Recombinant HIV-2 Nef protein (D205)

Objective We developed a mobile cognitive test of verbal learning and memory, the mobile verbal learning test (mVLT), to allow for brief, repeated and portable delivery of a 12-item list learning test through a smartphone. This study examined the psychometric properties of the mVLT among older persons with and without human immunodeficiency virus (HIV). Methods Sixty-eight persons with HIV and 36 HIV-negative individuals (aged 50-74) completed three trials of the mVLT on a smartphone once daily for 14 days. A different word list was administered each day. Results Participants completed 80% of the 14 mVLT administrations, equating to 1166 valid and complete mVLTs. Neither adherence nor mean mVLT total score (number correct in 3 recall trials) differed by HIV status. No practice effects from repeated mVLT administration were observed, and there were moderately strong correlations of mVLT performance with performance on the in-lab version of the task and with traditional cognitive assessments of cognitive processes contributing to memory. We found evidence of within-person learning across mVLT trials, with persons with HIV demonstrating less learning from trials 1 to 3 compared to HIV-negative participants. Conclusions The mVLT is a valid method to assess learning in the real world in older adults with and without HIV.

Macroautophagy/autophagy delivers cytoplasmic cargo to lysosomes for degradation. In yeast, the single Atg8 protein plays a role in the formation of autophagosomes whereas in mammalian cells there are five to seven paralogs, referred to as mammalian Atg8s (mAtg8s: GABARAP, GABARAPL1, GABARAPL2, LC3A, LC3B, LC3B2 and LC3C) with incompletely defined functions. Here we show that a subset of mAtg8s directly control lysosomal biogenesis. This occurs at the level of TFEB, the principal regulator of the lysosomal transcriptional program. mAtg8s promote TFEB's nuclear translocation in response to stimuli such as starvation. GABARAP interacts directly with TFEB, whereas RNA-Seq analyses reveal that knockout of six genes encoding mAtg8s, or a triple knockout of the genes encoding all GABARAPs, diminishes the TFEB transcriptional program. We furthermore show that GABARAPs in cooperation with other proteins, IRGM, a factor implicated in tuberculosis and Crohn disease, and STX17, are required during starvation for optimal inhibition of MTOR, an upstream kinase of TFEB, and activation of the PPP3/calcineurin phosphatase that dephosphorylates TFEB, thus promoting its nuclear translocation. In conclusion, mAtg8s, IRGM and STX17 control lysosomal biogenesis by their combined or individual effects on MTOR, TFEB, and PPP3/calcineurin, independently of their roles in the formation of autophagosomal membranes.