bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic Evaluation of Adiposity Indices as Predictors of Hypertension Risk in Children and Adolescents
Authors: Zhu Bowen , Zhan Shumin , Shi Hui , Wang Xingyun , Yue Jingwen , Gao Jianfang , Wang Tongshuai , Wang Rui , Guo Xirong , Fu Junfen
Published: November 2024

Objective

To systemically examine the concomitant impact of adiposity indices on hypertension in children and adolescents.

Methods

A community-based cohort study by China Health and Nutrition Survey (2009-2011) included 262 children and adolescents aged 7-17. Anthropometric and lipid profiles were analyzed for hypertension risk using logistic and cross-lagged models.

Results

Of the 227 participants (mean age, 16.5 [2.3] years), 147 (53.9%) were boys. Over a two-year period, 26.4% developed hypertension, 5.3% had elevated systolic blood pressure (SBP), and 25.6% had elevated diastolic blood pressure (DBP). After adjusting for covariates, higher body mass index (BMI), waist circumference (WC), hip circumference (HC), triceps skinfold thickness (TST), and body roundness index (BRI) were associated with increased hypertension risk. Incorporating these measures into a BP-based model improved the AUC for hypertension prediction from 0.551 (95% CI: 0.463, 0.640) to 0.670 (95% CI: 0.592, 0.748). A longitudinal relationship were observed between these adiposity indices and hypertension symptoms.

Conclusions

The study suggests anthropometry parameters are superior to blood lipid indicators in predicting the occurrence of hypertension in children. Abdominal obesity, as indicated by WC, HC, and BRI, accounts for a significant portion of the risk for hypertension, particularly in children aged 7 to 12 years.
A coarse-grained model of disordered RNA for simulations of biomolecular condensates
Authors: Yasuda Ikki , von Bülow Sören , Tesei Giulio , Yamamoto Eiji , Yasuoka Kenji , Lindorff-Larsen Kresten
Published: November 2024

Protein-RNA condensates are involved in a range of cellular activities. Coarse-grained molecular models of intrinsically disordered proteins have been developed to shed light on and predict single-chain properties and phase separation. An RNA model compatible with such models for disordered proteins would enable the study of complex biomolecular mixtures involving RNA. Here, we present a sequence-independent coarse-grained, two-bead-per-nucleotide model of disordered, flexible RNA based on a hydropathy scale. We parameterize the model, which we term CALVADOS-RNA, using a combination of bottom-up and top-down approaches to reproduce local RNA geometry and intramolecular interactions based on atomistic simulations and in vitro experiments. The model semi-quantitatively captures several aspects of RNA-RNA and RNA-protein interactions. We examined RNA-RNA interactions by comparing calculated and experimental virial coefficients, and non-specific RNA-protein interaction by studying reentrant phase behavior of protein-RNA mixtures. We demonstrate the utility of the model by simulating the formation of mixed condensates consisting of the disordered region of MED1 and RNA chains, and the selective partitioning of disordered regions from transcription factors into these, and compare the results to experiments. Despite the simplicity of our model we show that it captures several key aspects of protein-RNA interactions and may therefore be used as a baseline model to study several aspects of the biophysics and biology of protein-RNA condensates.
Preparing for Disease X requires CLARITY – Lessons learned from COVID-19 – A systematic Review
Authors: Boivin Michael , Bourbeau Jean , Sedeno Maria , Horvat Emily , Li Pei-Zhi , Noueihed Baraa , Connelly Kim A. , Jain Akshay B. , Lin Peter , Mazer Bruce D. , Saposnik Gustavo , Strain William D.
Published: November 2024

Objectives

The COVID-19 pandemic has highlighted the critical need for comprehensive preparedness strategies for future pandemics, particularly those caused by unknown pathogens, or Disease X.

Study Design

Our systematic review examined current literature on COVID-19 risk factors, identifying significant gaps and inconsistencies in data reporting.

Methods

A systematic literature search was conducted including all English language published retrospective and prospective observational studies which documented clinical outcomes of COVID-19 in adult patients, on Ovid MEDLINE(R) and Epub databases (December 2019 to March 2023).

Results

The search yielded 440 articles of which 29 were included in the systematic review. We identified major risk factors for severe outcomes. However, inconsistencies in reporting comorbidities, age, disease control levels, medication use, vaccination status, and variant type, limited our analysis. In many publications, this information was not included. Additionally, variations in public attitudes, knowledge, and behaviours regarding COVID-19 vaccines further complicated resource distribution. We propose the CLARITY model to address these gaps by standardizing risk factor reporting, encompassing detailed comorbidity profiles, disease control metrics, age analyses, medication and vaccination data, and variant-specific information.

Conclusions

Implementing the CLARITY model could improve preparedness and response strategies for Disease X, enabling healthcare professionals and systems to allocate resources more effectively and mitigate the impact of future pandemics. This review underscores the necessity for a coordinated global effort to enhance pandemic preparedness through improved data reporting and risk stratification.

Funding

This study received financial support from Moderna Biopharma Canada Corporation.

Trial Registration

PROSPERO Identifier CRD42023449647
Structural insights into the force-transducing mechanism of a motor-stator complex important for bacterial outer membrane lipid homeostasis
Authors: Yeow Jiang , Chia Chee Geng , Lim Nadege Zi-Lin , Chng Shu-Sin
Published: November 2024

Gram-negative bacteria assemble an asymmetric outer membrane (OM) that functions as an effective barrier against antibiotics. Building a stable and functional OM requires assembly and maintenance of balanced levels of proteins, lipopolysaccharides, and phospholipids into the bilayer. InEscherichia coli, the trans-envelope Tol-Pal complex has recently been established to play a primary role in maintaining OM lipid homeostasis. It is believed that the motor-stator complex TolQR exploits the proton motive force in the inner membrane to induce conformational changes in the TolA effector, ultimately generating a force across the cell envelope to activate processes at the OM. Molecular details of how such force transduction occurs via the TolQRA complex is unknown. Here, we solve structures of theE. coliTolQRA complex using single particle cryo-EM, capturing the transmembrane (TM) regions of the purified complex in two distinct states at ∼3.6 Å and ∼4.2 Å nominal resolutions. We define how the TolA N-terminal TM helix interacts with an asymmetric TolQ5R2sub-complex in two different positions, revealing how the two TolQRA states are related by rotation of the TolQ pentamer. By considering structural prediction of the periplasmic domains of the complex, we propose a working model for how proton passage through the complex induces rotary movement that can be coupled to TolA for force transduction across the cell envelope.
Modelling of brain dynamics reveals reduced switching between brain states in insomnia disorder - a resting state fMRI study
Authors: Jespersen Kira Vibe , Stevner Angus , Kringelbach Morten L , Van Someren Eus , Vidaurre Diego , Vuust Peter
Published: November 2024

Insomnia disorder is the most common sleep disorder, and neuroimaging research indicates that it is related to dysfunction in large-scale brain networks. Recently developed methods have enabled the investigation of the dynamic aspects of brain activity varying over time. In the present study, we used a novel data-driven approach to evaluate time-varying brain activity in adults with insomnia disorder compared to matched controls with no sleep problems. We acquired ten minutes resting state functional magnetic resonance images and T1-weighed images in all participants. We used Hidden Markov modelling for a data-driven definition of dynamic changes in whole-brain activity. The results showed that insomnia disorder is characterised by reduced switching rates between brain states. In line with the reduced switching, the HMM analyses suggested reduced prevalence of two whole-brain states - the default mode network and a fronto-parietal network - and an increase in just one brain state - a global activation state - in insomnia patients compared to controls. The findings suggest that insomnia disorder is characterised by less flexible transitions between brain states at wakeful rest, and thus highlight the importance of evaluating the spatiotemporal dynamics of brain activity to advance the understanding of the neural underpinnings of insomnia disorder.
Variable inhibition of different Legionella species by antagonistic bacteria
Authors: Cavallaro Alessio , Probst Silke , Duft Tobias , Rieder Max , El Fateh Oliver Abo , Stricker Josch , Gabrielli Marco , Robinson Serina , Hammes Frederik
Published: November 2024

The genus Legionella includes opportunistic pathogens inhabiting engineered aquatic ecosystems, where managing their presence and abundance is crucial for public health. In these environments, Legionella interact positively or negatively with multiple members of the microbial communities. Here, we identified bacteria and compounds with Legionella-antagonistic properties. We isolated 212 bacterial colonies from various water sources in Switzerland and screened them for their ability to inhibit one reference strain of L. pneumophila. Ten selected antagonistic isolates were subsequently tested with spot-on-lawn-assays for inhibition towards seven environmental and two clinical isolates of Legionella, representing different species and strains. The antagonists produced highly variable inhibition patterns, highlighting distinct differences in susceptibility among Legionella species, and even strains. Only three isolates, all identified as Pseudomonas lurida, inhibited all Legionella species. Furthermore, we analysed the genomes of the antagonistic bacteria, and identified genes for several probable inhibitory compounds. We specifically found the gene cluster for the biosurfactant viscosin to be uniquely encoded by three Pseudomonas lurida isolates. This compound was subsequently detected in the supernatant of co-cultures inoculated with the antagonists and Legionella. This study provides new insights on the ability of aquatic microorganisms to compete with Legionella in controlled laboratory settings. It also highlights the diversity across and within Legionella species in their resistance to external antagonistic stress, and confirms the anti-Legionella activity of selected biosurfactants. These results can contribute to the understanding of how different species inhabit separate niches in the environment, and expand the discussion around alternative Legionella mitigation strategies.
Resting-state alpha reactivity is reduced in Parkinson’s disease and associated with gait variability
Authors: Lirani-Silva Ellen , Silva Layla C. S. , Orcioli-Silva Diego , Beretta Victor S. , França Lucas G. S. , Coelho Daniel B. , Vitorio Rodrigo
Published: November 2024

Background

The extent to which the cholinergic system contributes to gait impairments in Parkinson’s disease (PD) remains unclear. Electroencephalography (EEG) alpha reactivity, which refers to change in alpha power over occipital electrodes upon opening the eyes, has been suggested as a marker of cholinergic function. We compared alpha reactivity between people with PD and healthy individuals and explored its potential association with gait measures.

Methods

Eyes-closed and eyes-open resting-state EEG data were recorded from 20 people with idiopathic PD and 19 healthy individuals with a 64-channel EEG system. Alpha reactivity was calculated as the relative change in alpha power (8-13 Hz) over occipital electrodes from eyes-closed to eyes-open. Gait spatiotemporal measures were obtained with an electronic walkway.

Results

Alpha reactivity was reduced in people with PD compared to healthy individuals (U = 105, p = 0.017); the rank-biserial correlation of 0.447 indicated a moderate effect size. When controlling for global cognition (Mini Mental State Examination), the group difference in alpha reactivity was no longer significant. Alpha reactivity associated with measures of gait variability only (rho = −0.437 to −0.532).

Conclusions

Reduced alpha reactivity in PD is driven by levels of global cognition and suggests impaired cholinergic function in PD. Reduced alpha reactivity was associated with greater gait variability, indicating a role of the cholinergic system in the mechanisms underlying gait variability. Therefore, the cholinergic system may represent a target for treatments aiming to reduce gait variability and alpha reactivity should be further explored as an endpoint for clinical trials.
Multi-stream predictions in human auditory cortex during natural music listening
Authors: Robert Paul , Van Cang Mathieu Pham , Mercier Manuel , Trébuchon Agnès , Bartolomei Fabrice , Arnal Luc H. , Morillon Benjamin , Doelling Keith
Published: November 2024

Real-world perception involves the prediction and integration of multiple dynamic objects and features in parallel, yet most research focuses on single-stream sequences. We present PolyRNN, a recurrent neural network designed to model predictions across multiple, simultaneous information streams, using polyphonic music as a case study. We recorded neurophysiological activity non invasively (MEG) and within the human cortex (intracranial EEG) while participants listened to real piano music. Musical expectations are encoded in P2- and P3-like components in auditory regions. Compared to a state-of-the-art generative music model, we demonstrate that parallelization better reflects the brain’s processing of simultaneous sequences compared to serialization. Overall, our approach enables the study of predictive processing in ecologically valid polyphonic music and provides a general framework for modeling predictions in simultaneous streams.
Mechanistic Insight into pH-Driven Phase Transition of Lipid Nanoparticles
Authors: Trollmann Marius F.W. , Böckmann Rainer A.
Published: November 2024

Lipid nanoparticles (LNPs) are essential delivery vehicles in mRNA-based vaccines, with their functionality largely governed by aminolipids. At low pH, protonated aminolipids facilitate efficient mRNA encapsulation, while their deprotonation at physiological pH drives LNP remodeling into a stable spherical structure, potentially aiding mRNA release during endosomal re-protonation and concomitant restructuring at low pH.

Our study uncovers the pH-dependent phase transition of theComirnatylipid formulation at the molecular scale, highlighting the intricate interplay between lipid reorganization and aminolipid protonation. We observe a substantial shift in the aminolipid pKa, from 7-8 at the LNP surface to below 4 within the hydrophobic LNP core, resulting in an overall apparent pKaof the lipid nanoparticle of 6.3. The pH-dependent protonation significantly affects the aminolipid’s localization, with protonated aminolipids enriched in vicinity of the mRNA and at the LNP surface at neutral pH. The lipid monolayer covering LNPs at neutral pH comprises cholesterol (60–65%), helper phospholipids (20–25%), PEGylated lipids (5%), and a mix of protonated and deprotonated aminolipids (5–10%). These findings provide mechanistic insights into aminolipids behavior in LNPs, offering a foundation for optimizing LNP design to enhance stability, tunable pH responses, and therapeutic efficacy.
Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques
Authors: Pratap Payal P. , Cottrell Christopher A. , Quinn James , Carnathan Diane G. , Bader Daniel L.V. , Tran Andy S. , Enemuo Chiamaka A. , Ngo Julia T. , Richey Sara T. , Gao Hongmei , Shen Xiaoying , Greene Kelli M. , Hurtado Jonathan , Michaels Katarzyna Kaczmarek , Ben-Akiva Elana , Allen Joel D. , Ozorowski Gabriel , Crispin Max , Briney Bryan , Montefiori David , Silvestri Guido , Irvine Darrell J. , Crotty Shane , Ward Andrew B.
Published: November 2024

Abstract/Summary

During infection, the fusion peptide (FP) of HIV envelope glycoprotein (Env) serves a central role in viral fusion with the host cell. As such, the FP is highly conserved and therefore an attractive epitope for vaccine design. Here, we describe a vaccination study in non-human primates (NHPs) where glycan deletions were made on soluble HIV Env to increase FP epitope exposure. When delivered via implantable osmotic pumps, this immunogen primed immune responses against the FP, which were then boosted with heterologous trimers resulting in a focused immune response targeting the conserved FP epitope. Although autologous immunizations did not elicit high affinity FP-targeting antibodies, the conserved FP epitope on a heterologous trimer further matured the lower affinity, FP-targeting B cells. This study suggests using epitope conservation strategies on distinct Env trimer immunogens can focus humoral responses on desired neutralizing epitopes and suppress immune-distracting antibody responses against non-neutralizing epitopes.
Hippocampal CA2 neurons disproportionately express AAV-delivered genetic cargo
Authors: Alexander Georgia M. , He Bo , Leikvoll Austin , Jones Stephanie , Wine Rob , Kara Prakash , Martin Negin , Dudek Serena M.
Published: November 2024

Hippocampal area CA2 is unique in many ways, largely based on the complement of genes expressed there. We and others have observed that CA2 neurons exhibit a uniquely robust tropism for adeno-associated viruses (AAVs) of multiple serotypes and variants. In this study, we aimed to systematically investigate the propensity for AAV tropism toward CA2 across a wide range of AAV serotypes and variants, injected either intrahippocampally or systemically, including AAV1, 2, 5, 6, 8, 9, DJ, PHP.B, PHP.eB, and CAP-B10. We found that most serotypes and variants produced disproportionally high expression of AAV-delivered genetic material in hippocampal area CA2, although two serotypes (AAV6 and DJ) did not. In an effort to understand the mechanism(s) behind this observation, we considered perineuronal nets (PNNs) that ensheathe CA2 pyramidal cells and, among other functions, buffer diffusion of ions and molecules. We hypothesized that PNNs might attract AAV particles and maintain them in close proximity to CA2 neurons, thereby increasing exposure to AAV particles. However, genetic deletion of PNNs from CA2 had no effect on AAV transduction. Next, we next considered the AAV binding factors and receptors known to contribute to AAV transduction. We found that the AAV receptor (AAVR), which is critical to transduction, is abundantly expressed in CA2, and knockout of AAVR nearly abolished expression of AAV-delivered material by all serotypes tested. Additionally, we found CA2 enrichment of several cell-surface glycan receptors that AAV particles attach to before interacting with AAVR, including heparan sulfate proteoglycans, N-linked sialic acid and N-linked galactose. Indeed, CA2 showed the highest expression of AAVR and the investigated glycan receptors within the hippocampus. We conclude that CA2 neurons are endowed with multiple factors that make it highly susceptible to AAV transduction, particularly to the systemically available PHP variants, including CAP-B10. Given the curved structure of hippocampus and the relatively small size of CA2, systemic delivery of engineered PHP or CAP variants could all but eliminate the need for intrahippocampal AAV injections, particularly when injecting recombinase-dependent AAVs into animals that express recombinases in CA2.
Deciphering Ca2+Permeation and Valence Selectivity in CaV1: Molecular Dynamics Simulations Reveal the Three-Ion Knock-on Mechanism
Authors: Xue Lingfeng , Yan Nieng , Song Chen
Published: November 2024

Voltage-gated calcium (CaV) channels are pivotal in cellular signaling due to their selective calcium ion permeation upon membrane depolarization. While previous studies have established the highly selective permeability of CaVchannels, the detailed molecular mechanism remains elusive. Here we use extensive atomistic molecular dynamics simulations to elucidate the mechanisms governing ion permeation and valence selectivity in CaV1 channels. Employing the electronic continuum correction method, we simulated a calcium conductance of approximately 9–11 pS, aligning closely with experimental measurement. Our simulations uncovered a three-ion knock-on mechanism critical for efficient calcium ion permeation, necessitating the binding of at least two calcium ions within the selectivity filter (SF) and the subsequent entry of a third ion.In silicomutation simulations further validated the importance of multi-ion coordination in the SF for efficient ion permeation, identifying two critical residues, D706 and E1101, that are essential for the binding of two calcium ions in the SF. Moreover, we explored the competitive permeation of calcium and sodium ions, and obtained a valence selectivity favoring calcium over sodium at a ratio of approximately 35:1 under the bi-cation condition. This selectivity arises from the strong electrostatic interactions of calcium ions in the confined SF and the three-ion knock-on mechanism. Our findings provide novel insights into the molecular underpinnings of CaVchannel function, with implications for understanding calcium-dependent cellular processes.
Mapping of the country-wide prevalence of non-malarial febrile illnesses in areas with varying malaria transmission intensities in Mainland Tanzania
Authors: Mandai Salehe S. , Kisambale Angelina J. , Petro Daniel A. , Bakari Catherine , Chacha Gervas A. , Budodo Rule , Madebe Rashid A. , Pereus Dativa , Challe Daniel P. , Moshi Ramadhani , Mbwambo Ruth B. , Kanyankole Grace K. , Aaron Sijenunu , Mbwambo Daniel , Kajange Stella , Lazaro Samwel , Kapologwe Ntuli , Mandara Celine I. , Seth Misago D. , Ishengoma Deus S.
Published: November 2024

Recent reports revealed a declining malaria burden, but non-malaria febrile illnesses (NMFIs) have either remained unchanged or increased. This study assessed the country-wide prevalence of NMFIs and their patterns across various malaria transmission settings in Mainland Tanzania. A cross-sectional study recruited patients aged ≥ 6 months from 86 health facilities in all 26 regions of Tanzania. All patients were tested for malaria using rapid diagnostic tests (RDTs) and the prevalence of NMFIs was determined for all patients with negative results. Logistic regression was used to determine factors associated with NMFIs. Of the 18,568 patients tested, 8,273 (44.6%) had NMFIs due to negative RDT results. Higher prevalence of NMFIs occurred in females (45.8%) than males (42.8%), adults (aged ≥ 15 years, with 50.6%) compared to under-fives (42.6%) and school children (aged 5 -< 15 years, 34.3%), and in very low (71.5%) compared to high transmission areas (33.9%). NMFIs were significantly more likely in females than in males (aOR = 1.14, 95% CI = 1.07–1.22), in very low transmission areas (aOR = 4.85, 95% CI = 4.42–5.33), adults (aOR = 1.60, 95% CI = 1.46–1.75) and under-fives (aOR = 1.60, 95% CI = 1.47–1.76). The findings show high prevalence of NMFIs overall, and higher prevalence and odds of NMFIs in females, under-fives and individuals from low and very low transmission areas. These groups should be targeted with appropriate point-of-care tests and treatment strategies.
Genomic Analysis ofLegionella pneumophilain the Drinking Water System of a Large Building over 25 Years
Authors: Seth-Smith Helena MB , Egli Adrian , Gautsch Sylvia , Bornstein Michael M. , Kulik Eva M.
Published: November 2024

Legionella pneumophila,the causative agent of Legionnaires’ disease, is often found in the plumbing systems of buildings from where it can be transmitted to humans via inhalation or aspiration of contaminated water drops. Annual routine water sampling from the potable water system of an occupational healthcare building in Basel over 25 years was performed in accordance with national guidelines. Overall, 309 water samples were collected at 38 time points over the period of 25 years.L. pneumophilawas recovered from 120 water samples (38.8%) from 26 time points. No clinical infections were recorded during this period. Initial decontamination measures were successful for approximately 12 years, after which an increase in the total number ofLegionellacolony forming units as well as ofL. pneumophila-positive sites was noticed, in 2008. Whole genome sequencing (WGS) analysis of n=123 isolates from n=113 samples showed allL. pneumophilato be sequence type (ST)-45 (Sequence based typing scheme). The isolates are closely related, with only 408 single nucleotide polymorphisms (SNPs) among all isolates after the bioinformatic removal of recombination events. Over the 25 years, a single lineage deriving from a recent common ancestor colonized the water system of this building. The phylogeny of isolate genomes can be interpreted as inferring good water circulation, possible recolonization from a common source after cleaning, with genome evolution and insertion / loss of large elements evident. Regular monitoring of waterlines in healthcare settings helps to identify concentrations ofLegionellaspp. and WGS is recommended for detailed investigation.

Data Summary

All data is submitted to the ENA under project PRJEB79004 under accession numbers ERR13662450-ERR13662572.

Impact Statement

This is the most detailed, long-term study ofL. pneumophilain the water system of a single building recorded to date. TheL. pneumophilaisolates found in the building over the sampling period of 25 years were all closely related, belonging to ST45. SNP analysis suggested that the common ancestor of the cluster was from around 1938 (range 1911 to 1959), and movement of a large genomic island and plasmid transfer were observed. Despite several decontamination measures, it was impossible to completely eradicateLegionellaspp. from the water system of the historic building. No infections could be attributed to the presence ofL. pneumophilain this building. To mitigate the risk of Legionellosis from such buildings, awareness, regular water testing based on official national guidelines and recommendations, and other control measures, such as the use of sterile water for critical procedures can be recommended.
Vacuolar pH regulates clathrin-mediated endocytosis through TORC1 signaling during yeast replicative aging
Authors: Antenor Kenneth Gabriel , Lee-Dadswell Jaime , Grishchenko Nina , Swaleh Shaimaa , Spangaro Allie , Usaj Mojca Mattiazzi
Published: November 2024

Clathrin-mediated endocytosis (CME) is a critical cellular process that regulates nutrient uptake, membrane composition and signalling. While cellular aging is associated with functional changes across many cellular components contributing to the collective decline in cellular function, little is known about how it affects CME. Here we show that CME dynamics are significantly altered during replicative aging in budding yeast, with older cells having slower assembly of early and coat CME modules, resulting in longer endocytic turnover and reduced cargo internalization. This change in CME dynamics is mother cell-specific and is not observed in daughter cells. We identified vacuolar pH, a key driver of aging phenotypes in budding yeast, as a central player in this modulation of CME dynamics during aging. Perturbing vacuolar pH in young cells mimics aging-like CME dynamics, while maintaining an acidic vacuolar pH in aging cells preserves CME dynamics typical of young cells. Finally, we demonstrate that the vacuolar pH effect on CME is regulated through TORC1 via the effector kinase Npr1. These findings establish vacuolar pH as a critical regulator of CME during cellular aging, and strengthen its role in the overall cellular aging process in budding yeast.
Revealing the diversity of commensal corynebacteria from a single human skin site
Authors: Herman Reyme , Meaden Sean , Rudden Michelle , Cornmell Robert , Wilkinson Holly N. , Hardman Matthew J. , Wilkinson Anthony J. , Murphy Barry , Thomas Gavin H.
Published: November 2024

Our understanding of the skin microbiome has dramatically improved since the pioneering studies and the improvements in sequencing technologies. Species of the genusCorynebacteriumare known to form a major part of the human skin microbiome but most detailed studies have focussed on other similarly prevalent genera likeStaphylococcusandCutibacteria. Prior to this study, there were few complete genomes for skin commensals of the genusCorynebacterium, with only 9 complete genomes available for the most commonly identified speciesC. tuberculostearicum. In this study we explored the genusCorynebacteriumfrom a single body site by swabbing the axilla/underarm of 4 individuals and using a selective media to enrich for corynebacteria. We then generated whole genome sequencing data of these corynebacteria enriched isolates using long-read sequencing and subsequent bioinformatics analysis to reveal an unparalleled diversity of this genus from a single skin site. Through this approach, we obtained the closed genomes of 215 isolates, 154 derived from a single individual. With this genetic information, we were able to identify 7 different species including species previously not associated to the skin and two novel species provisionally namedC. axilliensisandC. jamesii. We used pangenome analysis on 30 genetically distinct isolates spanning the 7 species to identify putative metabolic differences, antimicrobial resistance profiles, novel biosynthetic gene clusters (BGCs), prophages and phage defence systems. Our culture-based Nanopore sequencing approach has dramatically improved our overall knowledge of skin corynebacteria, and uniquely here also providing in-depth analysis from a single skin site, revealing a multitude of differences between the isolates. Here we not only improved our knowledge of axillary corynebacteria but also greatly expanded the publicly available number of cutaneous corynebacterial genomes complementing recent studies seeking to understand the diversity of skin corynebacteria.
Bidirectionally responsive thermoreceptors encode cool and warm
Authors: Bokiniec Phillip , Whitmire Clarissa J. , Poulet James F.A.
Published: November 2024

Thermal sensation is a fundamental sense initiated by the activity of primary afferent thermoreceptors. While considerable attention has been paid to the encoding of noxious temperatures by thermoreceptors, it is far less clear how they encode innocuous cool and warm which are more commonly encountered in the environment. To address this, we sampled the entire thermoreceptor population usingin vivotwo-photon calcium imaging in the lumbar dorsal root ganglia of awake and anesthetized mice. We found that the vast majority of thermoreceptors respond bidirectionally, with an enhanced response to cool and a suppressed response to warm. Usingin vivopharmacology and computational modelling, we demonstrate that conductance changes in the cool-sensitive TRPM8 channel are sufficient to explain this bidirectional response type. Our comprehensive dataset reveals the fundamental principles of the peripheral encoding of innocuous temperatures and suggests that the same population of thermoreceptors underlie the distinct sensations of cool and warm.
Characterization of widely conserved novel pigment production inBacillus subtilisspecies
Authors: Stannius Rune Overlund , Dunlap Christopher A. , Morvan Estelle , Berbon Mélanie , Lecomte Sophie , Loquet Antoine , Kovács Ákos T.
Published: November 2024

Bacillus subtilisis widely studied in the microbial secondary metabolite (SM) field due to its rich variety of important natural products and genetic tractability. However, identification of novel SMs and their biosynthetic gene cluster (BGCs) has become increasingly difficult, especially inBacilli, as the tools for screening and genome mining are dependent on clear function or similarity to already known BGCs. Pigments are SMs identified by their absorption of visible light, resulting in a certain color perceived by our eyes at sufficient concentrations. Thereby, pigments provide the evidence of a BGC without knowing the sequence or function. Expanding the known repertoire of SM BGCs with novel BGCs will further reinforce identification of a broader set of BGCs by mining tools such as antiSMASH. Here, we study a pigment observed inB. subtilissoil isolate MB9_B4 on certain media. We characterize the conditions where this pigment is produced and identify the corresponding BGC using a comparative genomic approach exploiting our strain collection containing other isolates with pigment production ability. The responsible BGC carried several genes, which were annotated as parts of the tryptophan biosynthesis pathway, possibly originating from a duplication and divergence of an originally primary metabolism. Identification of the pigment gene cluster additionally lead to the discovery of additional pigment BGC carrierB. subtilisisolates, some of which were described at the earliest in 1896 under the nameBacillus aterrimus, with a name referring to a dark pigmentation (the Latin “aterrimus” meaning very black). In addition, we employed solid-state nuclear magnetic resonance and Fourier transform infrared spectroscopies to characterize the chemical groups of the pigment. This study describes the chemical and biological features of a new class of SM BGC, which we hope will serve to improve the current BGC discovery pipelines inBacilli.
Using deep learning to predict internalizing problems from brain structure
Authors: Vandewouw Marlee M. , Syed Bilal , Barnett Noah , Arias Alfredo , Kelley Elizabeth , Jones Jessica , Ayub Muhammad , Iaboni Alana , Arnold Paul D. , Crosbie Jennifer , Schachar Russell J , Taylor Margot J , Lerch Jason P. , Anagnostou Evdokia , Kushki Azadeh
Published: November 2024

Internalizing problems are associated with a wide range of adverse outcomes. While we have some understanding about risk factors (e.g., neurodevelopmental conditions), biological markers are not well understood. Here, we used deep learning to predict cross-sectional (N=14,523) and worsening longitudinal trajectories (N=10,540) of internalizing problems from measures of brain structure. A stratified cross-validation scheme was used, and performance was evaluated using the area under the receiving operating characteristic curve (AUC). The cross-sectional model performed well across the sample, reaching an AUC of 0.80 [95% CI: 0.71, 0.88]. For the longitudinal model, while performance was sub-optimal for predicting worsening trajectories in a sample of the general population (AUC=0.66 [0.65, 0.67]), good performance was reached across individuals with a neurodevelopmental condition (AUC=0.73 [0.70, 0.76]). Deep learning with features of brain structure is a promising avenue for biomarkers of internalizing problems, particularly for individuals who have a higher likelihood of experiencing difficulties.
Higher frequency of transition mutation over transversion mutation in genomes: evidence from the binding energy calculation of base pairs using DFT
Authors: Deka Nishita , Gour Nand Kishor , Pant Pradeep , Satapathy Siddhartha Shankar , Hoda Nasimul , Deka Ramesh Chandra , Ray Suvendra Kumar
Published: November 2024

Base substitution mutations such as transition (ti) and transversion (tv) in organisms are major driving force in molecular evolution. In this study, different possible types of base pairing that can causetiandtvwere investigated using the density functional theory (DFT) method. The chemical structures of bases as well as base pairs were optimized using B3LYP hybrid functional along with 6-31G(d,p) basis set. We performed single point energy calculation of all optimized species using the same functional but combined with higher diffuse and polarized basis set i.e. 6-311++G(d,p) to get more refined energy of all species. The binding energy of various base pairs was calculated considering basis set superposition error (BSSE) as well as without BSSE. The binding energy of the base pairs leading totiwas found to be more stable than that of the base pairs leading totv. This was interesting considering the observations in organisms thattisare more frequent thantvs. Among the base pairs leading to the sameti, G(keto): T (enol)base pair was found to be more stable than A(imino):C(amino)base pair. This theoretical study of binding energy of different base pairs using the DFT method has provided additional evidences in support to the biological observations of a higher transition rate than transversion in genomes.
GABRA1frameshift variants impair GABAAreceptor proteostasis
Authors: Williams Marnie P. , Wang Ya-Juan , Kang Jing-Qiong , Perryman John H. , Mu Ting-Wei
Published: November 2024

The gamma-aminobutyric acid type A receptor (GABAAR) is the most common inhibitory neurotransmitter-gated ion channel in the central nervous system. Pathogenic variants in genes encoding GABAAR subunits can cause receptor dysfunction and lead to genetic epilepsy. Frameshift variants in these genes can result in a premature termination codon, producing truncated receptor subunit variants. However, the pathogenic molecular mechanism as well as functional implications of these frameshift variants remains inadequately characterized. This study focused on four clinical frameshift variants of the α1subunit of GABAAR (encoded by theGABRA1gene): K401fs (c.1200del), S326fs (c.975del), V290fs (c.869_888del), and F272fs (c.813del). These variants result in the loss of one to three transmembrane helices, whereas wild type α1 has four transmembrane helices. Therefore, these variants serve as valuable models to evaluate membrane protein biogenesis and proteostasis deficiencies of GABAARs. In HEK293T cells, all four frameshift variants exhibit significantly reduced trafficking to the cell surface, resulting in essentially non-functional ion channels. However, the severity of proteostasis deficiency varied among these four frameshift variants, presumably due to their specific transmembrane domain deletions. The variant α1subunits exhibited endoplasmic reticulum (ER) retention and activated the unfolded protein response (UPR) to varying extents. Our findings revealed that these frameshift variants ofGABRA1utilize overlapping yet distinct molecular mechanisms to impair proteostasis, providing insights into the pathogenesis of GABAAR-associated epilepsy.
Challenges and strategies related to serving customers with food allergies in private clubs in the US
Authors: Wen Han
Published: November 2024

Purpose

The purpose of this study was to explore the current issues and challenges related to serving customers with food allergies in club foodservice operations.

Design/methodology/approach

A total of 15 individual interviews were conducted with club managers in the US. Participants shared their strategies for preventing food allergy incidents, such as taking advantage of the member information management system, ensuring a proper communication line and preventing cross-contacts in both the front-of-the-house (FOH) and back-of-the-house (BOH).

Findings

Results indicated that food allergies posed challenges for club managers regarding the increasing populations and types of food allergies, customers not communicating their food allergies and the issues relating to providing allergen-free foods in large banquets. Balancing safety and satisfaction is critically important due to the nature of club operations.

Research limitations/implications

Implications to both club foodservice operators and customers with food allergies were provided.

Originality/value

This is the first research focusing on challenges and issues related to serving customers with food allergies in the club industry.
Unveiling knowledge dynamics for competitive advantage: insights into hiding, sharing and big data management
Authors: Rehman Shafique Ur , Bresciani Stefano , Riaz Adil , Giovando Guido
Published: November 2024

Purpose

This study investigates the influence of knowledge hiding in organizations (KHOs), knowledge sharing in organizations (KSOs) and big data knowledge management (BDKM) on knowledge management success. Monitoring (MNT) is used as a moderator between KHO and knowledge management success. Besides, knowledge management success and digital business intensity (DBI) are used to attain competitive advantage (CA). Finally, digital business intensity is used as a moderator between knowledge management success and competitive advantage.

Design/methodology/approach

Data were collected through questionnaires using simple random sampling, and a total of 433 questionnaires were used in the final analysis. Partial least squares structural equation modeling is used to test study hypotheses.

Findings

Results indicate that KSO, BDKM and monitoring are positive, but KHO is negatively related to knowledge management success. Monitoring moderates the relationship between KHO and knowledge management success. Knowledge management success and digital business intensity significantly attain competitive advantage. Digital business intensity significantly moderates the relationship between knowledge management success and competitive advantage.

Practical implications

Top managers can use study findings in decision-making if they want to attain a competitive advantage. KHO has a negative influence on knowledge management success, but this relationship can be changed by monitoring the employees. KSO, BDKM, knowledge management success and digital business intensity play a vital role in determining competitive advantage.

Originality/value

By building knowledge culture using the knowledge-based view, this study contributes to KHO, KSO, BDKM, monitoring, digital business intensity and competitive advantage literature.
Quality of working life in remote platform work: a systematic review of a fragmented field of research
Authors: Marà Claudia , Vermeerbergen Lander , Pulignano Valeria , Hannes Karin
Published: November 2024

Purpose

Revitalisation of quality of working life (QWL) research points to non-standard work such as remote platform work as a compelling setting where research on QWL is needed. Whereas the literature on working conditions in remote work platforms is rich, knowledge on the topic is fragmented. This systematic review aims to synthesize and integrate findings from existing literature to offer an encompassing and multidimensional understanding of QWL and the managerial practices linked to it in remote work platforms.

Design/methodology/approach

A systematic review of 24 empirical qualitative studies selected based on a multiple-database search using Boolean search engines. The selection of studies to be included in the review was performed through a four-steps procedure, following the PRISMA protocol. A thematic analysis of the studies was performed to synthesize findings.

Findings

We synthesize and show how remote platform workers experience a degrading QWL along five QWL dimensions, and we illustrate how these QWL dimensions are influenced by platforms’ managerial practices such as client-biased systems, rate-setting mechanisms, reputational systems, global competition schemes, lock-in systems, monitoring and nudging systems and information asymmetry.

Originality/value

The study contributes to reinvigorating QWL literature by producing a systematic synthesis of workers’ experience of QWL in the non-standard work context of remote platform work and the managerial practices that influence QWL. Our study overcomes two main shortcomings of the existing empirical studies published: (1) studies examine only a few QWL dimensions and/or (2) examine some platforms’ managerial practices that influence QWL, overlooking others.
Effect of squeeze motion on the tribo-performances of molybdenum disulfide powder lubricated textured cemented carbide specimens
Authors: Pang Minghua , Li Zhenjiang , Hu Yikun , Gan Zichen , Ma Lijie , Feng QigaoFeng
Published: November 2024

Purpose

This study aims to improve the lubrication performance of molybdenum disulfide powders at textured surface of cemented carbide materials, a squeeze motion of vibration assistance method was introduced and investigated.

Design/methodology/approach

Surface texture was fabricated on YT15 cemented carbide samples using a laser marking machine. After that, a tribological experiment was carried out on a self-built friction testing machine under different amplitude and frequency of squeeze motion conditions. Moreover, a simulation model was also established to verify the principle of squeeze motion on the lubrication performance improving of MoS2 particles at textured interfaces.

Findings

Analysis results indicated that surface texture on test sample can increase the storage ability of solid lubrication particles, and the lubrication film at the contact interface is more easily formed due to the reciprocating action. Squeeze motion can improve the storage ability of it due to an intermittent contact, which provides an opportunity for MoS2 particles infiltration, and then a more uniform distribution and load-bearing properties of force chain are also established and formed simultaneously. Thus, a better tribological performance at the contact interface is obtained.

Originality/value

The main contribution of this work is to provide a reference for the molybdenum disulfide powder lubrication with textured surface of cemented carbide materials.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-05-2024-0166/
The relationship between eWoM, security, quality of information and purchase behaviour at B2C e-commerce website: the moderating role of E-trustmarks
Authors: Quan Nguyen Hong , Ha Pham Thi , Tuan Vi Thanh , Nam Nguyen Hoai , Trang Le Thi Thuy , Mai Nguyen Truc
Published: November 2024

Purpose

This study aims to investigate the moderating role of e-trustmarks in the relationship between electronic word of mouth (eWoM), security, quality of information, and purchase behaviour of consumers on B2C e-commerce websites. The research was conducted in the context of emerging countries.

Design/methodology/approach

The research utilised partial least squares path modelling (PLS-SEM) to assess the model and its hypothesised relationships, drawing on data from a survey of 1993 consumers engaged in e-commerce websites with e-trustmarks. The study incorporated SOR theory, asymmetric information theory, and signalling theory.

Findings

E-trustmarks moderate the positive impact of eWoM, security, and quality of information on online trust. A moderating effect of e-trustmarks was also found, such that the positive association between purchase intention and purchase behaviour was stronger when e-trustmarks were higher.

Research limitations/implications

This study was conducted solely in Vietnam and focused only on a set of input variables without addressing specific industries or market segments. The research did not use demographic data, such as the age and income of the surveyors, to identify variations in the impact of variables on different target groups, indicating potential areas for future research.

Practical implications

Emerging countries should implement targeted policies regarding e-trustmarks and encourage businesses to adopt them to reduce information asymmetry in the online environment.

Originality/value

This study contributes to asymmetric theory and signalling theory by offering critical insights into how online businesses can make use of influence mechanisms in the model to ease asymmetric information. Integrating signalling theory and moderating e-trustmarks into the SOR model advances research on consumer behaviour in emerging countries’ e-commerce markets with asymmetric information.