bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bidirectional genetic and phenotypic links between smoking and striatal iron content involving dopaminergic and inflammatory pathways
Authors: Trofimova Olga , Iuliani Ilaria , Bergmann Sven 
Published: September 2024

AbstractTobacco smoking is a major modifiable risk factor for cardiovascular and lung diseases. A better understanding of its neurobiological underpinnings will benefit the prevention of smoking-related illnesses and mortality. Recent neuroimaging studies have identified a correlation between smoking and iron concentration in the brain’s striatum, a subcortical region involved in habit formation and compulsive behaviour, and a central node of dopamine activity. Moreover, iron accumulation in the striatum is associated with lower cognitive performance in adults. Here, we investigated phenotypic and genetic correlations, and causal relationships between smoking initiation (ever smoked regularly) and susceptibility-weighted magnetic resonance imaging (MRI)-derived markers of iron content–T2* and quantitative susceptibility mapping (QSM)–in the bilateral putamen, caudate, and accumbens nuclei. We computed correlations between smoking and striatal iron in the UK Biobank, adjusting for a vast set of imaging and non-imaging confounders. Using genome-wide association studies (GWAS) summary statistics, we performed global genetic correlation, cross-GWAS coherence tests at the gene level, and causality analysis using Mendelian randomisation and PascalX. Smoking was positively correlated with iron content in the bilateral putamen, caudate, and in the left accumbens, with the strongest effect found when contrasting current and never smokers. Striatal iron had a positive association with pack-years and a negative relationship with years since stopping smoking, indicating a possible reversal of iron accumulation after smoking cessation. Genetic correlation paralleled phenotypic correlation. Cross-GWAS signal was coherent in genes involved in the dopaminergic and glutamatergic systems, and synaptic function. There was evidence of a causal relationship from smoking to striatal iron through genes involved in synaptogenesis and plasticity, and to a lesser extent, from striatal iron to smoking through inflammatory and immune system related genes. Moreover, the heterogeneity of genes with correlated and anti-correlated signals suggests that the neurobiological mechanisms linking iron to smoking behaviour are highly complex. Overall our results show an association between cigarette smoking and iron concentration in the striatum with complex multi-directional causal mechanisms involving synaptic transmission and inflammatory circuits.
Longitudinal Changes in Lifestyle Behaviors and Cardiovascular Health During the Transition to Fatherhood: The Dad Bod Study Rationale and Design
Authors: Landry Matthew J. , Pineda Jocelyn P. , Lee Jaylen M. , Hoyt Michael A. , Edwards Karen L. , Lindsay Karen L. , Gardner Christopher D. , Wong Nathan D. 
Published: September 2024

AbstractBackgroundDespite the importance of the transition to fatherhood as a critical life stage among young adult men, much remains unknown about the factors predictive of ideal cardiovascular health (CVH) and how CVH is impacted as young men face new roles and responsibilities associated with fatherhood.MethodsTo address this gap, the Dad Bod Study is a prospective, longitudinal and observational study designed to examine how fatherhood affects young men’s CVH. A total of 125, first-time prospective fathers (men, 19-39 years) will be enrolled and followed over 1.5 years. Metrics of the American Heart Association’s “Life’s Essential 8” as well as demographic, social, and psychosocial factors will be collected at four time points ((baseline (during the pregnant partner’s 2nd trimester) 1-month postpartum, 6-months postpartum, and 1-year postpartum). The primary aims are to measure predictors of CVH among first-time fathers and describe longitudinal changes in CVH. A secondary aim is to identify best practices for recruitment, retention, and remote data collection in this population.SummaryThe Dad Bod Study offers a novel examination of CVH among first-time fathers, exploring how new paternal roles and responsibilities impact cardiovascular health. Findings may provide key insights into critical CVH behaviors and risk factors to monitor, preserve, and improve as young men transition to fatherhood.
The translation inhibitors kasugamycin, edeine and GE81112 target distinct steps during 30S initiation complex formation
Authors: Safdari Haaris A. , Morici Martino , Sanchez-Castro Ana , Dallapè Andrea , Paternoga Helge , Giuliodori Anna Maria , Fabbretti Attilio , Milón Pohl , Wilson Daniel N. 
Published: September 2024

AbstractDuring bacterial translation initiation, the 30S ribosomal subunit, initiation factors, and initiator tRNA define the reading frame of the mRNA. This process is inhibited by kasugamycin, edeine and GE81112, however, their mechanisms of action have not been fully elucidated. Here we present cryo-electron microscopy structures of 30S initiation intermediate complexes formed in the presence of kasugamycin, edeine and GE81112 at resolutions of 2.0-2.9 Å. The structures reveal that all three antibiotics bind within the E-site of the 30S and preclude 30S initiation complex formation. While kasugamycin and edeine affect early steps of 30S pre-initiation complex formation, GE81112 stalls pre-initiation complex formation at a further step by allowing start codon recognition, but impeding IF3 departure. Collectively, our work highlights how chemically distinct compounds binding at a conserved site on the 30S can interfere with translation initiation in unique manner.
Protocol for simultaneous evaluation of neuronal activity and neurotransmitter release following chronic amyloid-beta oligomer injections into the hippocampus
Authors: Hervé Vincent , Bonenfant Laurie , Amyot Mathilde , Balafrej Rime , Ali Obai Bin Ka’B , Benali Habib , Brouillette Jonathan 
Published: September 2024

SummaryIn Alzheimer’s disease, there is an imbalance in neurotransmitter release and altered neuronal activation. We present a novel approach to analyze neuronal activity by combining local field potential (LFP) recording with microdialysis within the same animal. This method measures glutamate and GABA levels following chronic hippocampal amyloid-beta oligomer (Aβo) injections in rats. We outline the design of our electrode and canula, the surgical procedure, and the steps for LFP recording, interstitial fluid collection, and Aβo injections simultaneously in living animal.Graphical abstract
Minimizing the number of phosphenes required for object recognition under prosthetic vision
Authors: Scialom Elsa , Ernst Udo A. , Rotermund David , Herzog Michael H. 
Published: September 2024

AbstractCortical prostheses offer the potential for partial vision restoration in individuals with blindness by stimulating V1 neurons to produce phosphenes. However, the low number of phosphenes that can be elicited in practice makes encoding of whole objects difficult, and the round shape of phosphenes lack the contour cues necessary for perceptual grouping. We propose a minimalistic encoding approach that focuses on essential visual information. We fragmented objects’ contours into either phosphenes or curved segments, providing either low or high local visual information. 46 participants identified these fragmented objects in a free-naming task. The number of fragments gradually increased to quantify the minimum number of phosphenes and segments necessary to recognize objects. Most objects could be recognized with only 65 phosphenes, which is in the range of implantable electrodes in human patients. Participants required 27% fewer segments than phosphenes to recognize objects. Including individual objects as a random effect in a linear mixed model substantially increased the explained variance, suggesting that the minimal number of fragments required for object recognition in prosthetic vision strongly depends on the particular object. Our results demonstrate that a minimalistic approach can substantially reduce the number of phosphenes required for recognition, emphasizing the importance of identifying critical object features to minimize brain stimulation in visual prostheses.
“Regressing Away Common Neural Choice Signals does not make them Artifacts. Comment on Frömer et al (2024, Nature Human Behaviour)”
Authors: O’Connell Redmond G. , Corbett Elaine A. , Parés-Pujolràs Elisabeth , Feuerriegel Daniel , Kelly Simon P. 
Published: September 2024

AbstractFrömer et al (2024, Nature Human Behaviour) apply a deconvolution method to correct for component overlap in the event-related potential. They report that this method eliminates signatures of sensory evidence accumulation from response-aligned measurements of the centro-parietal positivity (CPP), suggesting that these signatures arise artifactually.. Here, we argue that the analysis and interpretation of their perceptual choice data are critically flawed. We demonstrate with simulations that the deconvolution analyses used by the authors are not designed to reliably test for the presence or absence of bounded accumulation signals.
MALT1 protease inhibition restrains glioblastoma progression by reversing tumor-associated macrophage-dependent immunosuppression
Authors: Hofstätter Azambuja Juliana , Yerneni Saigopalakrishna S. , Maurer Lisa M. , Crentsil Hannah E. , Debom Gabriela N. , Klei Linda , Smyers Mei , Sneiderman Chaim T. , Schwab Kristina E. , Acharya Rajesh , Lin Wu Yijen , Ekambaram Prasanna , Hu Dong , Gough Pete J. , Bertin John , Melnick Ari , Kohanbash Gary , Bao Riyue , Lucas Peter C. , McAllister-Lucas Linda M. 
Published: September 2024

AbstractMALT1 protease is an intracellular signaling molecule that promotes tumor progression via cancer cell-intrinsic and cancer cell-extrinsic mechanisms. MALT1 has been mostly studied in lymphocytes, and little is known about its role in tumor-associated macrophages. Here, we show that MALT1 plays a key role in glioblastoma (GBM)-associated macrophages. Mechanistically, GBM tumor cells induce a MALT1-NF-κB signaling axis within macrophages, leading to macrophage migration and polarization toward an immunosuppressive phenotype. Inactivation of MALT1 protease promotes transcriptional reprogramming that reduces migration and restores a macrophage “M1-like” phenotype. Preclinicalin vivoanalysis shows that MALT1 inhibitor treatment results in increased immuno-reactivity of GBM-associated macrophages and reduced GBM tumor growth. Further, the addition of MALT1 inhibitor to temozolomide reduces immunosuppression in the tumor microenvironment, which may enhance the efficacy of this standard-of-care chemotherapeutic. Together, our findings suggest that MALT1 protease inhibition represents a promising macrophage-targeted immunotherapeutic strategy for the treatment of GBM.Graphical abstract.The effects of tumor cell-induced CARD9-BCL10-MALT1 (CBM) activation (left) and MALT1 protease inhibition (right) on GBM associated macrophages in the tumor microenvironment.Cartoon of cellular components of a GBM tumor with an immunosuppressive TME characterized by “M2-like macrophages” (left) and conversion to a more immune-reactive tumor microenvironment characterized by “M1-like macrophages and increased effector T-cells (right) as a result of MALT1 protease inhibition.
Sleep modulates neural timescales and spatiotemporal integration in the human cortex
Authors: Cusinato Riccardo , Seiler Andrea , Schindler Kaspar , Tzovara Athina 
Published: September 2024

AbstractSpontaneous neural dynamics manifest across multiple timescales, which are intrinsic to brain areas and exhibit hierarchical organization across the cortex. In wake, a hierarchy of timescales is thought to naturally emerge from microstructural properties, gene expression, and recurrent connections. A fundamental question is timescales’ organization and changes in sleep, where physiological needs are different. Here, we describe two coexisting but distinct measures of neural timescales, obtained from broadband activity and gamma power, which display complementary properties. We leveraged intracranial electroencephalography (iEEG) data to characterize timescale changes from wake to sleep across the cortical hierarchy. We show that both broadband and gamma timescales are globally longer in sleep than in wake. While broadband timescales increase along the sensorimotor-association axis, gamma ones decrease. During sleep, slow waves can explain the increase of broadband and gamma timescales, but only broadband ones show a positive association with slow-wave density across the cortex. Finally, we characterize spatial correlations and their relationship with timescales as a proxy for spatiotemporal integration, finding high integration at long distances in wake for broadband and at short distances in sleep for gamma timescales. Our results suggest that mesoscopic neural populations possess different timescales that are shaped by anatomy and are modulated by the sleep/wake cycle.Significance statementUnderstanding the organization of intrinsic neural dynamics is crucial for investigating brain functions in health and disease. A key question is: how do neural dynamics change in the sleeping brain? Here we focus on neural timescales, which measure temporal autocorrelation and are organized hierarchically across the cortex, and spatial correlations. We show that two types of timescales exist in neural populations recorded with intracranial electroencephalography in humans, corresponding to broadband (0.5-80 Hz) and gamma (40-80 Hz) frequency ranges. Both timescales increase in sleep, where slow waves have an important role, but follow opposite hierarchies: broadband timescales increase from sensory to associative areas, while gamma timescales show the reverse pattern. Finally, timescales covary with spatial correlations, suggesting higher spatiotemporal integration over long distances in wake compared to sleep.
EMT Induction In Normal Breast Epithelial Cells ByCOX2-Expressing Fibroblasts
Authors: Kang Minwoo , Devarasou Somayadineshraj , Kwon Tae Yoon , Shin Jennifer H. 
Published: September 2024

AbstractBackgroundThe tumor microenvironment (TME) plays a pivotal role in cancer progression, with cancer-associated fibroblasts (CAFs) significantly influencing tumor behavior. Especially, elevatedCOX2expressing fibroblasts within the TME, notably in collagen-dense tumors like breast cancer, has been recently emphasized in the literature. However, the specific effect ofCOX2-expressing CAFs (COX2+CAFs) on neighboring cells and their consequent role in cancer progression is not fully elucidated.MethodsWe inducedCOX2+fibroblasts by forcing the fibroblasts forming aggregates to undergo Nemosis as a proxy forCOX2+CAFs. This approach enabled us to simulate the paracrine interactions betweenCOX2+CAFs and normal breast epithelial cells via conditioned media fromCOX2+fibroblasts. We developed an innovativein vitroplatform that combines cell mechanics-based analysis and biomolecular assays to study the interactions betweenCOX2+fibroblasts and normal breast epithelial cells. By focusing on the mechanical characteristics of the cells and the EMT marker expressions, we aimed to elucidate the paracrine mechanisms through whichCOX2+CAFs influence the tumor microenvironment.ResultsOurin vitrofindings reveal thatCOX2+fibroblasts, through conditioned media, induce significant changes in the mechanical behavior of normal breast epithelial cells, facilitating their transition towards mesenchymal types. This transition was corroborated by increased expression of mesenchymal markers. By drawing parallels betweenCOX2+fibroblasts andCOX2+CAFs, we established a positive feedback loop involvingCOX2+CAFs, prostaglandin E2 (PGE2), and the EP4-SNAI1axes.ConclusionThis study advances our understanding of the potential mechanisms by whichCOX2+CAFs influence tumor progression within the breast tumor microenvironment (TME) through controlledin vitroinvestigations. By integrating cell mechanics-based analysis, biomolecular assays, and innovativein vitrocell-based modeling ofCOX2+CAFs, we have delineated the contributory role of these cells in a controlled setting. These insights lay a groundwork for future studies that could explore the implications of these findingsin vivo, potentially guiding targeted therapeutic strategies.
Metagenomic co-assembly reveals mobile antibiotic resistance genes in airborne microbiomes in the Eastern Mediterranean
Authors: Erkorkmaz Burak Adnan , Zeevi David , Rudich Yinon 
Published: September 2024

AbstractAntibiotic resistance is a significant threat to global ecological health. Mobile resistance genes are of particular concern due to their ability to transfer between organisms. In environmental settings and within the microbiota of humans and animals, these genes can sometime move into pathogens, promoting the spread of resistance. While various dispersal mechanisms have been studied, the role of air masses and dust storms in spreading antibiotic resistance genes globally remains largely unexplored. We analyzed air samples from non-dusty conditions and Middle Eastern dust storms using a metagenomic co-assembly approach to identify mobile antibiotic resistance genes dispersed by these air masses. Our analysis shows that co-assembling low-biomass air samples of similar origin produces longer genome fragments, allowing for a more detailed bioinformatic analysis that links functional features to specific taxa. Through this method, we identified genes associated with resistance to antibiotics such as aminoglycosides, beta-lactams, bleomycin, fosfomycin, chloramphenicol, daunorubicin, fluoroquinolones, glycopeptides, quinolones, streptomycin, and tetracyclines. Approximately 10% of these genes were linked to mobile genetic elements. These findings demonstrate the potential for global spread of resistance genes across ecosystems via air masses, particularly dust storms, and underscore the need for continuous atmospheric monitoring and further research to develop strategies that mitigate their impact on public health, the environment, and agriculture.
Executive dysfunction is associated with altered hippocampal-prefrontal functional connectivity in male 3xTg Alzheimer’s model mice
Authors: Cunliffe Grace , Tan Li Yang , Sangyong Jung , Turner Jonathan , Gigg John 
Published: September 2024

AbstractExecutive function depends on connectivity between the ventral hippocampus and medial prefrontal cortex (mPFC). How abnormalities in this pathway lead to cognitive dysfunction in Alzheimer’s disease (AD) have yet to be elucidated. Here, male 3xTg AD mice at 6-months displayed maladaptive decision-making in the rodent 4-Choice Gambling Task measure of executive function. Extracellular field recordings in the infralimbic cortex at this age showed layer-specific reductions in response amplitude and paired-pulse ratio following activation of hippocampal input fibres, indicating changes to short-term hippocampal-prefrontal synaptic plasticity. Bulk RNA sequencing of the mPFC in 6-month-old mice identified differential gene expression changes associated with calcium ion transport, glutamatergic, GABAergic, and dopaminergic neurotransmission. Seven of these genes (Gpm6b, Slc38a5, Ccr5, Kcnj10, Ddah1, Gad1, Slc17a8) were also differentially expressed in 3-month mice. These results reveal a pre-clinical deficit in executive function correlating with synaptic plasticity and gene expression changes in the mPFC of male 3xTg mice.
A persistent bacterialRegiellatransinfection in the bird cherry-oat aphidRhopalosiphum padiincreasing host fitness and decreasing plant virus transmission
Authors: Yu Wenjuan , Yang Qiong , Gill Alex , Chirgwin Evatt , Gu Xinyue , Joglekar Chinmayee , Umina Paul A. , Hoffmann Ary A. 
Published: September 2024

AbstractThe bird cherry-oat aphid,Rhopalosiphum padi, is a major pest of agriculture due to its ability to directly damage crops and transmit plant viruses. As industries move away from chemical pest control, there is interest in exploring new options to suppress the impact of this pest. Here we describe the production of a transinfected line ofR. padicarrying the bacterial endosymbiont,Regiella insecticola, originating from the green peach aphid,Myzus persicae. We show thatRegiellaincreases the fitness of its novel host despite decreasing fitness in its native host.Regiellaalso shows a low level of horizontal transmission. Importantly the infection suppresses the ability ofR. padito transmit the barley yellow dwarf virus which damages wheat plants. This transinfection could be released to suppress virus transmission by aphids with its ability to persist and spread, making it potentially suitable for wide area release.
Spatiotemporal variation in size-dependent growth rates in small isolated populations of Arctic charr (Salvelinus alpinus)
Authors: Mittell Elizabeth A. , Leblanc Camille A. , Kristjánsson Bjarni K. , Ferguson Moira M. , Räsänen Katja , Morrissey Michael B. 
Published: September 2024

AbstractAs a key life-history trait, growth rates are often used to measure individual performance and to inform parameters in demographic models. Furthermore, intra-specific trait variation generates diversity in nature. Therefore, partitioning out and understanding drivers of spatiotemporal variation in growth rate is of fundamental interest in ecology and evolution. However, this has rarely been attempted due to the amount of individual-level data required through both time and space, and issues with missing data in important covariates. Here we implemented a Bayesian state-space model using individual-level data from 20 populations of Arctic charr (Salvelinus alpinus) across 15 capture occasions, which allowed us to: (1) integrate over the uncertainty of missing recapture records; (2) robustly estimate size-dependence; and (3) include a covariate (water temperature) that contained missing data. Interestingly, although there was substantial spatial, temporal, and spatiotemporal variation in growth rate, this was only weakly associated with variation in water temperature and almost entirely independent of size, suggesting that spatiotemporal variation in other environmental conditions affected individuals across sizes similarly. This fine-scale spatiotemporal variation emphasises the importance of local conditions and highlights the potential for spatiotemporal variation in a size-dependent life-history trait, even when environmental conditions are apparently very similar.
The ‘sexual selection hypothesis’ for the origin of aposematism
Authors: Maisonneuve Ludovic , Aubier Thomas G. 
Published: September 2024

AbstractThe evolution of aposematism, in which prey exhibit conspicuous signals indicating the presence of anti-predator defenses, is puzzling. Before predators learn to associate the signal with defense, increased visibility makes the conspicuous prey highly vulnerable to predation. Although several hypotheses have been proposed to explain the evolution of aposematism, they often assume that these signals can only be recognized by predators. Yet, many studies show that aposematic signals can also be involved in mate choice. Here, we demonstrate that some aposematic signals may have originally evolved as mating signals driven by sexual selection. In this study, we analyze a mathematical model to explore how sexual selection can drive the evolution of aposematism. We thereby identify key features of this ‘sexual selection hypothesis’ for the origin of aposematism to be tested with empirical data. Our results show that the evolution of conspicuous signals through sexual selection increases the visibility of prey to predators and thus predation pressure. This, in turn, promotes the evolution of defense mechanisms, ultimately leading to aposematism when predators learn to associate the signal with defense. Additionally, we show that when sexual selection drives the evolution of aposematism, it often results in sexual dimorphism in both signaling and defense traits.