Proinsulin-Reactive CD4 T Cells in the Islets of Type 1 Diabetes Organ Donors.

Proinsulin is an abundant protein that is selectively expressed by pancreatic beta cells and has been a focus for development of antigen-specific immunotherapies for type 1 diabetes (T1D). In this study, we sought to comprehensively evaluate reactivity to preproinsulin by CD4 T cells originally isolated from pancreatic islets of organ donors having T1D. We analyzed 187 T cell receptor (TCR) clonotypes expressed by CD4 T cells obtained from six T1D donors and determined their response to 99 truncated preproinsulin peptide pools, in the presence of autologous B cells.

Clinical features, biochemistry, and HLA-DRB1 status in youth-onset type 1 diabetes in Sudan.

Objective: To further understand clinical and biochemical features, and HLA-DRB1 genotypes, in new cases of diabetes in Sudanese children and adolescents.

Research Design And Methods: Demographic characteristics, clinical information, and biochemical parameters (blood glucose, HbA1c, C-peptide, autoantibodies against glutamic acid decarboxylase 65 [GADA] and insulinoma-associated protein-2 [IA-2A], and HLA-DRB1) were assessed in 99 individuals <18 years, recently (<18 months) clinically diagnosed with T1D. HLA-DRB1 genotypes for 56 of these Arab individuals with T1D were compared to a mixed control group of 198 healthy Arab (75%) and African (25%) individuals without T1D.

Search for Dark Matter Produced in Association with a Dark Higgs Boson Decaying into W^{±}W^{∓} or ZZ in Fully Hadronic Final States from sqrt[s]=13 TeV pp Collisions Recorded with the ATLAS Detector.

Several extensions of the Standard Model predict the production of dark matter particles at the LHC. An uncharted signature of dark matter particles produced in association with VV=W^{±}W^{∓} or ZZ pairs from a decay of a dark Higgs boson s is searched for using 139  fb^{-1} of pp collisions recorded by the ATLAS detector at a center-of-mass energy of 13 TeV. The s→V(qq[over ¯])V(qq[over ¯]) decays are reconstructed with a novel technique aimed at resolving the dense topology from boosted VV pairs using jets in the calorimeter and tracking information.

Longitudinal Flow Decorrelations in Xe+Xe Collisions at sqrt[s_{NN}]=5.44 TeV with the ATLAS Detector.

The first measurement of longitudinal decorrelations of harmonic flow amplitudes v_{n} for n=2-4 in Xe+Xe collisions at sqrt[s_{NN}]=5.44  TeV is obtained using 3  μb^{-1} of data with the ATLAS detector at the LHC. The decorrelation signal for v_{3} and v_{4} is found to be nearly independent of collision centrality and transverse momentum (p_{T}) requirements on final-state particles, but for v_{2} a strong centrality and p_{T} dependence is seen.

Voices: Insulin and beyond.

Marking insulin's centennial, we share stories of researchers and clinicians whose seminal work has advanced our understanding of insulin, islet biology, insulin resistance, and diabetes. The past century of pursuing the "hormone of hormones" and advancing diabetes therapies is replete with stories of collaboration, perseverance, and triumph.

Islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes.

Dysregulation of glucagon secretion in type 1 diabetes (T1D) involves hypersecretion during postprandial states, but insufficient secretion during hypoglycemia. The sympathetic nervous system regulates glucagon secretion. To investigate islet sympathetic innervation in T1D, sympathetic tyrosine hydroxylase (TH) axons were analyzed in control non-diabetic organ donors, non-diabetic islet autoantibody-positive individuals (AAb), and age-matched persons with T1D.

Medium-Induced Modification of Z-Tagged Charged Particle Yields in Pb+Pb Collisions at 5.02 TeV with the ATLAS Detector.

The yield of charged particles opposite to a Z boson with large transverse momentum (p_{T}) is measured in 260  pb^{-1} of pp and 1.7  nb^{-1} of Pb+Pb collision data at 5.02 TeV per nucleon pair recorded with the ATLAS detector at the Large Hadron Collider.

Limited evidence for executive function load impairing selective copying in a win-stay lose-shift task.

The use of 'explicitly metacognitive' learning strategies has been proposed as an explanation for uniquely human capacities for cumulative culture. Such strategies are proposed to rely on explicit, system-2 cognitive processes, to enable advantageous selective copying. To investigate the plausibility of this theory, we investigated participants' ability to make flexible learning decisions, and their metacognitive monitoring efficiency, under executive function (EF) load.

Insulin Receptor-Expressing T Cells Appear in Individuals at Risk for Type 1 Diabetes and Can Move into the Pancreas in C57BL/6 Transgenic Mice.

Insulin receptor (IR) expression on the T cell surface can indicate an activated state; however, the IR is also chemotactic, enabling T cells with high IR expression to physically move toward insulin. In humans with type 1 diabetes (T1D) and the NOD mouse model, a T cell-mediated autoimmune destruction of insulin-producing pancreatic β cells occurs. In previous work, when purified IR and IR T cells were sorted from diabetic NOD mice and transferred into irradiated nondiabetic NOD mice, only those that received IR T cells developed insulitis and diabetes.

APOL1 genotype-associated morphologic changes among patients with focal segmental glomerulosclerosis.

Background: The G1 and G2 alleles of apolipoprotein L1 (APOL1) are common in the Black population and associated with increased risk of focal segmental glomerulosclerosis (FSGS). The molecular mechanisms linking APOL1 risk variants with FSGS are not clearly understood, and APOL1's natural absence in laboratory animals makes studying its pathobiology challenging.

Methods: In a cohort of 90 Black patients with either FSGS or minimal change disease (MCD) enrolled in the Nephrotic Syndrome Study Network (58% pediatric onset), we used kidney biopsy traits as an intermediate outcome to help illuminate tissue-based consequences of APOL1 risk variants and expression.

Low-Dose ATG/GCSF in Established Type 1 Diabetes: A Five-Year Follow-up Report.

Previously, we demonstrated low-dose antithymocyte globulin (ATG) and granulocyte colony-stimulating factor (GCSF) immunotherapy preserved C-peptide for 2 years in a pilot study of patients with established type 1 diabetes ( = 25). Here, we evaluated the long-term outcomes of ATG/GCSF in study participants with 5 years of available follow-up data ( = 15). The primary end point was area under the curve (AUC) C-peptide during a 2-h mixed-meal tolerance test.

Assessing the impact of body image concerns on functioning across life domains: Development and validation of the Body Image Life Disengagement Questionnaire (BILD-Q) among British adolescents.

Assessing the impact of body image on engagement in a range of life domains is important; however, there is a lack of validated measures for adolescents. The current research developed the Body Image Life Disengagement Questionnaire (BILD-Q) and validated it among four samples of British adolescents. Study 1 (N = 1707; 11-13 years) indicated a 9-item unidimensional scale based on Exploratory Factory Analysis.

Validation of a diagnosis-agnostic symptom questionnaire for asthma and/or COPD.

Background: The Respiratory Symptoms Questionnaire (RSQ) is a novel, four-item patient-reported diagnosis-agnostic tool designed to assess the frequency of respiratory symptoms and their impact on activity, without specifying a particular diagnosis. Our objective was to examine its validity in patients with asthma and/or chronic obstructive pulmonary disease (COPD).

Methods: Baseline data were randomly sampled from patients who completed the RSQ in the NOVELTY study (ClinicalTrials.

TCR/BCR dual-expressing cells and their associated public BCR clonotype are not enriched in type 1 diabetes.

Ahmed and colleagues recently described a novel hybrid lymphocyte expressing both a B and T cell receptor, termed double expresser (DE) cells. DE cells in blood of type 1 diabetes (T1D) subjects were present at increased numbers and enriched for a public B cell clonotype. Here, we attempted to reproduce these findings.

Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes.

Background: The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective birth cohort designed to study type 1 diabetes (T1D) by following children with high genetic risk. An integrative multi-omics approach was used to evaluate islet autoimmunity etiology, identify disease biomarkers, and understand progression over time.

Results: We identify a multi-omics signature that was predictive of islet autoimmunity (IA) as early as 1 year before seroconversion.

Modulation of Leukocytes of the Innate Arm of the Immune System as a Potential Approach to Prevent the Onset and Progression of Type 1 Diabetes.

Type 1 diabetes (T1D) is characterized by insulin deficiency resulting from the selective destruction of pancreatic β-cells by self-reactive T cells. Recent evidence demonstrates that innate immune responses substantially contribute to the pathogenesis of T1D, as they represent a first line of response to danger/damage signals. Here we discuss evidence on how, in a relapsing-remitting pattern, pancreas remodeling, diet, microbiota, gut permeability, and viral/bacterial infections induce the accumulation of leukocytes of the innate arm of the immune system throughout the pancreas.

Exocrine Pancreas Dysfunction in Type 1 Diabetes.

Objective: Type 1 diabetes (T1D) is characterized by autoimmune β-cell destruction, but exocrine pancreas abnormalities may also play a role in the disease pathophysiology. Herein, we review the current evidence of exocrine damage in T1D and discuss its underlying pathophysiology, clinical evaluation, and treatment.

Method: Extensive literature search was performed for "type 1 diabetes" and "exocrine dysfunction" on PubMed and Google Scholar databases.

Observation and Measurement of Forward Proton Scattering in Association with Lepton Pairs Produced via the Photon Fusion Mechanism at ATLAS.

The observation of forward proton scattering in association with lepton pairs (e^{+}e^{-}+p or μ^{+}μ^{-}+p) produced via photon fusion is presented. The scattered proton is detected by the ATLAS Forward Proton spectrometer, while the leptons are reconstructed by the central ATLAS detector. Proton-proton collision data recorded in 2017 at a center-of-mass energy of sqrt[s]=13  TeV are analyzed, corresponding to an integrated luminosity of 14.

The use of individual, social, and animated cue information by capuchin monkeys and children in a touchscreen task.

The distinctiveness of human cumulative culture raises the question of whether humans respond differently to information originating from social sources, compared with information from other sources. Further, does any such differential responding set humans apart from other species? We studied how capuchin monkeys and 2- to 5-year-old children used information originating from their own actions, those of a human demonstrator, or an animated cue. This information, presented via a touchscreen, always revealed in the first trial (T1) the reward value (rewarded or unrewarded) of one stimulus from a 2- or 3-item array, and could be used in a follow-up trial (T2) involving the same stimulus array.

Exocrine Pancreatic Enzymes Are a Serological Biomarker for Type 1 Diabetes Staging and Pancreas Size.

Exocrine pancreas abnormalities are increasingly recognized as features of type 1 diabetes. We previously reported reduced serum trypsinogen levels and in a separate study, smaller pancreata at and before disease onset. We hypothesized that three pancreas enzymes (amylase, lipase, and trypsinogen) might serve as serological biomarkers of pancreas volume and risk for type 1 diabetes.

Cognitive prerequisites for cumulative culture are context-dependent: Children's potential for ratcheting depends on cue longevity.

Human cumulative culture has been suggested to depend on human-unique cognitive mechanisms, explaining its apparent absence in other species. We show that the potential for exhibiting cumulative culture depends on the cognitive abilities of the agents and the demands associated with using information generated by others' activity. 154 children aged 3-6 years played a searching game ("Find the Treasure"), taking their turn after a puppet demonstrator.

Quantitative Proteomic Analysis Using Formalin-Fixed, Paraffin-Embedded (FFPE) Human Cardiac Tissue.

Clinical tissue archives represent an invaluable source of biological information. Formalin-fixed, paraffin-embedded (FFPE) tissue can be used for retrospective investigation of biomarkers of diseases and prognosis.Recently, the number of studies using proteome profiling of samples from clinical archives has markedly increased.