15 research outputs found
Green engagement: An investigation into the relationship of Millennial engagement and an organization’s sustainable performance score
Since the start of the 21st century, the issue of sustainability in business and Human Resource practices has been a central topic of interest. More recently, human resources has come under considerable pressure to prove its worth, primarily by producing a more productive and engaged workforce. Sustainability has, thus, become an extremely interesting avenue of study for HR professionals as, at its core, sustainable practices aim to better all parts of an organization from the social, to the environmental, to the financial (the three components of the triple bottom line). This study will investigate the relationship between the extent to which Millennials are engaged in an organization and that organization’s score on sustainable performance measures
ABCA7 frameshift deletion associated with Alzheimer disease in African Americans
Objective: To identify a causative variant(s) that may contribute to Alzheimer disease (AD) in African Americans (AA) in the ATP-binding cassette, subfamily A (ABC1), member 7 (ABCA7) gene, a known risk factor for late-onset AD.
Methods: Custom capture sequencing was performed on ∼150 kb encompassing ABCA7 in 40 AA cases and 37 AA controls carrying the AA risk allele (rs115550680). Association testing was performed for an ABCA7 deletion identified in large AA data sets (discovery n = 1,068; replication n = 1,749) and whole exome sequencing of Caribbean Hispanic (CH) AD families.
Results: A 44-base pair deletion (rs142076058) was identified in all 77 risk genotype carriers, which shows that the deletion is in high linkage disequilibrium with the risk allele. The deletion was assessed in a large data set (531 cases and 527 controls) and, after adjustments for age, sex, and APOE status, was significantly associated with disease (p = 0.0002, odds ratio [OR] = 2.13 [95% confidence interval (CI): 1.42–3.20]). An independent data set replicated the association (447 cases and 880 controls, p = 0.0117, OR = 1.65 [95% CI: 1.12–2.44]), and joint analysis increased the significance (p = 1.414 × 10−5, OR = 1.81 [95% CI: 1.38–2.37]). The deletion is common in AA cases (15.2%) and AA controls (9.74%), but in only 0.12% of our non-Hispanic white cohort. Whole exome sequencing of multiplex, CH families identified the deletion cosegregating with disease in a large sibship. The deleted allele produces a stable, detectable RNA strand and is predicted to result in a frameshift mutation (p.Arg578Alafs) that could interfere with protein function.
Conclusions: This common ABCA7 deletion could represent an ethnic-specific pathogenic alteration in AD
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Characterization of human cardiac troponin I ARG145GLY: A mutation associated with the disease hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) has been associated with several mutations in the gene encoding Human Cardiac Troponin I (HCTnI). A missense mutation, which occurs in the inhibitory region of HCTnI (HCTnIR145G ), replaces an arginine residue at position 145 with a glycine. In an attempt to determine the biochemical and physiological ramifications in muscle contraction due to HCTnIR145G and its association with the disease HCM, this study focused on how the missense mutation within HCTnI affects its inhibitory function and molecular interactions within the troponin complex. Results from several different assays indicate that the inhibitory function of HCTnIR145G in actin-tropomyosin (Tm) activated myosin ATPase assays was significantly reduced as compared to the wildtype protein. In reconstituted thin filament systems, when HCTnIR145G was complexed with HCTnC and HCTnT (TnR145G) only partial inhibition of the actin-Tm activated myosin ATPase activity was observed in the absence of Ca2+ compared to wildtype Tn complex (HCTnT-HCTnI-HCTnC). There was no significant difference in the maximum level of actin-Tm activated myosin ATPase activity between wildtype Tn and TnR145G in the presence of Ca2+ . To study the effects of HCTnIR145G on steady state force development and relaxation of unregulated force, HCTnI and HCTnIR145G complexed with HCTnC were used to reconstitute HCTnT displaced skinned cardiac muscle fibers. The results indicated a significant reduction in the ability of the HCTnC/HCTnIR145G complex to inhibit force in the absence of Ca2+. In addition, skinned fibers reconstituted with the mutant complex were not able to recover maximum force development as compared to the wildtype complex. Moreover, a moderate increase in the Ca2+ dependence of force development was observed in skinned fibers reconstituted with the mutant complex. These results demonstrate impaired inhibition in reconstituted and skinned muscle systems as well as impaired force development and an increase in the Ca2+ sensitivity to force development. HCTnIR145G could be associated with contractile dysfunction in cardiac muscle resulting from abnormal interactions within the thin filament and between the thin filament and thick filament of cardiac muscle. Biacore and fluorescence measurements did not reveal a significant change in the binding affinity between HCTnIR145G and HCTnC in different metal ion buffer conditions. However, the data did reveal a trend in that the WTHCTnI had a lower affinity for HCTnC than HCTnIR145G in the absence of Ca2+. Circular dichroism measurements, to access the effect of the Arg145Gly mutation on the secondary structure of TnI, revealed that the mutation does not change the alpha helical content of the protein. Furthermore, HCTnIR145G co-sediments with the actin-tropomyosin complex in the absence and presence of Ca2+. Clearly, we observe an alteration in the inhibitory function of HCTnIR145G, that could be due to an alteration in the interaction between TnI and TnC. These results do not eliminate the possibility that this mutation has an indirect effect on other troponin subunits that indirectly affects the ability of TnI to inhibit muscle contraction
Beyond the Barriers: Factors that Influence African Americans to Participate in Research
Abstract The objective of the paper is to describe educational profiles and motivations for health related research study participation of a distinct minority cohort, in a non-clinical setting. Many respondents (n=119) participated in at least two studies and reported that the main motivator was having a relative with the studied disease. More than 65% of this cohort had earned a bachelor degree or higher compared to 40% of those that had not participated in a health related research study. This study also documented that African Americans who participate in health related research studies are civic minded individuals that understand informed consent and are willing to submit a variety of biological samples for research
USE OF A UNIVERSITY OUTREACH CENTER TO UNDERSTAND AND ASSESS NEEDS OF AFRICAN AMERICAN ALZHEIMER'S CAREGIVERS
Relationship Between Depressive Symptoms and Cognition in Older, Non-demented African Americans
Knowledge of the relationship between depressive symptoms and cognition in older adults has primarily come from studies of clinically depressed, functionally impaired or cognitively impaired individuals, and in predominately White samples. Limited minority representation in depression research exposes the need to examine these associations in more ethnic/racially diverse populations. We sought to examine the relationship between depressive symptoms and cognition in a sample of non-demented older African Americans recruited from surrounding U.S. cities of New York, Greensboro, Miami, and Nashville (N = 944). Depressive symptoms were evaluated with the Geriatric Depression Scale (GDS). Cognition was evaluated with a comprehensive neuropsychological battery. Test scores were summarized into attention, executive function, memory, language, and processing speed composites. Controlling for age, education, reading level, and sex, African American older adults who endorsed more symptoms obtained significantly lower scores on measures of memory, language, processing speed, and executive functioning. Further investigation of the causal pathway underlying this association, as well as potential mediators of the relationship between depressive symptoms and cognitive test performance among older African Americans, such as cardiovascular and cerebrovascular disease, may offer potential avenues for intervention
Relationship Between Depressive Symptoms and Cognition in Older, Non-demented African Americans
Large repeat expansions in the C9ORF72 gene contribute to a spectrum of neurodegenerative disorders including Alzheimer's disease in Caucasians, but not African-Americans
Repeat expansions in the C9ORF72 gene contribute to Alzheimer's disease in Caucasians
Recently, a hexanucleotide repeat expansion in the C9ORF72 gene has been identified to account for a significant portion of Caucasian families affected by frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Given the clinical overlap of FTD with Alzheimer's disease (AD), we hypothesized that C9ORF72 expansions might contribute to AD. In Caucasians, we found C9ORF72 expansions in the pathogenic range of FTD/ALS (>30 repeats) at a proportion of 0.76% in AD cases versus 0 in control subjects (p = 3.3E-03; 1182 cases, 1039 controls). In contrast, no large expansions were detected in individuals of African American ethnicity (291 cases, 620 controls). However, in the range of normal variation of C9ORF72 expansions (0–23 repeat copies), we detected significant differences in distribution and mean repeat counts between Caucasians and African Americans. Clinical and pathological re-evaluation of identified C9ORF72 expansion carriers revealed 9 clinical and/or autopsy confirmed AD and 2 FTD final diagnoses. Thus, our results support the notion that large C9ORF72 expansions lead to a phenotypic spectrum of neurodegenerative disease including AD