Calcineurin inhibition enhances lifespan by defecation defects-mediated calorie restriction and nuclear hormone signaling.

Calcineurin is a highly conserved calcium/calmodulin-dependent serine/threonine protein phosphatase with diverse functions. Inhibition of calcineurin is known to enhance the lifespan of through multiple signaling pathways. Aiming to study the role of calcineurin in regulating innate immunity, we discover that calcineurin is required for the rhythmic defecation motor program (DMP) in .

A functional screen for ubiquitin regulation identifies an E3 ligase secreted by .

Ubiquitin signaling controls many aspects of eukaryotic biology, including targeted protein degradation and immune defense. Remarkably, invading bacterial pathogens have adapted secreted effector proteins that hijack host ubiquitination to gain control over host responses. These ubiquitin-targeted effectors can exhibit, for example, E3 ligase or deubiquitinase activities, often without any sequence or structural homology to eukaryotic ubiquitin regulators.

Neuronal NPR-15 modulates molecular and behavioral immune responses via the amphid sensory neuron-intestinal axis in .

The survival of hosts during infections relies on their ability to mount effective molecular and behavioral immune responses. Despite extensive research on these defense strategies in various species, including the model organism , the neural mechanisms underlying their interaction remain poorly understood. Previous studies have highlighted the role of neural G-protein-coupled receptors (GPCRs) in regulating both immunity and pathogen avoidance, which is particularly dependent on aerotaxis.

Utility of a Pediatric Psychosocial Screener in an Outpatient Burn Clinic.

Psychosocial concerns are common among youth who sustained a burn injury. Detecting psychosocial distress early is essential to ensure appropriate treatment and referrals. Thus far, research has focused largely on the long-term outcomes of pediatric burn survivors.

Neuronal NPR-15 modulates molecular and behavioral immune responses via the amphid sensory neuron-intestinal axis in .

The survival of hosts during infections relies on their ability to mount effective molecular and behavioral immune responses. Despite extensive research on these defense strategies in various species, including the model organism , the neural mechanisms underlying their interaction remain poorly understood. Previous studies have highlighted the role of neural G protein-coupled receptors (GPCRs) in regulating both immunity and pathogen avoidance, which is particularly dependent on aerotaxis.

Anti-inflammatory effects of vagus nerve stimulation in pediatric patients with epilepsy.

Introduction: The neural control of the immune system by the nervous system is critical to maintaining immune homeostasis, whose disruption may be an underlying cause of several diseases, including cancer, multiple sclerosis, rheumatoid arthritis, and Alzheimer's disease.

Methods: Here we studied the role of vagus nerve stimulation (VNS) on gene expression in peripheral blood mononuclear cells (PBMCs). Vagus nerve stimulation is widely used as an alternative treatment for drug-resistant epilepsy.

Cholinergic receptor-Wnt pathway controls immune activation by sensing intestinal dysfunction.

Alterations in the intestinal physiology caused by pathogen colonization result in immune activation. To provide insights into the mechanisms underlying the control of immune activation by changes in intestinal homeostasis, we conducted a forward genetic screen for suppressors of immune activation by intestinal distension in Caenorhabditis elegans. Our results indicate that C.

Dissection of a sensorimotor circuit underlying pathogen aversion in C. elegans.

Background: Altering animal behavior to reduce pathogen exposure is a key line of defense against pathogen attack. In Caenorhabditis elegans, alterations in intestinal physiology caused by pathogen colonization and sensation of microbial metabolites may lead to activation of pathogen aversive behaviors ranging from aversive reflexes to learned avoidance. However, the neural circuitry between chemosensory neurons that sense pathogenic bacterial cues and the motor neurons responsible for avoidance-associated locomotion remains unknown.

Descriptive Analysis of Current Burn Care for Plain Communities in Ohio and Pennsylvania: A Qualitative Study of Strengths and Needs in a Hospital-Community Partnership.

Plain communities present with a higher risk of sustaining burn injuries. Yet, little is known about the hospital-community partnerships with Plain caretakers to facilitate culturally competent burn care. The current study provides a qualitative analysis of Plain caretakers' perspectives on an existing hospital-community partnership for facilitating culturally sensitive burn care and their perspectives on the ongoing physical, structural, and behavioral health needs of this population.

The gut efflux pump MRP-1 exports oxidized glutathione as a danger signal that stimulates behavioral immunity and aversive learning.

Innate immune surveillance, which monitors the presence of potentially harmful microorganisms and the perturbations of host physiology that occur in response to infections, is critical to distinguish pathogens from beneficial microbes. Here, we show that multidrug resistance-associated protein-1 (MRP-1) functions in the basolateral membrane of intestinal cells to transport byproducts of cellular redox reactions to control both molecular and behavioral immunity in Caenorhabditis elegans. Pseudomonas aeruginosa infection disrupts glutathione homeostasis, leading to the excess production of the MRP-1 substrate, oxidized glutathione (GSSG).

The transcription factor HLH-26 controls probiotic-mediated protection against intestinal infection through up-regulation of the Wnt/BAR-1 pathway.

Probiotics play a critical role in the control of host intestinal microbial balance, protecting the host from gastrointestinal pathogens, modulating the host immune response, and decreasing host susceptibility to infection. To understand the mechanism underlying the protective effect of probiotics against infections through immune regulation, we examined protection against Salmonella enterica infection following exposure to nonpathogenic Enterococcus faecium in the nematode Caenorhabditis elegans. We found that the transcription factor HLH-26, a REF-1 family member of basic helix-loop-helix transcription factors, was required in the intestine for E.

Myotubularin-related protein protects against neuronal degeneration mediated by oxidative stress or infection.

Microbial infections have been linked to the onset and severity of neurodegenerative diseases such as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, but the underlying mechanisms remain largely unknown. Here, we used a genetic screen for genes involved in protection from infection-associated neurodegeneration and identified the gene mtm-10. We then validated the role of the encoded myotubularin-related protein, MTM-10, in protecting the dendrites of Caenorhabditis elegans from degeneration mediated by oxidative stress or Pseudomonas aeruginosa infection.

Coping in Pediatric Burn Survivors and Its Relation to Social Functioning and Self-Concept.

Pediatric burn survivors experience increased risk for bullying, stigmatization, body image concerns, and problematic social functioning. Although coping behaviors are associated with engagement in social supports and positive self-concept in multiple pediatric illness populations, their relation has not been examined in pediatric burns. This study examined coping in relation to social functioning and self-concept in 51 pediatric burn survivors aged 7-17years (=12.

Erratum: Cholesterol Regulates Innate Immunity via Nuclear Hormone Receptor NHR-8.

[This corrects the article DOI: 10.1016/j.isci.

Burn Resuscitation Practices in North America: Results of the Acute Burn ResUscitation Multicenter Prospective Trial (ABRUPT).

Objectives: ABRUPT was a prospective, noninterventional, observational study of resuscitation practices at 21 burn centers. The primary goal was to examine burn resuscitation with albumin or crystalloids alone, to design a future prospective randomized trial.

Summary Background Data: No modern prospective study has determined whether to use colloids or crystalloids for acute burn resuscitation.

Immunity-longevity tradeoff neurally controlled by GABAergic transcription factor PITX1/UNC-30.

A body of evidence indicates that metazoan immune and aging pathways are largely interconnected, but the mechanisms involved in their homeostatic control remain unclear. In this study, we find that the PITX (paired-like homeodomain) transcription factor UNC-30 controls the tradeoff between immunity and longevity from the nervous system in Caenorhabditis elegans. PITX/UNC-30 functional loss enhances immunity in a GATA/ELT-2- and p38 MAPK/PMK-1-dependent manner and reduced longevity by activating MXD/MDL-1 and the C2H2-type zinc finger transcription factor PQM-1.

TRPM channels mediate learned pathogen avoidance following intestinal distention.

Upon exposure to harmful microorganisms, hosts engage in protective molecular and behavioral immune responses, both of which are ultimately regulated by the nervous system. Using the nematode , we show that ingestion of leads to a fast pathogen avoidance behavior that results in aversive learning. We have identified multiple sensory mechanisms involved in the regulation of avoidance of The G-protein coupled receptor NPR-1-dependent oxygen-sensing pathway opposes this avoidance behavior, while an ASE neuron-dependent pathway and an AWB and AWC neuron-dependent pathway are directly required for avoidance.

Microbial colonization induces histone acetylation critical for inherited gut-germline-neural signaling.

The gut-neural axis plays a critical role in the control of several physiological processes, including the communication of signals from the microbiome to the nervous system, which affects learning, memory, and behavior. However, the pathways involved in gut-neural signaling of gut-governed behaviors remain unclear. We found that the intestinal distension caused by the bacterium Pseudomonas aeruginosa induces histone H4 Lys8 acetylation (H4K8ac) in the germline of Caenorhabditis elegans, which is required for both a bacterial aversion behavior and its transmission to the next generation.

Bacterial Lawn Avoidance and Bacterial Two Choice Preference Assays in .

Physical avoidance of pathogens is a crucial defense strategy used by the host to reduce pathogen infection. Hosts display the use of multiple strategies to sense and avoid pathogens, ranging from olfaction to sensing of damage caused by pathogen infection. Understanding various mechanisms of pathogen avoidance has the potential to uncover conserved host defense responses that are important against pathogen infections.

G-Protein-Coupled Receptor SRBC-48 Protects against Dendrite Degeneration and Reduced Longevity Due to Infection.

Increasing evidence suggests that deficient immune modulation and microbial infections underline neurodegeneration, but the mechanisms remain obscure. Here, we show that the G-protein-coupled receptor (GPCR) SRBC-48, which belongs to the class BC serpentine receptors, has a protective role in Caenorhabditis elegans dendrite degeneration caused by Pseudomonas aeruginosa infection. Our results indicate that SRBC-48 functions in a cell-autonomous manner in AWC neurons to protect against infection-associated dendrite degeneration.

Cholesterol Regulates Innate Immunity via Nuclear Hormone Receptor NHR-8.

Cholesterol is an essential nutrient for the function of diverse biological processes and for steroid biosynthesis across metazoans. However, the role of cholesterol in immune function remains understudied. Using the nematode Caenorhabditis elegans, which depends on the external environment for cholesterol, we studied the relationship between cholesterol and innate immunity.

Host Mucin Is Exploited by Pseudomonas aeruginosa To Provide Monosaccharides Required for a Successful Infection.

One of the primary functions of the mucosal barrier, found lining epithelial cells, is to serve as a first-line of defense against microbial pathogens. The major structural components of mucus are heavily glycosylated proteins called mucins. Mucins are key components of the innate immune system as they aid in the clearance of pathogens and can decrease pathogen virulence.

Neural control of behavioral and molecular defenses in C. elegans.

The nervous and immune systems use bi-directional communication to control host responses against microbial pathogens. Recent studies at the interface of the two systems have highlighted important roles of the nervous system in the regulation of both microbicidal pathways and pathogen avoidance behaviors. Studies on the neural circuits in the simple model host Caenorhabditis elegans have significantly improved our understanding of the roles of conserved neural mechanisms in controlling innate immunity.

Intestinal infection regulates behavior and learning via neuroendocrine signaling.

The recognition of pathogens and subsequent activation of defense responses are critical for the survival of organisms. The nematode recognizes pathogenic bacteria and elicits defense responses by activating immune pathways and pathogen avoidance. Here we show that chemosensation of phenazines produced by pathogenic , which leads to rapid activation of DAF-7/TGF-β in ASJ neurons, is insufficient for the elicitation of pathogen avoidance behavior.