PERK/ATF4-dependent expression of the stress response protein REDD1 promotes proinflammatory cytokine expression in the heart of obese mice.

Endoplasmic reticulum (ER) stress and inflammation are hallmarks of myocardial impairment. Here, we investigated the role of the stress response protein regulated in development and DNA damage 1 (REDD1) as a molecular link between ER stress and inflammation in cardiomyocytes. In mice fed a high-fat high-sucrose (HFHS, 42% kcal fat, 34% sucrose by weight) diet for 12 wk, REDD1 expression in the heart was increased in coordination with markers of ER stress and inflammation. In human AC16 cardiomyocytes exposed to either hyperglycemic conditions or the saturated fatty acid palmitate, REDD1 expression was increased coincident with ER stress and upregulated expression of the proinflammatory cytokines IL-1ß, IL-6, and TNFα. In cardiomyocytes exposed to hyperglycemic/hyperlipidemic conditions, pharmacological inhibition of the ER kinase protein kinase RNA-like endoplasmic reticulum kinase (PERK) or knockdown of the transcription factor ATF4 prevented the increase in REDD1 expression. REDD1 deletion reduced proinflammatory cytokine expression in both cardiomyocytes exposed to hyperglycemic/hyperlipidemic conditions and in the hearts of obese mice. Overall, the findings support a model wherein HFHS diet contributes to the development of inflammation in cardiomyocytes by promoting REDD1 expression via activation of a PERK/ATF4 signaling axis.NEW & NOTEWORTHY Interplay between endoplasmic reticulum stress and inflammation contributes to cardiovascular disease progression. The studies here identify the stress response protein known as REDD1 as a missing molecular link that connects the development of endoplasmic reticulum stress with increased production of proinflammatory cytokines in the hearts of obese mice.

Verbal and visual serial-order memory in deaf signers and hearing nonsigners: A systematic review and meta-analysis.

Previous research suggests Deaf signers may have different short-term and working memory processes compared with hearing nonsigners due to prolonged auditory deprivation. The direction and magnitude of these reported differences, however, are variable and dependent on memory modality (e.g., visual, verbal), stimulus type, and research design. These discrepancies have made consensus difficult to reach which, in turn, slows progress in areas such as education, medical decision-making, and cognitive sciences. The present systematic review and meta-analysis included 35 studies (N = 1,701 participants) that examined verbal (n = 15), visuospatial (n = 10), or both verbal and visuospatial (n = 10) serial-memory tasks comparing nonimplanted, Deaf signers to hearing nonsigners across the life span. Multivariate meta-analyses indicated a significant, negative effect of deafness on verbal short-term memory (forward recall), g = -1.33, SE = 0.17, p < .001, 95% CI [-1.68, -0.98], and working memory (backward recall), g = -0.66, SE = 0.11, p < .001, 95% CI [-0.89, -0.45], but no significant effect of deafness on visuospatial short-term memory, g = -0.055, SE = 0.17, p = 0.75, 95% CI [-0.39, 0.28]. Visuospatial working memory was not analyzed due to limited power. Population estimates for verbal and visuospatial short-term memory were moderated by age wherein studies with adults demonstrated a stronger hearing advantage than studies with children/adolescents. Quality estimates indicated most studies were of fair quality, with only 38% of studies involving Deaf authors. Findings are discussed in the context of both Deaf equity and models of serial memory.