Maintenance of X chromosome inactivation after T cell activation requires NF-κB signaling.

X chromosome inactivation (XCI) balances X-linked gene dosage between sexes. Unstimulated T cells lack cytological enrichment of X-inactive specific transcript (Xist) RNA and heterochromatic modifications on the inactive X chromosome (Xi), which are involved in maintenance of XCI, and these modifications return to the Xi after stimulation. Here, we examined allele-specific gene expression and epigenomic profiles of the Xi in T cells.

NF-κB Signaling is Required for X-Chromosome Inactivation Maintenance Following T cell Activation.

X Chromosome Inactivation (XCI) is a female-specific process which balances X-linked gene dosage between sexes. Unstimulated T cells lack cytological enrichment of RNA and heterochromatic modifications on the inactive X chromosome (Xi), and these modifications become enriched at the Xi after cell stimulation. Here, we examined allele-specific gene expression and the epigenomic profiles of the Xi following T cell stimulation.

The conneXion between sex and immune responses.

There are notable sex-based differences in immune responses to pathogens and self-antigens, with female individuals exhibiting increased susceptibility to various autoimmune diseases, and male individuals displaying preferential susceptibility to some viral, bacterial, parasitic and fungal infections. Although sex hormones clearly contribute to sex differences in immune cell composition and function, the presence of two X chromosomes in female individuals suggests that differential gene expression of numerous X chromosome-linked immune-related genes may also influence sex-biased innate and adaptive immune cell function in health and disease. Here, we review the sex differences in immune system composition and function, examining how hormones and genetics influence the immune system.

c-Myc uses Cul4b to preserve genome integrity and promote antiviral CD8 T cell immunity.

During infection, virus-specific CD8 T cells undergo rapid bursts of proliferation and differentiate into effector cells that kill virus-infected cells and reduce viral load. This rapid clonal expansion can put T cells at significant risk for replication-induced DNA damage. Here, we find that c-Myc links CD8 T cell expansion to DNA damage response pathways though the E3 ubiquitin ligase, Cullin 4b (Cul4b).

Impaired dynamic X-chromosome inactivation maintenance in T cells is a feature of spontaneous murine SLE that is exacerbated in female-biased models.

Objective: Systemic lupus erythematosus (SLE) is a highly female-biased systemic autoimmune disease, but the molecular basis for this female bias remains incompletely elucidated. B and T lymphocytes from patients with SLE and female-biased mouse models of SLE exhibit features of epigenetic dysregulation on the X chromosome which may contribute to this strong female bias. We therefore examined the fidelity of dynamic X-chromosome inactivation maintenance (dXCIm) in the pathogenesis of two murine models of spontaneous lupus-NZM2328 and MRL/lpr-with disparate levels of female-bias to determine whether impaired dXCIm contributes to the female bias of disease.

Time to get ill: the intersection of viral infections, sex, and the X chromosome.

Females have more robust immune responses than males, and viral infections are more severe for males. Hormones and genetic sex, namely the X chromosome, influence sex differences with immune responses. Here, we review recent findings underlying sexual dimorphism of disease susceptibility for two prevalent viral infections, influenza and SARS-CoV-2, which exhibit male-biased disease severity.

Ectromelia-encoded virulence factor C15 specifically inhibits antigen presentation to CD4+ T cells post peptide loading.

Smallpox and monkeypox pose severe threats to human health. Other orthopoxviruses are comparably virulent in their natural hosts, including ectromelia, the cause of mousepox. Disease severity is linked to an array of immunomodulatory proteins including the B22 family, which has homologs in all pathogenic orthopoxviruses but not attenuated vaccine strains.

Recombinant Poxviruses: Versatile Tools for Immunological Assays.

The study of antigen processing and presentation is critical to our understanding of the mechanisms that govern immune surveillance. A typical requirement of assays designed to examine antigen processing and presentation is the de novo biosynthesis of a model antigen. Historically, Vaccinia virus, a poxvirus closely related to Cowpox virus, has enjoyed widespread use for this purpose.

Poor Antigen Processing of Poxvirus Particles Limits CD4 T Cell Recognition and Impacts Immunogenicity of the Inactivated Vaccine.

CD4 T cells play critical roles in defending against poxviruses, both by potentiating cellular and humoral responses and by directly killing infected cells. Despite this central role, the basis for pox-specific CD4 T cell activation, specifically the origin of the poxvirus-derived peptides (epitopes) that activate CD4 T cells, remains poorly understood. In addition, because the current licensed poxvirus vaccines can cause serious adverse events and even death, elucidating the requirements for MHC class II (MHC-II) processing and presentation of poxviral Ags could be of great use.

NASA-TLX Assessment of Surgeon Workload Variation Across Specialties.

Objective: With advancements in surgical equipment and procedures, human-system interactions in operating rooms affect surgeon workload and performance. Workload was measured across surgical specialties using surveys to identify potential predictors of high workload for future performance improvement.

Summary Background Data: Surgical instrumentation and technique advancements have implications for surgeon workload and human-systems interactions.

Shortcut assessment: Can residents' operative performance be determined in the first five minutes of an operative task?

Background: The aim was to validate the potential use of a single, early procedure, operative task as a predictive metric for overall performance. The authors hypothesized that a shortcut psychomotor assessment would be as informative as a total procedural psychomotor assessment when evaluating laparoscopic ventral hernia repair performance on a simulator.

Methods: Using electromagnetic sensors, hand motion data were collected from 38 surgery residents during a simulated laparoscopic ventral hernia repair procedure.

Interruptions Experienced by Emergency Nurses: Implications for Subjective and Objective Measures of Workload.

Introduction: This study aimed to describe interruptions experienced by emergency nurses and establish convergence validity of 1 objective workload measure by linking interruption characteristics to objective and subjective measures of workload.

Methods: Interruptions were captured in real time across 8- or 12-hour shifts using a previously validated Workflow Interruptions Tool (WIT). Data collected on each interruption included type, priority, and location where the interruption occurred.

Ectromelia virus lacking the E3L ortholog is replication-defective and nonpathogenic but does induce protective immunity in a mouse strain susceptible to lethal mousepox.

All known orthopoxviruses, including ectromelia virus (ECTV), contain a gene in the E3L family. The protein product of this gene, E3, is a double-stranded RNA-binding protein. It can impact host range and is used by orthopoxviruses to combat cellular defense pathways, such as PKR and RNase L.

Characteristics of team briefings in gynecological surgery.

Preoperative briefings have been proven beneficial for improving team performance in the operating room. However, there has been minimal research regarding team briefings in specific surgical domains. As part of a larger project to develop a briefing structure for gynecological surgery, the study aimed to better understand the current state of pre-operative team briefings in one department of an academic hospital.

Physician, Interrupted: Workflow Interruptions and Patient Care in the Emergency Department.

Background: It is unclear how workflow interruptions impact emergency physicians at the point of care.

Objectives: Our study aimed to evaluate interruption characteristics experienced by academic emergency physicians.

Methods: This prospective, observational study collected interruptions during attending physician shifts.

Research Residents' perceptions of skill decay: Effects of repeated skills assessments and scenario difficulty.

Introduction: Skills decay is a known risk for surgical residents who have dedicated research time. We hypothesize that simulation-based assessments will reveal significant differences in perceived skill decay when assessing a variety of clinical scenarios in a longitudinal fashion.

Methods: Residents (N = 46; Returning: n = 16, New: n = 30) completed four simulated procedures: urinary catheterization, central line, bowel anastomosis, and laparoscopic ventral hernia repair.

Giving CD4+ T cells the slip: viral interference with MHC class II-restricted antigen processing and presentation.

Activation of CD4+ T cells through interactions with peptides bound to Major Histocompatibility Complex Class II (MHC-II) molecules is a crucial step in clearance of most pathogens. Consequently, many viruses have evolved ways of blocking this aspect of adaptive immunity, from specific targeting of processing and presentation components to modulation of signaling pathways that regulate peptide presentation in addition to many other host defense mechanisms. Such cases of interference are far less common compared to what has been elucidated in MHC-I processing and presentation.

Long-range enhancer activity determines Myc sensitivity to Notch inhibitors in T cell leukemia.

Notch is needed for T-cell development and is a common oncogenic driver in T-cell acute lymphoblastic leukemia. The protooncogene c-Myc (Myc) is a critical target of Notch in normal and malignant pre-T cells, but how Notch regulates Myc is unknown. Here, we identify a distal enhancer located >1 Mb 3' of human and murine Myc that binds Notch transcription complexes and physically interacts with the Myc proximal promoter.