogeneous, with sudden exposure of bacterial colonies to high drug doses resulting in the coexistence of recovered and arrested cells. The dynamics of the response is determined by regulatory circuits controlling the expression of resistance genes, which are in turn modulated by the drug’s action on cell growth and metabolism. Despite advances in understanding gene regulation at the molecular level, we still lack a framework to describe how feedback mechanisms resulting from the interdependence between expression of resistance and cell metabolism can amplify naturally occurring noise and create heterogeneity at the population level. To understand how this interplay affects cell survival upon exposure, we constructed a mathematical model of the dynamics of antibiotic responses that links metabolism and regulation of gene expression, based on the tetracycline resistancetetoperon inE. coli. We use this model to interpret measurements of growth and expression of resistance in microfluidic experiments, both in single cells and in biofilms. We also implemented a stochastic model of the drug response, to show that exposure to high drug levels results in large variations of recovery times and heterogeneity at the population level. We show that stochasticity is important to determine how nutrient quality affects cell survival during exposure to high drug concentrations. A quantitative description of how microbes respond to antibiotics in dynamical environments is crucial to understand population-level behaviors such as biofilms and pathogenesis.
Females translate male mRNA transferred during mating
Authors: Matzkin Luciano M. , Bono Jeremy M. , Pigage Helen K. , Allan Carson W. , Diaz Fernando , McCoy John R. , Green Clinton C. , Callan Jeffrey B. , Delahunt Stephen P. 
Published: September 2023

AbstractAlthough RNA is found in the seminal fluid of diverse organisms, it is unknown whether this RNA is functional within females. Here, we develop an experimental proteomic method called VESPA (VariantEnabledSILACProteomicAnalysis) to test the hypothesis thatDrosophilamale seminal fluid RNA is translated by females. We find strong evidence for 67 male-derived, female-translated proteins (mdFTPs) in female lower reproductive tracts at six hours postmating, many with predicted functions relevant to reproduction. Gene knockout experiments indicate that genes coding for mdFTPs play diverse roles in postmating interactions, with effects on fertilization efficiency, and the formation and persistence of the insemination reaction mass, a trait hypothesized to be involved in sexual conflict. These findings advance our understanding of reproduction by revealing a novel mechanism of postmating molecular interactions between the sexes that strengthens and extends male influences on reproductive outcomes in previously unrecognized ways. Given the diverse species known to carry RNA in seminal fluid, this discovery has broad significance for understanding molecular mechanisms of cooperation and conflict during reproduction.
In vivoevaluation ofClostridioides difficileenoyl-ACP reductase II (FabK) Inhibition by phenylimidazole unveils a promising narrow-spectrum antimicrobial strategy
Authors: Dureja Chetna , Rutherford Jacob T. , Pavel Fahad B. A. , Norseeda Krissada , Prah Isaac , Sun Dianqing , Hevener Kirk E. , Hurdle Julian G. 
Published: September 2023

ABSTRACTClostridioides difficileinfection (CDI) is a leading cause of hospital-acquired diarrhea, which often stem from disruption of the gut microbiota by broad-spectrum antibiotics. The increasing prevalence of antibiotic-resistantC. difficilestrains, combined with disappointing clinical trials results for recent antibiotic candidates, underscore the urgent need for novel CDI antibiotics. To this end, we investigatedC. difficileenoyl ACP reductase (CdFabK), a crucial enzyme inde novofatty acid synthesis, as a drug target for microbiome-sparing antibiotics. To test this concept, we evaluated the efficacy andin vivospectrum of activity of the phenylimidazole analog 296, which is validated to inhibit intracellularCdFabK. Against major CDI-associated ribotypes 296 had an MIC90of 2 µg/ml, which was comparable to vancomycin (1 µg/ml), a standard of care antibiotic. In addition, 296 achieved high colonic concentrations and displayed dosed-dependent efficacy in mice with colitis CDI. Mice that were given 296 retained colonization resistance toC. difficileand had microbiomes that resembled the untreated mice. Conversely, both vancomycin and fidaxomicin induced significant changes to mice microbiomes, in a manner consistent with prior reports.CdFabK therefore represents a potential target for microbiome-sparing CDI antibiotics, with phenylimidazoles providing a good chemical starting point for designing such agents.
A Complex Containing the Na+/K+ATPase Regulates Epileptogenesis inDrosophila melanogaster
Authors: Bermudez Sarah , Dean Derek M. , Alkin Victoria , Wang Ziming , Pham Huy , Kondo Emily , Amini Andrew , Deitcher David L. 
Published: September 2023

AbstractEpileptogenesis, the process through which the brain becomes seizure-prone, is not well understood. Previous work identified a novel gene inDrosophila,julius seizure(jus), that when mutated or developmentally knocked down, leads to epilepsy in adultDrosophila, providing a useful model for dissecting epileptogenesis. Here we report that when a GFP-tagged version of Jus was used as bait in a co-immunoprecipitation (co-IP) assay, a complex of 23 associated proteins was identified that included ATPalpha and Nervana 3, two subunits of the Na+/K+ATPase. RNAi-mediated knockdown of ATPalpha, Nervana 3, or any of 8 additional complex proteins enhanced seizure susceptibility. The critical period of Jus expression in epileptogenesis was further defined, occurring between pupal stages P4-7; remarkably, thejusseizure phenotype could be rescued by increasing neural activity ofjus-expressing neurons during these mid-pupal stages, suggesting that altered neural activity in these neurons may contribute to the seizure phenotype. Our data support a model that, in wild type flies, a protein complex containing Na+/K+ATPase and Jus prevents epileptogenesis, possibly by regulating neural activity.
Structural basis of transcription: RNA Polymerase II substrate binding and metal coordination at 3.0 Å using a free-electron laser
Authors: Lin Guowu , Barnes Christopher O. , Weiss Simon , Dutagaci Bercem , Qiu Chenxi , Feig Michael , Song Jihnu , Lyubimov Artem , Cohen Aina E. , Kaplan Craig D. , Calero Guillermo 
Published: September 2023

AbstractCatalysis and translocation of multi-subunit DNA-directed RNA polymerases underlie all cellular mRNA synthesis. RNA polymerase II (Pol II) synthesizes eukaryotic pre-mRNAs from a DNA template strand buried in its active site. Structural details of catalysis at near atomic resolution and precise arrangement of key active site components have been elusive. Here we present the free electron laser (FEL) structure of a matched ATP-bound Pol II, revealing the full active site interaction network at the highest resolution to date, including the trigger loop (TL) in the closed conformation, bonafide occupancy of both site A and B Mg2+, and a putative third (site C) Mg2+analogous to that described for some DNA polymerases but not observed previously for cellular RNA polymerases. Molecular dynamics (MD) simulations of the structure indicate that the third Mg2+is coordinated and stabilized at its observed position. TL residues provide half of the substrate binding pocket while multiple TL/bridge helix (BH) interactions induce conformational changes that could propel translocation upon substrate hydrolysis. Consistent with TL/BH communication, a FEL structure and MD simulations of the hyperactive Rpb1 T834P bridge helix mutant reveals rearrangement of some active site interactions supporting potential plasticity in active site function and long-distance effects on both the width of the central channel and TL conformation, likely underlying its increased elongation rate at the expense of fidelity.
Single cell analysis of dup15q syndrome reveals developmental and postnatal molecular changes in autism
Authors: Perez Yonatan , Velmeshev Dmitry , Wang Li , White Matthew , Siebert Clara , Baltazar Jennifer , Dutton Natalia Garcia , Wang Shaohui , Haeussler Maximilian , Chamberlain Stormy , Kriegstein Arnold 
Published: September 2023

AbstractDuplication 15q (dup15q) syndrome is the most common genetic cause of autism spectrum disorder (ASD). Due to a higher genetic and phenotypic homogeneity compared to idiopathic autism, dup15q syndrome provides a well-defined setting to investigate ASD mechanisms. Previous bulk gene expression studies identified shared molecular changes in ASD. However, how cell type specific changes compare across different autism subtypes and how they change during development is largely unknown. In this study, we used single cell and single nucleus mRNA sequencing of dup15q cortical organoids from patient iPSCs, as well as post-mortem patient brain samples. We find cell-type specific dysregulated programs that underlie dup15q pathogenesis, which we validate by spatial resolved transcriptomics using brain tissue samples. We find degraded identity and vulnerability of deep-layer neurons in fetal stage organoids and highlight increased molecular burden of postmortem upper-layer neurons implicated in synaptic signaling, a finding shared between idiopathic ASD and dup15q syndrome. Gene co-expression network analysis of organoid and postmortem excitatory neurons uncovers modules enriched with autism risk genes. Organoid developmental modules were involved in transcription regulation via chromatin remodeling, while postmortem modules were associated with synaptic transmission and plasticity. The findings reveal a shifting landscape of ASD cellular vulnerability during brain development.
Alcohol induces concentration-dependent transcriptomic changes in oligodendrocytes
Authors: Bazzi Sam A. , Maguire Cole , Mayfield R. Dayne , Melamed Esther 
Published: September 2023

AbstractOligodendrocytes are a key cell type within the central nervous system (CNS) that generate the myelin sheath covering axons, enabling fast propagation of neuronal signals. Alcohol consumption is known to affect oligodendrocytes and white matter in the CNS. However, most studies have focused on fetal alcohol spectrum disorder and severe alcohol use disorder. Additionally, the impact of alcohol dosage on oligodendrocytes has not been previously investigated. In this study, we evaluated transcriptomic changes in C57BL6/J cultured mature oligodendrocytes following exposure to moderate and high concentrations of alcohol. We found that high concentrations of alcohol elicited gene expression changes across a wide range of biological pathways, including myelination, protein translation, integrin signaling, cell cycle regulation, and inflammation. Further, our results demonstrate that transcriptomic changes are indeed dependent on alcohol concentration, with moderate and high concentrations of alcohol provoking distinct gene expression profiles. In conclusion, our study demonstrates that alcohol-induced transcriptomic changes in oligodendrocytes are concentration-dependent and may have critical downstream impacts on myelin production. Targeting alcohol-induced changes in cell cycle regulation, integrin signaling, inflammation, or protein translation regulation may uncover mechanisms for modulating myelin production or inhibition. Furthermore, gaining a deeper understanding of alcohol’s effects on oligodendrocyte demyelination and remyelination could help uncover therapeutic pathways that can be utilized independent of alcohol to aid in remyelinating drug design.
Analysis of output characteristics of wireless power transfer system based on LCC/S-S hybrid compensation structure
Authors: Wang Dangshu , Deng Xuan , Guan Zhimin , Liu Shulin , Yang Yaqiang , Wang Xinxia 
Published: September 2023

Purpose
To simplify the circuit design and control complexity of the magnetic coupling resonant wireless charging system, the radio energy transmission constant current and constant voltage charging is realized.

Design/methodology/approach
The purpose of this study is to simplify the circuit design and control complexity of the magnetic coupling resonance wireless charging system, in order to achieve constant current and constant voltage charging for wireless energy transmission. First, the principle of LCC/S-S compensation structure is analyzed, and the equivalent mathematical model is established; then, the system characteristics under constant current and constant voltage mode are analyzed, and the design method of system parameters is given; finally, a simulation and experimental system is built to verify the correctness and feasibility of the theoretical analysis.

Findings
The results show that the proposed hybrid topology can achieve a constant current output of 2 A and a constant voltage output of 30 V under variable load conditions, and effectively suppress the current distortion problem under light load conditions. The waveform distortion rate of the inverter current is reduced from 33.97% to 10.45%.

Originality/value
By changing the high-order impedance characteristics of the compensation structure, the distortion of the current waveform under light load is suppressed, and the overall stability and efficiency of the system are improved.
Improved numerical integration for locking treatment in the Peridynamic Timoshenko beam model
Authors: Bai Ruqing , Naceur Hakim , Zhao Jinglei , Yi Jin , Ma Jie , Pu Huayan , Luo Jun 
Published: September 2023

PurposeIn this paper, the standard Peridynamic Timoshenko beam model accounting for the shear deformation is chosen to describe the thick beam kinematics. Unfortunately, when applied to very thin beam structures, the standard Peridynamics (PD) encounters the shear locking phenomenon, leading to incorrect solutions.Design/methodology/approachPD differs from classical continuum mechanics and other nonlocal theories that do not involve spatial derivatives of the displacement field. PD is based on the integral equation instead of differential equations to handle discontinuities and other singularities.FindingsThe shear locking can be successfully alleviated using the developed selective integration method. In particular, this technique has been implemented in the standard PD, which allows an accurate result for a wide range of slenderness from very thin to thick (10 < L/t < 103) structures. It can also accelerate the computational time for particular dynamic problems using fewer neighboring integration particles. Several numerical examples are solved to demonstrate the effectiveness of the proposed method for modeling beam structures.Originality/valueThe paper highlights the severe shear locking phenomenon in the Peridynamic Timoshenko beam available in the literature, especially for very thin structures. A new alternative for the alleviation of shear locking in the Peridynamic Timoshenko beam, using selective integration. Hence the developed Peridynamic Timoshenko beam model is effective for thin and thick structures. A new peridynamic formulation for the low-velocity impact beam models is presented and validated.HighlightsThe paper highlights the severe shear locking phenomenon in the Peridynamic Timoshenko beam proposed in the literature, especially for very thin structures.The developed Peridynamic Timoshenko beam model based on selective integration is effective for thin and thick structures.A new peridynamic formulation for the low-velocity impact beam models is presented and validated.
The perceptions of diversity management and employee performance: UAE perspectives
Authors: Mahdi Abaker Mohamed Osman Shereif , Kemp Lindsey , Cho Boo Yun , Patterson Louise 
Published: September 2023

PurposeThe purpose of this article was to investigate the employee perceptions of diversity management and employee performance. To achieve this, employee respondents’ perceptions and perspectives have been tested, and findings are discussed.Design/methodology/approachTo address this study's purpose, survey data were collected from 250 employees of two organizations in the United Arab Emirates (UAE). Data were analyzed by age, gender and nationality for two variables: diversity management and employee performance.FindingsResults showed that respondents perceived an improvement in employee performance when diversity was managed for employees of different age groups, females/males working together and a workplace composed of employees from various nationalities.Research limitations/implicationsThe implication of this limited study is that further studies on the perception of diversity management for employee performance in the Middle East region needs to be conducted. The social implication is that organizational leaders can initiate diversity management to improve employee performance. The research is limited by the geographical context and access to the collection of data during the COVID-19 pandemic.Social implicationsThe implication of this limited study is that further studies on the perception of diversity management for employee performance in the Middle East region needs to be conducted. The social implication is that organizational leaders can initiate diversity management to improve employee performance.Originality/valueThe contribution to academic knowledge from this research is two-fold: findings from a novel study conducted in the Middle East evidenced diversity management improved perceptions of employee performance. The value of the study for praxis is to incorporate employees' belief in diversity management for its potential to improve employee performance.
Pedagogical and socio-emotional impacts of COVID-19 on Guinean school children: evidence from a mixed cross-sectional study
Authors: Maltais Stéphanie , Bourgeois Isabelle , Moumouni Aissata Boubacar , Yaya Sanni , Doumbouya Mohamed Lamine , Béavogui Gaston , Mabeu Marie Christelle , Pongou Roland 
Published: September 2023

Purpose
This study aims to determine the pedagogical and socio-emotional impacts of school closures caused by the COVID-19 pandemic in Guinea.

Design/methodology/approach
A descriptive, survey-based methodology was used to collect quantitative and qualitative data directly from parents and caregivers. Between February 24 and March 13, 2022, data was gathered from a study population comprising 2,955 adults residing in five communes and five prefectures of Guinea.

Findings
Half of all respondents stated that school closures had no particular impact on children in their household, and 42% stated that no intentional pedagogical activities took place during school closures. Approximately 15% of respondents stated that children experienced boredom, loneliness, sadness, depression, stress and anxiety during the school closures.

Originality/value
The study underscores the significance of school closure readiness and interactive learning while revealing limited emotional impact on children. The findings, while specific to Guinea, provide a foundational understanding, highlighting the complexity of pandemic effects on education and the need for adaptive strategies in vulnerable regions.
US road safety during COVID-19: motorist, pedestrian and bicyclist fatality trends
Authors: Ferenchak Nicholas N. 
Published: September 2023

Purpose
The purpose of this paper is to illustrate how COVID-19 lockdowns in the USA impacted traffic safety.

Design/methodology/approach
The authors explored the role of vehicle, user and built environment factors on traffic fatalities in the USA, comparing results during COVID-19 lockdowns (March 19th through April 30th, 2020) to results for the same time period during the five preceding years. The authors accomplished this through proportional comparisons and negative binomial regression models.

Findings
While traffic levels were 30%–50% below normal during the COVID-19 lockdowns, all traffic fatalities decreased by 18.3%, pedestrian fatalities decreased by 19.0% and bicyclist fatalities increased by 3.6%. Fatal COVID-19 crashes were more likely single-vehicle crashes involving fixed objects or rollovers. COVID-19 traffic fatalities were most common on arterial roadways and in lower density suburban built environments. Findings suggest the importance of vulnerable road users, speed management and holistic built environment policy when pursuing safety on the streets.

Originality/value
The findings have road safety implications not only for future pandemics and other similar events where we would expect decreases in motor vehicle volumes (such as natural disasters and economic downturns) but also for cities that are pursuing mode shift away from personal automobiles and toward alternative modes of transportation.
Nature-related features and children’s well-being in post-disaster school design
Authors: Atmodiwirjo Paramita , Ghaziani Rokhshid , Wungpatcharapon Supreeya , Djuwita Ratna , Yatmo Yandi Andri 
Published: September 2023

Purpose
This study aims to identify the role of nature-related features in promoting well-being from the perspective of children as the users of post-disaster schools. It highlights the importance of connectedness to nature in design strategies for post-disaster school reconstruction.

Design/methodology/approach
The mixed-method study was conducted in three primary schools reconstructed after the earthquakes in Lombok (Indonesia) and Chiang Rai (Thailand) that integrated some nature-related elements in their design. The questionnaire survey explored the children’s satisfaction with the post-disaster school environment as an indication of well-being.

Findings
The findings suggest that priority in post-disaster school design strategies should incorporate nature-related design features that provide opportunities for children to be with friends and to play, to learn in comfortable and safe conditions, to interact with nature and to be in a quiet and relaxing place.

Originality/value
Most post-disaster reconstruction prioritizes the speed of construction rather than the spatial qualities that could help children deal with the disaster. This study provides evidence on the potential of nature-related design features to support the children’s well-being after the disaster.
Working for a better future: exploring how network capital fosters Laotian migrant workers in Thai family SMEs
Authors: Daovisan Hanvedes , Charoenratana Sayamol , Akitsu Motoki 
Published: September 2023

Purpose
Transnational migration is a key challenge in migrant-sending and host-receiving countries. However, relatively little is known about how migrants use network capital to foster small and medium-sized enterprises (SMEs) in the ASEAN Economic Community (AEC). Therefore, the purpose of this study is to explore how network capital fosters Laotian migrant workers in Thai family SMEs.

Design/methodology/approach
This research was conducted using qualitative network analysis (QNA). Referral snowball sampling was used to draw 20 participants from December 2021 to March 2022. Data analysis was performed using Gephi, a software package developed for QNA (coding, network features, measure nodes and network metrics).

Findings
The main findings are the following four emerging themes: chain networks, social networks, human networks and financial networks are associated with network capital for fostering Laotian migrant workers in Thai family SMEs.

Originality/value
To the best of the authors’ knowledge, this study is the first QNA to explore how Laotian migrant workers use network capital in Thai family SMEs.