IgG autoantibodies in bullous pemphigoid directly induce a pathogenic MyD88-dependent pro-inflammatory response in keratinocytes.

Unlabelled: While autoantibodies in bullous pemphigoid (BP) are known to activate the innate immune response, their direct effect on keratinocytes, and the contribution of BP-IgG autoantibody-dependent keratinocyte responses to BP pathology is largely unknown. Herein, we performed multiplex immunoassays and bulk RNA-seq on primary keratinocytes treated with IgG from BP patients or controls. We identified a pro-inflammatory and proteolytic response with release of several cytokines (IL-6, IL-24, TGF-β1), chemokines (CXCL16, CTACK, MIP-3β, RANTES), C1s, DPP4, and MMP-9.

An Overview of Adolescent Psychostimulant Use.

Adolescence marks a period of significant neural maturation and development of lifelong habits, including the potential use of recreational psychostimulant drugs. Increased prevalence of drug adulteration and fatalities related to drug overdose pose new challenges for individuals who use drugs recreationally. As the prevalence of recreational psychostimulant use drastically increases during young adulthood, pediatric and adolescent health care providers can play a crucial role in the lifelong well-being of their patients by identifying those with risk factors for consequences associated with substance use at an early age.

Readiness assessments for gender-affirming surgical treatments: A systematic scoping review of historical practices and changing ethical considerations.

Transgender and gender diverse (TGD) are terms that refer to individuals whose gender identity differs from sex assigned at birth. TGD individuals may choose any variety of modifications to their gender expression including, but not limited to changing their name, clothing, or hairstyle, starting hormones, or undergoing surgery. Starting in the 1950s, surgeons and endocrinologists began treating what was then known as transsexualism with cross sex hormones and a variety of surgical procedures collectively known as sex reassignment surgery (SRS).

Isolation and Genome Analysis of an Amoeba-Associated Bacterium Strain Ely Copper Mine From Acid Rock Drainage in Vermont, United States.

Protozoa play important roles in microbial communities, regulating populations predation and contributing to nutrient cycling. While amoebae have been identified in acid rock drainage (ARD) systems, our understanding of their symbioses in these extreme environments is limited. Here, we report the first isolation of the amoeba from an ARD environment as well as the genome sequence and annotation of an associated bacterium, strain Ely Copper Mine, from Ely Brook at the Ely Copper Mine Superfund site in Vershire, Vermont, United States.

Multiple Variants of SARS-CoV-2 in a University Outbreak After Spring Break - Chicago, Illinois, March-May 2021.

To prevent transmission of SARS-CoV-2, the virus that causes COVID-19, colleges and universities have implemented multiple strategies including testing, isolation, quarantine, contact tracing, masking, and vaccination. In April 2021, the Chicago Department of Public Health (CDPH) was notified of a large cluster of students with COVID-19 at an urban university after spring break. A total of 158 cases of COVID-19 were diagnosed among undergraduate students during March 15-May 3, 2021; the majority (114; 72.

COVID-19 Outbreak Among a University's Men's and Women's Soccer Teams - Chicago, Illinois, July-August 2020.

Data on transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), among college athletes are limited. In August 2020, the Chicago Department of Public Health (CDPH) was notified of a cluster of COVID-19 cases among a university's men's and women's soccer teams. CDPH initiated an investigation, interviewed members of both teams, and collated laboratory data to understand transmission of SARS-CoV-2 within the teams.

Seasonal Ely Copper Mine Superfund site shotgun metagenomic and metatranscriptomic data analysis.

High throughput sequencing data collected from acid rock drainage (ARD) communities can reveal the active taxonomic and functional diversity of these extreme environments, which can be exploited for bioremediation, pharmaceutical, and industrial applications. Here, we report a seasonal comparison of a microbiome and transcriptome in Ely Brook (EB-90M), a confluence of clean water and upstream tributaries that drains the Ely Copper Mine Superfund site in Vershire, VT, USA. Nucleic acids were extracted from EB-90M water and sediment followed by shotgun sequencing using the Illumina NextSeq platform.

Characterization of an acid rock drainage microbiome and transcriptome at the Ely Copper Mine Superfund site.

The microbial oxidation of metal sulfides plays a major role in the formation of acid rock drainage (ARD). We aimed to broadly characterize the ARD at Ely Brook, which drains the Ely Copper Mine Superfund site in Vermont, USA, using metagenomics and metatranscriptomics to assess the metabolic potential and seasonal ecological roles of microorganisms in water and sediment. Using Centrifuge against the NCBI "nt" database, ~25% of reads in sediment and water samples were classified as acid-tolerant Proteobacteria (61 ± 4%) belonging to the genera Pseudomonas (2.

Genome Sequence of Marine-Derived sp. Strain F001, a Producer of Akashin A and Diazaquinomycins.

We report the 9.7-Mb genome sequence of sp. strain F001, isolated from a marine sediment sample from Raja Ampat, Indonesia.

Complete Genome Sequence of a USA100 Methicillin-Resistant Staphylococcus aureus Strain.

We report the genome sequence of a methicillin-resistant (MRSA) strain, isolated from a surgical intensive care unit. This completely closed genome of a USA100 isolate contains a major chromosome and a plasmid and will serve as a reference genome for genetic analysis of MRSA strains.

PCR effects of melting temperature adjustment of individual primers in degenerate primer pools.

Deep sequencing of small subunit ribosomal RNA (SSU rRNA) gene amplicons continues to be the most common approach for characterization of complex microbial communities. PCR amplifications of conserved regions of SSU rRNA genes often employ degenerate pools of primers to enable targeting of a broad spectrum of organisms. One little noticed feature of such degenerate primer sets is the potential for a wide range of melting temperatures between the primer variants.

Complete Genome of Micromonospora sp. Strain B006 Reveals Biosynthetic Potential of a Lake Michigan Actinomycete.

Actinomycete bacteria isolated from freshwater environments are an unexplored source of natural products. Here we report the complete genome of the Great Lakes-derived Micromonospora sp. strain B006, revealing its potential for natural product biosynthesis.

Making and Sequencing Heavily Multiplexed, High-Throughput 16S Ribosomal RNA Gene Amplicon Libraries Using a Flexible, Two-Stage PCR Protocol.

Deep sequencing of polymerase chain reaction (PCR)-amplified small subunit (16S or 18S) ribosomal RNA (rRNA) genes fragments is commonly employed to characterize the composition and structure of microbial communities. Preparing genomic DNA for sequencing of such gene fragments on Illumina sequencers can be performed in a straightforward, two-stage PCR method, described herein. The protocol described allows for up to 384 samples to be sequenced simultaneously, and provides great flexibility in choice of primers.

Bioinformatic analysis of neurotropic HIV envelope sequences identifies polymorphisms in the gp120 bridging sheet that increase macrophage-tropism through enhanced interactions with CCR5.

Macrophages express low levels of the CD4 receptor compared to T-cells. Macrophage-tropic HIV strains replicating in brain of untreated patients with HIV-associated dementia (HAD) express Envs that are adapted to overcome this restriction through mechanisms that are poorly understood. Here, bioinformatic analysis of env sequence datasets together with functional studies identified polymorphisms in the β3 strand of the HIV gp120 bridging sheet that increase M-tropism.

Human metapneumovirus infection in chimpanzees, United States.

Zoonotic disease transmission and infections are of particular concern for humans and closely related great apes. In 2009, an outbreak of human metapneumovirus infection was associated with the death of a captive chimpanzee in Chicago, Illinois, USA. Biosecurity and surveillance for this virus in captive great ape populations should be considered.

SHIV-162P3 infection of rhesus macaques given maraviroc gel vaginally does not involve resistant viruses.

Maraviroc (MVC) gels are effective at protecting rhesus macaques from vaginal SHIV transmission, but breakthrough infections can occur. To determine the effects of a vaginal MVC gel on infecting SHIV populations in a macaque model, we analyzed plasma samples from three rhesus macaques that received a MVC vaginal gel (day 0) but became infected after high-dose SHIV-162P3 vaginal challenge. Two infected macaques that received a placebo gel served as controls.

Differential MHC class I expression in distinct leukocyte subsets.

Background: MHC class I proteins are partly responsible for shaping the magnitude and focus of the adaptive cellular immune response. In humans, conventional wisdom suggests that the HLA-A, -B, and -C alleles are equally expressed on the majority of cell types. While we currently have a thorough understanding of how total MHC class I expression varies in different tissues, it has been difficult to examine expression of single MHC class I alleles due to the homogeneity of MHC class I sequences.

Gold nanoparticle-mediated gene delivery induces widespread changes in the expression of innate immunity genes.

The unique properties of oligonucleotide (and small interfering RNA)-modified gold nanoparticle conjugates make them promising intracellular gene regulation agents. We found that gold nanoparticles stably functionalized with covalently attached oligonucleotides activate immune-related genes and pathways in human peripheral blood mononuclear cells, but not an immortalized, lineage-restricted cell line. These findings have strong implications for the application of oligonucleotide-modified gold nanoparticle conjugates in translational research and in the development of therapeutics and gene delivery systems.

Human APOBEC3G-mediated editing can promote HIV-1 sequence diversification and accelerate adaptation to selective pressure.

Human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G, hereinafter referred to as A3G) is an innate virus restriction factor that inhibits human immunodeficiency virus type 1 (HIV-1) replication and induces excessive deamination of cytidine residues in nascent reverse transcripts. To test the hypothesis that this enzyme can also help generate viral sequence diversification and the evolution of beneficial viral variants, we have examined the impact of A3G on the acquisition of (-)2',3'-dideoxy-3'-thiacytidine (3TC) resistance in vitro. That characteristic resistance mutations are rapidly fixed in the presence of A3G and 3TC suggests that A3G-mediated editing can be an important source of genetic variation on which natural selection acts to shape the structure of HIV-1 populations.

Absence of xenotropic murine leukemia virus-related virus in blood cells of men at risk for and infected with HIV.

Xenotropic murine leukemia virus-related virus has been detected in blood cells of patients with chronic fatigue syndrome and in 3.7% of healthy controls from the same geographic region. We evaluated 996 men who were participants in the Multicenter AIDS Cohort Study for xenotropic murine leukemia virus-related virus sequences in blood cells by means of a real-time quantitative PCR assay.

Defining APOBEC3 expression patterns in human tissues and hematopoietic cell subsets.

Human APOBEC3 enzymes are cellular DNA cytidine deaminases that inhibit and/or mutate a variety of retroviruses, retrotransposons, and DNA viruses. Here, we report a detailed examination of human APOBEC3 gene expression, focusing on APOBEC3G (A3G) and APOBEC3F (A3F), which are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection but are suppressed by HIV-1 Vif. A3G and A3F are expressed widely in hematopoietic cell populations, including T cells, B cells, and myeloid cells, as well as in tissues where mRNA levels broadly correlate with the lymphoid cell content (gonadal tissues are exceptions).

Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960.

Human immunodeficiency virus type 1 (HIV-1) sequences that pre-date the recognition of AIDS are critical to defining the time of origin and the timescale of virus evolution. A viral sequence from 1959 (ZR59) is the oldest known HIV-1 infection. Other historically documented sequences, important calibration points to convert evolutionary distance into time, are lacking, however; ZR59 is the only one sampled before 1976.

Bioinformatic prediction programs underestimate the frequency of CXCR4 usage by R5X4 HIV type 1 in brain and other tissues.

Human immunodeficiency virus (HIV-1) variants in brain primarily use CCR5 for entry into macrophages and microglia, but dual-tropic (R5X4) HIV-1 has been detected in brain and cerebral spinal fluid (CSF) of some patients with HIV-associated dementia (HAD). Here, we sequenced the gp120 coding region of nine full-length dual-tropic (R5X4) env genes cloned directly from autopsy brain and spleen tissue from an AIDS patient with severe HAD. We then compiled a dataset of 30 unique clade B R5X4 Env V3 sequences from this subject and 16 additional patients (n = 4 brain and 26 lymphoid/blood) and used it to compare the ability of six bioinformatic algorithms to correctly predict CXCR4 usage in R5X4 Envs.

Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients.

Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA.