Mast cell-derived chymases are essential for the resolution of inflammatory pain in mice.

Unlabelled: Immune cells play a critical role in the transition from acute to chronic pain. However, the role of mast cells in pain remains under-investigated. Here, we demonstrated that the resolution of inflammatory pain is markedly delayed in mast-cell-deficient mice.

Early life adversity promotes gastrointestinal dysfunction through a sex-dependent phenotypic switch in enteric glia.

Irritable bowel syndrome and related disorders of gut-brain interaction (DGBI) are common and exhibit a complex, poorly understood etiology that manifests as abnormal gut motility and pain. Risk factors such as biological sex, stressors during critical periods, and inflammation are thought to influence DGBI vulnerability by reprogramming gut-brain circuits, but the specific cells affected are unclear. Here, we used a model of early life stress to understand cellular mechanisms in the gut that produce DGBIs.

Activity-dependent FosB gene expression negatively regulates mast cell functions.

Mast cells are innate immune cells that play a crucial role in numerous physiological processes across tissues by releasing pre-stored and newly synthesized mediators in response to stimuli, an activity largely driven by changes in gene expression. Given their widespread influence, dysfunction in mast cells can contribute to a variety of pathologies including allergies, long COVID, and autoimmune and neuroinflammatory disorders. Despite this, the specific transcriptional mechanisms that control mast cell mediator release remain poorly understood, significantly hindering the development of effective therapeutic strategies.

Investigating intestinal mast cell dynamics during acute heat stress in growing pigs.

Objectives were to examine the temporal pattern of intestinal mast cell dynamics and the effects of a mast cell stabilizer (ketotifen [Ket]) during acute heat stress (HS) in growing pigs. Crossbred barrows (n = 42; 32.3 ± 1.

Early weaning and biological sex shape long-term immune and metabolic responses in pigs.

During the early pre and postnatal life, host and environmental factors can impart a major influence on immune development, thus shaping lifelong disease resistance. Two major factors known to influence immune function and mortality in animals and people are early life stress and biological sex. How these two factors interact to shape long-term immune development and later life disease risk is poorly understood.

Negative Antigenuria in a Dog with Suspected Central Nervous System Localized Blastomycosis.

A 7 yr old female spayed mixed-breed dog was presented for a 1 wk history of neck pain and pelvic limb weakness. Examination revealed nonambulatory paraparesis and thoracolumbar hyperesthesia. MRI revealed extensive intramedullary T2-weighted/short tau inversion recovery hyperintensity and diffuse severe T1-post contrast meningeal enhancement of the thoracolumbar spinal cord.

Effects of a multi-strain -based direct-fed microbial on immunity markers and intestinal morphology in diets fed to weanling pigs.

The objective of this experiment was to evaluate the effects of a multi-strain -based direct-fed microbial (DFM) on nursery pig health as indicated by intestinal mucosal and blood plasma immunological markers and intestinal morphology. Eighty pigs, of equal number of barrows and gilts (initial BW: 7.0 ± 0.

Sex Differences in Mast Cell-Associated Disorders: A Life Span Perspective.

Mast cells are critical innate immune effectors located throughout the body that are crucial for host defense mechanisms via orchestrating immune responses to a variety of host and environmental stimuli necessary for survival. The role of mast cells in brain development and behavior, meningeal function, and stress-related disorders has also been increasingly recognized. While critical for survival and development, excessive mast cell activation has been linked with an increasing number of inflammatory, stress-associated, and neuroimmune disorders including allergy/anaphylaxis, autoimmune diseases, migraine headache, and chronic pain disorders.

Biological sex: an understudied factor driving disease susceptibility in pigs.

Biological sex is a major host factor influencing risk for infectious disease-associated mortality, and chronic inflammatory and metabolic diseases. Research in human and rodent models -has revealed sex differences that exist across organ systems during health and disease that may contribute to sex biases in disease risk. Despite the robust and growing literature on the role of sex as a risk factor in human disease, comparatively little attention has been focused on investigating the role of biological sex in disease susceptibility in agriculturally important animal populations such as the pig.

Early life adversity drives sex-specific anhedonia and meningeal immune gene expression through mast cell activation.

Exposure to early life adversity (ELA) in the form of physical and/or psychological abuse or neglect increases the risk of developing psychiatric and inflammatory disorders later in life. It has been hypothesized that exposure to ELA results in persistent, low grade inflammation that leads to increased disease susceptibility by amplifying the crosstalk between stress-processing brain networks and the immune system, but the mechanisms remain largely unexplored. The meninges, a layer of three overlapping membranes that surround the central nervous system (CNS)- dura mater, arachnoid, and piamater - possess unique features that allow them to play a key role in coordinating immune trafficking between the brain and the peripheral immune system.

Impaired KDM2B-mediated PRC1 recruitment to chromatin causes defective neural stem cell self-renewal and ASD/ID-like behaviors.

Recent clinical studies report that chromosomal 12q24.31 microdeletions are associated with autism spectrum disorder (ASD) and intellectual disability (ID). However, the causality and underlying mechanisms linking 12q24.

Future of biomedical, agricultural, and biological systems research using domesticated animals.

Increased knowledge of reproduction and health of domesticated animals is integral to sustain and improve global competitiveness of U.S. animal agriculture, understand and resolve complex animal and human diseases, and advance fundamental research in sciences that are critical to understanding mechanisms of action and identifying future targets for interventions.

Developmental alterations of intestinal SGLT1 and GLUT2 induced by early weaning coincides with persistent low-grade metabolic inflammation in female pigs.

Early-life adversity (ELA) is linked with the increased risk for inflammatory and metabolic diseases in later life, but the mechanisms remain poorly understood. Intestinal epithelial glucose transporters sodium-glucose-linked transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) are the major route for intestinal glucose uptake but have also received increased attention as modulators of inflammatory and metabolic diseases. Here, we tested the hypothesis that early weaning (EW) in pigs, an established model of ELA, alters the development of epithelial glucose transporters and coincides with elevated markers of metabolic inflammation.

Effects of a multi-strain -based direct-fed microbial on weanling pig growth performance and nutrient digestibility.

A study was conducted to evaluate the effects of a multi-strain -based direct-fed microbial (DFM) on growth performance and apparent nutrient digestibility of nursery pigs. Eighty pigs, of equal number of barrows and gilts (initial body weight: 7.0 ± 0.

Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors.

Autism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying molecular mechanisms linking ASH1L mutations to genesis of ASD/ID remain undetermined.

Neuroimmunology of depression.

Depression is one of the leading causes of disability worldwide and a major contributor to the global burden of disease, yet the cellular and molecular etiology of depression remain largely unknown. Major Depressive Disorder (MDD) is associated with a variety of chronic physical inflammatory and autoimmune disorders, and mood disorders may act synergistically with other medical disorders to worsen patient outcomes. Here, we outline the neuroimmune complement, explore the evidence for altered immune system function in MDD, and present some of the potential mechanisms by which immune cells and molecules may drive the onset and course of MDD.

Sleep Disorders in dogs: A Pathophysiological and Clinical Review.

Sleep is a fundamental process in mammals, including domestic dogs. Disturbances in sleep affect physiological functions like cognitive and physical performance, immune response, pain sensation and increase the risk of diseases. In dogs, sleep can be affected by several conditions, with narcolepsy, REM sleep behavior disorder and sleep breathing disorders being the most frequent causes.

Sex differences in viral entry protein expression and host transcript responses to SARS-CoV-2.

Epidemiological studies suggest that men exhibit a higher mortality rate to COVID-19 than women, yet the underlying biology is largely unknown. Here, we seek to delineate sex differences in the gene expression of viral entry proteins ACE2 and TMPRSS2, and host transcriptional responses to SARS-CoV-2 through large-scale analysis of genomic and clinical data. We first compiled 220,000 human gene expression profiles from three databases and completed the meta-information through machine learning and manual annotation.

Perinatal androgens organize sex differences in mast cells and attenuate anaphylaxis severity into adulthood.

Mast cell (MC)-associated diseases, including allergy/anaphylaxis and neuroinflammatory pain disorders, exhibit a sex bias, with females at increase risk. While much attention has been directed toward adult sex hormones as drivers of sex differences, that female sex bias in MC-associated diseases is evident in prepubertal children, suggesting early-life origins of sex differences which have yet to be explored. Utilizing rodent models of MC-mediated anaphylaxis, our data here reveal that, 1) compared with females, males exhibit significantly reduced severity of MC-mediated anaphylactic responses that emerge prior to puberty and persist into adulthood, 2) reduced severity of MC-mediated anaphylaxis in males is linked with the naturally high level of perinatal androgens and can be recapitulated in females by perinatal exposure to testosterone proprionate, 3) perinatal androgen exposure guides bone marrow MC progenitors toward a masculinized tissue MC phenotype characterized by decreased concentration of prestored MC granule mediators (e.

Androgen-Dependent Excitability of Mouse Ventral Hippocampal Afferents to Nucleus Accumbens Underlies Sex-Specific Susceptibility to Stress.

Background: Depression affects women nearly twice as often as men, but the neurobiological underpinnings of this discrepancy are unclear. Preclinical studies in male mice suggest that activity of ventral hippocampus (vHPC) neurons projecting to the nucleus accumbens (NAc) regulates mood-related behavioral responses to stress. We sought to characterize this circuit in both sexes and to investigate its role in potential sex differences in models of depression.

Perivascular Adipocytes Store Norepinephrine by Vesicular Transport.

Objective- Perivascular adipose tissue (PVAT) contains an independent adrenergic system that can take up, metabolize, release, and potentially synthesize the vasoactive catecholamine norepinephrine. Norepinephrine has been detected in PVAT, but the mechanism of its protection within this tissue is unknown. Here, we investigate whether PVAT adipocytes can store norepinephrine using VMAT (vesicular monoamine transporter).

Mast cell corticotropin-releasing factor subtype 2 suppresses mast cell degranulation and limits the severity of anaphylaxis and stress-induced intestinal permeability.

Background: Psychological stress and heightened mast cell (MC) activation are linked with important immunologic disorders, including allergy, anaphylaxis, asthma, and functional bowel diseases, but the mechanisms remain poorly defined. We have previously demonstrated that activation of the corticotropin-releasing factor (CRF) system potentiates MC degranulation responses during IgE-mediated anaphylaxis and psychological stress through corticotropin-releasing factor receptor subtype 1 (CRF) expressed on MCs.

Objective: In this study we investigated the role of corticotropin-releasing factor receptor subtype 2 (CRF) as a modulator of stress-induced MC degranulation and associated disease pathophysiology.

S. Typhimurium challenge in juvenile pigs modulates the expression and localization of enteric cholinergic proteins and correlates with mucosal injury and inflammation.

The cholinergic system plays a central role in regulating critical gastrointestinal functions, including motility, secretion, barrier and immune function. In rodent models of acute, non-infectious gastrointestinal injury, the cholinergic system functions to inhibit inflammation; however, during inflammation local expression and regulation of the cholinergic system is not well known, particularly during infectious enteritis. The objective of this study was to determine the intrinsic expression of the enteric cholinergic system in pig ileum following an acute challenge with Salmonella enterica serovar Typhimurium DT104 (S.