University of Alabama at Birmingham

About: University of Alabama at Birmingham is a education organization based out in Birmingham, Alabama, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 38523 authors who have published 86775 publications receiving 3930642 citations. The organization is also known as: UAB & The University of Alabama at Birmingham.

Histone Methylation Regulates Memory Formation

Abstract: It has been established that regulation of chromatin structure through post-translational modification of histone proteins, primarily histone H3 phosphorylation and acetylation, is an important early step in the induction of synaptic plasticity and formation of long-term memory. In this study, we investigated the contribution of another histone modification, histone methylation, to memory formation in the adult hippocampus. We found that trimethylation of histone H3 at lysine 4 (H3K4), an active mark for transcription, is upregulated in hippocampus 1 h following contextual fear conditioning. In addition, we found that dimethylation of histone H3 at lysine 9 (H3K9), a molecular mark associated with transcriptional silencing, is increased 1 h after fear conditioning and decreased 24 h after context exposure alone and contextual fear conditioning. Trimethylated H3K4 levels returned to baseline levels at 24 h. We also found that mice deficient in the H3K4-specific histone methyltransferase, Mll, displayed deficits in contextual fear conditioning relative to wild-type animals. This suggests that histone methylation is required for proper long-term consolidation of contextual fear memories. Interestingly, inhibition of histone deacetylases (HDACs) with sodium butyrate (NaB) resulted in increased H3K4 trimethylation and decreased H3K9 dimethylation in hippocampus following contextual fear conditioning. Correspondingly, we found that fear learning triggered increases in H3K4 trimethylation at specific gene promoter regions (Zif268 and bdnf) with altered DNA methylation and MeCP2 DNA binding. Zif268 DNA methylation levels returned to baseline at 24 h. Together, these data demonstrate that histone methylation is actively regulated in the hippocampus and facilitates long-term memory formation.

Older drivers and cataract: driving habits and crash risk.

Abstract: BACKGROUND: Cataract is a leading cause of vision impairment in older adults, affecting almost half of those over age 75 years. Driving is a highly visual task and, as with other age groups, older adults rely on the personal automobile for travel. The purpose of this study was to examine the role of cataract in driving. METHODS: Older adults (aged 55-85 years) with cataract (n = 279) and those without cataract (n = 105) who were legally licensed to drive were recruited from eye clinics to participate in a driving habits interview to assess driving status, exposure, difficulty, and "space" (the distance of driving excursions from home base). Crash data over the prior 5 years were procured from state records. Visual functional tests documented the severity of vision impairment. RESULTS: Compared to those without cataract, older drivers with cataract were approximately two times more likely to report reductions in days driven and number of destinations per week, driving slower than the general traffic flow, and preferring someone else to drive. Those with cataract were five times more likely to have received advice about limiting their driving. Those with cataract were four times more likely to report difficulty with challenging driving situations, and those reporting driving difficulty were two times more likely to reduce their driving exposure. Drivers with cataract were 2.5 times more likely to have a history of at-fault crash involvement in the prior 5 years (adjusted for miles driven/week and days driven/week). These associations remained even after adjustments for the confounding effects of advanced age, impaired general health, mental status deficit, or depression. CONCLUSIONS: Older drivers with cataract experience a restriction in their driving mobility and a decrease in their safety on the road. These findings serve as a baseline for our ongoing study evaluating whether improvements in vision following cataract surgery expand driving mobility and improve driver safety.

Induction of myeloid-derived suppressor cells by tumor exosomes

Abstract: Myeloid-derived suppressor cells (MDSCs) promote tumor progression. The mechanisms of MDSC development during tumor growth remain unknown. Tumor exosomes (T-exosomes) have been implicated to play a role in immune regulation, however the role of exosomes in the induction of MDSCs is unclear. Our previous work demonstrated that exosomes isolated from tumor cells are taken up by bone marrow myeloid cells. Here, we extend those findings showing that exosomes isolated from T-exosomes switch the differentiation pathway of these myeloid cells to the MDSC pathway (CD11b(+)Gr-1(+)). The resulting cells exhibit MDSC phenotypic and functional characteristics including promotion of tumor growth. Furthermore, we demonstrated that in vivo MDSC mediated promotion of tumor progression is dependent on T-exosome prostaglandin E2 (PGE2) and TGF-beta molecules. T-exosomes can induce the accumulation of MDSCs expressing Cox2, IL-6, VEGF, and arginase-1. Antibodies against exosomal PGE2 and TGF-beta block the activity of these exosomes on MDSC induction and therefore attenuate MDSC-mediated tumor-promoting ability. Exosomal PGE2 and TGF-beta are enriched in T-exosomes when compared with exosomes isolated from the supernatants of cultured tumor cells (C-exosomes). The tumor microenvironment has an effect on the potency of T-exosome mediated induction of MDSCs by regulating the sorting and the amount of exosomal PGE2 and TGF-beta available. Together, these findings lend themselves to developing specific targetable therapeutic strategies to reduce or eliminate MDSC-induced immunosuppression and hence enhance host antitumor immunotherapy efficacy.