bluuebunny/crossref_metadata_2025 huggingface dataset:
Lateralized nodose ganglia gene expression implicates cholecystokinin receptors in interoceptive reward signaling
Authors: Welch Hailey F. , Sankaranarayanan Ishwarya , Hong Veronica M. , Mazhar Khadijah , Kolber Benedict J. , Price Theodore J. , Thorn Catherine A.
Published: November 2024

The vagus nerves are important carriers of sensory information from the viscera to the central nervous system. Emerging evidence suggests that sensory signaling through the right, but not the left, vagus nerve evokes striatal dopamine release and reinforces appetitive behaviors. However, the extent to which differential gene expression within vagal sensory neurons contributes to this asymmetric reward-related signaling remains unknown. Here, we use single-cell RNA sequencing to identify genes that are differentially expressed between the left and right nodose ganglia (NG) to identify candidate genes likely to contribute to vagus-mediated reward signaling. We find that a group of neurons expressingChrna3(nicotinic acetylcholine receptor subunit 3) andCckar(cholecystokinin A receptor) is preferentially expressed in the right NG of both rats and mice. This result suggests that differential expression of gut-innervating nutrient sensors in NG neurons may contribute to asymmetric encoding of interoceptive rewards by the vagus nerves.
Differential destinations, dynamics, and functions of high- and low-order features in the feedback signal during object processing
Authors: Hou Wenhao , He Sheng , Zhang Jiedong
Published: November 2024

Brain is a hierarchical information processing system, in which the feedback signals from high-level to low-level regions are critical. The feedback signals may convey complex high-order features (e.g., category, identity) and simple low-order features (e.g., orientation, spatial frequency) to sensory cortex to interact with the feedforward information, but how these types of feedback information are represented and how they differ in facilitating visual processing is unclear. The current study used the peripheral object discrimination task, 7T fMRI, and MEG to isolate feedback from feedforward signals in human early visual cortex. The results showed that feedback signals conveyed both low-order features natively encoded in early visual cortex and high-order features generated in high-level regions, but with different spatial and temporal properties. The high-order feedback information targeted both superficial and deep layers, whereas the low-order feedback information reached only deep layers in V1. In addition, MEG results revealed that the feedback information from occipito-temporal to early visual cortex emerged around 200 ms after stimulus onset, and only the representational strength of high-order feedback information was significantly correlated with behavioral performance. These results indicate that the complex and simple components of feedback information play different roles in predictive processing mechanisms to facilitate sensory processing.
The presynaptic vesicle cluster transitions from a compact to loose organization during long-term potentiation
Authors: Garcia Guadalupe C. , Bartol Thomas M. , Kirk Lyndsey M. , Badala Priyal , Harris Kristen M. , Sejnowski Terrence J.
Published: November 2024

Functional and structural elements of synaptic plasticity are tightly coupled, as has been extensively shown for dendritic spines. Here, we interrogated structural features of presynaptic terminals in 3DEM reconstructions from CA1 hippocampal axons that had undergone control stimulation or theta-burst stimulation (TBS) to produce long-term potentiation (LTP). We reveal that after LTP induction, the synaptic vesicle (SV) cluster is less dense, and SVs are more dispersed. The distances between neighboring SVs are greater in less dense terminals and have more SV-associated volume. We characterized the changes to the SV cluster by measuring distances between neighboring SVs, distances to the active zone, and the dispersion of the SV cluster. Furthermore, we compared the distribution of SVs with randomized ones and provided evidence that SVs gained mobility after LTP induction. With a computational model, we can predict the increment of the diffusion coefficient of the SVs in the cluster. Moreover, using a machine learning approach, we identify presynaptic terminals that were potentiated after LTP induction. Lastly, we show that the local SV density is a volume-independent property under strong regulation. Altogether, these results provide evidence that the SV cluster is undergoing a transition during LTP.
The most significant differences between male and female rats regarding psychostimulant self-administration behavior are unrelated to biological sex
Authors: Showell Bryce H , Job Martin O
Published: November 2024

Background

The goals of this study were to 1) validate the MISSING (Mapping Intrinsic Sex Similarities as an Integral quality of Normalized Groups) model for psychostimulant self-administration (SA), and 2) utilize it to explain the inconsistencies in the observation of sex differences in psychostimulant SA.

Methods

We allowed male and female Long Evans rats (n = 40) to self-administer methamphetamine METH dose 0.1 mg/kg (male n = 9, female n = 18) and saline (male n = 3, female n = 10) via the intravenous route, FR1 schedule, 6 h per day, 5 days per week for 4 weeks. For the MISSING model, we identified behavioral clusters of males and females using normal mixtures clustering analysis of baseline intake, total intake and total intake normalized-to-baseline intake (NBI), followed by unpaired t-tests to compare clusters and Two-way ANOVA to determine if there were any SEX by cluster interactions. For the current model, we grouped our subjects according to biological sex and compared the above variables using unpaired t-tests. For both models, we employed Two-way repeated measures ANOVA and linear regression analysis to analyze SA time course.

Results

For saline and METH SA, there were no sex differences when we compared males and females generally, with sex differences evident only when we compared sexes from distinct clusters. The current model could not explain the inconsistencies in the observability of sex differences in METH SA.

Conclusions

We validated the MISSING model -it can explain the inconsistencies around sex differences in METH SA.
Notch signaling blockade links transcriptome heterogeneity in quiescent neural stem cells with their reactivation routes and potential
Authors: Morizet David , Foucher Isabelle , Alunni Alessandro , Bally-Cuif Laure
Published: November 2024

In the vertebrate brain, neural stem cell (NSC) quiescence is necessary for stemness maintenance. Using single cell RNA sequencing (scRNAseq) in the zebrafish adult telencephalon, we identified different molecular clusters of quiescent NSCs, interpreted to sign different quiescence depths(1). Here, we show that these clusters, when challengedin vivowith an inhibitor of Notch signaling -a major quiescence promoting pathway-, unfold different behaviors. Notably, deeply quiescent NSCs with astrocytic features display a unique activation phenotype that combines the maintenance of astrocytic markers with the rapid upregulation of activation and neuronal commitment genes, reminiscent to murine periventricular astrocytes activating upon lesion. In contrast, an NSC cluster predicted to be in the deepest quiescence state resists Notch blockade, and we demonstrate that the transcription factor Nr2f1b mediates this resistance to activationin vivo. These results together link the molecular heterogeneity of quiescent NSCs withbona fidebiological properties and their molecular regulators.
Genomic and Phenomic Prediction for Soybean Seed Yield, Protein, and Oil
Authors: Van der Laan Liza , Parmley Kyle , Saadati Mojdeh , Torres Pacin Hernan , Panthulugiri Srikanth , Sarkar Soumik , Ganapathysubramanian Baskar , Lorenz Aaron J. , Singh Asheesh K
Published: November 2024

Developments in genomics and phenomics have provided valuable tools for use in cultivar development. Genomic prediction (GP) has been used in commercial soybean [Glycine max L. (Merr.)] breeding programs to predict grain yield and seed composition traits. Phenomic prediction (PP) is a rapidly developing field that holds the potential to be used for the selection of genotypes early in the growing season. The objectives of this study were to compare the use and performance of GP and PP for predicting soybean seed yield, protein content, and oil content. We additionally conducted Genome Wide Association Studies (GWAS) to identify significant SNPs associated with the traits of interest. These SNPs were also used to train the GP models. The GWAS panel of 292 diverse accessions was grown in six environments in replicated trials. Spectral data were collected at three timepoints during the growing season. A GBLUP model was trained on 268 accessions, while three separate machine learning (ML) models were trained on vegetation indices (VIs) and canopy traits. We observed that for PP, Random Forest (RF) algorithm had the highest rank correlation between the predicted and the actual phenotype rank. PP had a higher correlation coefficient than GP for seed yield, while GP had higher correlation coefficients for seed protein and oil contents. VIs with high feature importance were used as covariates in a new GBLUP model, and a new RF model was trained with the inclusion of selected SNPs from the GWAS results. These models did not outperform the original GP and PP models. These results show the capability of using ML for in-season predictions for specific traits in soybean breeding and provide insights on PP and GP inclusions in breeding programs.
A geranylgeranyl reductase homolog required for cholesterol production in Myxococcota
Authors: Lee Alysha K. , Welander Paula V.
Published: November 2024

Myxococcota is a phylum of sterol producing bacteria. They exhibit a clade depth for sterol biosynthesis unparalleled in the bacterial domain and produce sterols of a biosynthetic complexity that rivals eukaryotes. Additionally, the sterol biosynthesis pathways found in this phylum have been proposed as a potential source for sterol biosynthesis in the last eukaryotic common ancestor, lending an evolutionary importance to our understanding of this pathway in Myxococcota. However, sterol production has only been characterized in a few species and outstanding questions about the evolutionary history of this pathway remain. Here, we identify two myxobacteria,Minicystis roseaandSandaracinus amylolyticus, capable of cholesterol biosynthesis. These two myxobacteria possess a cholesterol biosynthesis pathway that differs in both the ordering and enzymes involved in biosynthesis compared toEnhygromyxa salina, a myxobacterium previously demonstrated to produce cholesterol, as well as the canonical pathways found in eukaryotes. We characterize an alternative bacterial reductase responsible for performing C-24 reduction, further delineating bacterial cholesterol production from eukaryotes. Finally, we examine the distribution and phylogenetic relationships of sterol biosynthesis proteins across both cultured and uncultured Myxococcota species, providing evidence for multiple acquisition events and instances of both horizontal and vertical transfer at the family level. Altogether, this work further demonstrates the capacity of myxobacteria to synthesize eukaryotic sterols but with an underlying diversity in the biochemical reactions which govern sterol synthesis, suggesting a complex evolutionary history and refining our understanding of how myxobacterial cholesterol production relates to their eukaryotic counterparts.

Significance Statement

Sterols are essential and ubiquitous lipids in eukaryotes, but their significance in bacteria is less understood. Sterol production in Myxococcota, a phylum of developmentally complex predatory bacteria, has provided insight into novel sterol biochemistry and prompted discussion regarding the evolution of this pathway within both the eukaryotic and bacterial domains. Here, we characterize cholesterol biosynthesis in two myxobacteria, providing evidence for distinct pathway organization and identifying a unique protein responsible for C-24 reduction. We couple these results to phylogenomic analysis of sterol biosynthesis within Myxococcota revealing a complicated evolutionary history marked by vertical and horizontal transfer, suggesting a mosaic acquisition of this pathway in Myxococcota and highlighting the complex role myxobacteria may have had in sterol transfer to eukaryotes.
New Insights Into The Melanin Structure OfLomentospora prolificans
Authors: Liporagi-Lopes Livia C. , Chrissian Christine , Kacirani Arlind , Camacho Emma , Stark Ruth E. , Casadevall Arturo
Published: November 2024

Lomentospora prolificansis a filamentous fungus with a global distribution, manifesting particularly higher prevalence in human-impacted environments. This organism is associated with a wide spectrum of human infections, especially in immunosuppressed individuals, for whom it causes severe and debilitating illnesses with high morbidity and mortality that are compounded by its pan-resistant profile with respect to antifungal drugs. Melanin is a ubiquitous pigment among fungi with a broad range of actions that include promoting fungal virulence. Although melanin is one of the most studied virulence factors in pathogenic fungi, relatively little is known about the chemistry of this pigment inL. prolificans.In the current study we characterizedL. prolificans-associated melanin using chemical, biological, biophysical and structural techniques, also assessing the impact of inhibitors of distinct melanization pathways. Our results reveal that this pathogenic fungus makes multiple types of melanin pigments and suggests the possibility of a new type of melanin, which is synthesized together with a mixture of DHN-, DOPA- and pyomelanin types. These insights enhance our understanding ofL. prolificans’virulence mechanisms, paving the way for potential therapeutic interventions.
Suppressor of quenching 1 functions as a methionine sulfoxide reductase in the chloroplast lumen for regulation of photoprotective qH in Arabidopsis
Authors: Hao Jingfang , Johansson Alexander , Svensson Fall Johan , Duan Jianli , Hertle Alexander P. , Brooks Matthew D. , Niyogi Krishna K. , Yoshida Keisuke , Hisabori Toru , Malnoë Alizée
Published: November 2024

Photosynthetic organisms must balance light absorption and energy dissipation to prevent photo-oxidative damage. Non-photochemical quenching (NPQ) dissipates excess light energy as heat, with the quenching component qH providing sustained photoprotection. However, the molecular mechanism underlying qH induction remains unclear. Our study focuses on the thylakoid membrane protein SUPPRESSOR OF QUENCHING 1 (SOQ1) and its inhibition of qH through interaction with LIPOCALIN IN THE PLASTID (LCNP) inArabidopsis thaliana. Structural homology of SOQ1 lumenal domains with bacterial disulfide bond protein D suggested potential thiol-disulfide exchange activity.In vitroassays determined that both SOQ1 thioredoxin-like (Trx-like) and C-terminal (CTD) domains contain a redox-active cysteine pair and evidenced electron transfer from Trx-like to CTD. Importantly, we found that SOQ1 lumenal domains exhibit methionine sulfoxide reductase (Msr) activity converting oxidized methionine residues in LCNP back to methionine, which thereby inactivates LCNP and prevents qH formation. Mutational analyses identified cysteine residues in SOQ1-CTD and methionine residues in LCNP as critical for qH suppression, supporting their role in redox regulation. Additionally, we found that the redox state of SOQ1in vivois light-dependent, shifting from reduced to oxidized under stress conditions, indicating a dynamic regulation of its activity. We conclude that the Trx-like domain of SOQ1 provides reducing power to its CTD displaying Msr activity. SOQ1 is therefore an unusual example of a protein possessing both a disulfide reductase and Msr domain in tandem. Our findings elucidate the redox-regulation mechanism of qH involving SOQ1-mediated methionine reduction of LCNP, providing insights into the intricate control of photoprotective processes in chloroplasts and enhancing our understanding of plant resilience under environmental stress.
ArabidopsisSUFBand CLP protease regulate SUFBC2D to manipulate iron-sulfur cluster biosynthesis in chloroplast
Authors: Cheng Yuting , Liu Zhaoyang , Yang Bing , Jiao Qingsong , Ito Hisashi , Takabayashi Atsushi , Tanaka Ryouichi , Jia Ting , Hu Xueyun
Published: November 2024

Iron‒sulfur (Fe‒S) clusters are essential cofactors for Fe‒S proteins. SUFBC2D complex is the scaffold responsible for Fe‒S cluster assembly in chloroplasts. However, the regulatory mechanism on SUFBC2D remains elusive. In this study, we report that the transcription ofSUFBresponds rapidly to leaf senescence, whereas the transcription ofSUFCandSUFDdoes not. Intriguingly, their protein contents remain stable during leaf senescence. We further found that leaf death was occurred only whenSUFBRNAi was induced, and SUFB and SUFC contents decreased much faster in theSUFB-RNAi lines than in theSUFC-RNAi lines, indicating that SUFB had a faster turnover rate than SUFC. Moreover, overexpressingSUFBincreased the contents of SUFC and SUFD, and SUFBC2D, whereas overexpressingSUFCdid not increase SUFB and SUFD. Our findings reveal that SUFB stabilizes SUFC and SUFD via forming SUFBC2D, whereas SUFC lacks this function. Furthermore,SUFBexpression was sharply downregulated when the plants were subjected to iron deficiency, whereasSUFCandSUFDexpression was not. Interestingly, the contents of all three SUF members decreased, indicating that plants degrade SUFBC2D in response to iron deficiency by downregulatingSUFBtranscription. We subsequently studied the degradation mechanism of SUFBC2D. Our results indicated that all SUFs are substrates of the caseinolytic protease (CLP) because they all accumulated in the CLP impaired mutant, and they physically interact with CLPS1, the substrate recognition adaptor of CLP. Collectively, our findings provide novel insights into how plants regulate SUFBC2D complex viaSUFBto adapt to leaf senescence and iron deficiency.
DJ-1 deficiency in SH-SY5Y cells reveals dysregulated networks of genes and pathways involved in neuronal function and disease
Authors: Gock Nathan , Kim Grace , Morin Tessa , Mahal Amar , Kostka Julia , Beischlag Timothy V. , Lee Frank J.S.
Published: November 2024

Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting between 2 – 3% of the population aged 65 and older. Although the etiology of idiopathic PD is still to be elucidated, the study of heritable forms of the disease can provide new understanding into disease mechanisms. Recessively inherited loss of function mutations in thePARK7/DJ-1gene has been found to be causative for familial, early-onset PD. Importantly,PARK7/DJ-1related forms of familial PD replicate common disease phenotypes seen in idiopathic PD, including degeneration of substantia nigra dopaminergic neurons, and Parkinsonism. In this study, we evaluate the loss of function ofPARK7/DJ-1on a human neuronal cell line, SH-SY5Y. Following ablation of thePARK7/DJ-1gene via CRISPR-Cas9, RNA sequencing and the DESEQ2 tool kit were utilized to filter differentially expressed genes betweenPARK7/DJ-1knockouts and control SH- SY5Y cells. 5684 genes were identified to be significantly differentially expressed. 3 genes from each of the top 10 upregulated (ATOH8, LAYN, TLX2) and downregulated (CACNA1B, CPLX2, SV2C) gene lists were selected and confirmed via RT-PCR. Differentially expressed gene lists were run through the WebGestalt functional enrichment analysis toolkit to identify enriched gene ontology (GO) terms for biological processes, cellular components, molecular function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways respectively. Among the top 10 significantly enriched KEGG pathways for upregulated genes were those related to neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease (p-adj ≤ 0.05). Differentially expressed genes were run through the STRING database to predict protein-protein interactions (PPI). A highly significant PPI enrichment was observed (p < 1.0e-16). Our results indicate that loss of DJ-1 function in human neuronal cells leads to dysregulation of networks of connected genes and pathways that are implicated in neurodegenerative disease as well as neuronal function.
Inhibitors of lysinoalanine crosslinking in the flagella hook as antimicrobials against spirochetes
Authors: Lynch Michael J. , Kurniyati Kurni , Deshpande Maithili , Charon Nyles W. , Li Chunhao , Crane Brian R.
Published: November 2024

Spirochetes are especially invasive bacteria that are responsible for several human diseases, including Lyme disease, periodontal disease, syphilis and leptospirosis. Spirochetes rely on an unusual form of motility based on periplasmic flagella (PFs) to infect hosts and evade the immune system. The flexible hook of these PFs contains a post-translational modification in the form of a lysinoalanine (Lal) crosslink between adjacent subunits of FlgE, which primarily comprise the hook. Lal crosslinking has since been found in key species across phylum and involves residues that are highly conserved. The requirement of the Lal crosslink for motility of the pathogensTreponema denticola(Td) andBorreliella burgdorferi(Bb) establish Lal as a potential therapeutic target for the development of anti-microbials. Herein, we present the design, development and application of a NanoLuc-based high-throughput screen that was used to successfully identify two, structurally related Lal crosslink inhibitors (hexachlorophene and triclosan) from a library of clinically approved small molecules. A structure-activity relationship study further expanded the inhibitor set to a third compound (dichlorophene) and each inhibitor was demonstrated to biochemically block autocatalytic crosslinking of FlgE from several pathogenic spirochetes with varied mechanisms and degrees of specificity. The most potent inhibitor, hexachlorophene, alters Lal crosslinking in cultured cells of Td and reduces bacterial motility in swimming plate assays. Overall, these results provide a proof-of-concept for the discovery and development of Lal-crosslink inhibitors to combat spirochete-derived illnesses.
Isoprene deters insect herbivory by priming plant hormone responses
Authors: Sahu Abira , Mostofa Mohammad Golam , Xu Yuan , Serda Bianca M. , Keefe James O’ , Sharkey Thomas D.
Published: November 2024

Isoprene, emitted by some plants, enhances plant abiotic resilience but its role in biotic stress resilience remains elusive. We used tobacco plants engineered to emit isoprene (IE) and the corresponding azygous non-emitting control (NE) to investigate isoprene emission and biotic stress resilience. IE plants were more resistant to insect herbivory than NE plants. Worms preferred to feed on NE rather than IE leaves. IE plants showed less decline in photosynthesis during worm feeding. Insect feeding increased jasmonate levels in IE leaves, suggesting isoprene-mediated priming of the jasmonic acid response. Wound-induced increase in isoprene emission corresponded with elevation of methyl-D-erythritol-4-phosphate pathway and Calvin-Benson cycle metabolites. The results highlight interactive functions of isoprene and jasmonic acid and advance our understanding of how isoprene emission enhances plant resilience.
Tcf4Deficiency Causes Recurrent Seizures in Mice
Authors: Craciun Laura , DeNittis Vivianna R. , Davis Matthew T. , Paz Jeanne T. , Saijo Kaoru
Published: November 2024

Transcription factor 4 (TCF4) is a transcription factor that is critical for the normal development and function of the central nervous system. Haploinsufficiency ofTCF4causes Pitt-Hopkins Syndrome (PTHS), a lifelong neurodevelopmental disorder characterized by seizures and intellectual disability. To expand our currently limited understanding of TCF4 function and PTHS pathophysiology, we created a mouse model of PTHS with largely astrocyte-specific heterozygous knockout ofTcf4. These mice developed severe recurrent seizures and had decreased lifespans. In addition, we found that these mice had astrogliosis as well as increased neuronal activity in the cortex, hippocampus, amygdala, and hypothalamus. Furthermore, single nucleus RNA sequencing analysis revealed global changes in the gene expression profiles of excitatory neurons, inhibitory neurons, astrocytes, and oligodendrocytes of PTHS compared to wild-type mice. Overall, this is the first report of a PTHS mouse model with seizures, providing the field with a tool to investigate the mechanisms of PTHS development and progression and develop therapeutics for PTHS and its associated epilepsy.

HIGHLIGHTS

Novel PTHS mouse model that targets astrocytes develops epilepsy

PTHS mice exhibit astrogliosis and increased neuron activity

Changes in gene expression profile observed in PTHS mice across neurons and glial cells
Intraductal infection with H5N1 clade 2.3.4.4b influenza virus
Authors: Roubidoux Ericka Kirkpatrick , Meliopoulos Victoria , Livingston Brandi , Brigleb Pamela H. , Schultz-Cherry Stacey
Published: November 2024

The ongoing outbreak of highly pathogenic avian influenza (HPAI) H5N1 of the clade 2.3.4.4b in dairy cows has led to numerous questions including how the virus transmits amongst cattle given the limited respiratory infection. One hypothesis is that the virus is spreading through fomites from udder to udder. In these studies, we demonstrate that intraductal inoculation of H5N1 but not H1N1 influenza virus results in infection in mice. This model will be useful to our understanding of the impact of influenza virus on the mammary gland, the potential as a new route of transmission, and can be used to assess if antiviral treatments prevent infections in the mammary gland.
Heart tube morphogenesis is regulated by segment-specific gene regulatory networks controlled by MEF2C
Authors: Muncie-Vasic Jonathon M. , Sinha Tanvi , Clark Alexander P. , Brower Emily F. , Saucerman Jeffrey J. , Black Brian L. , Bruneau Benoit G.
Published: November 2024

The transcription factor MEF2C plays a critical role in the development of the linear heart tube, but the specific transcriptional networks controlled by MEF2C remain largely undefined. To address this, we performed combined single-nucleus RNA-and ATAC-sequencing on wild type and MEF2C-null embryos at distinct stages of development. We identified a broadly “posteriorized” cardiac gene signature and chromatin landscape throughout the heart tube in the absence of MEF2C. By integrating our gene expression and chromatin accessibility data in a deep-learning based model, we were able to construct developmental trajectories for each of the outflow tract, ventricular, and inflow tract lineages and determined how each of these segment-specific trajectories were distinctly altered in the MEF2C-null embryos. We computationally identified potential segment-specific MEF2C-dependent enhancers, and from these candidates, identified novel enhancers with activity in the developing heart tube using transgenesis in zebrafish. Finally, using inferred gene regulatory networks we discovered a genetic interaction betweenMef2cand the atrial nuclear hormone receptorNr2f2, revealing that the MEF2C-null heart malformations are partly driven by a transcriptional network with increased NR2F2 activity. These studies not only provide a rich description of the genomic regulation of early heart tube development, but provide a generalizable framework for using genetic mutants to dissect the transcriptional networks that govern developmental processes.
Network-based representation learning reveals the impact of time and diet on the gut microbial and metabolomic environment of infants
Authors: Price Adelle , Rasolofomanana-Rajery Sakaiza , Manpearl Keenan , Robertson Charles E. , Krebs Nancy F. , Frank Daniel N. , Hendricks Audrey E. , Krishnan Arjun , Tang Minghua
Published: November 2024

While studies have explored differences in gut microbiome development regarding infant liquid diets (breastmilk, formula), surprisingly little is known about the impact of complementary foods on the infant gut microbiome. Indeed, current dietary recommendations for infants and toddlers are not formulated with knowledge of how the developing gut microbiome metabolizes complementary foods. Here, we investigated how different protein-rich foods (i.e., meat vs. dairy) affect fecal metagenomics and metabolomics during early complementary feeding from 5-12 months in formula-fed infants. We used a network node embedding to model the time-dependent, complex interactions between microbiome features, metabolomic compound features, and diet. We then used the embedded space to detect features associated with baseline or endpoint and meat or dairy diet-finding enriched networks of microbiome and metabolomic features, and compared the results to those found using a more traditional differential abundance analysis.
CandidaSpecies Isolated in Female Patients of Reproductive Age with Vaginal Candidiasis in Gualeguaychú, Entre Ríos, Argentina
Authors: Iván Rodrigo Pérez Duarte , Georgina Razetto , Érica Leiva Silvina , Luciano Torres , Josefina Juárez María
Published: November 2024

Objective: To identify theCandidaspecies isolated in female patients of reproductive age with vaginal candidiasis. To determine the antifungal (ATF) sensitivity profile of the isolatedCandidaspecies.Materials and methods: Cross-sectional descriptive study, in which 124Candida sppstrains from vaginal discharge samples were isolated in Sabouraud medium supplemented with glucose.CHRO Magar Candidawas used for species identification and complementary tests such as germ tube, chlamydoconidia development and investigation of trehalose assimilation were performed.In vitrosensitivity was investigated by diffusion method with ATF discs fluconazole (FLU), itraconazole (ITRA) and amphotericin B (AMB).Results: C. albicanswas observed in 85.5% of the isolates followed byC. glabratawith 7.3%,C. krusei4%,C. tropicalis2.4% and otherCandidaspecies. For FLU, 0.9% ofC. albicans, 11.1% ofC. glabrataand 100% ofC. kruseiisolates showed resistance. For ITRA, 17% ofC. albicansisolates, 55.6% ofC. glabrataand 100% ofC. kruseiwere resistant. There were no isolates resistant to AMB.Conclusions: Vaginal candidiasis continues to presentCandida albicansas the main etiological agent, which is widely sensitive to ATFs.C. glabrataandC. kruseispecies show increased resistance to azoles. The results obtained ratify the growing need forCandidaspecies identification tests and determination ofin vitrosensitivity to ATFs in order to guide the treatment of vaginal candidiasis towards therapeutic success.
Consumer self-protection behavior of online meal safety during the COVID-19 pandemic: the impact of risk perception and effect of satisfaction with management safety performance
Authors: Liu Weijun , Cao Mengzhen , Florkowski Wojciech J.
Published: November 2024

Purpose

This study aims to assess the effects of risk perception and management subject satisfaction on consumers' online meal food safety self-protection behavior during the COVID-19 pandemic.

Design/methodology/approach

This study uses 742 questionnaires collected via a two-stage online survey conducted during the COVID-19 pandemic, between December 2021 and January 2022. The entropy method, descriptive statistics, ordered logit model, stepwise regression models, interaction terms and decentralization method were used in the quantitative analysis. Respondents’ written responses to self-protection behavior were categorized into five groups.

Findings

Less than half of consumers were aware that online food products carry the risk of SARS-COV-2 (44.48%). Between 30 and 40% of consumers took insufficient or no self-protection measures. Risk perception significantly and positively affected self-protection behavior during the COVID-19 pandemic. Consumers' management subject satisfaction has a positive moderating effect on risk perception, with the moderating effect of the satisfaction of online retailers being significant at the 5% level. Risk perception significantly and positively influences consumer self-protection behavior in provinces not affected by the pandemic.

Originality/value

The findings stress the benefits of synergistic interventions by consumers and management subject to food safety measures and the inclusion of tailored interventions during events threatening public health to effectively address food safety. The study offers valuable insights contributing to the improvement of public health outcomes, customer trust and service quality within the online food delivery industry.
Christians and the Parable of the Vineyard Workers: Christianity, distributive justice perception, and job satisfaction
Authors: Yoon Yeongjoon , Almond Brad
Published: November 2024

Purpose

Despite recent efforts to link religion with job satisfaction, the current state of research lacks the knowledge of why there may be a positive relationship between the two variables. This study tries to fill this gap by testing the notion that Christians are more likely to exhibit a higher level of distributive justice perception, which leads to a higher level of job satisfaction. The study also tries to identify Christianity as the moderator in the relationship between distributive justice and job satisfaction.

Design/methodology/approach

This study uses secondary data. The study analyzes 13,289 employees in 27 countries in the 2010 European Social Survey, which contains information on the levels of distributive justice perceptions and job satisfaction, as well as the religious affiliations of the respondents. The country fixed effect regression analysis was conducted.

Findings

The analyses first reveal that Protestants, compared to non-Protestants, exhibit a higher level of distributive justice perception, which leads to a higher level of job satisfaction. The analyses also demonstrate that the positive relationship between distributive justice perception and job satisfaction is weaker for Protestants than non-Protestants. These relationships, however, were not evident for people affiliated with other denominations of Christianity.

Practical implications

Protestant employees are likely to maintain a higher level of distributive justice perception, and distributive justice perception matters less in shaping their job satisfaction. As a result, organizations may want to focus more on the other aspects of organizational justice, such as procedural and interactional justices in managing protestant employees, if maintaining job satisfaction level is a concern. With many “Christian-based” companies operating and being supported in today’s economy, the findings in this study can be useful to these organizations that are more likely to attract and have Christians as their employees.

Originality/value

The current study provides evidence that employees’ religious affiliation (i.e. Protestantism in this case) can be a predictor of job satisfaction through the mediation of distributive justice perception. It also offers a basis for future studies on employee morale (e.g. job satisfaction and justice perceptions) to consider religious factors. Finally, the findings also identify Protestant affiliation as a moderator in the distributive justice–job satisfaction relationship.
Finding grace in responses to adverse cybersecurity incidents
Authors: Dupuis Marc , Searle Rosalind , Renaud Karen V.
Published: November 2024

Purpose

The purpose of this study was to investigate the role of grace in the aftermaths of adverse cybersecurity incidents. Adverse incidents are an inescapable fact of life in organizational settings; consequences could be significant and costly. Increasingly, the cause may be a cybersecurity exploit, such as a well-targeted phishing email. In the aftermath, line managers have a choice in responding to the individual who caused the incident. Negative emotions, such as shame and regret, may deliberately be weaponized. Alternatively, positive emotions, such as grace, forgiveness and mercy, may come into play.

Design/methodology/approach

We detail a study with 60 participants to explore attribution differences in response to adverse incidents, both non-cybersecurity and cybersecurity. We examined the stages that occur in the aftermath of such adverse incidents where grace may be observed.

Findings

Our participants generally believed that grace was indicated toward those who triggered an adverse cybersecurity incident, pointing to situational causes. This was in stark contrast to their responses to the non-cybersecurity incident, where the individual was often blamed, with punishment being advocated.

Research limitations/implications

The role of positive emotions merits investigation in the cybersecurity context if we are to understand how best to manage the aftermaths of adverse cybersecurity incidents.

Practical implications

Organizations that mismanage aftermaths of adverse incidents by blaming, shaming and punishing those who make mistakes will harm the individual who made the mistake, other employees and the long-term health of their organization in the long run.

Originality/value

To the best of the authors’ knowledge, this is the first study to reveal the grace phenomenon in the cybersecurity context.
Latino adolescents’ experiences of residential risks on social media and mental health implications
Authors: Campos‐Castillo Celeste , Groh Sarah M. , Laestadius Linnea I.
Published: November 2024

Despite alarms raised that adolescents’ social media use can aggravate the harmful impact of residential risks (e.g. local violence) to their mental health, the mechanisms are poorly understood. To better understand potential mechanisms, we interviewed Latino adolescents living in a hypersegregated U.S. city, for whom social media may aggravate existing inequalities in residential risks to their mental health. Through an abductive analysis, we identified two processes suggesting how social media can amplify the deleterious impact of residential risks to their mental health. We refer to the first as additive, whereby social media heightens awareness of residential risks. The second is extension, whereby social media lengthens one’s risk awareness, speeds up potential for risk awareness and multiplies who may become aware. We found evidence suggestive of parallel processes yielding diminution, whereby social media can minimise the deleterious effects of residential risks via adding and extending exposure to mental health resources, like collective efficacy. Further, the potential for extension (to both risks and resources) appears limited because social media practices (e.g. reposting, seeking viral attention) can foster indifference. Findings suggest the need to consider how adolescents activate resources via social media to avoid overstating its negative impact on mental health.
Harnessing Gram‐negative bacteria for novel anti‐Gram‐negative antibiotics
Authors: Birkelbach Joy , Seyfert Carsten E. , Walesch Sebastian , Müller Rolf
Published: November 2024

Natural products have proven themselves as a valuable resource for antibiotics. However, in view of increasing antimicrobial resistance, there is an urgent need for new, structurally diverse agents that have the potential to overcome resistance and treat Gram‐negative pathogens in particular. Historically, the search for new antibiotics was strongly focussed on the very successful Actinobacteria. On the other hand, other producer strains have been under‐sampled and their potential for the production of bioactive natural products has been underestimated. In this mini‐review, we highlight prominent examples of novel anti‐Gram negative natural products produced by Gram‐negative bacteria that are currently in lead optimisation or preclinical development. Furthermore, we will provide insights into the considerations and strategies behind the discovery of these agents and their putative applications.
TMEM16F regulates pathologic α‐synuclein secretion and spread in cellular and mouse models of Parkinson's disease
Authors: Cohen‐Adiv Stav , Amer‐Sarsour Fatima , Berdichevsky Yevgeny , Boxer Emily , Goldstein Orly , Gana‐Weisz Mali , Tripathi Utkarsh , Rike Wote Amelo , Prag Gali , Gurevich Tanya , Giladi Nir , Stern Shani , Orr‐Urtreger Avi , Friedmann‐Morvinski Dinorah , Ashkenazi Avraham
Published: November 2024

One of the main hallmarks of Parkinson's disease (PD) pathology is the spread of the aggregate‐prone protein α‐synuclein (α‐syn), which can be detected in the plasma and cerebrospinal fluid of patients as well as in the extracellular environment of neuronal cells. The secreted α‐syn can exhibit “prion‐like” behavior and transmission to naïve cells can promote conformational changes and pathology. The precise role of plasma membrane proteins in the pathologic process of α‐syn is yet to be fully resolved. The TMEM16 family of lipid scramblases and ion channels has been recently associated with cancer and infectious diseases but is less known for its role in aging‐related diseases. To elucidate the role of TMEM16F in α‐syn spread, we transduced neurons derived from TMEM16F knockout mice with a reporter system that enables the distinction between donor and recipient neurons of pathologic α‐synA53T. We found that the spread of α‐synA53T was reduced in neurons derived from TMEM16F‐knockout mice. These findings were recapitulated in vivo in a mouse model of PD, where attenuated α‐synA53T spread was observed when TMEM16F was ablated. Moreover, we identified a single nucleotide polymorphism in TMEM16F of Ashkenazi Jewish PD patients resulting in a missense Ala703Ser mutation with enhanced lipid scramblase activity. This mutation is associated with altered regulation of α‐synA53T extracellular secretion in cellular models of PD. Our study highlights TMEM16F as a novel regulator of α‐syn spread and as a potential therapeutic target in synucleinopathies.
Safety and efficacy of surgical revascularization with percutaneous ventricular assist device for acute myocardial infarction complicated by cardiogenic shock: Japanese national registry study
Authors: Fujii Masahiko , Okino Shinichi , Sakata Tomoki , Mogi Kenji , Sakurai Manabu , Takahara Yoshiharu ,   J‐PVAD Registry Investigators
Published: November 2024

Background

This study aims to assess the safety of coronary artery bypass grafting (CABG) with percutaneous ventricular assist device (PVAD) in patients with acute myocardial infarction complicated by cardiogenic shock (AMI‐CS).

Methods

A retrospective analysis was conducted on 1198 patients with AMI‐CS from the J‐PVAD registry, who underwent PVAD support using Impella® (Abiomed Inc., Danvers, MA) and subsequent revascularization between February 2020 and December 2021. Patients were divided into two groups based on the method of coronary revascularization: percutaneous coronary intervention (PCI, n = 1084) and CABG (n = 114). The study assessed short‐term all‐cause and cardiac‐related mortality.

Results and conclusion

The CABG group exhibited significantly lower short‐term all‐cause mortality compared with the PCI group (30‐day: 26.2% vs. 39.9%, 90‐day: 45.5% vs. 58.4%, log‐rank p = 0.004). Short‐term cardiac‐related mortality was similar toward low in the CABG group compared with the PCI group (30‐day: 18.7% vs. 25.6%, 90‐day: 29.4% vs. 35.5%, log‐rank p = 0.084). Multivariable analysis using the Cox proportional hazard model did not identify revascularization strategy as a risk factor for both all‐cause mortality (Hazard ratio (HR): 0.743, 95% confidence intervals (CI): 0.457–1.208, p = 0.231) and cardiac‐related mortality (HR: 0.762, 95% CI: 0.390–1.490, p = 0.427). These results were not attenuated even in subgroup analyses separately comparing CABG alone and hybrid therapy with PCI after propensity score matching. Thus, CABG can be a treatment option with feasible short‐term outcomes in patients with AMI‐CS under PVAD support.
Higher initial levothyroxine doses and very early treatment start may lead to better cognitive outcomes in children with congenital hypothyroidism
Authors: Danner Emmi , Niuro Laura , Lapinoja Sonja , Huopio Hanna , Viikari Liisa A. , Kero Jukka , Jääskeläinen Jarmo , Niinikoski Harri
Published: November 2024

Aim

This study aimed to assess the cognitive development of individuals with congenital hypothyroidism.

Methods

Using hospital records, we identified 180 patients with congenital hypothyroidism born between 1980 and 2018 in Turku and Kuopio University Hospital catchment areas. Cognitive development was evaluated in 22 adults (7 males and 15 females) and 20 children (8 males and 12 females) using age‐specific Wechsler Intelligence Scales. Full‐scale IQ (FSIQ) and the four indices were compared to standardisation samples. Simple linear regression was used to test whether treatment‐related variables predicted FSIQ.

Results

FSIQ and its four indices differed significantly from the standardisation sample in adults with congenital hypothyroidism (FSIQ 87.64, SD 13.70, p < 0.001) but not in children (FSIQ 97.90, SD 15.12). Adults had received a lower initial levothyroxine dose than children (8.1 mg/kg, 95% CI 7.2–9.0 vs. 10.2 mg/kg 9.7–10.7, p < 0.001), and their treatment was initiated later (4.8 days, 95% CI 4.0–5.6 vs. 3.6 days, 2.9–4.2, p = 0.018).

Conclusion

Adults with congenital hypothyroidism had a significantly lower FSIQ compared to the population standard, while children's FSIQ did not differ. Our findings suggest that a higher initial levothyroxine dose together with very early treatment start may lead to better cognitive outcomes.
Epidemiology of paediatric winter sports‐related injuries in France: The WINTRAUMA‐1 retrospective cohort study
Authors: Mugniery Quentin , Ricard Cécile , Mirtain Suzanne , Navarre Manon , Tanné Corentin
Published: November 2024

Aim

To describe the epidemiology of injuries related to winter sports in patients younger than 15 years in France.

Methods

We conducted a retrospective observational multicentre cohort study of patients younger than 15 years who were seen by mountain‐community general practitioners for winter‐sports injuries in 1999–2022.

Results

Of the 108 619 patients (mean age, 11.4 ± 2.8 years), 76 724 (70.6%), 26 186 (24.1%) and 2132 (2.0%) were injured while skiing, snowboarding and sledding, respectively. Helmet use was noted in 50 164 (46.2%) patients and increased over time but remained low among sledders. A collision was the mechanism in 12.3% of patients overall and 32.1% of sledders. The most common injuries overall were wrist fractures (48.5%), head and trunk injuries (42.3%), and anterior cruciate ligament (ACL) tears (23.7%), with wrist fractures being more common in beginners (24.7%) and head/trunk injuries and ACL tears in advanced participants (18.3% and 2.6%, respectively). Only 3699 (3.4%) patients were admitted after the general‐practitioner visit, notably for leg or ankle fractures (9.5%).

Conclusion

Winter sports‐related injuries vary according to age, sex, skill level and sport. Admission rates are low but might be further decreased by better prevention. Protective measures should be tailored to each sport and individual.