STAT6 tunes maximum T cell IL-4 production from stochastically regulated Il4 alleles.

T helper 2 (Th2) cells stochastically express from the Il4 locus but it has not been determined whether allelic expression is linked or independent. Here, we provide evidence that alleles are independently activated and inactivated. We compared Il4 locus expression in T cells from hemizygous IL-4 reporter mice in culture and in vivo following exposure to type 2 immunogens.

The impact of cash incentives on mental health among adults initiating antiretroviral therapy in Tanzania.

Mental illness is prevalent among people living with HIV (PLHIV) and hinders engagement in HIV care. While financial incentives are effective at improving mental health and retention in care, the specific effect of such incentives on the mental health of PLHIV lacks quantifiable evidence. We evaluated the impact of a three-arm randomized controlled trial of a financial incentive program on the mental health of adult antiretroviral therapy (ART) initiates in Tanzania.

Recent Academic Research on Clinically Relevant Digital Measures: Systematic Review.

Background: Digital clinical measures collected via various digital sensing technologies such as smartphones, smartwatches, wearables, ingestibles, and implantables are increasingly used by individuals and clinicians to capture health outcomes or behavioral and physiological characteristics of individuals. Although academia is taking an active role in evaluating digital sensing products, academic contributions to advancing the safe, effective, ethical, and equitable use of digital clinical measures are poorly characterized.

Objective: We performed a systematic review to characterize the nature of academic research on digital clinical measures and to compare and contrast the types of sensors used and the sources of funding support for specific subareas of this research.

Fever supports CD8 effector T cell responses by promoting mitochondrial translation.

Fever can provide a survival advantage during infection. Metabolic processes are sensitive to environmental conditions, but the effect of fever on T cell metabolism is not well characterized. We show that in activated CD8 T cells, exposure to febrile temperature (39 °C) augmented metabolic activity and T cell effector functions, despite having a limited effect on proliferation or activation marker expression.

Point absorbers in Advanced LIGO.

Small, highly absorbing points are randomly present on the surfaces of the main interferometer optics in Advanced LIGO. The resulting nanometer scale thermo-elastic deformations and substrate lenses from these micron-scale absorbers significantly reduce the sensitivity of the interferometer directly though a reduction in the power-recycling gain and indirect interactions with the feedback control system. We review the expected surface deformation from point absorbers and provide a pedagogical description of the impact on power buildup in second generation gravitational wave detectors (dual-recycled Fabry-Perot Michelson interferometers).

Effects of unfamiliar diverse names on elementary students' passage comprehension.

Elementary school multicultural reading curricula include characters with diverse proper names, which are often unfamiliar and differ phonetically from students' native language. These names could impact reading outcomes by increasing students' cognitive load and/or creating cognitive disfluency. In Study 1, students in grades 1 through 2 read a standard passage including common names and a matched passage including unfamiliar names of Russian origin.

Acetate Promotes T Cell Effector Function during Glucose Restriction.

Competition for nutrients like glucose can metabolically restrict T cells and contribute to their hyporesponsiveness during cancer. Metabolic adaptation to the surrounding microenvironment is therefore key for maintaining appropriate cell function. For instance, cancer cells use acetate as a substrate alternative to glucose to fuel metabolism and growth.

Inflammatory macrophage dependence on NAD salvage is a consequence of reactive oxygen species-mediated DNA damage.

The adoption of Warburg metabolism is critical for the activation of macrophages in response to lipopolysaccharide. Macrophages stimulated with lipopolysaccharide increase their expression of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in NAD salvage, and loss of NAMPT activity alters their inflammatory potential. However, the events that lead to the cells' becoming dependent on NAD salvage remain poorly defined.

Evaluating Flexible Modeling of Continuous Covariates in Inverse-Weighted Estimators.

Correct specification of the exposure model is essential for unbiased estimation in marginal structural models with inverse-probability-of-treatment weights. However, although flexible modeling is commonplace when estimating effects of continuous covariates in outcome models, its use is less frequent in estimation of inverse probability weights. Using simulations, we assess the accuracy of the treatment effect estimates and covariate balance obtained with different exposure model specifications when the true relationship between a continuous, possibly time-varying covariate Lt and the logit of the probability of exposure is nonlinear.

IL-4 Is a Key Requirement for IL-4- and IL-4/IL-13-Expressing CD4 Th2 Subsets in Lung and Skin.

Although IL-4 is long associated with CD4 Th2 immune responses, its role in Th2 subset development in non-lymphoid tissues is less clear. We sought to better define IL-4's role in CD4 Th2 responses by using transgenic mice that express a dual IL-4 AmCyan/IL-13 DsRed (IL-4AC/IL-13DR) fluorescent reporter on an IL-4-sufficient or IL-4-deficient background. Using primary Th2 immune response models against house dust mite or () allergens, we examined the requirement for IL-4 by each of the defined Th2 subsets in the antigen draining lymph node, skin, and lung tissues.

Unraveling the Complex Interplay Between T Cell Metabolism and Function.

Metabolism drives function, on both an organismal and a cellular level. In T cell biology, metabolic remodeling is intrinsically linked to cellular development, activation, function, differentiation, and survival. After naive T cells are activated, increased demands for metabolic currency in the form of ATP, as well as biomass for cell growth, proliferation, and the production of effector molecules, are met by rewiring cellular metabolism.

Impaired insulin signaling in unaffected siblings and patients with first-episode psychosis.

Patients with psychotic disorders are at high risk for type 2 diabetes mellitus, and there is increasing evidence that patients display glucose metabolism abnormalities before significant antipsychotic medication exposure. In the present study, we examined insulin action by quantifying insulin sensitivity in first-episode psychosis (FEP) patients and unaffected siblings, compared to healthy individuals, using a physiological-based model and comprehensive assessment battery. Twenty-two unaffected siblings, 18 FEP patients, and 15 healthy unrelated controls were evaluated using a 2-h oral glucose tolerance test (OGTT), with 7 samples of plasma glucose and serum insulin concentration measurements.

Thymic stromal lymphopoietin drives the development of IL-13 Th2 cells.

T helper 2 (Th2) cells are pivotal in the development of allergy. Allergen exposure primes IL-4 Th2 cells in lymph node, but production of effector cytokines including IL-5 and IL-13 is thought to require additional signals from antigen and the environment. Here we report that a substantial proportion of naive CD4 T cells in spleen and lymph node express receptors for the epithelium-derived inflammatory cytokine thymic stromal lymphopoietin (TSLP).

Mitochondrial Priming by CD28.

T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand.

Abnormalities in High-Energy Phosphate Metabolism in First-Episode Bipolar Disorder Measured Using P-Magnetic Resonance Spectroscopy.

Background: Brain energy metabolism is critical for supporting synaptic function and information processing. A growing body of evidence suggests abnormalities in brain bioenergetics in psychiatric disorders, including both bipolar disorder (BD) and schizophrenia. P magnetic resonance spectroscopy provides a noninvasive window into these processes in vivo.

Brain bioenergetics and redox state measured by P magnetic resonance spectroscopy in unaffected siblings of patients with psychotic disorders.

Background: Brain bioenergetic anomalies and redox dysregulation have been implicated in the pathophysiology of psychotic disorders. The present study examined brain energy-related metabolites and the balance between nicotinamide adenine dinucleotide metabolites (oxidized NAD+ and reduced NADH) using P-magnetic resonance spectroscopy (P-MRS) in unaffected siblings, compared to first episode psychosis (FEP) patients and healthy controls.

Methods: 21 unaffected siblings, 32 FEP patients (including schizophrenia spectrum and affective psychoses), and 21 controls underwent P-MRS in the frontal lobe (6×6×4cm) on a 4T MR scanner, using custom-designed dual-tuned surface coil with outer volume suppression.

Health-selective migration among patients with rheumatoid arthritis in Québec: a cohort study using administrative data.

Little is known about how rheumatoid arthritis (RA) affects an individual's ability to relocate. The current literature suggests the relationship between health and migration is often disease-specific. We sought to estimate the impact of RA diagnosis on migration within a Canadian province, comparing migration rates in residents before and after RA diagnosis.