CD28 shapes T cell receptor signaling by regulating Lck dynamics and ZAP70 activation.

Introduction: T cell activation requires T cell receptor (TCR) engagement by its specific ligand. This interaction initiates a series of proximal events including tyrosine phosphorylation of the CD3 and TCRζ chains, recruitment, and activation of the protein tyrosine kinases Lck and ZAP70, followed by recruitment of adapter and signaling proteins. CD28 co-stimulation is also required to generate a functional immune response.

Otolaryngological Presentations of Klippel-Feil Syndrome: A Systematic Review.

Klippel-Feil syndrome (KFS) is a rare congenital condition characterized by the fusion of cervical vertebrae. It classically presents with a triad of symptoms: limited cervical range of motion, a low posterior hairline, and a short neck. Common otolaryngological manifestations include hearing loss, dysphagia, cleft palate, jaw disorders, thyroid abnormalities, and ear malformations, highlighting the importance of KFS awareness in the field of otolaryngology.

CD28 Shapes T Cell Receptor Signaling by Regulating ZAP70 Activation and Lck Dynamics.

T cell activation requires T cell receptor (TCR) engagement, which initiates a series of proximal events including tyrosine phosphorylation of the CD3 and TCRζ chains, recruitment, and activation of the protein tyrosine kinases Lck and ZAP70, followed by recruitment of adapter and signaling proteins. CD28 co-stimulation is also required to generate a functional immune response. Currently we lack a full understanding of the molecular mechanism of CD28 activation.

Microsporidian coinfection reduces fitness of a fungal pathogen due to rapid host mortality.

Infection outcomes can be strongly context dependent, shifting a host-symbiont relationship along a parasitism-mutualism continuum. Numerous studies show that under stressful conditions, symbionts that are typically mutualistic can become parasitic. The reverse possibility, a parasite becoming mutualistic, has received much less study.

Influenza vaccination stimulates maturation of the human T follicular helper cell response.

The differentiation and specificity of human CD4 T follicular helper cells (T cells) after influenza vaccination have been poorly defined. Here we profiled blood and draining lymph node (LN) samples from human volunteers for over 2 years after two influenza vaccines were administered 1 year apart to define the evolution of the CD4 T cell response. The first vaccination induced an increase in the frequency of circulating T (cT) and LN T cells at week 1 postvaccination.

Generation of antitumor chimeric antigen receptors incorporating T cell signaling motifs.

Chimeric antigen receptor (CAR) T cells have been used to successfully treat various blood cancers, but adverse effects have limited their potential. Here, we developed chimeric adaptor proteins (CAPs) and CAR tyrosine kinases (CAR-TKs) in which the intracellular ζ T cell receptor (TCRζ) chain was replaced with intracellular protein domains to stimulate signaling downstream of the TCRζ chain. CAPs contain adaptor domains and the kinase domain of ZAP70, whereas CAR-TKs contain only ZAP70 domains.

Maturation of germinal center B cells after influenza virus vaccination in humans.

Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination.

Unilateral Choanal Atresia in a Child With Prolonged Nasal Congestion.

Choanal atresia obstructs the nasal passage due to abnormal bony or soft tissue remnants owing to the faulty canalization of the nasal passages during fetal development. The clinical manifestations are more pronounced in bilateral cases, often presenting immediately after birth with cyanosis turning pink when crying, as newborns are obligatory nasal breathers. This contrasts in unilateral cases, where the condition may present with mild symptoms and be diagnosed later in life.

Phylogeny, morphology, virulence, ecology, and host range of (Ordosporidae), a microsporidian symbiont of spp.

Unlabelled: The impacts of microsporidia on host individuals are frequently subtle and can be context dependent. A key example of the latter comes from a recently discovered microsporidian symbiont of , the net impact of which was found to shift from negative to positive based on environmental context. Given this, we hypothesized low baseline virulence of the microsporidian; here, we investigated the impact of infection on hosts in controlled conditions and the absence of other stressors.

A Consultation for Pediatric Neck Mass Resulting in a Rare Diagnosis of Klippel-Feil Syndrome: A Case Report.

Klippel-Feil syndrome (KFS) is a rare congenital cervical vertebrae fusion syndrome characterized by the clinical triad of low posterior hairline, limited head and neck range of motion, and short neck. The gene defects described with this syndrome are involved in the maturation and differentiation of bone during embryological development. As such, related defects seen in patients with KFS include genitourinary anomalies, cardiac defects, neurological abnormalities, and other musculoskeletal anomalies.

Different demographic responses of three species of container Aedes (Diptera: Culicidae) larvae to timing of extrinsic mortality.

Mortality imposed on a population can interact with negatively density-dependent mortality to produce overcompensation, wherein added mortality results in more survivors. Experimental mortality can cause overcompensation in mosquito larvae, which would be counterproductive if it resulted from mosquito control in nature. We tested for different demographic responses to mortality among 3 container Aedes species when impacted by density dependence.

Spatiotemporal development of the human T follicular helper cell response to Influenza vaccination.

We profiled blood and draining lymph node (LN) samples from human volunteers after influenza vaccination over two years to define evolution in the T follicular helper cell (TFH) response. We show LN TFH cells expanded in a clonal-manner during the first two weeks after vaccination and persisted within the LN for up to six months. LN and circulating TFH (cTFH) clonotypes overlapped but had distinct kinetics.

Heterogeneity of Signaling Complex Nanostructure in T Cells Activated Via the T Cell Antigen Receptor.

Activation of the T cell antigen receptor (TCR) is a key step in initiating the adaptive immune response. Single-molecule localization techniques have been used to investigate the arrangement of proteins within the signaling complexes formed around activated TCRs, but a clear picture of nanoscale organization in stimulated T cells has not emerged. Here, we have improved the examination of T cell nanostructure by visualizing individual molecules of six different proteins in a single sample of activated Jurkat T cells using the multiplexed antibody-size limited direct stochastic optical reconstruction microscopy (madSTORM) technique.

1-Year Incidence of Tuberculosis Infection and Disease Among Household Contacts of Rifampin- and Multidrug-Resistant Tuberculosis.

Background: Tuberculosis infection (TBI) and TB disease (TBD) incidence remains poorly described following household contact (HHC) rifampin-/multidrug-resistant TB exposure. We sought to characterize TBI and TBD incidence at 1 year in HHCs and to evaluate TB preventive treatment (TPT) use in high-risk groups.

Methods: We previously conducted a cross-sectional study of HHCs with rifampin-/multidrug-resistant TB in 8 high-burden countries and reassessed TBI (interferon-gamma release assay, HHCs aged ≥5 years) and TBD (HHCs all ages) at 1 year.

'Persistent germinal center responses: slow-growing trees bear the best fruits'.

Germinal centers (GCs) are key microanatomical sites in lymphoid organs where responding B cells mature and undergo affinity-based selection. The duration of the GC reaction has long been assumed to be relatively brief, but recent studies in humans, nonhuman primates, and mice indicate that GCs can last for weeks to months after initial antigen exposure. This review examines recent studies investigating the factors that influence GC duration, including antigen persistence, T-follicular helper cells, and mode of immunization.

SARS-CoV-2 Omicron boosting induces de novo B cell response in humans.

The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses and the development of vaccines aimed at the new variants. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells. However, it remains unclear whether the additional doses induce germinal centre reactions whereby re-engaged B cells can further mature, and whether variant-derived vaccines can elicit responses to variant-specific epitopes.

SARS-CoV-2 Omicron boosting induces de novo B cell response in humans.

The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses of these vaccines and the development of new variant-derived ones . SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells (MBCs) . It remains unclear, however, whether the additional doses induce germinal centre (GC) reactions where reengaged B cells can further mature and whether variant-derived vaccines can elicit responses to novel epitopes specific to such variants.

Isoniazid Adherence Reduces Mortality and Incident Tuberculosis at 96 Weeks Among Adults Initiating Antiretroviral Therapy With Advanced Human Immunodeficiency Virus in Multiple High-Burden Settings.

Background: People with human immunodeficiency virus (HIV) and advanced immunosuppression initiating antiretroviral therapy (ART) remain vulnerable to tuberculosis (TB) and early mortality. To improve early survival, isoniazid preventive therapy (IPT) or empiric TB treatment have been evaluated; however, their benefit on longer-term outcomes warrants investigation.

Methods: We present a 96-week preplanned secondary analysis among 850 ART-naive outpatients (≥13 years) enrolled in a multicountry, randomized trial of efavirenz-containing ART plus either 6-month IPT ( = 426) or empiric 4-drug TB treatment ( = 424).

L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis.

Macrophage adhesion and stretching have been shown to induce interleukin (IL)-1β production, but the mechanism of this mechanotransduction remains unclear. Here we specify the molecular link between mechanical tension on tissue-resident macrophages and activation of the NLRP3 inflammasome, which governs IL-1β production. NLRP3 activation enhances antimicrobial defense, but excessive NLRP3 activity causes inflammatory tissue damage in conditions such as pulmonary fibrosis and acute respiratory distress syndrome.

Detrimental effects of a failed infection by a co-invasive parasite on a native congeneric parasite and its native host.

Biological invaders often are accompanied by co-invasive parasites that can alter ecosystem function and established native host-parasite relationships. When these co-invasive parasites establish in a community, they can affect native host fitness and native parasite infection intensity, prevalence, and success within the native host. The mosquito, , is North American host to protozoan parasite, .

Feasibility of video observed therapy to support controller inhaler use among children in West Baltimore.

Objective: To assess feasibility of a novel video directly observed therapy (DOT)-based digital asthma program intended to support correct inhaled corticosteroid (ICS) use among children.

Methods: We conducted a 60-day pilot study among patients 2-18 years attending a primary care clinic with prescribed ICS and sub-optimally controlled asthma (recent hospitalization, ICS nonadherence, frequent rescue inhaler use, therapy escalation, or Asthma Control Test <20). Participants used a mobile application to receive reminders, submit videos of ICS doses (video DOT), and receive asynchronous feedback on adherence and inhaler technique.

How do noncompetent hosts cause dilution of parasitism? Testing hypotheses for native and invasive mosquitoes.

Parasite dilution occurs in varied systems, via multiple potential mechanisms. We used laboratory manipulation and field surveys to test for invader-induced parasite dilution via two specific mechanisms: host-host competition and encounter reduction. In the laboratory, single Aedes triseriatus larvae were exposed to one of eight combinations of: parasitic Ascogregarina barretti, +/-1 cohabiting Aedes albopictus larva during parasite exposure, and +/-1 cohabiting A.

Human germinal centres engage memory and naive B cells after influenza vaccination.

Influenza viruses remain a major public health threat. Seasonal influenza vaccination in humans primarily stimulates pre-existing memory B cells, which differentiate into a transient wave of circulating antibody-secreting plasmablasts. This recall response contributes to 'original antigenic sin'-the selective increase of antibody species elicited by previous exposures to influenza virus antigens.