Inhibition of ATM-directed antiviral responses by HIV-1 Vif.

Emerging evidence indicates that HIV-1 hijacks host DNA damage repair (DDR) pathways to facilitate multiple facets of virus replication. Canonically, HIV-1 engages proviral DDR responses through the accessory protein Vpr, which induces constitutive activation of DDR kinases ATM and ATR. However, in response to prolonged DDR signaling, ATM directly induces pro-inflammatory NF-κB signaling and activates multiple members of the TRIM family of antiviral restriction factors, several of which have been previously implicated in antagonizing retroviral and lentiviral replication.

Decoupling SARS-CoV-2 ORF6 localization and interferon antagonism.

Like many pathogenic viruses, SARS-CoV-2 must overcome interferon (IFN)-mediated host defenses for infection establishment. To achieve this, SARS-CoV-2 deploys overlapping mechanisms to antagonize IFN production and signaling. The strongest IFN antagonist is the accessory protein ORF6, which localizes to multiple membranous compartments, including the nuclear envelope, where it directly binds nuclear pore component Nup98-Rae1 to inhibit nuclear translocation of activated STAT1 and IRF3 transcription factors.

IL-17RA-signaling in Lgr5 intestinal stem cells induces expression of transcription factor ATOH1 to promote secretory cell lineage commitment.

The Th17 cell-lineage-defining cytokine IL-17A contributes to host defense and inflammatory disease by coordinating multicellular immune responses. The IL-17 receptor (IL-17RA) is expressed by diverse intestinal cell types, and therapies targeting IL-17A induce adverse intestinal events, suggesting additional tissue-specific functions. Here, we used multiple conditional deletion models to identify a role for IL-17A in secretory epithelial cell differentiation in the gut.

Comparative meta-omics for identifying pathogens associated with prosthetic joint infection.

Prosthetic joint infections (PJI) are economically and personally costly, and their incidence has been increasing in the United States. Herein, we compared 16S rRNA amplicon sequencing (16S), shotgun metagenomics (MG) and metatranscriptomics (MT) in identifying pathogens causing PJI. Samples were collected from 30 patients, including 10 patients undergoing revision arthroplasty for infection, 10 patients receiving revision for aseptic failure, and 10 patients undergoing primary total joint arthroplasty.

Effects of FUdR on gene expression in the C. elegans bacterial diet OP50.

Objective: Many C. elegans aging studies use the compound 5-fluro-2'-deoxyuridine (FUdR) to produce a synchronous population of worms. However, the effects of FUdR on the bacterial gene expression of OP50 E.

Nrf2 through Aryl Hydrocarbon Receptor Regulates IL-22 Response in CD4 T Cells.

IL-17A and IL-22 derived from Th17 cells play a significant role in mucosal immunity and inflammation. TGF-β and IL-6 promote Th17 differentiation; however, these cytokines have multiple targets. The identification and screening of additional molecules that regulate IL-17A and IL-22 responses in certain inflammatory conditions is of great clinical significance.

Arsenic disturbs the gut microbiome of individuals in a disadvantaged community in Nepal.

Arsenic is ubiquitous in nature, highly toxic, and is particularly abundant in Southern Asia. While many studies have focused on areas like Bangladesh and West Bengal, India, disadvantaged regions within Nepal have also suffered from arsenic contamination levels, with wells and other water sources possessing arsenic contamination over the recommended WHO and EPA limit of 10 μg/L, some wells reporting levels as high as 500 μg/L. Despite the region's pronounced arsenic concentrations within community water sources, few investigations have been conducted to understand the impact of arsenic contamination on host gut microbiota health.

Integrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in Clostridioides difficile Infection.

There has been no prior application of matched metagenomics and metatranscriptomics in infection (CDI) evaluating the role of fungi in CDI or identifying community functions that contribute to the development of this disease. We collected diarrheal stools from 49 inpatients (18 of whom tested positive for CDI) under stringent inclusion criteria. We utilized a tiered sequencing approach to identify enriched bacterial and fungal taxa, using 16S and internal transcribed spacer (ITS) rRNA gene amplicon sequencing, with matched metagenomics and metatranscriptomics performed on a subset of the population.

Using Bacterial Transcriptomics to Investigate Targets of Host-Bacterial Interactions in Caenorhabditis elegans.

The interactions between a host and its resident microbes form complicated networks that can affect host physiology. Disentangling these host-microbe interactions can help us better understand mechanisms by which bacteria affect hosts, while also defining the integral commensal protection that host-associated microbiota offer to promote health. Here we utilize a tractable genetic model organism, Caenorhabditis elegans, to study the effects of host environments on bacterial gene expression and metabolic pathways.

Antibiotic Treatments for Infection Are Associated with Distinct Bacterial and Fungal Community Structures.

infection (CDI) is the most common nosocomial infection in the United States, being associated with high recurrence and persistence rates. Though the relationship between intestinal dysbiosis and CDI is well known, it is unclear whether different forms of dysbiosis may potentially affect the course of CDI. How this is further influenced by -directed antibiotics is virtually uninvestigated.