The association between educational parameters and a cognitive screening measure in older blacks.

ABSTRACTBackground:To expand on prior literature by examining how various education parameters (performance-based reading literacy, years of education, and self-rated quality of education) relate to a cognitive screening measure's total and subscale scores of specific cognitive abilities. METHODS: Black adults (age range: 55-86) were administered self-rated items years of education and quality of education, and a measure of performance-based reading literacy. The Mini-Mental State Examination (MMSE) was used to screen for overall cognitive functioning as well as performance on specific cognitive abilities. RESULTS: Sixty-nine percent of the sample had reading grade levels that were less than their reported years of education. Lower years of education and worse reading literacy are associated with poorer MMSE performance, particularly on the attention and calculation subscales. CONCLUSIONS: Years of education, a commonly used measure for education, may not be reflective of Black adults' educational experiences/qualities. Thus, it is important to account for the unique educational experiences of adults that could influence their MMSE performance. Incorporating quality and quantity of education will provide a more comprehensive understanding of the individual's performance on cognitive measures, specifically as it relates to sociocultural differences.

Unfolded protein response and angiogenesis in malignancies.

Cellular stress, arising from accumulation of unfolded proteins, occurs frequently in rapidly proliferating cancer cells. This cellular stress, in turn, activates the unfolded protein response (UPR), an interconnected set of signal transduction pathways that alleviate the proteostatic stress. The UPR is implicated in cancer cell survival and proliferation through upregulation of pro-tumorigenic pathways that ultimately promote malignant metabolism and neoangiogenesis. Here, we reviewed mechanisms of signaling crosstalk between the UPR and angiogenesis pathways, as well as transmissible ER stress and the role in tumor growth and development. To characterize differences in UPR and UPR-mediated angiogenesis in malignancy, we employed a data mining approach using patient tumor data from The Cancer Genome Atlas (TCGA). The analysis of TCGA revealed differences in UPR between malignant samples versus their non-malignant counterparts.

Biallelic, Selectable, Knock-in Targeting of CCR5 via CRISPR-Cas9 Mediated Homology Directed Repair Inhibits HIV-1 Replication.

Transplanting HIV-1 positive patients with hematopoietic stem cells homozygous for a 32 bp deletion in the chemokine receptor type 5 (CCR5) gene resulted in a loss of detectable HIV-1, suggesting genetically disrupting CCR5 is a promising approach for HIV-1 cure. Targeting the CCR5-locus with CRISPR-Cas9 was shown to decrease the amount of CCR5 expression and HIV-1 susceptibility in vitro as well as in vivo. Still, only the individuals homozygous for the CCR5-Δ32 frameshift mutation confer complete resistance to HIV-1 infection. In this study we introduce a mechanism to target CCR5 and efficiently select for cells with biallelic frameshift insertion, using CRISPR-Cas9 mediated homology directed repair (HDR). We hypothesized that cells harboring two different selectable markers (double positive), each in one allele of the CCR5 locus, would carry a frameshift mutation in both alleles, lack CCR5 expression and resist HIV-1 infection. Inducing double-stranded breaks (DSB) via CRISPR-Cas9 leads to HDR and integration of a donor plasmid. Double-positive cells were selected via fluorescence-activated cell sorting (FACS), and CCR5 was analyzed genetically, phenotypically, and functionally. Targeted and selected populations showed a very high frequency of mutations and a drastic reduction in CCR5 surface expression. Most importantly, double-positive cells displayed potent inhibition to HIV-1 infection. Taken together, we show that targeting cells via CRISPR-Cas9 mediated HDR enables efficient selection of mutant cells that are deficient for CCR5 and highly resistant to HIV-1 infection.

Targeting TRAF3IP2 inhibits angiogenesis in glioblastoma.

Increased vascularization, also known as neoangiogenesis, plays a major role in many cancers, including glioblastoma multiforme (GBM), by contributing to their aggressive growth and metastasis. Although anti-angiogenic therapies provide some clinical improvement, they fail to significantly improve the overall survival of GBM patients. Since various pro-angiogenic mediators drive GBM, we hypothesized that identifying targetable genes that broadly inhibit multiple pro-angiogenic mediators will significantly promote favorable outcomes. Here, we identified TRAF3IP2 (TRAF3-interacting protein 2) as a critical regulator of angiogenesis in GBM. We demonstrated that knockdown of TRAF3IP2 in an intracranial model of GBM significantly reduces vascularization. Targeting TRAF3IP2 significantly downregulated VEGF, IL6, ANGPT2, IL8, FZGF2, PGF, IL1ß, EGF, PDGFRB, and VEGFR2 expression in residual tumors. Our data also indicate that exogenous addition of VEGF partially restores angiogenesis by TRAF3IP2-silenced cells, suggesting that TRAF3IP2 promotes angiogenesis through VEGF- and non-VEGF-dependent mechanisms. These results indicate the anti-angiogenic and anti-tumorigenic potential of targeting TRAF3IP2 in GBM, a deadly cancer with limited treatment options.

Older Black Adults' Satisfaction and Anxiety Levels After Completing Alternative Versus Traditional Cognitive Batteries.

OBJECTIVE: The objective of this study was to examine satisfaction, test anxiety, and performance using computer-based cognitive batteries versus a paper-and-pencil neuropsychological battery among older Blacks. METHOD: Self-identified Black adults (n = 87, age range: 55-86; mean education = 14) completed two computer-based tests (CogState and Joggle) and a paper-and-pencil neuropsychological battery. After each battery, participants reported their testing anxiety and satisfaction using the batteries. Descriptive, correlational, and regression analyses compared satisfaction, anxiety, and performance across the batteries. RESULTS: Majority of the participants reported more satisfaction with the computer-based (Joggle: 66%; CogState: 77%) than the neuropsychological (52%) battery. Participants also reported less testing anxiety after completing the computer-based batteries than the neuropsychological battery, F(2, 172) = 22.96, p < .001. Older adults' familiarity and comfort level with the computer were not associated with their performance on the computer-based tests (p > .05). Although testing anxiety was not associated with performance across the batteries, age and education quality were uniquely associated with performance on the CogState and neuropsychological batteries. CONCLUSIONS: Computer-based cognitive batteries appear to be less intimidating than the commonly used paper-and-pencil neuropsychological tests for Black adults. Thus, these cognitive batteries may be useful tools for monitoring older Blacks' cognitive status.