Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells.

Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.

Parameterization of a Fluctuating Charge Model for Complexes Containing 3d Transition Metals.

Metalloproteins widely exist in biology, playing pivotal roles in diverse life processes. Meanwhile, molecular dynamics (MD) simulations based on classical force fields has emerged as an important tool in scientific research. Partial charges are critical parameters within classical force fields and usually derived from quantum mechanical (QM) calculations.

Umbilical Artery Doppler and Adverse Outcomes in Severe Preeclampsia Without Fetal Growth Restriction: A Retrospective Cohort Study.

Background and objective Severe preeclampsia may be managed expectantly before 34 weeks gestation with close surveillance. Utilized in fetal growth restriction (FGR), evidence supports umbilical artery (UA) Doppler preventing neonatal morbidity from hypertensive disease and predicting adverse outcomes in preeclampsia. We evaluated the association of abnormal UA Doppler waveforms with early delivery (before 34 weeks gestation) and adverse maternal-fetal outcomes in patients with early severe preeclampsia without FGR.

Protein-truncating variant in APOL3 increases chronic kidney disease risk in epistasis with APOL1 risk alleles.

BACKGROUNDTwo coding alleles within the APOL1 gene, G1 and G2, found almost exclusively in individuals genetically similar to West African populations, contribute substantially to the pathogenesis of chronic kidney disease (CKD). The APOL gene cluster on chromosome 22 contains a total of 6 APOL genes that have arisen as a result of gene duplication.METHODSUsing a genome-first approach in the Penn Medicine BioBank, we identified 62 protein-altering variants in the 6 APOL genes with a minor allele frequency of >0.

Vitamin D Levels and SARS-CoV-2 Infection among Medically Underserved Populations in the Minority and Rural Coronavirus Insights Study.

Background: Extant literature presents contradictory findings on the role of vitamin D on SARS-CoV-2 infection. Our study included an examination of the relationship between vitamin D levels and SARS-CoV-2 infection among the Minority and Rural Coronavirus Insights Study (MRCIS) cohort, a diverse population of medically underserved persons presenting at five Federally qualified health centers in the United States.

Methods: We conducted a descriptive analysis to explore the relationship between vitamin D levels and SARS-CoV-2 infection among medically underserved participants.

Nucleocapsid and Spike Protein-Based Anti-SARS-CoV-2 Assay Performance in the Minority and Rural Coronavirus Insights Study: Characteristics of Socioeconomically Disadvantaged Populations with Health Disparities.

Background: COVID-19 has had a devastating impact on Black, Hispanic, and other underserved, disadvantaged populations. Here anti-SARS-CoV-2 tests are characterized in disadvantaged patients to examine equivalence in US populations.

Methods: Underserved participant adults (age > 18 years) were enrolled before the availability of SARS-CoV-2 vaccines in Federal Qualified Health Centers in California, Florida, Louisiana, Illinois, and Ohio and contributed samples to the Minority and Rural Coronavirus Insights Study (MRCIS).

Development of a Fluctuating Charge Model for Zinc-Containing Metalloproteins.

Metalloproteins widely exist in biology and play important roles in various processes. To accurately simulate metalloprotein systems, modeling polarization and charge transfer effects is vital. The fluctuating charge (FQ) model can efficiently generate atomic charges and simulate the charge transfer effect; it has been developed for a wide range of applications, but few models have been specifically tailored for metalloproteins.

The intracellular growth of the vacuolar pathogen is dependent on the acyl chain composition of host membranes.

is an accidental human bacterial pathogen that infects and replicates within alveolar macrophages causing a severe atypical pneumonia known as Legionnaires' disease. As a prototypical vacuolar pathogen establishes a unique endoplasmic reticulum (ER)-derived organelle within which bacterial replication takes place. Bacteria-derived proteins are deposited in the host cytosol and in the lumen of the pathogen-occupied vacuole via a type IVb (T4bSS) and a type II (T2SS) secretion system respectively.

Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans.

Gold nanoparticles (GNPs) have been used in the development of novel therapies as a way of delivery of both stimulatory and tolerogenic peptide cargoes. Here we report that intradermal injection of GNPs loaded with the proinsulin peptide C19-A3, in patients with type 1 diabetes, results in recruitment and retention of immune cells in the skin. These include large numbers of clonally expanded T-cells sharing the same paired T-cell receptors (TCRs) with activated phenotypes, half of which, when the TCRs were re-expressed in a cell-based system, were confirmed to be specific for either GNP or proinsulin.

HLA-DQ8 Supports Development of Insulitis Mediated by Insulin-Reactive Human TCR-Transgenic T Cells in Nonobese Diabetic Mice.

In an effort to improve HLA-"humanized" mouse models for type 1 diabetes (T1D) therapy development, we previously generated directly in the NOD strain CRISPR/Cas9-mediated deletions of various combinations of murine MHC genes. These new models improved upon previously available platforms by retaining β2-microglobulin functionality in FcRn and nonclassical MHC class I formation. As proof of concept, we generated H2-Db/H2-Kd double knockout NOD mice expressing human HLA-A*0201 or HLA-B*3906 class I variants that both supported autoreactive diabetogenic CD8+ T cell responses.

The Minority and Rural Coronavirus Insights Study: Design and Baseline Characteristics of a Minority Cohort.

The Minority and Rural Coronavirus Insights Study (MRCIS) is an ongoing prospective cohort study examining health disparities associated with SARS-CoV-2 infection among medically underserved populations. This report describes procedures implemented to establish the MRCIS cohort and examines the factors associated with the molecular and serological assessment of SARS-CoV-2 infection status at participant enrollment. Participants were recruited from 5 geographically dispersed federally qualified health centers between November 2020 and April 2021.

Conserved spatiotemporal expression landscape of dominant tRNA genes in human and mouse.

Transfer RNAs are integral for protein synthesis and the interpretation of the information contained in DNA. To date, a few methods, including custom microarrays and custom targeted sequencing, have been used to quantify tRNA. However, methods using available RNA-sequencing data have not yet been reported.

Interferon-α promotes neo-antigen formation and preferential HLA-B-restricted antigen presentation in pancreatic β-cells.

Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but its effect on the repertoire of HLA Class I (HLA-I)-bound peptides presented by pancreatic β-cells is unknown. Using immunopeptidomics, we characterized the peptide/HLA-I presentation in resting and IFN-α-exposed β-cells. IFN-α increased HLA-I expression and peptide presentation, including neo-sequences derived from alternative mRNA splicing, post-translational modifications - notably glutathionylation - and protein -splicing.

Corrigendum: COVID-19 pandemic's disproportionate impact on childhood bereavement for youth of color: reflections and recommendations.

[This corrects the article DOI: 10.3389/fped.2023.

COVID-19 pandemic's disproportionate impact on childhood bereavement for youth of color: Reflections and recommendations.

The COVID-19 pandemic devastated public welfare worldwide, bringing excess deaths connected to causes such as homicide, substance abuse, and heart disease. In the U.S.

Consequences of Overfitting the van der Waals Radii of Ions.

Atomic radii play important roles in scientific research. The covalent radii of atoms, ionic radii of ions, and van der Waals (VDW) radii of neutral atoms can all be derived from crystal structures. However, the VDW radii of ions are a challenge to determine because the atomic distances in crystal structures were determined by a combination of VDW interactions and electrostatic interactions, making it unclear how to define the VDW sphere of ions in such an environment.

Haemodynamic effects of prophylactic post-operative hydrocortisone following cardiopulmonary bypass in neonates undergoing cardiac surgery.

Multiple studies have endeavoured to define the role of steroids in paediatric congenital heart surgery; however, steroid utilisation remains haphazard. In September, 2017, our institution implemented a protocol requiring that all neonates undergoing cardiac surgery with the use of cardiopulmonary bypass receive a five-day post-operative hydrocortisone taper. This single-centre retrospective study was designed to test the hypothesis that routine post-operative hydrocortisone administration reduces the incidence of capillary leak syndrome, leads to favourable postoperative fluid balance, and less inotropic support in the early post-operative period.

Demographic Determinants and Geographical Variability of COVID-19 Vaccine Hesitancy in Underserved Communities: Cross-sectional Study.

Background: COVID-19 hospitalizations and deaths disproportionately affect underserved and minority populations, emphasizing that vaccine hesitancy can be an especially important public health risk factor in these populations.

Objective: This study aims to characterize COVID-19 vaccine hesitancy in underserved diverse populations.

Methods: The Minority and Rural Coronavirus Insights Study (MRCIS) recruited a convenience sample of adults (age≥18, N=3735) from federally qualified health centers (FQHCs) in California, the Midwest (Illinois/Ohio), Florida, and Louisiana and collected baseline data in November 2020-April 2021.

Precision Public Health Initiatives in Cancer: Proceedings from the Transdisciplinary Conference for Future Leaders in Precision Public Health.

Background: Precision public health is an emergent field that requires transdisciplinary collaborations and leverages innovative approaches to improve population health. These opportunities have inspired a new generation of precision public health researchers. Despite burgeoning interest in precision public health, there are limited opportunities for researchers to convene and continue the momentum of this field.

Decreasing Hospital Readmissions Utilizing an Evidence-Based COPD Care Bundle.

Purpose: Chronic obstructive pulmonary disease (COPD) is a chronic condition that leads to significant morbidity and mortality. Management of COPD hospitalizations utilizing an evidence-based care bundle can provide consistent quality of care and may reduce readmissions.

Methods: This single-center retrospective cohort study evaluated readmission rates in patients hospitalized with a COPD exacerbation.

Using a Participatory Approach to Develop Research Priorities for Future Leaders in Cancer-Related Precision Public Health.

Precision public health is an emerging discipline combining principles and frameworks of precision health with the goal of improving population health. The development of research priorities drawing on the strengths of precision and public health is critical to facilitate the growth of the discipline to improve health outcomes. We held an interactive workshop during a virtual conference bringing together early-career researchers across public health disciplines to identify research priorities in precision public health.

[Experience in pediatric patients with COVID-19 during the first pandemic wave].

Coronavirus 2 infection has spread rapidly throughout the world. Most of the current publications describe different behavior between an adult and pediatric population, this last one is associated with less clinical severity. The purpose of this study was to analyze the process of care, the epidemiological and clinical features, the evolution and the use of resources in pediatric patients with SARS-Cov-2 infection, treated during the first pandemic wave, at the beginning of 2020.