Murine gut microbiota dysbiosis via enteric infection modulates the foreign body response to a distal biomaterial implant.

Unlabelled: The gut microbiota influences systemic immunity and the function of distal tissues, including the brain, liver, skin, lung, and muscle. However, the role of the gut microbiota in the foreign body response (FBR) and fibrosis around medical implants is largely unexplored. To investigate this connection, we perturbed the homeostasis of the murine gut microbiota via enterotoxigenic (ETBF) infection and implanted the synthetic polymer polycaprolactone (PCL) into a distal muscle injury.

Genetic changes linked to two different syndromic forms of autism enhance reinforcement learning in adolescent male but not female mice.

Unlabelled: Autism Spectrum Disorder (ASD) is characterized by restricted and repetitive behaviors and social differences, both of which may manifest, in part, from underlying differences in corticostriatal circuits and reinforcement learning. Here, we investigated reinforcement learning in mice with mutations in either or , both high-confidence ASD risk genes associated with major syndromic forms of ASD. Using an odor-based two-alternative forced choice (2AFC) task, we tested adolescent mice of both sexes and found male and heterozygote (Het) mice showed enhanced learning performance compared to their wild type (WT) siblings.

Initiation of primary T cell-B cell interactions and extrafollicular antibody responses in an organized microphysiological model of the human lymph node.

Antibody production is central to protection against new pathogens and cancers, as well as to certain forms of autoimmunity. Antibodies often originate in the lymph node (LN), specifically at the extrafollicular border of B cell follicles, where T and B lymphocytes physically interact to drive B cell maturation into antibody-secreting plasmablasts. In vitro models of this process are sorely needed to predict aspects of the human immune response.

Environmental, Developmental, and Genetic Conditions Shaping Monarch Butterfly Migration Behavior.

Monarch butterflies in North America migrate south each autumn, but the mechanisms that initiate their migratory flight remain incompletely understood. We investigated environmental, developmental, and genetic factors that contribute to directional flight by testing summer and autumn-generation monarchs in three flight simulators: two at ground level (with and without wind blockage) and a novel balloon-based system that raised butterflies 30 meters into the air. Monarchs reared under autumn-like conditions in a growth chamber during the summer were also tested to explore the influence of developmental cues.

RNA sequencing reveals key factors modulating TNFα-stimulated odontoblast-like differentiation of dental pulp stem cells.

Inflammation is a complex host response to harmful infections or injuries, playing both beneficial and detrimental roles in tissue regeneration. Notably, clinical dentinogenesis associated with caries development occurs within an inflammatory environment. Reparative dentinogenesis is closely linked to intense inflammation, which triggers the recruitment and differentiation of dental pulp stem cells (DPSCs) into the dentin lineage.

Modification of Non-photochemical Quenching Pathways in the C Model Plant Revealed Shared and Unique Photoprotection Mechanisms as Compared to C Plants.

Light is essential for photosynthesis; however, excess light can increase the accumulation of photoinhibitory reactive oxygen species that reduce photosynthetic efficiency. Plants have evolved photoprotective non-photochemical quenching (NPQ) pathways to dissipate excess light energy. In tobacco and soybean (C plants), overexpression of three NPQ genes, e ( V DE), ( P sbS), and ( Z EP), hereafter VPZ, resulted in faster NPQ induction and relaxation kinetics, and increased crop yields in field conditions.

Experience-dependent reorganization of inhibitory neuron synaptic connectivity.

Organisms continually tune their perceptual systems to the features they encounter in their environment . We have studied how ongoing experience reorganizes the synaptic connectivity of neurons in the olfactory (piriform) cortex of the mouse. We developed an approach to measure synaptic connectivity , training a deep convolutional network to reliably identify monosynaptic connections from the spike-time cross-correlograms of 4.

Partial Wwox Loss of Function Increases Severity of Murine Sepsis and Neuroinflammation.

Rationale: WW domain-containing oxidoreductase ( ) is a gene associated implicated in both neurologic and inflammatory diseases and is susceptible to environmental stressors. We hypothesize partial loss of Wwox function will result in increased sepsis severity and neuroinflammation.

Methods: mice, generated by CRISPR/Cas9, and mice were treated with intraperitoneal PBS vs LPS (10mg/kg) and euthanized 12 hours post-injection.

The virulence regulator is required for nutrient-induced filamentation in .

Bacteria can change morphology in response to stressors and changes in their environment, including infection of a host. We previously identified the bacterial species, , which uses nutrient-induced filamentation as a novel mechanism for cell-to-cell spreading in the intestinal epithelial cells of a nematode host. To further investigate the conservation of nutrient-induced filamentation in Bordetellae, we utilized the turkey-infecting species which filaments in vitro when switched from a standard growth media to an enriched media.

Detection of Iron Protein Supercomplexes in by Native Metalloproteomics.

is a major contributor to infections in humans and is widely distributed in the environment. It is capable of aerobic and anaerobic growth, providing adaptability to environmental changes and in confronting immune responses. We applied high-throughput native 2-dimensional metalloproteomics to under oxic and anoxic conditions.

Identification of two glycosyltransferases required for synthesis of membrane glycolipids in .

Unlabelled: infections cause over 12,000 deaths and an estimated one billion dollars in healthcare costs annually in the United States. The cell membrane is an essential structure that is important for protection from the extracellular environment, signal transduction, and transport of nutrients. The polar membrane lipids of are ∼50% glycolipids, a higher percentage than most other organisms.

Machine learning identifies routine blood tests as accurate predictive measures of pollution-dependent poor cognitive function.

Background: Several modifiable risk factors for dementia and related neurodegenerative diseases have been identified including education level, socio-economic status, and environmental exposures - however, how these population-level risks relate to individual risk remains elusive. To address this, we assess over 450 potential risk factors in one deeply clinically and demographically phenotyped cohort using random forest classifiers to determine predictive markers of poor cognitive function. This study aims to understand early risk factors for dementia by identifying predictors of poor cognitive performance amongst a comprehensive battery of imaging, blood, atmospheric pollutant and socio-economic measures.

Ribosomal protein phylogeography offers quantitative insights into the efficacy of genome-resolved surveys of microbial communities.

The increasing availability of microbial genomes is essential to gain insights into microbial ecology and evolution that can propel biotechnological and biomedical advances. Recent advances in genome recovery have significantly expanded the catalogue of microbial genomes from diverse habitats. However, the ability to explain how well a set of genomes account for the diversity in a given environment remains challenging for individual studies or biome-specific databases.

Admixture and environmental fluctuations shape the evolutionary history of a predator radiation in East Africa's Lake Tanganyika.

Unlabelled: Top predators have oversized impacts on food webs and ecosystem dynamics, and introducing a novel predator to a naive environment can have dramatic consequences for endemic biodiversity. Lake Tanganyika is unique among African lakes in the diversity of the pelagic top predators in the genus , where four species are endemic to the lake. Using a combination of reduced-representation and whole genome resequencing data, and pairing these with phylogenetic and demographic modeling approaches, we find that colonization of Lake Tanganyika was much more recent (∼1-2 Mya) than other major and diverse clades within the lake.

Rescue of hippocampal synaptic plasticity and memory performance by Fingolimod (FTY720) in APP/PS1 model of Alzheimer's disease is accompanied by correction in metabolism of sphingolipids, polyamines, and phospholipid saturation composition.

Previously, our metabolomic, transcriptomic, and genomic studies characterized the ceramide/sphingomyelin pathway as a therapeutic target in Alzheimer's disease, and we demonstrated that FTY720, a sphingosine-1-phospahate receptor modulator approved for treatment of multiple sclerosis, recovers synaptic plasticity and memory in APP/PS1 mice. To further investigate how FTY720 rescues the pathology, we performed metabolomic analysis in brain, plasma, and liver of trained APP/PS1 and wild-type mice. APP/PS1 mice showed area-specific brain disturbances in polyamines, phospholipids, and sphingolipids.

Crb3 and NF2: A dynamic duo that controls assembly of the apical junctions and barrier function via Rho/ROCK signaling.

The gastrointestinal epithelium serves as a critical barrier separating intestinal lumen contents from the underlying tissue environment. Structure and function of the apical junctional complex (AJC), comprising tight and adherens junctions, are essential for establishing and maintaining a polarized and functional epithelial barrier. In this study, we investigated mechanisms by which an apical polarity protein Crumbs homolog 3 (CRB3) regulates AJC assembly and barrier function in primary murine intestinal epithelial cells.

Temporal Microenvironment Mapping (μMap) of Intracellular Trafficking Pathways of Cell-Penetrating Peptides Across the Blood-Brain Barrier.

Peptides play critical roles in cellular functions such as signaling and immune regulation, and peptide-based biotherapeutics show great promise for treating various diseases. Among these, cell-penetrating peptides (CPPs) are particularly valuable for drug delivery due to their ability to cross cell membranes. However, the mechanisms underlying CPP-mediated transport, especially across the blood-brain barrier (BBB), remain poorly understood.

Genomic resistance in historical clinical isolates increased in frequency and mobility after the age of antibiotics.

Unlabelled: Antibiotic resistance is frequently observed shortly after the clinical introduction of an antibiotic. Whether and how frequently that resistance occurred before the introduction is harder to determine, as isolates could not have been tested for resistance before an antibiotic was discovered. Historical collections, like the British National Collection of Type Cultures (NCTC), stretching back to 1885, provide a window into this history.

Keystone engineering enables collective range expansion in microbial communities.

Keystone engineers profoundly influence microbial communities by altering their shared environment, often by modifying key resources. Here, we show that in an antibiotic-treated microbial community, bacterial spread is controlled by keystone engineering affecting dispersal- an effect hidden in well-mixed environments. Focusing on two pathogens, non-motile Klebsiella pneumoniae and motile Pseudomonas aeruginosa, we found that both tolerate a β-lactam antibiotic, with Pseudomonas being more resilient and dominating in well-mixed cultures.

The Role of Genetic Variation in Shaping Phenotypic Responses to Diet in Aging .

Nutrition plays a central role in healthy living, however, extensive variability in individual responses to dietary interventions complicates our understanding of its effects. Here we present a comprehensive study utilizing the Genetic Reference Panel (DGRP), investigating how genetic variation influences responses to diet and aging. Quantitative genetic analyses of the impact of dietary restriction on lifespan, locomotor activity, dry weight, and heat knockdown time were performed.

Lithospheric strike-slip faulting in central Tibet since 35-32 Ma and implications for the incipient Asian extrusional tectonics.

The onset age and depth of the central Tibet strike-slip faults are two still unresolved fundamental issues with regard to the Cenozoic tectonic evolution of central Tibet. Here we present a comprehensive dataset of geochronological, geochemical and structural data on recently discovered en-echelon dykes representing the incipient development of strike-slip faulting from the Lunpola basin in central Tibet. Our results provide evidence for mantle-derived, bimodal magmatism linked to lithospheric-scale strike-slip faulting at 35-32 Ma, and demonstrate that the central Tibet strike-slip faults are at least 20 Ma older than previously estimated (15-8 Ma).

Cancer vaccine designed from homologous ferritin-based fusion protein with enhanced DC-T cell crosstalk for durable adaptive immunity against tumors.

Peptide vaccines based on tumor antigens face the challenges of rapid clearance of peptides, low immunogenicity, and immune suppressive tumor microenvironment. However, the traditional solution mainly uses exogenous substances as adjuvants or carriers to enhance innate immune responses, but excessive inflammation can damage adaptive immunity. In the current study, we propose a straightforward novel nanovaccine strategy by employing homologous human ferritin light chain for minimized innate immunity and dendritic cell (DC) targeting, the cationic KALA peptide for enhanced cellular uptake, and suppressor of cytokine signaling 1 (SOCS1) siRNA for modulating DC activity.

Dual physiological responsive structural color hydrogel particles for wound repair.

Hydrogel-based patches have demonstrated their values in diabetic wounds repair, particularly those intelligent dressings with continuous repair promoting and monitoring capabilities. Here, we propose a type of dual physiological responsive structural color particles for wound repair. The particles are composed of a hyaluronic acid methacryloyl (HAMA)-sodium alginate (Alg) inverse opal scaffold, filled with oxidized dextran (ODex)/quaternized chitosan (QCS) hydrogel.

Learning, economies of scale, and knowledge gap effects on power generation technology cost improvements.

Cost reductions are essential for accelerating clean technology deployment. Because multiple factors influence costs, traditional one-factor learning models, solely relying on cumulative installed capacity as an explanatory variable, may oversimplify cost dynamics. In this study, we disentangle learning and economies of scale effects at unit and project levels and introduce a knowledge gap concept to quantify rapid technological change's impact on costs.

Environmental impacts of restructuring the EU's natural gas supply and consumption: Learnings from the 2022 energy crisis.

In 2022, the European Union put forward the REPowerEU plan in response to Russia's invasion of Ukraine, aiming at enhancing short-term energy security by diversifying imports and reducing natural gas demand while accelerating the deployment of renewable alternatives in the long term. Here, we quantify the life cycle environmental impacts of both REPowerEU's short-term measures, including the controversial extended coal-fired power plant operations, and how the first year of the crisis was managed in practice. We find that the policy measures' impact on greenhouse gas (GHG) emissions would be negligible, although they could have detrimental effects on other environmental categories.