Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection.

Introduction: Upon infection, T cell-driven B cell responses in GC reactions induce memory B cells and antibody-secreting cells that secrete protective antibodies. How formation of specifically long-lived plasma cells is regulated via the interplay between specific B and CD4+ T cells is not well understood. Generally, antibody levels decline over time after clearance of the primary infection.

Modeling antigen-specific T cell dynamics following Hepatitis B Vaccination indicates differences between conventional and regulatory T cell dynamics.

Our study aims to investigate the dynamics of conventional memory T cells (Tconv) and regulatory memory T cells (Treg) following activation, and to explore potential differences between these two cell types. To achieve this, we developed advanced statistical mixed models based on mathematical models of ordinary differential equations (ODE), which allowed us to transform post-vaccination immunological processes into mathematical formulas. These models were applied to in-house data from a de novo Hepatitis B vaccination trial.

Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation.

The role of T cell receptor (TCR) diversity in infectious disease susceptibility is not well understood. We use a systems immunology approach on three cohorts of herpes zoster (HZ) patients and controls to investigate whether TCR diversity against varicella-zoster virus (VZV) influences the risk of HZ. We show that CD4 T cell TCR diversity against VZV glycoprotein E (gE) and immediate early 63 protein (IE63) after 1-week culture is more restricted in HZ patients.

Diagnosing Viral Infections Through T-Cell Receptor Sequencing of Activated CD8+ T Cells.

T-cell-based diagnostic tools identify pathogen exposure but lack differentiation between recent and historical exposures in acute infectious diseases. Here, T-cell receptor (TCR) RNA sequencing was performed on HLA-DR+/CD38+CD8+ T-cell subsets of hospitalized coronavirus disease 2019 (COVID-19) patients (n = 30) and healthy controls (n = 30; 10 of whom had previously been exposed to severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]). CDR3α and CDR3β TCR regions were clustered separately before epitope specificity annotation using a database of SARS-CoV-2-associated CDR3α and CDR3β sequences corresponding to >1000 SARS-CoV-2 epitopes.

Integrated Drivers of Basal and Acute Immunity in Diverse Human Populations.

Prior studies have identified genetic, infectious, and biological associations with immune competence and disease severity; however, there have been few integrative analyses of these factors and study populations are often limited in demographic diversity. Utilizing samples from 1,705 individuals in 5 countries, we examined putative determinants of immunity, including: single nucleotide polymorphisms, ancestry informative markers, herpesvirus status, age, and sex. In healthy subjects, we found significant differences in cytokine levels, leukocyte phenotypes, and gene expression.

Single-cell analysis reveals dynamics of human B cell differentiation and identifies novel B and antibody-secreting cell intermediates.

Differentiation of B cells into antibody-secreting cells (ASCs) is a key process to generate protective humoral immunity. A detailed understanding of the cues controlling ASC differentiation is important to devise strategies to modulate antibody formation. Here, we dissected differentiation trajectories of human naive B cells into ASCs using single-cell RNA sequencing.

Distinct dynamics of antigen-specific induction and differentiation of different CD11cTbet B-cell subsets.

Background: CD11cTbet B cells are enriched in autoimmunity and chronic infections and also expand on immune challenge in healthy individuals. CD11cTbet B cells remain an enigmatic B-cell population because of their intrinsic heterogeneity.

Objectives: We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen-specific development and differentiation properties of 3 separate CD11c B-cell subsets-age-associated B cells (ABCs), double-negative 2 (DN2) B cells, and activated naive B cells-and compared them to their canonical CD11c counterparts.

Current status of biopsy markers for the breast in clinical settings.

Introduction: A breast biopsy marker is a very small object that is introduced into the breast to serve as a tissue marker. The placement of a breast marker following a biopsy or to mark an abnormality in the breast has become standard practice in the clinical setting. Breast biopsy markers offer a wide range of benefits which includes the prevention of re-biopsy of a benign tumor, differentiating multiple lesions within the breast, evaluation of the extent of a tumor, and increased precision during surgery.

Preexisting memory CD4 T cells in naïve individuals confer robust immunity upon hepatitis B vaccination.

Antigen recognition through the T cell receptor (TCR) αβ heterodimer is one of the primary determinants of the adaptive immune response. Vaccines activate naïve T cells with high specificity to expand and differentiate into memory T cells. However, antigen-specific memory CD4 T cells exist in unexposed antigen-naïve hosts.

Moving Toward a More Comprehensive Analysis of Acceleration Profiles in Elite Youth Football.

In football, having greater acceleration ability may decide the most important moments within matches. Up to now, commonly used acceleration variables have typically been investigated in isolation, with each variable suffering from unique limitations. Subsequently, any findings may provide a limited representation of what specific acceleration demands had actually occurred.

Transcriptomic profiling of different responder types in adults after a Priorix® vaccination.

Thanks to the recommendation of a combined Measles/Mumps/Rubella (MMR) vaccine, like Priorix®, these childhood diseases are less common now. This is beneficial to limit the spread of these diseases and work towards their elimination. However, the measles, mumps and rubella antibody titers show a large variability in short- and long-term immunity.

Activation-induced surface proteins in the identification of antigen-responsive CD4 T cells.

Identification of antigen specificity of CD4 T cells is instrumental in understanding adaptive immune responses in health and disease. The high diversity of CD4 T cell repertoire combined with the functional heterogeneity of the compartment poses a challenge to the assessment of CD4 T cell responses. In spite of that, multiple technologies allow direct or indirect interrogation of antigen specificity of CD4 T cells.

Tracking Dye-Independent Approach to Identify and Isolate In Vitro Expanded T Cells.

T cell proliferation is routinely identified in vitro using tracking dyes or through detecting intracellular upregulation of the nuclear protein, Ki-67. However, labeling with tracking dyes is cumbersome, associated with cellular toxicity, while Ki-67 cannot be used to identify and isolate viable T cells, and both techniques are incompatible with MACS technology. Here, we introduce a simple tool to identify and isolate in vitro T cell expansion that is tracking dye-independent and allows for sorting of viable T cells.

The Individual and Combined Effects of Multiple Factors on the Risk of Soft Tissue Non-contact Injuries in Elite Team Sport Athletes.

Relationships between athlete monitoring-derived variables and injury risk have been investigated predominantly in isolation. The aim of this study was to evaluate the individual and combined effects of multiple factors on the risk of soft-tissue non-contact injuries in elite team sport athletes. Fifty-five elite Australian footballers were prospectively monitored over two consecutive seasons.

Safety and feasibility of high speed resistance training with and without balance exercises for knee osteoarthritis: A pilot randomised controlled trial.

Objectives: People with knee osteoarthritis (OA) have increased risk of falling with impaired ability to rapidly respond and generate lower limb muscle power to arrest a fall. We examined the feasibility and safety of a high speed resistance training program with and without balance exercises.

Design: A randomised controlled pilot trial comparing pre and post 8 weeks intervention within 3 groups: control, high speed resistance training (HSRT), high speed resistance training plus balance exercises (HSRTB).

Memory CD4 T cell receptor repertoire data mining as a tool for identifying cytomegalovirus serostatus.

Pathogens of past and current infections have been identified directly by means of PCR or indirectly by measuring a specific immune response (e.g., antibody titration).

Normal Variability of Weekly Musculoskeletal Screening Scores and the Influence of Training Load across an Australian Football League Season.

The sit and reach test (S&R), dorsiflexion lunge test (DLT), and adductor squeeze test (AST) are commonly used in weekly musculoskeletal screening for athlete monitoring and injury prevention purposes. The aim of this study was to determine the normal week to week variability of the test scores, individual differences in variability, and the effects of training load on the scores. Forty-four elite Australian rules footballers from one club completed the weekly screening tests on day 2 or 3 post-main training (pre-season) or post-match (in-season) over a 10 month season.

Increased herpes zoster risk associated with poor HLA-A immediate early 62 protein (IE62) affinity.

Around 30% of individuals will develop herpes zoster (HZ), caused by the varicella zoster virus (VZV), during their life. While several risk factors for HZ, such as immunosuppressive therapy, are well known, the genetic and molecular components that determine the risk of otherwise healthy individuals to develop HZ are still poorly understood. We created a computational model for the Human Leukocyte Antigen (HLA-A, -B, and -C) presentation capacity of peptides derived from the VZV Immediate Early 62 (IE62) protein.

High-speed resistance training and balance training for people with knee osteoarthritis to reduce falls risk: study protocol for a pilot randomized controlled trial.

Background: The number of falls experienced by people with knee osteoarthritis (OA) is almost double the number experienced by people with no OA. The neuromuscular elements required to arrest a fall are more impaired in people with knee OA compared to their asymptomatic counterparts. Therefore, these elements may need to be incorporated into an exercise intervention to reduce the risk of falling.

Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections.

Varicella zoster virus (VZV) typically causes chickenpox upon primary infection. In rare cases, VZV can give rise to life-threatening disease in otherwise healthy people, but the immunological basis for this remains unexplained. We report 4 cases of acute severe VZV infection affecting the central nervous system or the lungs in unrelated, otherwise healthy children who are heterozygous for rare missense mutations in POLR3A (one patient), POLR3C (one patient), or both (two patients).

Effects of Training Load and Leg Dominance on Achilles and Patellar Tendon Structure.

Purpose: Detrimental changes in tendon structure increase the risk of tendinopathies. The aim of this study was to investigate the influence of individual internal and external training loads and leg dominance on changes in the Achilles and patellar tendon structure.

Methods: The internal structure of the Achilles and patellar tendons of both limbs of 26 elite Australian footballers was assessed using ultrasound tissue characterization at the beginning and the end of an 18-wk preseason.

Does the recent internal load and strain on players affect match outcome in elite Australian football?

Objectives: To compare recent internal training load and strain of elite Australian football players for match outcome.

Design: Case study.

Methods: Load was quantified from session rating of perceived exertion (sRPE) for individual players from one team in 141 professional Australian football matches over six seasons, then averaged for players that competed for the team each week.

Neurosteroid analogues. 18. Structure-activity studies of ent-steroid potentiators of γ-aminobutyric acid type A receptors and comparison of their activities with those of alphaxalone and allopregnanolone.

A model of the alignment of neurosteroids and ent-neurosteroids at the same binding site on γ-aminobutyric acid type A (GABAA) receptors was evaluated for its ability to identify the structural features in ent-neurosteroids that enhance their activity as positive allosteric modulators of this receptor. Structural features that were identified included: (1) a ketone group at position C-16, (2) an axial 4α-OMe group, and (3) a C-18 methyl group. Two ent-steroids were identified that were more potent than the anesthetic steroid alphaxalone in their threshold for and duration of loss of the righting reflex in mice.

Adult colocolic intussusception and literature review.

Intussusception occurs when a proximal segment of the gastrointestinal tract, called intussusceptum, telescopes into the lumen of an adjacent segment, also known as intussuscipiens. Although common in early childhood, intussusceptions are very rare in the adult population. Most intussusceptions in adults are due to a lead point, which is an identifiable pathological abnormality, in opposition to children which there are no identifiable pathological lead points.