Identification of a novel PDC-E2 epitope in primary biliary cholangitis: Application for engineered Treg therapy.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease, characterized by progressive destruction of small intrahepatic bile ducts and portal inflammation. Treatment options are limited, with reliance on liver transplantation in advanced cases. The adaptive immune response is implicated in disease pathogenesis by the presence of anti-mitochondrial antibodies targeting the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2) in 90-95 % of patients and T cells infiltrating the portal tracts.

Nutrient Analysis of Raw United States Beef Offal Items.

Nutrient composition of beef offal was evaluated to expand availability of nutrient data for the following beef items: beef heart, liver, kidney, tongue, honeycomb tripe, oxtail, marrow bones, testicles, and blood. These items are consumed both domestically and internationally, with significant regional variations that can be contributed to unique cultural meals and dietary patterns. Standardized procedures were used to dissect and homogenize beef offal samples.

Nutrient Analysis of Raw and Cooked USDA Prime Beef Cuts.

Nutrient composition data that accurately represent available beef products are critical to understanding beef's role in healthy dietary patterns. The quality of beef products has changed over the past several decades, and updated nutrient data are warranted as USDA Prime beef cuts become more available. In an effort to provide a complete nutrient profile for frequently purchased USDA Prime beef cuts, five USDA Prime cuts; strip loin steak, tenderloin steak, ribeye steak, top sirloin steak, and rib roast were collected from retail stores in six geographical locations over three collections for macro- and micronutrient analysis in both the raw and cooked state.

Dual-locus, dual-HDR editing permits efficient generation of antigen-specific regulatory T cells with robust suppressive activity.

Adoptive regulatory T (Treg) cell therapy is predicted to modulate immune tolerance in autoimmune diseases, including type 1 diabetes (T1D). However, the requirement for antigen (ag) specificity to optimally orchestrate tissue-specific, Treg cell-mediated tolerance limits effective clinical application. To address this challenge, we present a single-step, combinatorial gene editing strategy utilizing dual-locus, dual-homology-directed repair (HDR) to generate and specifically expand ag-specific engineered Treg (EngTreg) cells derived from donor CD4+ T cells.

SARS-CoV-2 infection augments species- and age-specific predispositions in cotton rats.

Heterogeneity of COVID-19 manifestations in human population is vast, for reasons unknown. Cotton rats are a clinically relevant small animal model of human respiratory viral infections. Here, we demonstrate for the first time that SARS-CoV-2 infection in cotton rats affects multiple organs and systems, targeting species- and age-specific biological processes.

Bell's palsy and lip HSV-1 infection: importance of subcutaneous access.

Although HSV-1 has been implicated in facial palsy for a long time, testing and treating for HSV is not routine. The lack of a meaningful demonstration of how HSV-1 would cause facial palsy has limited progress in this field. Herein we demonstrate that the depth of the lip HSV-1 infection defines the course of the disease, with deeper subcutaneous infection allowing virus access to the facial nerve and causing facial palsy.

Pancreatic islet-specific engineered T exhibit robust antigen-specific and bystander immune suppression in type 1 diabetes models.

Adoptive transfer of regulatory T cells (T) is therapeutic in type 1 diabetes (T1D) mouse models. T that are specific for pancreatic islets are more potent than polyclonal T in preventing disease. However, the frequency of antigen-specific natural T is extremely low, and ex vivo expansion may destabilize T, leading to an effector phenotype.

Effect of aging on immunogenicity and efficacy of inactivated influenza vaccines in cotton rats .

Inactivated influenza vaccines are known to be less immunogenic in human elderly in regards to serologic antibody response induced by vaccination. Accumulating evidence, however, points to a comparable effectiveness of influenza vaccines in the young and the elderly individuals. In the current study, we assessed immunogenicity and effectiveness of trivalent inactivated vaccine FluLaval in young and aged cotton rats and found that while serologic response to immunization was indeed reduced in older animals, comparable protection against influenza infection was afforded by prime-boost vaccination in both young and aged cotton rats.

Herpes Simplex Virus 1 Induces Brain Inflammation and Multifocal Demyelination in the Cotton Rat Sigmodon hispidus.

Demyelinating central nervous system (CNS) disorders like multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) have been difficult to study and treat due to the lack of understanding of their etiology. Numerous cases point to the link between herpes simplex virus (HSV) infection and multifocal CNS demyelination in humans; however, convincing evidence from animal models has been missing. In this work, we found that HSV-1 infection of the cotton rat via a common route (lip abrasion) can cause multifocal CNS demyelination and inflammation.

Integrative taxonomy and preliminary assessment of species limits in the Liolaemus walkeri complex (Squamata, Liolaemidae) with descriptions of three new species from Peru.

Species delimitation studies based on integrative taxonomic approaches have received considerable attention in the last few years, and have provided the strongest hypotheses of species boundaries. We used three lines of evidence (molecular, morphological, and niche envelopes) to test for species boundaries in Peruvian populations of the Liolaemus walkeri complex. Our results show that different lines of evidence and analyses are congruent in different combinations, for unambiguous delimitation of three lineages that were "hidden" within known species, and now deserve species status.