Pro-Inflammatory Signaling Upregulates a Neurotoxic Conotoxin-Like Protein Encrypted Within Human Endogenous Retrovirus-K.

Motor neuron degeneration and spinal cord demyelination are hallmark pathological events in Amyotrophic Lateral Sclerosis (ALS). Endogenous retrovirus-K (ERVK) expression has an established association with ALS neuropathology, with murine modeling pointing to a role for the ERVK envelope () gene in disease processes. Here, we describe a novel viral protein cryptically encoded within the ERVK transcript, which resembles two distinct cysteine-rich neurotoxic proteins: conotoxin proteins found in marine snails and the Human Immunodeficiency Virus (HIV) Tat protein.

Oil pipelines and food sovereignty: threat to health equity for Indigenous communities.

Energy projects may profoundly impact Indigenous peoples. We consider effects of Canada's proposed Trans Mountain oil pipeline expansion on the health and food sovereignty of the Tsleil-Waututh Nation (TWN) through contamination and impeded access to uncontaminated traditional foods. Federal monitoring and TWN documentation show elevated shellfish biotoxin levels in TWN's traditional territory near the terminus where crude oil is piped.

Uncoupling protein 2 regulates daily rhythms of insulin secretion capacity in MIN6 cells and isolated islets from male mice.

Objective: Upregulation of uncoupling protein 2 (UCP2) is associated with impaired glucose-stimulated insulin secretion (GSIS), which is thought to be an important contributor to pathological β cell failure in obesity and type 2 diabetes (T2D); however, the physiological function of UCP2 in the β cell remains undefined. It has been suggested, but not yet tested, that UCP2 plays a physiological role in β cells by coordinating insulin secretion capacity with anticipated fluctuating nutrient supply, such that upregulation of UCP2 in the inactive/fasted state inhibits GSIS as a mechanism to prevent hypoglycemia. Therefore, we hypothesized that daily cycles of GSIS capacity are dependent on rhythmic and predictable patterns of gene expression such that low in the active/fed phase promotes maximal GSIS capacity, whereas elevated expression in the inactive/fasted phase supresses GSIS capacity.

Exploring the role of the HNF-1αG319S polymorphism in β cell failure and youth-onset type 2 diabetes: Lessons from MODY and Hnf-1α-deficient animal models.

The prevalence of youth-onset type 2 diabetes (T2D) is rapidly increasing worldwide, disproportionately affecting Indigenous youth with Oji-Cree heritage from central Canada. Candidate gene screening has uncovered a novel and private polymorphism in the Oji-Cree population in the hepatocyte nuclear factor-1 alpha (HNF-1α) gene, where a highly conserved glycine residue at position 319 is changed to a serine (termed HNF-1αG319S or simply G319S). Oji-Cree youth who carry one or two copies of the "S-allele" present at diagnosis with less obesity, reduced indicators of insulin resistance, and lower plasma insulin levels at diagnosis, suggestive of a primary defect in the insulin-secreting β cells.