bluuebunny/crossref_metadata_2025_split huggingface dataset:
LOSS OF CLDN5 -AND INCREASE IN IRF7- IN THE HIPPOCAMPUS AND CEREBRAL CORTEX OF DIABETIC MICE AT THE EARLY SYMPTOMATIC STAGE
Authors: Carús-Cadavieco Marta , González de la Fuente Sandra , Berenguer Inés , Serrano-Lope Miguel A. , Aguado Begoña , Palomer Ernest , Guix Francesc , Dotti Carlos G. 
Published: November 2023

AbstractAnalyzing changes in gene expression within specific brain regions of individuals with Type 2 Diabetes (T2DM) who do not exhibit significant cognitive deficits can yield valuable insights into the mechanisms that may underlie the progression toward a more severe phenotype, for example as when individuals age. Here, we present evidence that adult mice with long-term type 2 diabetes mellitus (T2DM) and minor cognitive deficits display alterations in the expression of 27 genes in the cerebral cortex and 16 genes in the hippocampus compared to non-T2DM mice. Only six of these genes undergo the same type of change both in the cortex and hippocampus: Interferon regulatory factor 7 (Irf7), Hypoxia-inducible factor 3 alpha (Hif-3α), period circadian clock 2 (Per2), xanthine dehydrogenase (Xdh), and Transforming growth factor β-stimulated clone 22/TSC22 (Tscd3) are all upregulated, while Claudin-5 (Cldn5) is downregulated. At the protein level, Claudin5 and IRF7 showed equivalente changes: downregulation of CLDN5 and upregulation of IRF7. These results suggest that cognitive deficits linked to chronic T2DM may stem from compromised blood-brain barrier integrity and an abnormal inflammatory response in the early stages of the disease. This underscores the potential for therapeutic interventions targeting CLDN5 and IRF7.
Back to the holobiont: ecophysiological and systemic responses of rooted-cuttings inoculated with a synthetic community
Authors: Sandrini Marco , Chitarra Walter , Pagliarani Chiara , Moffa Loredana , Petrozziello Maurizio , Colla Paola , Balestrini Raffaella , Nerva Luca 
Published: November 2023

AbstractDespite microbe-based products for grapevine protection and growth improvement are already available, a few of them contain microbes directly isolated from vine tissues. For this reason, a collection of endophytic bacterial isolates obtained directly from grapevine woody tissues has been used for producing anad-hocinoculum. The selected bacterial isolates were tested in biocontrol assays against some of the main grapevine pathogens (e.g.,Botrytis cinerea,Guignardia bidwellii,Neofusicoccum parvum) and the best performing ones were screened for plant growth promoting (PGP)-traits (e.g., phosphorous solubilization, indole-acetic acid and siderophore production). Before being planted, rooted cuttings were inoculated with two different synthetic communities: the first one was anad-hocdeveloped microbial community (SynCom), whereas the second was a commercial consortium formed by arbuscular mycorrhizal fungi (AMF) and a rhizosphere bacterial strain (AMF+B). Physiological parameters were monitored to evaluate effects on plant performances, and samples for biochemical and molecular analyses were collected. Integration of physiological data with metabolite profiling and transcriptome sequencing highlighted that the SynCom treatment shaped the plant growth-defence trade-off, by regulating photosynthesis and diverting energy sources towards the activation of defence metabolic pathways. On the other hand, the AMF+B treatment led to a more balanced growth-defence trade-off, though a mild activation of defence mechanisms was also observed in these plants. Our findings suggest that an experimental approach considering both the features of associated microbes and their impacts on plant growth and defence could shed light on the “dark-side effects” of SynCom application, thereby enabling their exploitation with a refined awareness.
Distinct members of theC. elegansCeMbio reference microbiota exert cryptic virulence and infection protection
Authors: Gonzalez Xavier , Irazoqui Javier E. 
Published: November 2023

AbstractMicrobiotas are complex microbial communities that colonize specific niches in the host and provide essential organismal functions that are important in health and disease. A key aspect is the ability of each distinct community member to promote or impair host health, alone or in the context of the community, in hosts with varied levels of immune competence. Understanding such interactions is limited by the complexity and experimental accessibility of current systems and models. Recently, a reference twelve-member microbiota for the model organismC. elegans,known as CeMbio, was defined to aid the dissection of conserved host-microbiota interactions. Understanding the physiological impact of the CeMbio bacteria onC. elegansis in its infancy. Here, we show the differential ability of each CeMbio bacterial species to activate innate immunity through the conserved PMK-1/p38 MAPK, ACh/WNT, and HLH-30/TFEB pathways. Using immunodeficient animals, we uncovered several examples of bacterial ‘cryptic’ virulence, or virulence that was masked by the host defense response. The ability to activate the PMK-1/p38 pathway did not correlate with bacterial virulence in wild type or immunodeficient animals. In contrast, ten out of twelve species activated HLH-30/TFEB, and most showed virulence towardshlh-30-deficient animals. In addition, we identifiedPseudomonas luridaas a pathogen in wild type animals, andAcinetobacter guillouiaeas avirulent despite activating all three pathways. Moreover, short pre-exposure toA. guillouiaepromoted host survival of infection withP. lurida,which was dependent on PMK-1/p38 MAPK and HLH-30/TFEB. These results suggest that the microbiota ofC. elegansis rife with “opportunistic” pathogens, and that HLH-30/TFEB is a fundamental and key host protective factor. Furthermore, they support the idea that bacteria likeA. guillouiaeevolved the ability to induce host innate immunity to improve host fitness when confronted with pathogens, providing new insights into how colonization order impacts host health.
Disturbance-generated competitive coexistence
Authors: Trigos-Raczkowski U. A. , Lyons R. , Delgadino M. G. , Ackleh A. S. , Ostling A. 
Published: November 2023

AbstractExplaining how competing species coexist remains a challenge in ecology. A major hypothesis is that disturbance opens up the opportunity for types with different “life history” strategies to coexist, allowing types better at getting to and using recently disturbed patches to coexist with better competitor types. A simple model introduced several decades ago demonstrated this, but its focus on patch dynamics (i.e. the dynamics of the number of patches a species occupies) gives limited insight into how coexistence-enabling variation arises from within-patch demographic strategies. Here we present, and demonstrate how to analyze, a partial differential equation model that captures the emergence of larger-scale competitive dynamics from within-patch population dynamics of species competing for patches subject to disturbance. We analyze key cases of the model framework, with competition acting in turn on each aspect of within-patch demography included in the model: reproduction, offspring-survival, and adult-survival. Insights arising from these analyses include: 1) variation between species on a simple reproduction-adult-survival trade-off can enable disturbance-generated coexistence, 2) variation along trade-offs with species’ robustness-to-competition can also generate coexistence 3) disturbance-generated coexistence may or may not involve classical “successional dynamics” within patches, and 4) coexistence is easier to generate at intermediate disturbance rates. Our work here provides new tools for more complete development of the theory of disturbance-generated coexistence.
Molecular Forecasting of Domoic Acid during a Pervasive Toxic Diatom Bloom
Authors: Brunson John K. , Thukral Monica , Ryan John P. , Anderson Clarissa R. , Kolody Bethany C. , James Chase , Chavez Francisco P. , Leaw Chui Pin , Rabines Ariel J. , Venepally Pratap , Zheng Hong , Kudela Raphael M. , Smith G. Jason , Moore Bradley S. , Allen Andrew E. 
Published: November 2023

AbstractIn 2015, the largest recorded harmful algal bloom (HAB) occurred in the Northeast Pacific, causing nearly 100 million dollars in damages to fisheries and killing many protected marine mammals. Dominated by the toxic diatomPseudo-nitzschia australis, this bloom produced high levels of the neurotoxin domoic acid (DA). Through molecular and transcriptional characterization of 52 near-weekly phytoplankton net-tow samples collected at a bloom hotspot in Monterey Bay, California, we identified active transcription of known DA biosynthesis (dab) genes from the three identified toxigenic species, includingP. australisas the primary origin of toxicity. Elevated expression of silicon transporters (sit1) during the bloom supports the previously hypothesized role of dissolved silica (Si) exhaustion in contributing to bloom physiology and toxicity. We find that co-expression of thedabAandsit1genes serves as a robust predictor of DA one week in advance, potentially enabling the forecasting of DA-producing HABs. We additionally present evidence that low levels of iron could have co-limited the diatom population along with low Si. Iron limitation represents a previously unrecognized driver of both toxin production and ecological success of the low iron adaptedPseudo-nitzschiagenus during the 2015 bloom, and increasing pervasiveness of iron limitation may fuel the escalating magnitude and frequency of toxicPseudo-nitzschiablooms globally. Our results advance understanding of bloom physiology underlying toxin production, bloom prediction, and the impact of global change on toxic blooms.SignificancePseudo-nitzschiadiatoms form oceanic harmful algal blooms that threaten human health through production of the neurotoxin domoic acid (DA). DA biosynthetic gene expression is hypothesized to control DA production in the environment, yet what regulates expression of these genes is yet to be discovered. In this study, we uncovered expression of DA biosynthesis genes by multiple toxigenicPseudo-nitzschiaspecies during an economically impactful bloom along the North American West Coast, and identified genes that predict DA in advance of its production. We discovered that iron and silica co-limitation restrained the bloom and likely promoted toxin production. This work suggests that increasing iron limitation due to global change may play a previously unrecognized role in driving bloom frequency and toxicity.
Coordination among leaf and fine root traits across a strong natural soil fertility gradient
Authors: Guilbeault-Mayers Xavier , Lambers Hans , Laliberté Etienne 
Published: November 2023

AbstractUnravelling how fundamental axes of trait variation correlate among leaves and roots and relate to nutrient availability is crucial for understanding plant distribution. While the leaf trait variation axis is linked to nutrient availability gradients, the response of root trait variation to the same gradients yields inconsistent results.We studied leaf and root trait variation among 23 co-occurring plant species along a 2-million year soil chronosequence to assess how leaf and root traits coordinate and how this resulting joint axis of variation relates to soil fertility.Mycorrhizal association types primarily structured the axes of leaf and root trait variation. However, when considering species abundance, soil nutrient availability was an important driver of trait distribution. Leaves that support rapid growth in younger, fertile soils were associated with roots of larger diameter and arbuscular mycorrhizal colonization. In contrast, leaves that favour nutrient conservation in nutrient-impoverished soil were associated with greater root hair length and phosphorus-mobilizing root exudates.At the species level, the signals deviated from the community-wide results presented above, highlighting the challenge of generalizing a specific set of root trait values that consistently meet the requirements of leaves supporting either rapid growth or survival.
Non-apical plateau potentials and persistent firing induced by metabotropic cholinergic modulation in layer 2/3 pyramidal cells in the rat prefrontal cortex
Authors: Hagger-Vaughan Nicholas , Kolnier Daniel , Storm Johan F. 
Published: November 2023

AbstractThe prefrontal cortex (PFC) is important for executive functions, including attention, planning, decision-making, and memory, and is proposed by some leading theories to be crucial for consciousness. In particular, the global neuronal workspace theory proposes that PFC layer 2/3 pyramidal cells (L2/3PCs) contribute crucially to the ‘global workspace’, and hence to consciousness, due to their long-range connections to other cortical areas.Plateau potentials, periods of depolarisation with action potential firing outlasting the stimuli that induced them, have been suggested to help maintain working memory and to contribute to executive functions and consciousness.We therefore investigated plateau potentials and their mechanisms in PFC layer 2/3 pyramidal neurons. Using whole-cell somatic recordings from L2/3PCs in rat PFC brain slices, we found that the metabotropic cholinergic agonist muscarine reliably induced long-lasting plateau potentials with spiking following a train of evoked action potentials. Similar plateaus were induced by a metabotropic glutamate receptor (mGluR) agonist. Pharmacological tests suggested that these plateaus were dependent on transient receptor potential (TRP) cation channels, both TRPC4 and TRPC5, and required the presence of external calcium (Ca2+) and internal Ca2+stores, but not voltage-gated Ca2+channels. Using local Ca2+applications, we found that the responsible Ca2+influx is most likely distributed on the somatic and/or basal dendritic compartments rather than on the (distal) apical dendrite. We used knife cuts to disconnect apical dendrites, sometimes less than 50 µm from the soma, and found that the plateaus did not depend on the distal apical dendrite, since truncated cells generated plateaus with as many spikes as control cells. These results indicate that layer 2/3PCs can generate plateau potentials with sustained spiking independently of distal apical dendrites.
Rapid nongenomic estrogen signaling controls alcohol drinking behavior
Authors: Zallar Lia J. , Rivera-Irizarry Jean K. , Hamor Peter U. , Pigulevskiy Irena , Rico Rozo Ana-Sofia , Mehanna Hajar , Liu Dezhi , Welday Jacqueline P. , Bender Rebecca , Asfouri Joseph J. , Levine Olivia B. , Skelly Mary Jane , Hadley Colleen K. , Fecteau Kristopher M. , Nelson Scottie , Miller John , Ghazal Pasha , Bellotti Peter , Singh Ashna , Hollmer Lauren V. , Erikson David W. , Geri Jacob , Pleil Kristen E. 
Published: November 2023

AbstractOvarian-derived estrogen is a key modulator of numerous physiological processes via genomic and nongenomic mechanisms, including signaling non-canonically at membrane-associated estrogen receptors in the brain to rapidly regulate neuronal function. However, the mechanisms mediating estrogen regulation of behaviors such as alcohol consumption remain unclear. Early alcohol drinking confers greater risk for alcohol use disorder in women than men, and binge alcohol drinking is correlated with high circulating estrogen levels, but a causal role for estrogen signaling in driving alcohol drinking in gonadally-intact animals has not been established. We found that female mice displayed greater binge alcohol drinking and reduced avoidance behavior when circulating estrogen was high during the proestrus phase of the estrous cycle than when it was low, contributing to sex differences in these behaviors. The pro-drinking, but not anxiolytic, effect of high endogenous estrogen state occurred via rapid estrogen signaling at membrane-associated estrogen receptor alpha in the bed nucleus of the stria terminalis, which promoted synaptic excitation of corticotropin-releasing factor neurons and facilitated their activity during alcohol drinking behavior. This study is the first to demonstrate a rapid, nongenomic signaling mechanism for ovarian-derived estrogen signaling in the brain controlling behavior in gonadally intact females, and it establishes a causal role for estrogen in an intact hormonal context for driving alcohol consumption that contributes to known sex differences in this behavior.
BHLHE40 drives protective polyfunctional CD4 T cell differentiation in the female reproductive tract againstChlamydia
Authors: Mercado Miguel A. B. , Li Qiang , Quick Charles M. , Kim Yejin , Palmer Rachel , Huang Lu , Li Lin-Xi 
Published: November 2023

AbstractThe protein basic helix-loop-helix family member e40 (BHLHE40) is a transcription factor recently emerged as a key regulator of host immunity to infections, autoimmune diseases and cancer. In this study, we investigated the role ofBhlhe40in protective T cell responses to the intracellular bacteriumChlamydiain the female reproductive tract (FRT). Mice deficient inBhlhe40exhibited severe defects in their ability to controlChlamydia muridarumshedding from the FRT. The heightened bacterial burdens inBhlhe40−/−mice correlated with a marked increase in IL-10-producing T regulatory type 1 (Tr1) cells and decreased polyfunctional CD4 T cells co-producing IFN-γ, IL-17A and GM-CSF. Genetic ablation of IL-10 or functional blockade of IL-10R increased CD4 T cell polyfunctionality and partially rescued the defects in bacterial control inBhlhe40−/−mice. Using single-cell RNA sequencing coupled with TCR profiling, we detected a significant enrichment of stem-like T cell signatures inBhlhe40-deficient CD4 T cells, whereas WT CD4 T cells were further down on the differentiation trajectory with distinct effector functions beyond IFN-γ production by Th1 cells. Altogether, we identifiedBhlhe40as a key molecular driver of CD4 T cell differentiation and polyfunctional responses in the FRT againstChlamydia.
Differential genetic expression within reward-specific ensembles in mice
Authors: Litif Carl G. , Flom Levi T. , Sandum Kathryn L. , Hodgins Skylar L. , Vaccaro Lucio , Stitzel Jerry A. , Blouin Nicolas A. , Mannino Maria Constanza , Gigley Jason P. , Schoborg Todd A. , Bobadilla Ana-Clara 
Published: November 2023

AbstractMaladaptive reward seeking is a hallmark of cocaine use disorder. To develop therapeutic targets, it is critical to understand the neurobiological changes specific to cocaine-seeking without altering the seeking of natural rewards, e.g., sucrose. The prefrontal cortex (PFC) and the nucleus accumbens core (NAcore) are known regions associated with cocaine- and sucrose-seeking ensembles, i.e., a sparse population of co-activated neurons. Within ensembles, transcriptomic alterations in the PFC and NAcore underlie the learning and persistence of cocaine- and sucrose-seeking behavior. However, transcriptomes exclusively driving cocaine seeking independent from sucrose seeking have not yet been defined using a within-subject approach. Using Ai14:cFos-TRAP2 transgenic mice in a dual cocaine and sucrose self-administration model, we fluorescently sorted (FACS) and characterized (RNAseq) the transcriptomes defining cocaine- and sucrose-seeking ensembles. We found reward- and region-specific transcriptomic changes that will help develop clinically relevant genetic approaches to decrease cocaine-seeking behavior without altering non-drug reward-based positive reinforcement.
Microscale visualization of cellular features in adult macaque visual cortex
Authors: Balaram Pooja , Takasaki Kevin , Hellevik Ayana , Tandukar Jamuna , Turschak Emily , MacLennan Bryan , Ouellette Naveen , Torres Russel , Laughland Connor , Gliko Olga , Seshamani Sharmistaa , Perlman Eric , Taormina Mike , Peterson Erica , Juneau Zoe , Potekhina Lydia , Glaser Adam , Chandrashekar Jayaram , Logsdon Molly , Cao Kevin , Dylla Celeste , Hatanaka Gaku , Chatterjee Soumya , Ting Jonathan , Vumbaco David , Waters Jack , Bair Wyeth , Tsao Doris , Gao Ruixuan , Reid Clay 
Published: November 2023

AbstractExpansion microscopy and light sheet imaging enable fine-scale resolution of intracellular features that comprise neural circuits. Most current techniques visualize sparsely distributed features across whole brains or densely distributed features within individual brain regions. Here, we visualize dense distributions of immunolabeled proteins across early visual cortical areas in adult macaque monkeys. This process may be combined with multiphoton or magnetic resonance imaging to produce multimodal atlases in large, gyrencephalic brains.
Single-nucleus transcriptomics of epicardial adipose tissue from females reveals exercise control of innate and adaptive immune cells
Authors: Ahmad Irshad , Gupta Shreyan , Faulkner Patricia , Mullens Destiny , Thomas Micah , Sytha Sharanee P. , Ivanov Ivan , Cai James J. , Heaps Cristine L. , Newell-Fugate Annie E. 
Published: November 2023

AbstractCoronary artery disease (CAD) is a leading cause of death in women. Although exercise mitigates CAD, the mechanisms by which exercise impacts epicardial adipose tissue (EAT) are unknown. We hypothesized that exercise promotes an anti-inflammatory microenvironment in EAT from female pigs. Yucatan pigs (n=7) were assigned to sedentary (Sed) or exercise (Ex) treatments and coronary arteries were occluded (O) with an ameroid to mimic CAD or remained non-occluded (N). EAT was collected for bulk and single nucleus transcriptomic sequencing (snRNA-seq). Exercise upregulated G-protein coupled receptor, S100 family, and FAK pathways and downregulated the coagulation pathway. Exercise increased the interaction between immune, endothelial, and mesenchymal cells in the insulin-like growth factor pathway and between endothelial and other cell types in the platelet endothelial cell adhesion molecule 1 pathway. Sub- clustering revealed nine cell types in EAT with fibroblast and macrophage populations predominant in O-Ex EAT and T cell population predominant in N-Ex EAT. Coronary occlusion impacted the largest number of genes in T and endothelial cells. Genes related to fatty acid metabolism were the most highly upregulated in non-immune cells from O-Ex EAT. Sub-clustering of endothelial cells revealed that N-Ex EAT separated from other treatments. In conclusion, aerobic exercise increased interaction amongst immune and mesenchymal and endothelial cells in female EAT. Exercise was minimally effective at reversing alterations in gene expression in endothelial and mesenchymal cells in EAT surrounding occluded arteries. These findings lay the foundation for future work focused on the impact of exercise on cell types in EAT.Significance StatementCoronary artery disease (CAD) is a leading cause of death in women. However, the role of epicardial adipose tissue (EAT) in the development of CAD in females and how exercise, which is recommended to slow CAD progression, impacts EAT are unknown. The effect of aerobic exercise on gene expression in EAT was investigated with RNA-sequencing, revealing significant alterations in fatty acid processing and immunoregulatory processes. This study provides valuable insights into the molecular and cellular changes induced in EAT by exercise in the context of chronic ischemic heart disease in females. These findings bolster current understanding of the impact of aerobic exercise on cardiac health in females and provide a foundation for future research in the field of exercise science.