bluuebunny/crossref_metadata_2025 huggingface dataset:
Human plasma metabolic environment favours HIV replication in primary CD4 T lymphocytes
Authors: Chauveau Lise , Fortuin Annemarie , Lecante Arnaud , Lager-Lachaud Nina , Boulay Aude , Blanchet Fabien P , Bellvert Floriant , Briant Laurence , Battini Jean-Luc
Published: December 2024

Cellular metabolism provides all molecules essential for the cell’s functions including nucleic acids, amino acids and fatty acids, but also energy via glycolysis and mitochondrial respiration (also known as OXPHOS). Viruses hijack these pathways to support the different steps of their replication, making the metabolic state of the infected cell a key factor influencing viral replication. In particular, Human Immunodeficiency virus (HIV) remains latent in resting, metabolically inactive CD4 T lymphocytes but actively replicates in activated CD4 T cells. In these cells, enhanced glycolysis and OXPHOS, and access to the major carbon sources such as glucose and glutamine are required for infection. Here, we took advantage of the recently developed Human Plasma-Like Medium (HPLM), that mimics physiological plasma concentration of metabolites, including carbon sources, to investigate how this physiologic environment would modulate HIV-1 infection of primary CD4 T cells. Using CD4 T cells activated in the conventional culture medium (RPMI) or HPLM, we show that HPLM enhanced HIV-1 infection despite similar levels of cell activation, proliferation and expression of viral receptor. Specifically, HPLM increases the reverse transcription step of the HIV-1 replication cycle. In contrast with previous studies performed in RPMI only, this increased infection in HPLM correlated with decreased glycolysis and mitochondrial metabolism, reflecting the low concentration of glucose and glutamine in this medium. Adjusting glucose and glutamine concentrations in RPMI or decreasing energy metabolism using chemical inhibitors did not increase infection to levels similar to HPLM suggesting that other metabolic pathways are involved. Taken together, this study shows that the metabolic state of activated CD4 T cells in a physiologically relevant environment is more permissive to HIV-1 infection than previously suggested by studies using conventional cell culture media. Our study demonstrates the importance of physiologic culture conditions to study viral infections while also highlighting the importance of non-energetic cell metabolism in HIV-1 infection.
A generalized theoretical framework to investigate multicomponent actin dynamics
Authors: Nandi Mintu , Shekhar Shashank , Choubey Sandeep
Published: December 2024

The length of actin filaments is regulated by the combined action of hundreds of actin-binding proteins. While the roles of individual proteins are well understood, how they combine to regulate actin dynamics in vivo remains unclear. Recent advances in microscopy have enabled precise, high-throughput measurements of filament lengths over time. However, the absence of a unified theoretical framework has hindered a mechanistic understanding of the multicomponent regulation of actin dynamics. To address this, we propose a general kinetic model that captures the combined effects of multiple regulatory proteins on actin dynamics. We provide closed-form expressions for both time-dependent and steady-state moments of the filament length distribution. Our framework not only differentiates between various regulatory mechanisms but also serves as a powerful tool for interpreting current data and driving future experiments.
CRISPR-based environmental biosurveillance assisted via artificial intelligence design of guide-RNAs
Authors: DuránVinet Benjamín , Stanton Jo-Ann L. , Jeunen Gert-Jan , von Ammon Ulla , Treece Jackson , Pochon Xavier , Zaiko Anastasija , Gemmell Neil J.
Published: December 2024

Environmental biosecurity challenges are worsening for aquatic ecosystems as climate change and increased anthropogenic pressures facilitate the spread of invasive species, thereby broadly impacting ecosystem composition, functioning, and services. Environmental DNA (eDNA) has transformed traditional biomonitoring through detection of trace DNA fragments left by organisms in their surroundings, primarily by application of the quantitative polymerase chain reaction (qPCR). However, qPCR presents challenges, including limited portability, reliance on precise thermal cycling, and susceptibility to inhibitors. To address these challenges and enable field-deployable monitoring, isothermal amplification techniques such as Recombinase Polymerase Amplification (RPA) paired with Clustered Regularly Interspaced Short Palindromic Repeats and associated proteins (CRISPR-Cas) have been proposed as alternatives. We report here the development of CORSAIR (CRISPR-based envirOnmental biosuRveillance aSsisted viaArtificialIntelligence guide-RNAs), that harnesses the programmability of the CRISPR-Cas technology, RPA and the artificial intelligence (AI)-based tool Activity-informed Design with All-inclusive Patrolling of Targets (ADAPT) to deploy a swift RPA-CRISPR-Cas13a-based method that detects eDNA from two invasive species as proof of concept:Sabella spallanzaniiandUndaria pinnatifida. CORSAIR showcased a robust, streamlined method augmented by ADAPT, reaching a high specificity when tested against co-occurring species and a 100% agreement with 12 PCR-benchmarked eDNA samples, reaching a sensitivity of 0.34 copies uL-1in 1 hour with a cost of 3.5 USD per sample; thus highlighting CORSAIR as a powerful environmental biosurveillance platform for environmental nucleic acid detection.Graphical abstract
Single-cell transcriptomics of X-ray irradiatedDrosophilawing discs reveals heterogeneity related to cell-cycle status and cell location
Authors: Cruz Joyner , Sun Willam Y. , Verbeke Alexandra , Hariharan Iswar K.
Published: December 2024

Even seemingly homogeneous populations of cells can express phenotypic diversity in response to environmental changes. Thus, X-ray irradiation of tissues composed of diverse cell types can have complex outcomes. We have used single-cell RNA-sequencing to study the effects of X-ray radiation on theDrosophilawing imaginal disc, a relatively simple tissue composed mostly of epithelial cells. Transcriptomic clustering of cells collected from the wing disc generates clusters that are mainly grouped based on proximodistal cell location. To quantify heterogeneity of gene expression among clusters, we adapted a metric used to study market concentration, the Herfindahl-Hirschman Index. Genes involved in DNA damage repair, defense against reactive oxygen species, cell cycle progression, and apoptosis are expressed relatively uniformly. In contrast, genes encoding a subset of ligands, notably cytokines that activate the JAK/STAT pathway, some transcription factors includingEts21C, previously implicated in regeneration, and several signaling proteins are expressed more regionally. Though the radiation-responsive transcription factor p53 is expressed relatively uniformly in the wing disc, several regionally-induced genes still require p53 function, indicating that regional and radiation-induced factors combine to regulate their expression. We also examined heterogeneity within regions using a clustering approach based on cell cycle gene expression. A subpopulation of cells, characterized by high levels oftribblesexpression, is amplified in irradiated discs. Remarkably, this subpopulation accounts for a considerable fraction of radiation-induced gene expression, indicating that cellular responses are non-uniform even within regions. Thus, both inter-regional and intra-regional heterogeneity are important features of tissue responses to X-ray radiation.
Regional disparity in surgical residency training and work environment between urban and regional hospitals: an additional perspective from a nationwide survey for surgical residents
Authors: Watanabe Genki , Watanabe Jun , Hayashi Saki , Konishi Takaaki , Poudel Saseem , Kiyasu Yoshiyuki , Fukumoto Masayuki , Korai Takahiro , Nomura Shinsuke , Yamamoto Naohiro , Nakajima Masao , Hosoya Keiko , Saito Mitsue
Published: December 2024

Structured Abstract

Purpose

To investigate the current status of regional disparity of surgical residency training between urban and regional hospitals.

Methods

Based on a nationwide online questionnaire survey for newly certified surgical trainees, the responding residents were divided into two groups according to the size of the city where they had trained: an urban city (>1 million, UC group) versus a regional city (<1 million, RC group). These groups were compared regarding surgical education and work environment.

Results

The UC group (n = 317, 42%) included surgeons with more post-graduate years, older age, females, and full-time working partners compared to the RC group (n = 439, 58%). More residents in the UC group were from urban areas, while the RC group had more residents from regional areas. No differences were observed in the number of experienced surgeries, published papers, opportunities for off-the-job training, or satisfaction with the surgical residency training program. Except for a higher income in the RC group, no differences were observed for other factors regarding the work environment.

Conclusions

There was little regional disparity regarding the impressions of surgical residency training between urban and regional cities including surgical education and work environment.
Beyond Accuracy: A Cost-Aware Approach to Skin Lesion Detection Across Skin Tone Imbalances
Authors: Hasan Md Mohit , Suchi Mahbuba Tasnime , Habib Md Hasibul , Akter Sumya , Rothy Zarin Tasnim , Islam A.M.Tayeful , Pias Tanmoy Sarkar , Eisenberg David , Bin Akter Simon
Published: December 2024

Skin lesion prediction using artificial intelligence (AI) models is highly dependent on skin tone, yet current approaches largely overlook this critical factor. The Fitzpatrick 17k dataset, which contains six skin tone categories: lighter to darker, is severely imbalanced, with most models biased toward lighter skin tones. Previous efforts to improve overall accuracy fall short: overall accuracy fails to reflect true performance across imbalances. This creates a significant gap, as effective skin lesion detection must work across all skin tones, not just a few. To address this, we introduce the Cost-Aware EfficientNet (CAEN) model, combining cost-sensitive learning (CSL) and attention mechanisms to tackle imbalanced data and ensure the model generalizes well across all skin tones with detailed interpretability. Rather than simply improving accuracy, our model enhances class-specific performance, achieving 79% recall for non-neoplastic, 88% for benign, and 80% for malignant lesions. This indicates an overall improvement in darker tones of approximately 44.86% compared to state-of-the-art results from prior studies. Furthermore, it remains robust across augmented test conditions, such as changes in brightness, contrast, blur, and zoom, providing balanced outcomes for diverse skin tones. This novel approach offers a significant leap toward fair and reliable skin lesion prediction for all skin tones with interpretability.
Renal arterial dysfunction, impaired pressure natriuresis and salt-sensitivity in a mouse model of Cushing syndrome
Authors: Costello Hannah M , Grenier Céline , Ivy Jessica R , Jones Natalie K. , Stewart Kevin , Holmes Megan C , Livingstone Dawn E.W. , Dhaun Neeraj , Bailey Matthew A
Published: December 2024

Background

Cushing Syndrome arises from endogenous overproduction of ACTH by a tumour or is acquired through chronic exposure to glucocorticoid medication. Hypertension is a major complication, increasing cardiovascular risk, but underlying mechanisms are not clearly defined.

Methods

We infused male C57BL/6J mice with ACTH or vehicle for 14-21 days, inducing cardinal features of Cushing Syndrome. The renal pressure natriuresis response was measured under anesthesia and ex vivo artery function assessed by myography.

Results

ACTH infusion blunted the natriuretic and diuretic responses to incremental increases in blood pressure. Renal hemodynamics did not change with blood pressure in controls, but renal autoregulation was impaired in ACTH mice. Theex vivocontractile response of the renal artery to phenylephrine was diminished in Cushing Syndrome mice, as was endothelium-dependent and endothelium-independent relaxation. On 0.3% sodium diet, there was no evidence of sodium retention in ACTH-treated mice but the diurnal rhythm of sodium excretion was abnormal and mice had non-dipping BP. The Cushing Syndrome model also displayed enhanced salt preference and amplified salt-sensitive blood pressure.

Conclusion

Cushing Syndrome induces a cluster of phenotypes impacting sodium homeostasis and blood pressure regulation. Hypertension, salt-sensitivity and non-dipping blood pressure are important cardiovascular risk factors, and, beyond Cushing Syndrome, our findings are relevant to obesity and the metabolic syndrome, in which tissue glucocorticoid homeostasis is abnormal.
New insights into the cultivability of human milk microbiota from ingestion to digestion and implications for its immunomodulatory properties
Authors: Bras Charles Le , Mouchard Alizé , Rault Lucie , Cochet Marie-Françoise , Ménard Olivia , Jacquet Nolwenn , Chuat Victoria , Valence Florence , Loir Yves Le , Bellanger Amandine , Deglaire Amélie , Huërou-Luron Isabelle Le , Even Sergine
Published: December 2024

Human milk (HM) microbiota is increasingly studied for its potential health benefits. However, the physiological state of HM bacteria and consequently their effects on gut homeostasis remain a question. This study investigated the physiological state of the HM microbiota by characterizing its cultivable fraction, as it might be at the point of ingestion and assessing the effects of digestion on the cultivability and immunomodulatory properties of six prevalent HM strains. The microbiota of 28 HM samples was analysed by 16S metabarcoding either directly on raw milk (raw milk microbiota, RM) or on the complete cultivable fraction obtained from seven non-selective media (cultivable milk microbiota, CM). Diversity was lower in CM than in RM, with 32 versus 435 genera and a median of 7 versus 69 genera per sample in CM and RM, respectively. CM also showed under-representation of strictly anaerobic genera. Factors like parity and iron or vitamin supplementation affected RM and/or CM.In vitrogastrointestinal digestion moderately impacted strain cultivability. However, most strains partially or completely lost their immunomodulatory properties on the monocyte THP1 cell line after digestion, excepta Staphylococcus epidermidisstrain that gained immunomodulatory potential.
Msp1 and Pex19-Pex3 cooperate to achieve correct localization of Pex15 to peroxisomes
Authors: Matsumoto Shunsuke , Kogure Yoshiki , Ono Suzuka , Numata Tomoyuki , Endo Toshiya
Published: December 2024

Yeast Msp1 is a dual-localized AAA-ATPase on the mitochondrial outer membrane (OM) and peroxisomal membrane. We previously showed that Msp1 transfers mistargeted tail-anchored (TA) proteins from mitochondria to the endoplasmic reticulum (ER) for degradation or delivery to their original destinations. However, the mechanism by which Msp1 in mitochondria and peroxisomes handles authentic peroxisomal TA proteins remains unclear. We show that newly synthesized Pex15 is targeted to peroxisomes primarilyviathe Pex19- and Pex3-dependent pathway. Mistargeted Pex15 on the mitochondrial OM is extracted by mitochondrial Msp1, and transferred to the ERviathe guided-entry of TA proteins pathway for degradation or to peroxisomesviathe Pex19-Pex3 pathway. Intriguingly, endogenous Pex15 localized in peroxisomes is also extracted from the membranes by peroxisomal Msp1, but returns to peroxisomesviathe Pex19-Pex3 pathway. These results suggest that correct Pex15 localization to peroxisomes relies on not only the initial targeting by Pex19-Pex3 but also the constant re-routing by Msp1 and Pex19-Pex3.
Serotonin system development and adult function are regulated by GDNF
Authors: Garton Daniel R. , Runneberger Isabel , Casserly Laoise , Schorling Tabea , Montaño-Rodríguez Ana R. , Iivananen Vilma , Kopra Jaakko J. , Mätlik Kärt , Fagerström-Billai Fredrik , Damdimopoulos Anastasios , Petteri Piepponen T. , Andressoo Jaan-Olle
Published: December 2024

Cognitive functions, neuropsychiatric disorders and behaviors from feeding to mood relate to the serotonin (5-hydroxytryptamine; 5-HT) system. We report that expression of glial cell line-derived neurotrophic factor (GDNF), a known potent stimulator of the brain dopamine system, correlates with serotonergic markers in humans, and increased GDNF defines a subset of psychiatric patients with a characteristic 5-HT-related gene expression pattern. A similar ∼1.5- to 2-fold upregulation of endogenous GDNF expression in mice increases brain 5-HT levels and function, both developmentally and during adulthood, and modulates response to fluoxetine. Notably, increasing GDNF more than approximately 2-fold does not increase 5-HT further and instead produces an inverted U-shaped curve of 5-HT levels, suggesting why the GDNF/5-HT correlation has remained controversial. Collectively, our data indicate that GDNF levels fine-tune 5-HT system development and adult function while excess GDNF exclusively associates with neuropsychiatric illness, making it an important target for future research.
Lipid specificity of action of SARS-CoV-2 fusion peptide fragments on model membranes
Authors: Shekunov Egor V. , Volynsky Pavel E. , Efimova Svetlana S. , Aliper Elena T. , Efremov Roman G. , Ostroumova Olga S.
Published: December 2024

The study focuses on investigating the interaction of SARS-CoV-2 fusion peptide fragment with model membranes of various lipid composition to elucidate the molecular mechanisms of peptide-derived membrane fusion. The work utilized the short fragment of SARS-CoV-2 fusion peptide which is homologous to 816-827 region of the native SARS-CoV-2 FP (FP816-827) and contains the highly conserved LLF motif responsible for membrane fusion, and its ineffective analogue (mFP816-827), where LLF motif was replaced for AAA. Using fluorescence fusion assay, it was demonstrated that the LLF motif plays a key role in inducing liposome fusion, whereas its replacement completely abolishes this capability. The fusogenic activity of the peptide strictly depended on the vesicle lipid composition. It was potentiated by phosphatidylethanolamine and inhibited by phosphatidylserine. Molecular dynamics revealed that both peptides predominantly adopt an α-helical conformation; however, the native peptide interacts more strongly with the hydrophobic core of the membrane by increasing peptide-lipid hydrophobic contacts, while the mutant version exhibits a more superficial localization. Differential scanning microcalorimetry data indicated that the ability of FP816-827to disturb lipid packing increased with decreasing membrane lipid tail length. The molecular mechanisms underlying the fusogenic activity of the SARS-CoV-2 fusion peptide were identified, specifically its ability to cluster phospholipid head groups in its own vicinity. As a result, local regions with positive spontaneous curvature are formed in the outer monolayer, facilitating membrane fusion. The findings highlight the role of membrane composition and lipid architecture in the mechanism of viral fusion with host cells.
Lifespan Normative Models of White Matter Fractional Anisotropy: Applications to Early Psychosis
Authors: Cirstian Ramona , Forde Natalie J. , Zhang Gary , Hellemann Gerhard S. , Beckmann Christian F. , Kraguljac Nina V. , Marquand Andre F.
Published: December 2024

This study presents large-scale normative models of white matter (WM) organization across the lifespan, using diffusion MRI data from over 25,000 healthy individuals aged 0-100 years. These models capture lifespan trajectories and inter-individual variation in fractional anisotropy (FA), a marker of white matter integrity. By addressing non-Gaussian data distributions, race, and site effects, the models offer reference baselines across diverse ages, ethnicities, and scanning conditions. We applied these FA models to the HCP Early Psychosis cohort and performed a multivariate analysis to map symptoms onto deviations from multimodal normative models using multi-view sparse canonical correlation analysis (msCCA). Our results reveal extensive white matter heterogeneity in psychosis, which is not captured by group-level analyses, with key regions identified, including the right uncinate fasciculus and thalami. These normative models offer valuable tools for individualized WM deviation identification, improving precision in psychiatric assessments. All models are publicly available for community use.

Teaser

Lifespan models of white matter offer insights into brain health, providing tools for tracking individual deviations across ages.
RegVelo: gene-regulatory-informed dynamics of single cells
Authors: Wang Weixu , Hu Zhiyuan , Weiler Philipp , Mayes Sarah , Lange Marius , Wang Jingye , Xue Zhengyuan , Sauka-Spengler Tatjana , Theis Fabian J.
Published: December 2024

RNA velocity has emerged as a popular approach for modeling cellular change along the phenotypic landscape but routinely omits regulatory interactions between genes. Conversely, methods that infer gene regulatory networks (GRNs) do not consider the dynamically changing nature of biological systems. To integrate these two currently disconnected fields, we present RegVelo, an end-to-end dynamic, interpretable, and actionable deep learning model that learns a joint model of splicing kinetics and gene regulatory relationships and allows us to perform in silico perturbation predictions. When applied to datasets of the cell cycle, human hematopoiesis, and murine pancreatic endocrinogenesis, RegVelo demonstrates superior predictive power for interactions and perturbation simulations, for example, compared to methods that focus solely on dynamics or GRN inference. To leverage RegVelo’s full potential, we studied the dynamics of zebrafish neural crest development and underlying regulatory mechanisms using our Smart-seq3 dataset and shared gene expression and chromatin accessibility measurements. Using RegVelo’s in silico perturbation predictions, validated by CRISPR/Cas9-mediated knockout and single-cell Perturb-seq, we establish transcription factortfecas an early driver andelf1as a novel regulator of pigment cell fate and propose a gene-regulatory circuit involvingtfecandelf1interactions via the toggle-switch model.
Food-Derived Compounds Extend the Shelf-Life of Frozen Human Milk
Authors: Silpe Justin E. , Damian-Medina Karla , Bassler Bonnie L.
Published: December 2024

Breastmilk is known to provide optimal nutrition for infant growth and development. A cross-sectional analysis of nationally representative US data from 2016 to 2021 revealed that >90% of lactating mothers reported using breast pumps to express milk.1We conducted a survey ofn= 1,049 lactating or recently lactating individuals from a US nationally representative population to explore breastmilk storage practices among this group. The data revealed that 83% of respondents store breastmilk in their homes, with 68% using freezers to do so for >1 month. The lowest available temperature in most household freezers is -20 °C, a temperature that is inadequate to maintain human milk’s emulsified structure, leading to separation, degradation of fats, loss of key vitamins, and changes in palatability. We developed a first-of-its-kind high-throughput screening platform to identify food-derived compounds and combinations of compounds that, when added to human breastmilk, preserve fat content, retain antioxidant capacity, and reduce production of rancid-associated free fatty acids during extended freezer storage. These formulations represent leads for the development of safe and affordable frozen breastmilk shelf-life extenders for easy at-home use to increase the longevity of stored breastmilk.
Sorbate Induces Lysine Sorbylation Through Non-Canonical Activities of Class I HDACs to Regulate the Expression of Inflammation Genes
Authors: Sin Yi-Cheng , Abernathy Breann , Mashek Douglas G. , Chen Yue
Published: December 2024

Metabolic and environmental factors may impact gene expression through the production of active metabolites and epigenetic modifications of histones and transcription factors. In this study, we discovered that cellular uptake of sorbate, an FDA-approved and widely used food preservative, can induce lysine sorbylation (Ksor), a new posttranslational modification and epigenetic mark. We identified over 40 Ksor sites on core histones from mammalian cells and tissue upon sorbate uptake and further showed that the dynamics of histone Ksor could be regulated by the non-canonical activities of Class I histone deacetylases (HDAC1-3). We demonstrated that Class I HDACs catalyzed sorbylation upon sorbate uptake and desorbylation in the absence of sorbate both in vitro and in vivo. Sorbate uptake in mice livers led to a significant increase in histone Ksor without affecting overall histone acetylation, which correlated with the decreased expression of genes in inflammation signaling pathways. Accordingly, sorbate treatment in macrophage RAW264.7 cells upon LPS stimulation dose-dependently downregulated the expression of proinflammatory genes and production of nitric oxide. Global proteomic profiling revealed widespread lysine sorbylation substrates in diverse metabolic and signaling pathways and identified RelA (p65), a component of the NF-ĸB complex, and its interacting proteins as bona fide Ksor targets. Sorbate treatment significantly decreased NF-ĸB transcriptional activities in response to LPS stimulation in RAW264.7 cells. Taken together, our study demonstrated a non-canonical mechanism of sorbate uptake in regulating epigenetic histone modifications and inflammatory gene expression.
Effects of transmembrane phenylalanine residues on γ-secretase-mediated Notch-1 proteolysis
Authors: Malvankar Shweta R. , Wolfe Michael S.
Published: December 2024

γ-Secretase is a presenilin-containing intramembrane aspartyl protease complex that cleaves within the transmembrane domain (TMD) of nearly 150 substrates, with the amyloid precursor protein (APP) being the most well studied. APP cleavage by γ-secretase generates amyloid β-peptides (Aβ) that pathologically deposit in Alzheimer’s disease. APP TMD substrate undergoes initial endoproteolysis (ε-cleavage) followed by processive carboxypeptidase trimming of long Aβ intermediates in ∼tripeptide intervals. Although γ-secretase cleavage of Notch1 is essential in developmental biology and altered in many cancers, the processing of this cell-surface receptor is relatively understudied. Only one sequence specificity rule is known for γ-secretase substrate processing: Aromatic residues such as phenylalanine are not tolerated in the P2’ position with respect to any processing event on the APP TMD. Here we show using biochemical and mass spectrometry (MS) techniques that this specificity rule holds for Notch1 as well. Analysis of products from the reactions of purified enzyme complex and Notch1 TMD substrate variants revealed that P2’ Phe relative to ε-site cleavage reduced proteolysis and shifted initial cleavage N-terminally by one residue. Double Phe mutation near the ε site resulted in reduced proteolysis with shifting to two major initial cleavage sites, one N-terminally and one C-terminally, both of which avoid Phe in the P2’ position. Additionally, three natural Phe residues were mutated to corresponding residues in the APP TMD, which led to increased ε proteolysis. Thus, Phe residues can affect the enzyme reaction rate as well as cleavage site specificity in the Notch1 TMD.
ThePseudomonas aeruginosaPrrF sRNAs promote biofilm formation at body temperature
Authors: Chourashi Rhishita , Weiner Jacob , Hoang Tra-My , Ouattara Khady , Oglesby Amanda G.
Published: December 2024

Pseudomonas aeruginosais a Gram-negative opportunistic pathogen that causes both acute and chronic infections in vulnerable populations. Treatment ofP. aeruginosainfections is increasingly challenging due to multi-drug resistance as well as biofilm formation that further increases antibiotic tolerance. Iron, which is sequestered by the host innate immune system, is also a key nutrient that required forP. aeruginosabiofilm formation. Previous work showed that the iron-responsive PrrF small regulatory RNAs (sRNAs), which are key toP. aeruginosa’siron starvation response and required for virulence in murine lung infection, are dispensable for biofilm formation. However, these studies were performed using flow-cell biofilms at room temperature. Here we demonstrate a temperature dependency for PrrF inP. aeruginosabiofilm formation – the genes for these sRNAs are required for optimal biofilm formation at 37°C but not 25°C. We further show that the ΔprrFmutant lacks a yet-to-be identified surface appendage that is produced at 37°C but not 25°C. These studies demonstrate that the importance of the PrrF sRNAs inP. aeruginosabiofilm formation at body temperature and reveal a previously under-appreciated role of temperature in iron homeostasis andP. aeruginosabiofilm physiology.

IMPORTANCE

Biofilm formation is a critical aspect of pathogenesis for many microbial pathogens as it confers increased tolerance to the host immune system and antimicrobial treatments.Pseudomonas aeruginosais an opportunistic pathogen that forms biofilms during infection, resulting in antimicrobial tolerance and treatment failure. Iron is a known requirement forP. aeruginosabiofilm formation, yet the precise role of iron homeostasis in biofilm physiology remains unclear. Here we show that temperature alters the requirement for the PrrF small regulatory RNAs, key components ofP. aeruginosa’siron starvation response, for biofilm formation. Specifically, PrrF is required for the optimal formation of biofilms in flow cells at 37°C but not 25°C, yet most flow-cell biofilm studies are conducted at 25°C. These results demonstrate a previously under-appreciated role of temperature inP. aeruginosabiofilm physiology.
Staphylococcus aureusCOL: An Atypical Model Strain of MRSA that Exhibits Slow Growth and Antibiotic Tolerance
Authors: Stevens Claire E. , Deventer Ashley T. , Johnston Paul R. , Lowe Phillip T. , Boraston Alisdair B. , Hobbs Joanne K.
Published: December 2024

Methicillin-resistantStaphylococcus aureus(MRSA) has been a pathogen of global concern since its emergence in the 1960s. As one of the first MRSA strains isolated, COL has become a common model strain ofS. aureus. Here we report that COL is, in fact, an atypical strain of MRSA that exhibits slow growth (extended lag and doubling times) and multidrug tolerance, with minimum duration of killing (MDK) values 50-300% greater than other “model” strains ofS. aureus.Genomic analysis identified three mutated genes in COL (rpoB, gltXandprs) with links to tolerance. Allele swapping experiments between COL and the closely related, non-tolerant Newman strain uncovered a complex interplay between these genes. However, Prs (phosphoribosyl pyrophosphate [PRPP] synthetase) accounted for most of the growth and tolerance phenotype of COL. ppGpp quantitation and transcriptomic comparison of COL and Newman revealed that COL does not exhibit slow growth as a result of partial stringent response activation, as previously proposed. Instead, COL exhibits downregulation of purine, histidine and tryptophan synthesis, three pathways that rely on PRPP. Overall, our findings indicate that COL is an atypical, antibiotic-tolerant strain of MRSA whose isolation predates the previous first report of tolerance among clinical isolates.
Maintaining the methionine residues of the chaperone Spy in a reduced state is crucial for periplasmic proteostasis
Authors: Loiseau Laurent , Visch Nathan De , Vergnes Alexandra , Armengaud Jean , Vincent Maxence S. , Ezraty Benjamin
Published: December 2024

The bacterial cell envelope is exposed to various stresses, including oxidative stress caused by different types of oxidants, such as reactive oxygen species (ROS) and reactive chlorine species (RCS). InE. coli, the reduction of chlorate into chlorite, a toxic RCS compound, induces the expression of the MsrPQ system, which repairs periplasmic proteins oxidized at methionine residues (methionine sulfoxide, Met-O). In this study, using a proteomic-based approach, we show that chlorite stress also triggers the overproduction of the periplasmic chaperone Spy. This response is mediated by the activation of the BaeSR two-component system. Furthermore, bothin vivoandin vitroevidence reveal that Spy’s susceptibility to oxidation is critical for its chaperone activity. We demonstrate that the MsrPQ repair system ensures Spy’s functionality by reducing its Met-O, thereby safeguarding its role in periplasmic protein homeostasis. Overall, this work reveals Spy as a key target of chlorite-induced oxidative damage and underscores the essential role of MsrPQ in preserving periplasmic protein quality control.
A Dual-Functional Needle-Based VOC Sensing Platform for Rapid Vegetable Quality Examination
Authors: Hossain Oindrila , Wang Yan , Li Mingzhuo , Jamalzadegan Sina , Mohammad Noor , Velayati Alireza , Poonam Aditi Dey , Wei Qingshan
Published: December 2024

Volatile organic compounds (VOCs) are common constituents of fruits, vegetables, and crops, and are closely associated with their quality attributes, such as firmness, sugar level, ripeness, translucency, and pungency levels. While VOCs are vital for assessing vegetable quality, traditional detection methods, such as Gas Chromatography-Mass Spectrometry (GC-MS) and Proton Transfer Reaction Mass Spectrometry (PTR-MS) are limited by expensive equipment, complex sample preparation, and slow turnaround time. Additionally, the transient nature of VOCs complicates their detection using these methods. Here, we developed a paper-based colorimetric sensor array combined with needles that could induce vegetable VOC release in a minimally invasive fashion and analyze VOCsin situwith a smartphone reader device. The colorimetric sensor array was optimized using sulfur compounds as main targets and classified fourteen different vegetable VOCs, including sulfoxides, sulfides, mercaptans, thiophenes, and aldehydes. By combining principal components analysis (PCA) analysis, the integrated sensor platform proficiently discriminated between four vegetable subtypes originating from two major categories within 2 min of testing time. This rapid and minimally invasive sensing technology holds great promise for conducting field-based vegetable quality monitoring.

Graphical abstract
Leveraging scientific modeling to engage pre-med undergraduates in physics lab courses
Authors: Harmer Madeline , Bennion Adam , Hopps-McDaniel Alexandra M. , Lawler Jeannette , Powers Nathan
Published: December 2024

Undergraduate students on track for medical school are often required to take general physics lab courses. Many of these students carry an attitude of obligation into these courses which can make it challenging for instructors to engage students in course material. We address the question: How does engaging with medically based models in introductory physics labs affect pre-med undergraduate perceptions of the modeling process and their perceptions of science? We redesigned an electricity and magnetism lab in an introductory physics lab course, where approximately 70% of the undergraduates reported plans to attend medical school. We situated the lab in the mechanics of MRI magnetic resonance and collected data on the participants’ experiences through surveys and lab submissions. As a part of the analysis, we modified a rubric to evaluate engagement in modeling and applied grounded coding theory to the survey responses to develop themes of the participants’ understanding of scientific modeling. The participants’ understanding and engagement in scientific modeling increased during the newly developed lab and remained high for subsequent labs. We recommend that instructors of undergraduate nonmajor labs consider the demographic of their student population and design lab experiences situated within their interests and focus on central science practices like modeling.

Published by the American Physical Society
2024
Binary solvent participation in crystals of a multi-aromatic 1,2,3-triazole
Authors: Filley Jonathan
Published: December 2024

The X-ray crystal structure of a multi-aromatic substituted 1,2,3-triazole is presented, which shows an extensive three-dimensional hydrogen-bonding network involving two water molecules and two acetonitrile molecules. The structure of 4-{[(4-{[1-({[(3,4-dimethoxyphenyl)methyl](3-acetamidophenyl)carbamoyl}methyl)-1H-1,2,3-triazol-4-yl]methoxy}-3-methoxyphenyl)methyl]amino}benzoic acid–acetonitrile–water (1/2/2), C37H38N6O8·2C2H3N·2H2O, features amine-linked aromatic groups that have a variety functionality including a carboxylic acid, an acetamido group, and methoxy ethers. All X—H groups, and seven out of ten heteroatoms with available lone-pair electrons, participate in hydrogen bonding, with the aid of dimer-bridging water molecules and acetonitrile molecules whose methyl groups form close contacts with oxygen atoms. The triazole itself is a dimer made using click chemistry from readily available and inexpensive starting materials and is a precursor to larger oligomers, as well as to compounds with a wide array of readily manipulated functionality.
Bank performance and general specialization vs agricultural loan specialization: an analysis of US banks
Authors: Kashian Russ , Drago Robert
Published: December 2024

Purpose

The effects of bank lending specialization are unclear. To explore this issue, we contrast the performance effects of general lending specialization and agricultural specialization. The latter is important given small or community banks account for a significant share of all agricultural lending, while the number of such banks continues to shrink.

Design/methodology/approach

This article develops a novel measure of general lending specialization for the percentage of loans that could be shifted across seven categories to mimic market allocations. Using US government data, we analyze small-, medium- and large-sized banks for four performance indicators in random effects regressions for 2011–2019, with four sets of subsidiary analyses.

Findings

Results suggest specialized lending reduces risk for small, community banks, and that large-sized banks face a risk-reward trade-off such that general specialization improves returns, but increases risk. Agricultural lending is associated with improved returns and lower risk for small-sized banks, particularly in rural locations, but with poorer performance for large-sized banks. Analyses of bank performance around the global financial crisis and COVID-19 pandemics suggest these were black swan events. Overall results suggest that both general lending specialization and agricultural specialization warrant separate analytical treatment and that small, community banks continue to play a crucial role in the US economy.

Originality/value

This is the first article to contrast general and agricultural lending, and across small-, medium- and large-sized banks, finding distinct effects. Future studies of other types of lending specialization are warranted.
Research on the coordinated development evaluation of manufacturing and logistics industry: a case study of Jiangsu province and Shandong province
Authors: Liu Rongkun , Zhao Furui
Published: December 2024

Purpose

The integrated and coordinated development of the manufacturing and logistics industries is crucial for promoting deep integration and innovative development between the two sectors. It aids in reducing costs and enhancing efficiency, which is significant for high-quality economic growth and the acceleration of modern industrial system construction.

Design/methodology/approach

This paper explores the integrated development status of the two industries in Shandong and Jiangsu provinces. Based on the relevant data of 44 indicators from the manufacturing and logistics industries in these provinces from 2010 to 2021, a comprehensive evaluation index system is constructed. The study employs coupling coordination degree and grey correlation models to comparatively analyze the integrated development status of the two industries in the provinces.

Findings

The findings indicate that the coupling coordination degree of Jiangsu and Shandong provinces has shown a gentle spiraling upward trend. By 2021, Jiangsu province had achieved intermediate coordination, and Shandong province had achieved good coordination. The grey correlation degree is within the moderate and strong correlation range, but the impact of efficiency indicators is weak.

Research limitations/implications

The research has limitations, including a focus on specific provinces, potential data constraints and a need for further exploration of the dynamic and influencing factors of the industries' coordinated development for more comprehensive conclusions.

Practical implications

The research provides practical significance by offering insights into the coordinated development of manufacturing and logistics industries, which can inform policymaking and strategic planning for regional economic integration and supply chain efficiency.

Social implications

The study’s findings offer actionable insights for policymakers, promoting regional economic synergy and supply chain optimization. It emphasizes the crucial role of industry integration in advancing high-quality economic growth, aligning with modern industrial system development goals.

Originality/value

This research’s innovation lies in its comprehensive evaluation index system and the application of coupling coordination degree and grey relational analysis models, offering a nuanced assessment of the integrated development between manufacturing and logistics industries in Jiangsu and Shandong provinces. It provides valuable insights for policymakers aiming to enhance regional economic integration and supply chain efficiency.
Exploring the interdependent drivers of tourism competitiveness: insights from the Travel and Tourism Development Index
Authors: Qazi Abroon
Published: December 2024

Purpose

The purpose of this study is to investigate the relative importance of the five dimensions and 17 associated pillars of the Travel and Tourism Development Index (TTDI) to understand their contributions to overall tourism competitiveness.

Design/methodology/approach

Using Bayesian Belief Networks (BBNs), this study analyzes data from 2024 for 119 countries to model the interactions between the dimensions and pillars of the TTDI. The BBN approach allows for a probabilistic understanding of how these elements influence tourism competitiveness.

Findings

The analysis reveals that “infrastructure and services” and “information and communication technology (ICT) readiness” play a critical role in enhancing tourism competitiveness. This study underscores the interconnectedness of various tourism factors, highlighting how strategic emphasis on these key areas can drive overall success in the sector.

Originality/value

This study contributes to the literature by empirically validating the factors that significantly impact tourism competitiveness. This study provides actionable insights for policymakers and industry leaders to enhance tourism development through a robust, data-driven framework that supports sustainable tourism management.
Is blockchain truly improving supply chain information quality? A positivist case study research
Authors: Alkhudary Rami
Published: December 2024

Purpose

This paper advances the understanding of how blockchain technology enhances the quality of information within the supply chain by employing the information-processing view as a theoretical lens.

Design/methodology/approach

Our research begins with a review of the existing literature and formulates a set of propositions. We then employ a positivist case study approach in various industries across Europe, the USA and Argentina, encompassing agriculture, fisheries, e-commerce and pharmaceuticals, to empirically investigate these propositions.

Findings

Our study confirms that blockchain enhances the dimensions of information quality by reinforcing traceability and transparency. Nevertheless, the degree of traceability and transparency depends on the supply chain’s internal processes, blockchain configurations and willingness to share information. Moreover, blockchain does not ensure perfect information security, lacking guaranteed immutability and decentralization in present supply chain applications. Furthermore, the integration of complementary technologies with blockchain to reconcile the divide between physical and digital realms remains largely untested, introducing uncertainty about its influence on information accuracy. Consequently, this study cautions against viewing blockchain as a wholesale replacement for inter-organizational trust.

Originality/value

Blockchain technology is widely regarded as having substantial potential to revolutionize supply chain information systems. However, only a limited number of studies have critically examined the value added by blockchain within an inter-organizational context.
Exploring uncharted territories: a classification of unconventional perspectives on homo Islamicus
Authors: Sholihin Muhammad , Annisa Arna Asna
Published: December 2024

Purpose

This study aims to analyze the definition and contextual variations of homo islamicus in literature across disciplines, including beyond Islamic economics, and to explore their implications for Islamic economic agents.

Design/methodology/approach

Using a machine learning-based text analysis approach, 61 articles will be examined to classify definitions and identify contextual clusters for homo islamicus.

Findings

This study reveals eight classifications of homo islamicus definitions and three distinct contexts. These findings suggest significant divergence between the concept of homo islamicus in Islamic economic tradition and its interpretation by non-Islamic scholars, attributable to underlying values and ideologies rather than methodological differences.

Research limitations/implications

This study focuses solely on textual analysis of articles using the term “homo islamicus” across disciplines, precluding the formulation of epistemological and ontological frameworks. Future research could expand on these aspects.

Practical implications

By presenting diverse perspectives on homo islamicus, this paper facilitates a more comprehensive understanding among scholars of Islamic economics, aiding in the resolution of disagreements within the field.

Originality/value

This study introduces novel classifications of homo islamicus definitions and contextualizes them, providing insights into their implications for Islamic economic agents.
For prime customers only: consumer decision-making towards targeted mobile coupons
Authors: Gong Siyu , Suo Danni , Dai Jiatong
Published: December 2024

Purpose

This study aims to investigate the effectiveness of exclusive promotions in the form of targeted m-coupons and to uncover the potential psychological mechanisms underpinning consumer redemption behaviour.

Design/methodology/approach

Three experimental studies were conducted to elucidate the mechanisms of psychological ownership as well as perceived intrusiveness and to examine the moderating effect of the timing of delivery in these relationships.

Findings

The findings suggest that consumers demonstrate a higher intention to redeem targeted m-coupons than for untargeted m-coupons. Psychological ownership and perceived intrusiveness act as dual mediators in this relationship. However, delivering m-coupons on special dates helps mitigate the discrepancies in consumer responses between targeted and untargeted m-coupons.

Originality/value

This research contributes to existing literature on targeted promotion by comparing the effectiveness of two types of m-coupons and elucidating the dual mechanisms of psychological ownership and perceived intrusiveness. Furthermore, this study identifies a boundary condition that modifies the positive effects of targeted m-coupons.