Reduced function of the adaptor SH2B3 promotes T1D via altered gc cytokine-regulated, T cell intrinsic immune tolerance.

Unlabelled: Genome-wide association studies have identified as an important non-MHC gene for islet autoimmunity and type 1 diabetes (T1D). In this study, we found a single haplotype significantly associated with increased risk for human T1D, and this haplotype carries the single nucleotide variant rs3184504*T in To better characterize the role of SH2B3 in T1D, we used mouse modeling and found a T cell-intrinsic role for SH2B3 regulating peripheral tolerance. SH2B3 deficiency had minimal effect on TCR signaling or proliferation across antigen doses, yet enhanced cell survival and cytokine signaling including common gamma chain-dependent and interferon-gamma receptor signaling.

The IFIH1-A946T risk variant promotes diabetes in a sex-dependent manner.

Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic islet β-cells are attacked by the immune system, resulting in insulin deficiency and hyperglycemia. One of the top non-synonymous single-nucleotide polymorphisms (SNP) associated with T1D is in the interferon-induced helicase C domain-containing protein 1 (), which encodes an anti-viral cytosolic RNA sensor. This SNP results in an alanine to threonine substitution at amino acid 946 () and confers an increased risk for several autoimmune diseases, including T1D.

The IFIH1-A946T risk variant promotes diabetes in a sex-dependent manner.

Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic islet β-cells are attacked by the immune system, resulting in insulin deficiency and hyperglycemia. One of the top non-synonymous single-nucleotide polymorphisms (SNP) associated with T1D is in the interferon-induced helicase C domain-containing protein 1 ( ), which encodes an anti-viral cytosolic RNA sensor. This SNP results in an alanine to threonine substitution at amino acid 946 (IFIH1 ) and confers an increased risk for several autoimmune diseases, including T1D.

From bench to bedside via bytes: Multi-omic immunoprofiling and integration using machine learning and network approaches.

A significant surge in research endeavors leverages the vast potential of high-throughput omic technology platforms for broad profiling of biological responses to vaccines and cutting-edge immunotherapies and stem-cell therapies under development. These profiles capture different aspects of core regulatory and functional processes at different scales of resolution from molecular and cellular to organismal. Systems approaches capture the complex and intricate interplay between these layers and scales.

NUcore at 10: A Decade of Experience Developing a Core Facilities Management Application.

Implementing an effective software solution is an important step in managing a portfolio of core facilities. Though commercial options are available, developing or adopting a custom platform is a viable path for many institutions. At Northwestern University (NU), the cores program was reorganized beginning in 2008, and we pursued the latter path in order to retain control of the development priorities and to ensure integration with other enterprise systems.

The Autoimmune Risk R262W Variant of the Adaptor SH2B3 Improves Survival in Sepsis.

The single-nucleotide polymorphism (SNP) rs3184504 is broadly associated with increased risk for multiple autoimmune and cardiovascular diseases. Although the allele is uniquely enriched in European descent, the mechanism for the widespread selective sweep is not clear. In this study, we find the rs3184504*T allele had a strong association with reduced mortality in a human sepsis cohort.

Germline SAMD9L truncation variants trigger global translational repression.

SAMD9L is an interferon-induced tumor suppressor implicated in a spectrum of multisystem disorders, including risk for myeloid malignancies and immune deficiency. We identified a heterozygous de novo frameshift variant in SAMD9L in an infant with B cell aplasia and clinical autoinflammatory features who died from respiratory failure with chronic rhinovirus infection. Autopsy demonstrated absent bone marrow and peripheral B cells as well as selective loss of Langerhans and Purkinje cells.

Heme oxygenase-1 deficiency presenting with interstitial lung disease and hemophagocytic flares.

Background: Heme oxygenase-1 (HMOX1) catalyzes the metabolism of heme into carbon monoxide, ferrous iron, and biliverdin. Through biliverdin reductase, biliverdin becomes bilirubin. HMOX1-deficiency is a rare autosomal recessive disorder with hallmark features of direct antibody negative hemolytic anemia with normal bilirubin, hyperinflammation and features similar to macrophage activation syndrome.

Building a Sustainable Portfolio of Core Facilities: a Case Study.

Core facilities are an integral component of modern research institutions. Here, we describe our efforts over the past decade to build a sustainable portfolio of core facilities at Northwestern University. Through careful strategic planning, coordination, investment, and oversight, we have developed a model for managing core facilities that addresses researchers' needs within 3 schools across 2 campuses.

Improvement of the visual field index in clinical glaucoma care.

Objective: This article investigates the prevalence and attributes of patients with open-angle glaucoma who exhibit improvement of visual field loss in a clinical setting.

Design: We conducted a retrospective chart review of patients in a clinical glaucoma practice.

Participants: We identified 719 glaucoma patients with at least 5 SITA strategy visual field tests and a minimum continuous follow-up period of 5 years.

Germline De Novo Mutations in GNB1 Cause Severe Neurodevelopmental Disability, Hypotonia, and Seizures.

Whole-exome sequencing of 13 individuals with developmental delay commonly accompanied by abnormal muscle tone and seizures identified de novo missense mutations enriched within a sub-region of GNB1, a gene encoding the guanine nucleotide-binding protein subunit beta-1, Gβ. These 13 individuals were identified among a base of 5,855 individuals recruited for various undiagnosed genetic disorders. The probability of observing 13 or more de novo mutations by chance among 5,855 individuals is very low (p = 7.

From Knowledge Production to Implementation: Research Challenges and Imperatives.

As evidence-based practice is increasingly accepted in social work, the challenges associated with its actual implementation become more apparent and pressing. This article identifies implementation as a critical issue for research; implementation itself must be better understood if evidence-based practices are to be used and resultant improvements to practice are to be realized. Social work needs to engage more fully in (a) service system research and (b) implementation research, each of which complements and has potential to extend the benefits of efficacy and effectiveness research.

Implementation of evidence-based practice in community behavioral health: agency director perspectives.

Despite a growing supply of evidence-based mental health treatments, we have little evidence about how to implement them in real-world care. This qualitative pilot study captured the perspectives of agency directors on the challenge of implementing evidence-based practices in community mental health agencies. Directors identified challenges as limited access to research, provider resistance, and training costs.