Search

Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity anti-IgE mAb and the only rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to that of omalizumab in phase IIb but not in phase III. This report features the antigenic-functional characteristics of UB-221, an anti-IgE mAb of a newer class that is distinct from omalizumab and ligelizumab. UB-221, in free form, bound abundantly to CD23-occupied IgE and, in oligomeric mAb-IgE complex forms, freely engaged CD23, while ligelizumab reacted limitedly and omalizumab stayed inert toward CD23; these observations are consistent with UB-221 outperforming ligelizumab and omalizumab in CD23-mediated downregulation of IgE production. UB-221 bound IgE with a strong affinity to prevent FcԑRI-mediated basophil activation and degranulation, exhibiting superior IgE-neutralizing activity to that of omalizumab. UB-221 and ligelizumab bound cellular IgE and effectively neutralized IgE in sera of patients with atopic dermatitis with equal strength, while omalizumab lagged behind. A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)–knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level.

Background: Overseas screening for tuberculosis (TB) has sought to reduce the burden of active TB in the United States. The duration of time between two unchanged, or stable, chest X-rays (CXRs) taken four to six months apart has been considered clinically useful in the evaluation of suspected pulmonary TB disease, but this relationship has not been previously quantified. Objective: To investigate the association between pre-treatment CXR stability duration and future clinical or culture-confirmed (Class 3) diagnosis of pulmonary TB in San Diego, California, USA. Methods: This retrospective record review included County of San Diego TB clinic patients with abnormal CXR results who were started on treatment between 2012 and 2017; multivariable logistic regression was used to analyze the clinical data. Results: Pre-treatment CXR stability duration of at least four months was not significantly associated with a Class 3 pulmonary TB diagnosis (adjusted odds ratio [AOR], 0.83; 95 % confidence interval [CI], 0.20–3.48), nor was pre-treatment CXR stability duration of at least six months (AOR, 0.97; 95 % CI, 0.30–3.10). Similar results were obtained when four-to-six-month stability was considered (AOR, 0.78; 95 % CI, 0.16–3.89). Patients screened overseas (B1 notification) were less likely to develop Class 3 TB (unadjusted OR, 0.15; 95 % CI 0.05–0.44). Conclusion: Pre-treatment chest X-ray stability duration was not associated with excluding Class 3 pulmonary TB in this setting, and CXR stability duration cut points may not be as clinically informative as previously understood, but overseas screening is likely an important step in reducing active TB disease burden in the U.S.

Taiwan Blue Magpie (Urocissa caerulea) is endemic to Taiwan and listed as threatened species protected by law. In this study, we first determined and described the complete mitochondrial genome of Taiwan Blue Magpie. The circle genome is 16,928 bp in length, and contains 13 protein coding, 22 tRNA, two rRNA genes, and one non-coding control region (CR). The overall base composition of the mitochondrial DNA is 30.99% for A, 24.69% for T, 30.07% for C, and 14.25% for G. The percentage of G + C content is 44.32%. This work provides fundamental molecular data which will be useful for evolution and phylogeny studies on Corvidae in the future.

Uncovering the regulators of cellular aging will unravel the complexity of aging biology and identify potential therapeutic interventions to delay the onset and progress of chronic, aging-related diseases. In this work, we systematically compared genesets involved in regulating the lifespan of Saccharomyces cerevisiae (a powerful model organism to study the cellular aging of humans) and those with expression changes under rapamycin treatment. Among the functionally uncharacterized genes in the overlap set, YBR238C stood out as the only one downregulated by rapamycin and with an increased chronological and replicative lifespan upon deletion. We show that YBR238C and its paralog RMD9 oppositely affect mitochondria and aging. YBR238C deletion increases the cellular lifespan by enhancing mitochondrial function. Its overexpression accelerates cellular aging via mitochondrial dysfunction. We find that the phenotypic effect of YBR238C is largely explained by HAP4- and RMD9-dependent mechanisms. Furthermore, we find that genetic- or chemical-based induction of mitochondrial dysfunction increases TORC1 (Target of Rapamycin Complex 1) activity that, subsequently, accelerates cellular aging. Notably, TORC1 inhibition by rapamycin (or deletion of YBR238C) improves the shortened lifespan under these mitochondrial dysfunction conditions in yeast and human cells. The growth of mutant cells (a proxy of TORC1 activity) with enhanced mitochondrial function is sensitive to rapamycin whereas the growth of defective mitochondrial mutants is largely resistant to rapamycin compared to wild type. Our findings demonstrate a feedback loop between TORC1 and mitochondria (the TORC1–MItochondria–TORC1 (TOMITO) signaling process) that regulates cellular aging processes. Hereby, YBR238C is an effector of TORC1 modulating mitochondrial function.

Abstract Gerontology research on anti-aging interventions with drugs could be an answer to age-related diseases, aiming at closing the gap between lifespan and healthspan. Here, we present two methods for assaying chronological lifespan in human cells: (1) a version of the classical outgrowth assay with quantitative assessment of surviving cells and (2) a version of the PICLS method (propidium iodide fluorescent-based measurement of cell death). Both methods are fast, simple to conduct, cost-effective, produce quantitative data for further analysis and can be used with diverse human cell lines. Whereas the first method is ideal for validation and testing the post-intervention reproductive potential of surviving cells, the second method has true high-throughput screening potential. The new technologies were validated with known anti-aging compounds (2,5-anhydro-d-mannitol and rapamycin). Using the high-throughput screening method, we screened a library of 162 chemical entities and identified three compounds that extend the longevity of human cells.

A quiz about ocular prophylaxis for gonococcal ophthalmia neonatorum is presented.