Defective Proinsulin Handling Modulates the MHC I Bound Peptidome and Activates the Inflammasome in β-Cells.

How immune tolerance is lost to pancreatic β-cell peptides triggering autoimmune type 1 diabetes is enigmatic. We have shown that loss of the proinsulin chaperone glucose-regulated protein (GRP) 94 from the endoplasmic reticulum (ER) leads to mishandling of proinsulin, ER stress, and activation of the immunoproteasome. We hypothesize that inadequate ER proinsulin folding capacity relative to biosynthetic need may lead to an altered β-cell major histocompatibility complex (MHC) class-I bound peptidome and inflammasome activation, sensitizing β-cells to immune attack.

Spliced Peptides and Cytokine-Driven Changes in the Immunopeptidome of Melanoma.

Antigen recognition by CD8 T cells is governed by the pool of peptide antigens presented on the cell surface in the context of HLA class I complexes. Studies have shown not only a high degree of plasticity in the immunopeptidome, but also that a considerable fraction of all presented peptides is generated through proteasome-mediated splicing of noncontiguous regions of proteins to form novel peptide antigens. Here, we used high-resolution mass spectrometry combined with new bioinformatic approaches to characterize the immunopeptidome of melanoma cells in the presence or absence of IFNγ.

Human Plasma Protein Corona of Aβ Amyloid and Its Impact on Islet Amyloid Polypeptide Cross-Seeding.

Alzheimer's disease (AD) is the most severe form of neurological disorder, characterized by the presence of extracellular amyloid-β (Aβ) plaques and intracellular tau tangles. For decades, therapeutic strategies against the pathological symptoms of AD have often relied on the delivery of monoclonal antibodies to target specifically Aβ amyloid or oligomers, largely to no avail. Aβ can be traced in the brain as well as in cerebrospinal fluid and the circulation, giving rise to abundant opportunities to interact with their environmental proteins.

Graphene quantum dots rescue protein dysregulation of pancreatic β-cells exposed to human islet amyloid polypeptide.

The amyloid aggregation of peptides and proteins is a hallmark of neurological disorders and type 2 diabetes. Human islet amyloid polypeptide (IAPP), co-secreted with insulin by pancreatic β-cells, plays dual roles in both glycemic control and the pathology of type 2 diabetes. While IAPP can activate the NLRP3 inflammasome and modulate cellular autophagy, apoptosis and extracellular matrix metabolism, no data is available concerning intracellular protein expression upon exposure to the polypeptide.

Incidence, prevalence, and mortality associated with head and neck cancer in India: Protocol for a systematic review.

Background: Head and neck cancer (HNC) is a heterogeneous tumor at various anatomic sites and one of the most common cancers in India. Published and existing reports and studies highlight an alarming increase in the incidence, prevalence, and mortality of HNC. Despite its high incidence, there is a dearth of more precise estimates of reliable epidemiological data pertaining to HNC in India.

Head and neck cancer risk factors in India: protocol for systematic review and meta-analysis.

Introduction: Demographic, behavioural and environmental factors have been associated with increased risk of head and neck cancer (HNC). We will review published reports and explore connections between risk factors and HNC incidence. This protocol aims to provide strategies for a systematic review and meta-analysis of HNC risk factor analysis in India.