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Diet modulates the gut microbiome, which in turn can impact the immune system. Here, we determined how two microbiota-targeted dietary interventions, plant-based fiber and fermented foods, influence the human microbiome and immune system in healthy adults. Using a 17-week randomized, prospective study (n = 18/arm) combined with -omics measurements of microbiome and host, including extensive immune profiling, we found diet-specific effects. The high-fiber diet increased microbiome-encoded glycan-degrading carbohydrate active enzymes (CAZymes) despite stable microbial community diversity. Although cytokine response score (primary outcome) was unchanged, three distinct immunological trajectories in high-fiber consumers corresponded to baseline microbiota diversity. Alternatively, the high-fermented-food diet steadily increased microbiota diversity and decreased inflammatory markers. The data highlight how coupling dietary interventions to deep and longitudinal immune and microbiome profiling can provide individualized and population-wide insight. Fermented foods may be valuable in countering the decreased microbiome diversity and increased inflammation pervasive in industrialized society.Apoptosis can potently defend against intracellular pathogens by directly killing microbes and eliminating their replicative niche. However, the reported ability of Mycobacterium tuberculosis to restrict apoptotic pathways in macrophages in vitro has led to apoptosis being dismissed as a host-protective process in tuberculosis despite a lack of in vivo evidence. Here we define crucial in vivo functions of the death receptor-mediated and BCL-2-regulated apoptosis pathways in mediating protection against tuberculosis by eliminating distinct populations of infected macrophages and neutrophils and priming T cell responses. We further show that apoptotic pathways can be targeted therapeutically with clinical-stage compounds that antagonize inhibitor of apoptosis (IAP) proteins to promote clearance of M. Panobinostat datasheet tuberculosis in mice. These findings reveal that any inhibition of apoptosis by M. tuberculosis is incomplete in vivo, advancing our understanding of host-protective responses to tuberculosis (TB) and revealing host pathways that may be targetable for treatment of disease.Cells counter DNA damage through repair or apoptosis, yet a direct mechanism for this choice has remained elusive. When facing interstrand crosslinks (ICLs), the ICL-repair protein FANCI heterodimerizes with FANCD2 to initiate ICL excision. We found that FANCI alternatively interacts with a pro-apoptotic factor, PIDD1, to enable PIDDosome (PIDD1-RAIDD-caspase-2) formation and apoptotic death. FANCI switches from FANCD2/repair to PIDD1/apoptosis signaling in the event of ICL-repair failure. Specifically, removing key endonucleases downstream of FANCI/FANCD2, increasing ICL levels, or allowing damaged cells into mitosis (when repair is suppressed) all suffice for switching. Reciprocally, apoptosis-committed FANCI reverts from PIDD1 to FANCD2 after a failed attempt to assemble the PIDDosome. Monoubiquitination and deubiquitination at FANCI K523 impact interactor selection. These data unveil a repair-or-apoptosis switch in eukaryotes. Beyond ensuring the removal of unrepaired genomes, the switch’s bidirectionality reveals that damaged cells can offset apoptotic defects via de novo attempts at lesion repair.

We report the final analysis of the French ACROSTUDY, using data revised and enriched since the 2013 interim analysis. Our objective was to validate the use of pegvisomant (PEGV) in the treatment of acromegaly and to determine efficacy and safety.

Patients with acromegaly treated with PEGV and followed up for at least 5 years were included. Eighty-eight investigators from 62 clinical centers in France included patients from April 2007 to April 2014. PEGV dose and administration frequency were determined by the physicians, based on their clinical evaluation and local habits. No additional examinations beyond those performed in normal follow-up were required. Minimum recommended follow-up included check-ups at treatment initiation, 6 months, 12 months and then annually.

312 patients were enrolled. Mean age was 46.1 ± 14.3 years at introduction of PEGV. Median PEGV treatment duration was 6.3 years and median follow-up was 5.6 years. Median dose at initiation was 10 mg/day. The percentages of patients with tion of IGF-1 levels in 64.4% of a real-life cohort of patients, mostly with uncontrolled disease despite multiple prior therapies. Long-term follow-up showed a sustained effectiveness and good long-term safety.

Suboptimal vaccine immunogenicity and antigenic mismatch, compounded by poor uptake, means that influenza remains a major global disease. T-cells recognising peptides derived from conserved viral proteins could enhance vaccine-induced cross-strain protection.

To investigate the kinetics, phenotypes and function of influenza virus-specific CD8+ resident-memory T-cells (Trm) in the lower airway and infer the molecular pathways associated with their response to infection in vivo.

Healthy volunteers, aged 18-55, were inoculated intranasally with influenza A(H1N1)2009. Blood, upper and (in a subgroup) lower airway samples were obtained throughout infection. Symptoms were assessed using self-reported diaries and nasal viral load by qPCR. T-cell responses were analysed by three-colour FluoroSpot, flow cytometry with MHC I-peptide tetramers and RNAseq, with candidate markers confirmed using immunohistochemistry of endobronchial biopsies.

Following challenge, 57% of participants became infected. Pre-existing ie immunity. Clinical trial registration available at http://www.clinicaltrials.gov, ID NCT02755948.Purpose The purpose of the study was to determine the effect of hearing aid technology level on listener outcome measures. In addition, we aimed to determine if individual characteristics such as noise acceptance and the demands of the listening environment impacted performance and preference. Method A repeated-measures, single-blinded research design was utilized. Twenty-four adults recruited by mail from The University of Tennessee Health Science Center Audiology Clinic participated in this experiment (15 men and nine women). Participants completed two 2-week trial periods using Unitron T Moxi Fit FLEXTRIAL devices programmed as basic or premium technology levels. A data-logging feature, Log It All (LIA), quantified the demands of the listening environment. At the end of each trial, outcome measures were obtained using Pascoe’s High-Frequency Word List, the Hearing in Noise Test, the Quick Speech-in-Noise Test, the Acceptable Noise Level (ANL), the Speech, Spatial and Qualities of Hearing short form, satisfaction ratings, and preference.