bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal body condition affects the response of larval spined toads’ faecal microbiome to a widespread contaminant
Authors: Tartu Sabrina , Pollet Nicolas , Clavereau Isabelle , Bouchard Gauthier , Brischoux François 
Published: December 2023

AbstractGlyphosate’s primary metabolite, aminomethylphosphonic acid (AMPA), is the most detected pollutant in surface waters. Recent studies have raised concerns about its toxicity, yet underlying mechanisms remain poorly understood. A disruption of the gut microbiome, which plays a crucial role in host health, could mediate most of the adverse effects. We investigated the impact of AMPA exposure on the gut microbiome of spined toad tadpoles (Bufo spinosus). We hypothesized that AMPA could alter the gut microbiota composition and that these effects could depend on the microbiota source. We exposed tadpoles to minute concentrations of AMPA and analyzed their faecal microbiota using 16S rRNA gene sequencing as a proxy of the gut microbiota. AMPA exposure decreased the gut bacterial biomass and affected the bacterial community composition of tadpole’s faeces. Furthermore, we observed interactions between AMPA exposure and maternal body condition on the Bacteroidota and Actinobacteriota phyla abundances. This suggests a maternal effect on early-life microbial colonizers that could influence the response of the gut microbiome to AMPA. These findings highlight the importance of considering the gut microbiome when studying the effects of environmental contaminants. Further research is needed to elucidate the long-term implications of this microbiome alteration for amphibian health.
Targeting HIV-1 with CRISPR/Cas9 delivered by retargeted adenoviruses effectively suppresses viral replication
Authors: Klinnert Sarah , Freitag Patrick C. , Plückthun Andreas , Metzner Karin J. 
Published: December 2023

AbstractIntegrated, intact, latent HIV-1 viruses in infected cells are the main obstacle to curing HIV-1 infections. Targeted inactivation of HIV-1 proviruses with CRISPR/Cas9 is a promising strategy to eradicate HIV-1. In addition, CRISPR/Cas9 is able to target replicating HIV-1 and could be used as a therapy during productive infection.Here, we combine the CRISPR/Cas9 system with a novel adenovirus (Ad) targeted delivery technology to test it as a therapeutic approach to inhibit HIV-1. First, we selected six HIV-1-specific gRNAs targeting the HIV-1 LTRs and thegaggene and tested their efficacy in inhibiting HIV-1 virion production in an HEK 293T cell co-transfection screen. The gRNA-TAR showed the most robust and potent inhibition of HIV-1 by >99% alone or in combination with the gRNA-p24, which induced a ∼1 kb deletion between both gRNA target sites in HIV-1 DNA. Delivery of this dual gRNA-TAR/p24 CRISPR/Cas9 system with CD3-CD28-IL2-retargeted Ads was highly effective, transducing 62.3±23.3% of cells and suppressing HIV-1 replication by 88.0±4.5% in primary CD4+T cells from three independent donors.Our dual gRNA-TAR/p24-CRISPR/Cas9-Ad strategy represents a novel therapeutic approach to effectively inhibit HIV-1 in a highly HIV-1 and T cell-specific manner.
Pathogen-microbiome interactions and the virulence of an entomopathogenic fungus
Authors: Kolp Matthew R. , de Anda Acosta Yazmin , Brewer William , Nichols Holly L. , Goldstein Elliott B. , Tallapragada Keertana , Parker Benjamin J. 
Published: December 2023

AbstractBacteria shape interactions between hosts and fungal pathogens. In some cases, bacteria associated with fungi are essential for pathogen virulence. In other systems, host associated microbiomes confer resistance against fungal pathogens. We studied an aphid-specific entomopathogenic fungus calledPandora neoaphidisin the context of both host and pathogen microbiomes. Aphids host several species of heritable bacteria, some of which confer resistance againstPandora. We first found that spores that emerged from aphids that harbored protective bacteria were less virulent against subsequent hosts and did not grow on plate media. We then used 16S amplicon sequencing to study the bacterial microbiome of fungal mycelia and spores during plate culturing and host infection. We found that the bacterial community is remarkably stable in culture despite dramatic changes in pathogen virulence. Last, we used an experimentally transformed symbiont of aphids to show thatPandoracan acquire hostassociated bacteria during infection. Our results uncover new roles for bacteria in the dynamics of aphidpathogen interactions and illustrate the importance of the broader microbiological context in studies of fungal pathogenesis.
Initial amino acid:codon assignments and strength of codon:anticodon binding
Authors: Su Meng , Roberts Samuel J. , Sutherland John D. 
Published: December 2023

AbstractThe ribosome brings 3′-aminoacyl-tRNA and 3′-peptidyl-tRNAs together to enable peptidyl transfer by binding them in two major ways. Firstly, their anticodon loops are bound to mRNA, itself anchored at the ribosomal subunit interface, by contiguous anticodon:codon pairing augmented by interactions with the decoding centre of the small ribosomal subunit. Secondly, their acceptor stems are bound by the peptidyl transferase centre which aligns the 3′-aminoacyl- and 3′-peptidyl-termini for optimal interaction of the nucleophilic amino group and electrophilic ester carbonyl group. Reasoning that intrinsic codon:anticodon binding might have been a major contributor to bringing tRNA 3′-termini into proximity at an early stage of ribosomal peptide synthesis, we wondered if primordial amino acids might have been assigned to those codons that bind the corresponding anticodon loops most tightly. By measuring the binding of anticodon stem loops to short oligonucleotides, we determined that family box codon:anticodon pairings are typically tighter than split box codon:anticodon pairings. Furthermore, we find that two family box anticodon stem loops can tightly bind a pair of contiguous codons simultaneously whereas two split box anticodon stem loops cannot. The amino acids assigned to family boxes correspond to those accessible by what has been termed cyanosulfidic chemistry, supporting the contention that these limited amino acids might have been the first used in primordial coded peptide synthesis.Table of Contents (TOC) graphic
Machine Learning and Metabolic Model Guided CRISPRi Reveals a Central Role for Phosphoglycerate Mutase inChlamydia trachomatisPersistence
Authors: Chowdhury Niaz Bahar , Pokorzynski Nick , Rucks Elizabeth A. , Ouellette Scot P. , Carabeo Rey A. , Saha Rajib 
Published: December 2023

SUMMARYUpon nutrient starvation,Chlamydia trachomatisserovar L2 (CTL) shifts from its normal growth to a non-replicating form, termed persistence. It is unclear if persistence is an adaptive response or lack of it. To understand that transcriptomics data were collected for nutrient-sufficient and nutrient-starved CTL. Applying machine learning approaches on transcriptomics data revealed a global transcriptomic rewiring of CTL under stress conditions without having any global stress regulator. This indicated that CTL’s stress response is due to lack of an adaptive response mechanism. To investigate the impact of this on CTL metabolism, we reconstructed a genome-scale metabolic model of CTL (iCTL278) and contextualized it with the collected transcriptomics data. Using the metabolic bottleneck analysis on contextualizediCTL278, we observed phosphoglycerate mutase (pgm)regulates the entry of CTL to the persistence. Later,pgmwas found to have the highest thermodynamics driving force and lowest enzymatic cost. Furthermore, CRISPRi-driven knockdown ofpgmand tryptophan starvation experiments revealed the importance of this gene in inducing persistence. Hence, this work, for the first time, introduced thermodynamics and enzyme-cost as tools to gain deeper understanding on CTL persistence.
Nitrogen signaling factor triggers a respiration-like gene expression program
Authors: Ohsawa Shin , Schwaiger Michaela , Iesmantavicius Vytautas , Hashimoto Rio , Moriyama Hiromitsu , Matoba Hiroaki , Hirai Go , Sodeoka Mikiko , Hashimoto Atsushi , Matsuyama Akihisa , Yoshida Minoru , Yashiroda Yoko , Bühler Marc 
Published: December 2023

ABSTRACTMicrobes have evolved intricate communication systems that enable individual cells of a population to send and receive signals in response to changes in their immediate environment. In the fission yeastSchizosaccharomyces pombe, the oxylipin Nitrogen Signaling Factor (NSF) is part of such communication system, which functions to regulate the usage of different nitrogen sources. Yet, the pathways and mechanisms by which NSF acts are poorly understood. Here, we show that NSF physically interacts with the mitochondrial sulfide:quinone oxidoreductase Hmt2 and that it prompts a change from a fermentation- to a respiration-like gene expression program independently of the carbon source. Our results suggest that NSF activity is not restricted to nitrogen metabolism alone and that it could function as a rheostat to prepare a population ofS. pombecells for an imminent shortage of their preferred nutrients.
Impact of the clinically approved BTK inhibitors on the conformation of full-length BTK and analysis of the development of BTK resistance mutations in chronic lymphocytic leukemia
Authors: Joseph Raji E. , Wales Thomas E. , Jayne Sandrine , Britton Robert G. , Fulton D. Bruce , Engen John R. , Dyer Martin J. S. , Andreotti Amy H. 
Published: December 2023

ABSTRACTInhibition of Bruton’s tyrosine kinase (BTK) has proven to be highly effective in the treatment of B-cell malignancies such as chronic lymphocytic leukemia (CLL), autoimmune disorders and multiple sclerosis. Since the approval of the first BTK inhibitor (BTKi), Ibrutinib, several other inhibitors including Acalabrutinib, Zanubrutinib, Tirabrutinib and Pirtobrutinib have been clinically approved. All are covalent active site inhibitors, with the exception of the reversible active site inhibitor Pirtobrutinib. The large number of available inhibitors for the BTK target creates challenges in choosing the most appropriate BTKi for treatment. Side-by-side comparisons in CLL have shown that different inhibitors may differ in their treatment efficacy. Moreover, the nature of the resistance mutations that arise in patients appears to depend on the specific BTKi administered. We have previously shown that Ibrutinib binding to the kinase active site causes unanticipated long-range effects on the global conformation of BTK (Joseph, R.E., et al., 2020,https://doi.org/10.7554/eLife.60470). Here we show that binding of each of the five approved BTKi to the kinase active site brings about distinct allosteric changes that alter the conformational equilibrium of full-length BTK. Additionally, we provide an explanation for the resistance mutation bias observed in CLL patients treated with different BTKi and characterize the mechanism of action of two common resistance mutations: BTK T474I and L528W.
Branched-chain keto acids promote an immune-suppressive and neurodegenerative microenvironment in leptomeningeal disease
Authors: Khaled Mariam Lotfy , Ren Yuan , Kundalia Ronak , Alhaddad Hasan , Chen Zhihua , Wallace Gerald C. , Evernden Brittany , Ospina Oscar E. , Hall MacLean , Liu Min , Darville Lancia N.F. , Izumi Victoria , Chen Y. Ann , Pilon-Thomas Shari , Stewart Paul A. , Koomen John M. , Corallo Salvatore A. , Jain Michael D. , Robinson Timothy J. , Locke Fredrick L. , Forsyth Peter A. , Smalley Inna 
Published: December 2023

AbstractLeptomeningeal disease (LMD) occurs when tumors seed into the leptomeningeal space and cerebrospinal fluid (CSF), leading to severe neurological deterioration and poor survival outcomes. We utilized comprehensive multi-omics analyses of CSF from patients with lymphoma LMD to demonstrate an immunosuppressive cellular microenvironment and identified dysregulations in proteins and lipids indicating neurodegenerative processes. Strikingly, we found a significant accumulation of toxic branched-chain keto acids (BCKA) in the CSF of patients with LMD. The BCKA accumulation was found to be a pan-cancer occurrence, evident in lymphoma, breast cancer, and melanoma LMD patients. Functionally, BCKA disrupted the viability and function of endogenous T lymphocytes, chimeric antigen receptor (CAR) T cells, neurons, and meningeal cells. Treatment of LMD mice with BCKA-reducing sodium phenylbutyrate significantly improved neurological function, survival outcomes, and efficacy of anti-CD19 CAR T cell therapy. This is the first report of BCKA accumulation in LMD and provides preclinical evidence that targeting these toxic metabolites improves outcomes.
scResolve: Recovering single cell expression profiles from multi-cellular spatial transcriptomics
Authors: Chen Hao , Lee Young Je , Ovando Jose A. , Rosas Lorena , Rojas Mauricio , Mora Ana L. , Bar-Joseph Ziv , Lugo-Martinez Jose 
Published: December 2023

AbstractMany popular spatial transcriptomics techniques lack single-cell resolution. Instead, these methods measure the collective gene expression for each location from a mixture of cells, potentially containing multiple cell types. Here, we developed scResolve, a method for recovering single-cell expression profiles from spatial transcriptomics measurements at multi-cellular resolution. scResolve accurately restores expression profiles of individual cells at their locations, which is unattainable from cell type deconvolution. Applications of scResolve on human breast cancer data and human lung disease data demonstrate that scResolve enables cell type-specific differential gene expression analysis between different tissue contexts and accurate identification of rare cell populations. The spatially resolved cellular-level expression profiles obtained through scResolve facilitate more flexible and precise spatial analysis that complements raw multi-cellular level analysis.
Complete persistence of the primary somatosensory system in zebrafish
Authors: Acedo Joaquín Navajas 
Published: December 2023

AbstractThe somatosensory system detects peripheral stimuli that are translated into behaviors necessary for survival. Fishes and amphibians possess two somatosensory systems in the trunk: the primary somatosensory system, formed by the Rohon-Beard neurons, and the secondary somatosensory system, formed by the neural crest cell-derived neurons of the Dorsal Root Ganglia. Rohon-Beard neurons have been characterized as a transient population that mostly disappears during the first days of life and is functionally replaced by the Dorsal Root Ganglia. Here, I comprehensively follow Rohon-Beard neuronsin vivoand show that the entire repertoire remains present in zebrafish from 1-day post-fertilization until the juvenile stage, 15-days post-fertilization. These data indicate that zebrafish retain two complete somatosensory systems until at least up to a developmental stage when the animals display complex behavioral repertoires.
The effect of perceived corporate social responsibility on purchase intention in mobile commerce: mediating roles of trusting beliefs and satisfaction
Authors: Urinbaeva Gulrukhsor , Khasanova Dilfuzakhon , Clugston Christopher John 
Published: December 2023

PurposeCorporate social responsibility (CSR) activities of companies have been reported to generate favorable consumer attitudes towards the business, which in turn, encourages positive consumer behavior. But the application of this conclusion in the mobile commerce domain remains limited. Drawing on social exchange theory, the authors examined the mediating role of trusting beliefs and satisfaction in the relationship between CSR and purchase intention in mobile commerce.Design/methodology/approachUsing nonprobability convenience sampling, the authors administered a cross-sectional survey with 314 students from Keimyung University in Korea. Initially, SPSS-Amos was utilized to run confirmatory factor analysis. The proposed hypotheses were tested using structural equation modeling.FindingsThis study showed that two components of trusting beliefs, namely benevolence and competence, had a positive effect on the association between CSR and the purchase intention on mobile shopping applications. This relationship was partially mediated by trusting beliefs. Further findings demonstrated that the impact of CSR on purchase intention was also partially mediated by satisfaction.Originality/valueThe authors' contribution includes extending the social exchange theory to the mobile commerce setting by establishing mechanisms that explain the ways CSR influences purchase intention in the mobile commerce framework. The authors integrated trusting beliefs and satisfaction in the CRS chain link with purchase intention. Additionally, the authors examined the individual effects of three trusting beliefs components. Based on the results, the authors proposed suggestions for the mobile shopping application business on the methods they can implement to boost the outcomes of their CSR activities.
Evaluation of predicted fault tolerance based on C5.0 decision tree algorithm in irrigation system of paddy fields
Authors: Rahi Majid , Ebrahimnejad Ali , Motameni Homayun 
Published: December 2023

PurposeTaking into consideration the current human need for agricultural produce such as rice that requires water for growth, the optimal consumption of this valuable liquid is important. Unfortunately, the traditional use of water by humans for agricultural purposes contradicts the concept of optimal consumption. Therefore, designing and implementing a mechanized irrigation system is of the highest importance. This system includes hardware equipment such as liquid altimeter sensors, valves and pumps which have a failure phenomenon as an integral part, causing faults in the system. Naturally, these faults occur at probable time intervals, and the probability function with exponential distribution is used to simulate this interval. Thus, before the implementation of such high-cost systems, its evaluation is essential during the design phase.Design/methodology/approachThe proposed approach included two main steps: offline and online. The offline phase included the simulation of the studied system (i.e. the irrigation system of paddy fields) and the acquisition of a data set for training machine learning algorithms such as decision trees to detect, locate (classification) and evaluate faults. In the online phase, C5.0 decision trees trained in the offline phase were used on a stream of data generated by the system.FindingsThe proposed approach is a comprehensive online component-oriented method, which is a combination of supervised machine learning methods to investigate system faults. Each of these methods is considered a component determined by the dimensions and complexity of the case study (to discover, classify and evaluate fault tolerance). These components are placed together in the form of a process framework so that the appropriate method for each component is obtained based on comparison with other machine learning methods. As a result, depending on the conditions under study, the most efficient method is selected in the components. Before the system implementation phase, its reliability is checked by evaluating the predicted faults (in the system design phase). Therefore, this approach avoids the construction of a high-risk system. Compared to existing methods, the proposed approach is more comprehensive and has greater flexibility.Research limitations/implicationsBy expanding the dimensions of the problem, the model verification space grows exponentially using automata.Originality/valueUnlike the existing methods that only examine one or two aspects of fault analysis such as fault detection, classification and fault-tolerance evaluation, this paper proposes a comprehensive process-oriented approach that investigates all three aspects of fault analysis concurrently.
How effective are digital/e-health interventions for supporting prisoners with mental ill-health? An integrative review
Authors: Bright Ann-Marie , Higgins Agnes , Grealish Annmarie 
Published: December 2023

Purpose
There has been a move towards the implementation of digital/e-health interventions for some time. Digital/e-health interventions have demonstrable efficacy in increasing individual empowerment, providing timely access to psychological interventions for those experiencing mental ill-health and improving outcomes for those using them. This study aims to determine the efficacy of digital/e-health interventions for individuals detained in prison who experience mental ill-health.

Design/methodology/approach
A systematic search of five academic databases – CINAHL, ASSIA, PsycINFO, Embase and Medline – was completed in December 2020 and updated in February 2022. The review was guided by the Whittemore and Knafl (2005) framework for integrative reviews. A total of 6,255 studies were returned and screened by title and abstract. A full-text screening of nine (n = 9) studies was conducted.

Findings
No study met the inclusion criteria for the clinical efficacy of digital/e-health interventions in a prison setting. Subsequently, a review of the literature that made it to the full-text review stage was conducted, and gaps in the literature were identified to inform policy, practice and future research.

Originality/value
To the best of the authors’ knowledge, this is the first integrative review conducted on the efficacy of digital/e-health interventions for mental ill-health in prison settings.
Drivers and outcomes of online customer engagement – evidence from Balkan countries
Authors: Jashari-Mani Fitore , Zeqiri Jusuf 
Published: December 2023

Purpose
Due to the worldwide internet usage and online presence of businesses, digital marketing is an integrated part of the overall marketing strategy. One of the main investments in this field is the investment on more creative content that engages more potential customers. Online brand communities (OBCs) are used by businesses as a tool to have higher rates of engagement. Many researchers have developed customer engagement (CE) models to better understand it, but the transition economies like the countries of the Balkan are somehow left aside. Due to this identified gap in the literature, this paper aims to provide a model explaining the drivers and outcomes of CE, specifically on OBCs.

Design/methodology/approach
The research is based on primary data collected with an online questionnaire. Sample consisted of 764 respondents from four Balkan countries (Kosovo, North Macedonia, Albania and Montenegro). Data were analyzed using SPSS Statistics and IBM AMOS 26. To test the research model and hypotheses, confirmatory factor analysis and structural equation modeling were used.

Findings
First, the study found a positive impact of entertainment and customer satisfaction, and celebrities’ endorsement in CE. Furthermore, the results revealed a positive impact of CE on customer purchase intention and customer loyalty.

Practical implications
The research findings aim to help businesses of Balkan countries to better understand the importance and operation of CE in OBC.

Originality/value
This paper enriches the existing digital marketing literature of transition economies with a model of online CE.