Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans

INTRODUCTION: African Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power. METHODS: We conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs. RESULTS: Two SNPs at novel loci, rs112404845 (P = 3.8 × 10-8), upstream of COBL, and rs16961023 (P = 4.6 × 10-8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability. DISCUSSION: An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS

0D Nanocrystals as Light-Driven, Localized Charge Injection Sources for the Contactless Manipulation of Atomically Thin 2D Materials

We report a new localized and electrodeless charge injection scheme that quasi-permanently modifies monolayer (1L-)MoS2 doping levels to extents competing with electrostatic gating. The key innovation is to use Sn-doped In2O3 (ITO) nanocrystals (NCs) as contactless light-driven charge injection sources triggered solely by light. Each nanocrystal can store and transfer multiple charges after ultraviolet illumination within the diffraction limited laser spot. This results in reductions in carrier density in the underlying 1L-MoS2 up to 1×1013 cm-2 and is observed throughout the extent of the 2D material flake. The long-distance charge separation proliferates up to 40 µm away from the localized charge injection and persists over months. The apparent driving force for carrier relocation is the initial inhomogeneous electronic landscape of the 2D material. These studies demonstrate a novel all-optically controlled tool to locally inject carriers with sub-micrometer precision. This new ability allows us to extract important aspects of inhomogeneity in 2D materials undisturbed by bulky electronic contacts and indicates that local 2D material manipulation can serve as a key element for novel nanoscale device design

Acclimation to a High‐Salt Diet Is Sex Dependent

Background Premenopausal women are less likely to develop hypertension and salt‐related complications than are men, yet the impact of sex on mechanisms regulating Na+ homeostasis during dietary salt challenges is poorly defined. Here, we determined whether female rats have a more efficient capacity to acclimate to increased dietary salt intake challenge. Methods and Results Age‐matched male and female Sprague Dawley rats maintained on a normal‐salt (NS) diet (0.49% NaCl) were challenged with a 5‐day high‐salt diet (4.0% NaCl). We assessed serum, urinary, skin, and muscle electrolytes; total body water; and kidney Na+ transporters during the NS and high‐salt diet phases. During the 5‐day high‐salt challenge, natriuresis increased more rapidly in females, whereas serum Na+ and body water concentration increased only in males. To determine if females are primed to handle changes in dietary salt, we asked the question whether the renal endothelin‐1 natriuretic system is more active in female rats, compared with males. During the NS diet, female rats had a higher urinary endothelin‐1 excretion rate than males. Moreover, Ingenuity Pathway Analysis of RNA sequencing data identified the enrichment of endothelin signaling pathway transcripts in the inner medulla of kidneys from NS‐fed female rats compared with male counterparts. Notably, in human subjects who consumed an Na+‐controlled diet (3314–3668 mg/day) for 3 days, women had a higher urinary endothelin‐1 excretion rate than men, consistent with our findings in NS‐fed rats. Conclusions These results suggest that female sex confers a greater ability to maintain Na+ homeostasis during acclimation to dietary Na+ challenges and indicate that the intrarenal endothelin‐1 natriuretic pathway is enhanced in women