Sickle cell disease (SCD) is an inherited blood disorder most common among African American and Hispanic American persons. The disease can cause substantial, long-term, and costly health problems, including infections, stroke, and kidney failure, many of which can reduce life expectancy. Disparities in receiving health care among African Americans and other racial/ethnic minority groups in the United States are well known and directly related to poor outcomes associated with SCD. As an orphan disease—one that affects <200 000 persons nationwide—SCD does not receive the research funding and pharmaceutical investment directed to other orphan diseases. For example, cystic fibrosis affects fewer than half the number of persons but receives 3.5 times the funding from the National Institutes of Health and 440 times the funding from national foundations. In this review, we discuss the health inequities affecting persons with SCD, describe programs intended to improve their care, and identify actions that could be taken to further reduce these inequities, improve care, control treatment costs, and ease the burden of disease.

We report real-time voltammetric detection of potential lung cancer biomarkers, namely, interleukin-10 (IL-10) and osteopontin (OPN), using localized silica nanowires as templates, through an electrochemical alkaline phosphatase (AP) based assay. The high surface to volume ratio associated with nanowires enhances the loading of a specific capture antibody toward a particular cancer antigen. An AP enzyme attached to the cancer antigens (IL-10 and OPN) via detector antibodies hydolyses (dephosphorylates) the p-nitrophenyl phosphate substrate to a yellow, water-soluble product, p-nitrophenol (pNP). This was detected in a small test volume of 3 µL, using a microelectrode cell fabricated in Au. The electro-oxidation of pNP occurs between 0.85 and 0.9 V with anodic peak current showing linear dependence with the capture antibody and antigen concentrations, respectively. The detection of IL-10 down to 1 fg/mL in ideal pure solution and 1 pg/mL in clinically relevant samples was achieved reproducibly. Moreover, both the concentration of the capture antibody and the cancer antigen were found to have a strong influence on the anodic peak current, as demonstrated considering specific example of OPN.

No abstract

Dominant mutations in tyrosyl-tRNA synthetase (YARS1) and six other tRNA ligases cause Charcot-Marie-Tooth peripheral neuropathy (CMT). Loss of aminoacylation is not required for their pathogenicity, suggesting a gain-of-function disease mechanism. By an unbiased genetic screen in Drosophila, we link YARS1 dysfunction to actin cytoskeleton organization. Biochemical studies uncover yet unknown actin-bundling property of YARS1 to be enhanced by a CMT mutation, leading to actin disorganization in the Drosophila nervous system, human SH-SY5Y neuroblastoma cells, and patient-derived fibroblasts. Genetic modulation of F-actin organization improves hallmark electrophysiological and morphological features in neurons of flies expressing CMT-causing YARS1 mutations. Similar beneficial effects are observed in flies expressing a neuropathy-causing glycyl-tRNA synthetase. Hence, in this work, we show that YARS1 is an evolutionary-conserved F-actin organizer which links the actin cytoskeleton to tRNA-synthetase-induced neurodegeneration.