Background: The success of therapeutic options for treatment of Alzheimer's disease (AD) and the growing emphasis for such treatment to commence in the pre-clinical phase makes it necessary to have robust empirical models of clinical disease progression to understand findings from clinical trials, allow clinicians to evaluate effects of new drugs, and to select individuals for future trials. Such models have been developed from relatively small samples, with incomplete data/substantial loss to follow-up. The ADOPIC consortium provides the largest complete AD natural history sample to date.
View Article and Find Full Text PDFBackground And Aims: Low-density lipoprotein (LDL) aggregation is nowadays considered a therapeutic target in atherosclerosis. DP3, the retro-enantio version of the sequence Gly-Cys of LRP1, efficiently inhibits LDL aggregation and foam cell in vitro formation. Here, we investigate whether DP3 modulates atherosclerosis in a humanized ApoB100, LDL receptor (LDLR) knockout mice (LdlrhApoB100 Tg) and determine the potential LDL-related underlying mechanisms.
View Article and Find Full Text PDFWe present the complete sequence of the genomic RNA of an isolate of squash vein yellowing virus () from California (SqVYV-CA) and show it is a recombinant virus with a highly divergent 5' UTR and proximal P1a gene. The evolution of SqVYV-CA involved an intrageneric event between unknown potyviruses, related to isolates of papaya ringspot virus () from the Old World, and an intergeneric event between this recombinant potyvirus (minor parent) and an isolate of SqVYV from Israel (SqVYV-IL) (major parent). These events occurred in mixed infections and in the potyvirus P1 and ipomovirus P1a recombination hotspots and resulted in SqVYV-CA having a potyvirus 5' UTR and chimeric P1-P1a gene/protein and the remainder of the genome from SqVYV-IL.
View Article and Find Full Text PDFTomato spotted wilt orthotospovirus (TSWV) causes substantial economic loss to tomato production, and the Sw-5b resistance gene is widely deployed for management. Here, we show (i) the emergence of resistance-breaking (RB) TSWV strains in processing and fresh market tomato production in California over the past ten years, and (ii) evolutionary relationships with RB strains from other areas. A specific RT-PCR test was used to show the C118Y RB strain that emerged in Fresno County in 2016 quickly became predominant in the central production area and remained so through this study.
View Article and Find Full Text PDFBackground: In 2023, Tennessee replaced $6.2 M in US Centers for Disease Control and Prevention (CDC) human immunodeficiency virus (HIV) prevention funding with state funds to redirect support away from men who have sex with men (MSM), transgender women (TGW), and heterosexual Black women (HSBW) and to prioritize instead first responders (FR), pregnant people (PP), and survivors of sex trafficking (SST).
Methods: We used a simulation model of HIV disease to compare the clinical impact of Current, the present allocation of condoms, preexposure prophylaxis (PrEP), and HIV testing to CDC priority risk groups (MSM/TGW/HSBW); with Reallocation, funding instead increased HIV testing and linkage of Tennessee-determined priority populations (FR/PP/SST).