bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid packing and cholesterol content regulate membrane wetting and remodeling by biomolecular condensates
Authors: Mangiarotti Agustín , Sabri Elias , Schmidt Kita Valerie , Hoffmann Christian , Milovanovic Dragomir , Lipowsky Reinhard , Dimova Rumiana 
Published: July 2024

AbstractBiomolecular condensates play a pivotal role in cellular processes by interacting with membranes and leading to wetting transitions and to mutual remodeling. Using a combination of hyperspectral imaging, phasor analysis, and fluid-elastic parameter measurements, we investigated how membrane lipid packing affects condensate wetting. Our results show that it is not only the membrane phase state, but rather the degree of lipid packing that determines the condensate affinity for membranes. Increasing lipid chain length or cholesterol content enhances lipid packing, thereby decreasing condensate affinity. This regulatory mechanism is consistent across various condensate-membrane systems, underscoring the critical role of the membrane interface. Additionally, protein adsorption promotes extensive membrane remodeling, including tube and double-membrane sheet formation. This work provides a novel mechanism by which membrane composition fine-tunes condensate wetting, highlighting its potential impact on cellular functions and organelle interactions.
Mapping kinase domain resistance mechanisms for the MET receptor tyrosine kinase via deep mutational scanning
Authors: Estevam Gabriella O. , Linossi Edmond M. , Rao Jingyou , Macdonald Christian B. , Ravikumar Ashraya , Chrispens Karson M. , Capra John A. , Coyote-Maestas Willow , Pimentel Harold , Collisson Eric A. , Jura Natalia , Fraser James S. 
Published: July 2024

AbstractMutations in the kinase and juxtamembrane domains of the MET Receptor Tyrosine Kinase are responsible for oncogenesis in various cancers and can drive resistance to MET-directed treatments. Determining the most effective inhibitor for each mutational profile is a major challenge for MET-driven cancer treatment in precision medicine. Here, we used a deep mutational scan (DMS) of ∼5,764 MET kinase domain variants to profile the growth of each mutation against a panel of 11 inhibitors that are reported to target the MET kinase domain. We validate previously identified resistance mutations, pinpoint common resistance sites across type I, type II, and type I ½ inhibitors, unveil unique resistance and sensitizing mutations for each inhibitor, and verify non-cross-resistant sensitivities for type I and type II inhibitor pairs. We augment a protein language model with biophysical and chemical features to improve the predictive performance for inhibitor-treated datasets. Together, our study demonstrates a pooled experimental pipeline for identifying resistance mutations, provides a reference dictionary for mutations that are sensitized to specific therapies, and offers insights for future drug development.
Single-strain mobilome sequencing quantifies bacterial genetic response to stress, including activity of IS elements, prophages, RNAs, and REPINs
Authors: Nielsen Tue Kjærgaard , Hansen Lars Hestbjerg 
Published: July 2024

ABSTRACTMicrobial genomes are continuously being rearranged by mobile genetic elements (MGEs), leading to genetic configurations that may confer novel phenotypic traits such as antibiotic resistance, degradation of novel compounds, or other metabolic features. Standard genomic sequencing provides a snapshot of a genome in one configuration, but this static image does not give insight into the dynamics of genomic evolution and whether MGEs are actively changing a given genome. We applied single-strain mobilome sequencing toEscherichia coliK-12 substrain MG1655 under various stress conditions: UV, SDS, nalidixic acid, tetracycline, cetrimide, and copper. Under these conditions, we quantified the activity of a range of genetic elements, including extrachromosomal circular DNA (eccDNA) from IS elements, RNA genes, the UV-inducible e14 prophage, and intergenic repetitive sites (REP). Of the investigated stressors, copper and SDS are among the largest inducers of eccDNA formation from groups of IS elements, while elevated levels of hypothetical RNA/DNA heteroduplexes of ribosomal and transfer RNAs, and Rhs-nuclease proteins are induced under stress various stressors, especially copper and SDS. This approach holds promise for quantifying the genetic response to environmental stress and implications for genome plasticity. The observed mobilization of IS elements upon copper and other stressors helps to explain co-selection of heavy metals with antibiotic resistance genes and MGEs.
Identification of novel small molecule chaperone activators for neurodegenerative disease treatment
Authors: Ho Anita , Jeganathan Fiona , Bictash Magda , Chen Han-Jou 
Published: July 2024

AbstractA pathological hallmark of neurodegenerative disease is the accumulation of aberrant protein aggregates which contribute to the cytotoxicity and are therefore a target for new therapy development. One key machinery to manage cellular protein homeostasis is the chaperones proteins, the heat shock proteins (HSPs) which are known to target aberrant proteins including TDP-43, tau and amyloid and rescue neurodegeneration in various disease models. As an attempt to target HSP activation for neurodegeneration therapy, we develop a drug screening assay to search compounds that activate the master regulator of HSPs, the transcription factor heat shock factor 1 (HSF1). As HSF1 is bound by HSP90 which prevents its activation, we develop a NanoBRET assay, which allows us to monitor and quantify the HSF1-HSP90 interaction in living cells to screen for compounds disrupting this interaction and thereby releasing HSF1 for activation. After the assay was optimised and validated for its robustness and reliability, a two thousand compound library was screened which produced 10 hits including a couple of known HSP90 inhibitors. Follow-up functional study showed that one of the hit oxyphenbutazone (OPB) significantly reduces the accumulation of insoluble TDP-43 in a cell model, displaying no signs of stress or toxicity. Further works are needed to characterise the mode-of-action of OPB in HSF1 activation and aberrant protein reduction, and the physiological impact of OPB on TDP-43 needs to be examined in an in vivo model. However, this study demonstrates a viable strategy for new drug discovery in targeting aberrant proteins and identifies potential candidates for translation into neurodegenerative disease treatment.
Exploring the impact of digestive physicochemical parameters of adults and infants on the pathophysiology ofCryptosporidium parvumusing the dynamic TIM-1 gastrointestinal model
Authors: Tottey Julie , Etienne-Mesmin Lucie , Chalançon Sandrine , Sausset Alix , Denis Sylvain , Mazal Carine , Blavignac Christelle , Sallé Guillaume , Laurent Fabrice , Blanquet-Diot Stéphanie , Lacroix-Lamandé Sonia 
Published: July 2024

ABSTRACTBackgroundHuman cryptosporidiosis is distributed worldwide, and it is recognised as a leading cause of acute diarrhoea and death in infants in low- and middle-income countries. Besides immune status, the higher incidence and severity of this gastrointestinal disease in young children could also be attributed to the digestive environment. For instance, human gastrointestinal physiology undergoes significant changes with age, however the role this variability plays inCryptosporidium parvumpathogenesis is not known. In this study, we analysed for the first time the impact of digestive physicochemical parameters onC. parvuminfection in a human and age-dependent context using a dynamicin vitrogastrointestinal model.ResultsOur results showed that the parasite excystation, releasing sporozoites from oocysts, occurs in the duodenum compartment after one hour of digestion in both child (from 6 months to 2 years) and adult experimental conditions. In the child small intestine, slightly less sporozoites were released from excystation compared to adult, however they exhibited a higher luciferase activity, suggesting a better physiological state. Sporozoites collected from the child jejunum compartment also showed a higher ability to invade human intestinal epithelial cells compared to the adult condition. Global analysis of the parasite transcriptome through RNA-sequencing demonstrated a more pronounced modulation in ileal effluents compared to gastric ones, albeit showing less susceptibility to age-related digestive condition. Further analysis of gene expression and enriched pathways showed that oocysts are highly active in protein synthesis in the stomach compartment, whereas sporozoites released in the ileum showed downregulation of glycolysis as well as strong modulation of genes potentially related to gliding motility and secreted effectors.ConclusionsDigestion in a sophisticatedin vitrogastrointestinal model revealed that invasive sporozoite stages are released in the small intestine, and are highly abundant and active in the ileum compartment, supporting reportedC. parvumtissue tropism. Our comparative analysis suggests that physicochemical parameters encountered in the child digestive environment can influence the amount, physiological state and possibly invasiveness of sporozoites released in the small intestine, thus potentially contributing to the higher susceptibility of young individuals to cryptosporidiosis.
Bacterial defense and phage counter-defense lead to coexistence in a modeled ecosystem
Authors: Kimchi Ofer , Meir Yigal , Wingreen Ned S. 
Published: July 2024

AbstractBacteria have evolved many defenses against invading viruses (phage). Typically, each bacterium carries several defense systems, while each phage may carry multiple counter-defense systems. Despite the many bacterial defenses and phage counter-defenses, in most environments, bacteria and phage coexist, with neither driving the other to extinction. How is coexistence realized in the context of the bacteria/phage arms race, and how are the sizes of the bacterial immune and phage counter-immune repertoires determined in conditions of coexistence? Here we develop a simple mathematical model to consider the evolutionary and ecological dynamics of competing bacteria and phage with different immune/counter-immune repertoires. An analysis of our model reveals an ecologically stable fixed point exhibiting coexistence. This fixed point agrees with the experimental observation that each individual bacterium typically carries multiple defense systems, though fewer than the maximum number possible. However, in simulations, the populations typically remain dynamic, exhibiting chaotic fluctuations around this fixed point. We obtain quantitative predictions for the mean, amplitude, and timescale of these dynamics. Our results provide a framework for understanding the evolutionary and ecological dynamics of the bacteria/phage arms race, and demonstrate how bacteria/phage coexistence can stably arise from the coevolution of bacterial defense systems and phage counter-defense systems.
Clostridioides difficilecolonization is not mediated by bile salts and utilizes Stickland fermentation of proline in anin vitromodel
Authors: Huang Xiaoyun , Johnson April E. , Brehm Joshua N. , Thanh Do Thi Van , Auchtung Thomas A. , McCullough Hugh C. , Lerma Armando I. , Haidacher Sigmund J. , Hoch Kathleen M. , Horvath Thomas D. , Sorg Joseph A. , Haag Anthony M. , Auchtung Jennifer M. 
Published: July 2024

ABSTRACTTreatment with antibiotics is a major risk factor forClostridioides difficileinfection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limitC. difficilecolonization include conversion of conjugated primary bile salts into secondary bile salts toxic toC. difficilegrowth, and competition between the microbiota andC. difficilefor limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with six clinically-used antibiotics influenced susceptibility toC. difficileinfection in 12 different microbial communities cultivated from healthy individuals. Antibiotic treatment reduced microbial richness; disruption varied by antibiotic class and microbiota composition, but did not correlate withC. difficilesusceptibility. Antibiotic treatment also disrupted microbial bile salt metabolism, increasing levels of the primary bile salt, cholate. However, changes in bile salt did not correlate with increasedC. difficilesusceptibility. Further, bile salts were not required to inhibitC. difficilecolonization. We tested whether amino acid fermentation contributed to persistence ofC. difficilein antibiotic- treated communities.C. difficilemutants unable to use proline as an electron acceptor in Stickland fermentation due to disruption of proline reductase (prdB-) had significantly lower levels of colonization than wild-type strains in four of six antibiotic-treated communities tested. Inability to ferment glycine or leucine as electron acceptors, however, was not sufficient to limit colonization in any communities. This data provides further support for the importance of bile salt-independent mechanisms in regulating colonization ofC. difficile.IMPORTANCEC. difficileis one of the leading causes of hospital-acquired infections and antibiotic-associated diarrhea. Several potential mechanisms through which the microbiota can limitC. difficileinfection have been identified and are potential targets for new therapeutics. However, it is unclear which mechanisms ofC. difficileinhibition represent the best targets for development of new therapeutics. These studies demonstrate that in a complexin vitromodel ofC. difficileinfection, colonization resistance is independent of microbial bile salt metabolism. Instead, the ability ofC. difficileto colonize is dependent upon its ability to metabolize proline, although proline-dependent colonization is context-dependent and is not observed in all disrupted communities. Altogether, these studies support the need for further work to understand how bile- independent mechanisms regulateC. difficilecolonization.
Accounting talks – how operations managers nuance their frontstage performance with backstage negotiations
Authors: Curry Amanda 
Published: July 2024

PurposeThis paper analyzes the ways in which accounting enables operations managers to enter and perform multiple roles in their interplay with organizational groups on the shop floor and in management, and the associated negotiations that operations managers have with “the self.”Design/methodology/approachUsing field-based studies in a mining organization, the study draws on Goffman’s backstage–frontstage metaphor to analyze how operations managers enter and perform several roles with the aid of accounting.FindingsThe findings show that accounting legitimizes operations managers when they cross organizational boundaries, as accounting gives them an “entry ticket” that legitimizes their presence with the group. Accounting further allows operations managers to embrace more than one role by “putting on a mask” to become an outsider or insider in relation to a group. In performing their roles, operations managers exhibit varying attributes and knowledge. Accounting can thereby be withheld from, or shared with, organizational groups. The illusion of accounting as deterministic presented frontstage is not necessarily negotiated that way backstage. Rather, alternatives discussed backstage often become silenced in the frontstage performance. The study concludes that operations managers cross boundaries, embrace roles and exert agency as they navigate with accounting, enrolling it into their performance simultaneously as they backstage reflect upon accounting and its role for their everyday work.Originality/valueThis study relies on the frontstage/backstage metaphor to visualize the discrepancies in how accounting is enrolled into role performances and how seemingly categorical fronts do not necessarily share that dominant position backstage.
Aerodynamic design of an electronics pod to maximise its carriage envelope on a fast-jet aircraft
Authors: du Rand Ruan , Jamison Kevin , Huyssen Barbara 
Published: July 2024

Purpose
The purpose of this paper is to reshape a fast-jet electronics pod’s external geometry to ensure compliance with aircraft pylon load limits across its carriage envelope while adhering to onboard system constraints and fitment specifications.

Design/methodology/approach
Initial geometric layout determination used empirical methods. Performance approximation on the aircraft with added fairings and stabilising fin configurations was conducted using a panel code. Verification of loads was done using a full steady Reynolds-averaged Navier–Stokes solver, validated against published wind tunnel test data. Acceptable load envelope for the aircraft pylon was defined using two already-certified stores with known flight envelopes.

Findings
Re-lofting the pod’s geometry enabled meeting all geometric and pylon load constraints. However, due to the pod's large size, re-lofting alone was not adequate to respect aircraft/pylon load limitations. A flight restriction was imposed on the aircraft’s roll rate to reduce yaw and roll moments within allowable limits.

Practical implications
The geometry of an electronics pod was redesigned to maximise the permissible flight envelope on its carriage aircraft while respecting the safe carriage load limits determined for its store pylon. Aircraft carriage load constraints must be determined upfront when considering the design of fast-jet electronic pods.

Originality/value
A process for determining the unknown load constraints of a carriage aircraft by analogy is presented, along with the process of tailoring the geometry of an electronics pod to respect aerodynamic load and geometric constraints.
Employee-customer identification and service quality in the hospitality industry
Authors: Schwepker Jr Charles H. , Dimitriou Christina K. 
Published: July 2024

PurposeThis research seeks to better understand the impact of employee-customer identification on critical job outcomes such as customer orientation and commitment to service quality.Design/methodology/approachA sample of 316 hotel/motel employees was used for the study. Structural equation modeling was used to analyze the data.FindingsResults show a positive relationship between ethical values person-organization fit and employee-customer identification indicating that when customer-contact service employees’ ethical values align with those of the organization, they identify with customers more closely. Results also suggest that when employees identify with customers they are likely to be more customer-oriented and committed to providing service quality.Originality/valueWe learn how the relationship between employee and organization impacts employee-customer identification. Furthermore, we better comprehend the impact of employee-customer identification on critical outcomes in the hospitality industry such as customer orientation and commitment to service quality.
Ethical leadership, employees’ job satisfaction and job stress in the restaurant industry
Authors: Yasir Muhammad , Javed Asim 
Published: July 2024

Purpose
This paper aims to investigate how employees’ perception of the ethical conduct of their leaders affects their level of job stress and job satisfaction in the restaurant industry, specifically in the context of Pakistan. Therefore, this research investigated the relationship between ethical leadership and job satisfaction, and job stress as a mediator between ethical leadership and job satisfaction.

Design/methodology/approach
This research is based on a quantitative method, employed a survey strategy, utilized a cross-sectional research design, and data was collected using a convenient sampling technique. In all, 236 questionnaires from the front-line employees of the restaurants were used for data analysis. Initially, normality (univariate and multivariate), demographic description, descriptive analysis and common method bias were computed using Statistical Package for Social Sciences (SPSS v23) software. Moreover, direct and indirect effects were conducted using SmartPLS v3 software.

Findings
Results of this research indicate a (i) negative relationship between ethical leadership and job stress, (ii) positive relationship between ethical leadership and job satisfaction, (iii) negative relationship between job stress and job satisfaction and (iv) job stress play a mediating role in the relationship between ethical leadership and job satisfaction.

Research limitations/implications
This study highlights several theoretical and practical implications, thereby providing more insight into how job satisfaction can be maximized in the restaurants of Pakistan.

Originality/value
This research is novel, as it highlights the direct and indirect effect of ethical leadership behavior on job satisfaction, specifically in the context of the restaurants of Pakistan.
Citizenship, language and digital rights: the question of language in the process of decolonising the internet and digital rights
Authors: Nyabola Nanjala 
Published: July 2024

Purpose
Much of the vocabulary of digital rights have not been translated into Kiswahili. This means that technology experts and digital rights defenders often use English words when they are discussing technology. This contributes to the frailty of efforts to defend digital rights because those who attempt to explain the importance of these issues to the broader societies are forced to rely on English vocabulary that is not rooted in or connected to Kiswahili contexts. This paper aims to discuss the importance of inviting people to use African languages on the internet.

Design/methodology/approach
Kiswahili is the most widely spoken African language in the world. Nearly 140 million people in East Africa speak Kiswahili as a first or second language, including in Kenya and Tanzania where it is the national language. There is a long history of Kiswahili writing, publishing and cultural production in Kiswahili. Kiswahili is also the only African language that is an official language at the African Union. Even so, Kiswahili lags behind significantly in the development of a vocabulary and grammar of technology.

Findings
Beyond vocabulary, the use of African languages online is important to strengthening democracy on the internet because language is keenly connected to identity. Efforts to translate the vocabulary of technology into Kiswahili are aimed at encouraging societies in East Africa to build communities online that represent their interests keenly. This article therefore looks at the importance of language in building society and the efforts by residents of East Africa to decolonise the internet, so that they are able to exist in their fullness on the internet. The article further examines the semiotics of language in digital innovation, and the importance of representing Kiswahili language communities properly online in efforts to decolonise the internet. This paper does not presume that Kiswahili is the only African language that can decolonise the internet, because even Kiswahili has a history of domination over other language communities in the region. Rather, the article uses the example of Kiswahili to urge the use of indigenous languages to defend digital diversity.

Originality/value
The importance of this article is in demonstrating the importance of language in the movement to develop digital rights and especially to remove colonial approaches to technology, an issue that, to the best of the author’s knowledge, has never been discussed in relation to the Kiswahili language.