Two transcription factors, CRP and CytR, mediate positive and negative control of nine cistrons involved in nucleoside catabolism and recycling in Escherichia coli. The ability of multiple ...transcription factors to combine in different ways to confer differential gene regulation is of significant interest in both prokaryotic and eukaryotic gene regulation. Analysis of cooperative interactions between CytR and CRP at the deoP2 and udpP promoters has implicated the importance of promoter architecture in controlling repression and induction. These studies have also identified competition between CytR and CRP as an additional contributor to differential regulation. The pattern and energetics of CytR and CRP interactions at the cdd promoter, the most strongly activated of the CytR-regulated promoters, have been delineated using DNase I footprinting. Surprisingly, CRP has greater affinity for the promoter proximal site at cddP, CRP1, than for the distal site, CRP2, in contrast to promoters studied previously. This difference is a major contributor to unusually high CRP-mediated activation of cddP. Additionally, while cytidine binding to CytR nearly eliminates the pairwise interactions between CytR and CRP bound at CRP1, it has little effect on pairwise cooperativity between CytR and CRP bound at CRP2 or as a consequence on the overall cooperativity of the three-protein complex in which CRP is bound to both sites. The effect of cytidine binding on cooperativity differs between the three promoters studied thus far. We propose that the different patterns of interaction reflect the spacing between CytR half-sites and the location of the CytR operator in relation to the two CRP sites.
Blacks/African Americans have been reported to be ∼2-4 times more likely to develop clinical Alzheimer's disease (AD) compared to Whites. Unfortunately, study design challenges (e.g., recruitment ...bias), racism, mistrust of healthcare providers and biomedical researchers, confounders related to socioeconomic status, and other sources of bias are often ignored when interpreting differences in human subjects categorized by race. Failure to account for these factors can lead to misinterpretation of results, reification of race as biology, discrimination, and missed or delayed diagnoses. Here we provide a selected historical background, discuss challenges, present opportunities, and suggest considerations for studying health outcomes among racial/ethnic groups. We encourage neuroscientists to consider shifting away from using biologic determination to interpret data, and work instead toward a paradigm of incorporating both biological and socio-environmental factors known to affect health outcomes with the goal of understanding and improving dementia treatments for Blacks/African Americans and other underserved populations.
The objective of this study was to determine whether chronic use of medications with anticholinergic (AC) properties impact older adults' cognitive functioning.
Six years of cognitive test data from ...two groups of older adults (AC and control) were examined retrospectively (N = 592).
Declines over time were found for the AC group on parts A and B of the Trail Making Test.
Physicians prescribing ACs to older adult patients should be aware of their potential effects on psychomotor speed and executive functioning. These cognitive effects may lead to impairments in daily functioning resulting in the need to reevaluate patient medications.
Cognitively intact elderly research volunteers at the University of Kentucky have been recruited, followed longitudinally, and autopsied with extensive neuropathological evaluations since 1989. To ...date, the cohort has recruited 1,030 individuals with 552 participants being actively followed, 363 deceased, and 273 autopsied. An extensive database has been constructed with continuous updates that include textured clinical, neuropsychological, neuroimaging, and pathological information. The history, demographics, clinical observations, and pathological features of this research cohort are described. We also explain some of the evolving methodologies and the academic contributions that have been made due to this motivated group of older Kentuckians.
Practice effects are a known threat to reliability and validity in clinical trials. Few studies have investigated the potential influence of practice on repeated screening measures in longitudinal ...clinical trials with a focus on dementia prevention. The current study investigates whether practice effects exist on a screening measure commonly used in aging research, the Memory Impairment Screen (MIS).
The PREADViSE trial is a clinical intervention study evaluating the efficacy of vitamin E and selenium for Alzheimer's disease prevention. Participants are screened annually for incident dementia with the MIS. Participants with baseline and three consecutive follow-ups who made less than a perfect score at one or more assessments were included in the current analyses (N=1,803). An additional subset of participants with four consecutive assessments but who received the same version of the MIS at baseline and first follow-up (N=301) was also assessed to determine the effects of alternate forms on mitigating practice. We hypothesized that despite efforts to mitigate practice effects with alternate versions, MIS scores would improve with repeated screening. Linear mixed models were used to estimate mean MIS scores over time.
Among men with four visits and alternating MIS versions, although there is little evidence of a significant practice effect at the first follow-up, mean scores clearly improve at the second and third follow-ups for all but the oldest participants. Unlike those who received alternate versions, men given the same version at first follow-up show significant practice effects.
While increases in the overall means were small, they represent a significant number of men whose scores improved with repeated testing. Such improvements could bias case ascertainment if not taken into account.
: The AutoMate Express™ Forensic DNA Extraction System was developed for automatic isolation of DNA from a variety of forensic biological samples. The performance of the system was investigated ...using a wide range of biological samples. Depending on the sample type, either PrepFiler™ lysis buffer or PrepFiler BTA™ lysis buffer was used to lyse the samples. After lysis and removal of the substrate using LySep™ column, the lysate in the sample tubes were loaded onto AutoMate Express™ instrument and DNA was extracted using one of the two instrument extraction protocols. Our study showed that DNA was recovered from as little as 0.025 μL of blood. DNA extracted from casework‐type samples was free of detectable PCR inhibitors and the short tandem repeat profiles were complete, conclusive, and devoid of any PCR artifacts. The system also showed consistent performance from day‐to‐day operation.
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) set of tests is frequently used for tracking cognition longitudinally in both clinical and research settings. Repeated cognitive ...assessments are an important component in measuring such changes; however, practice effects and attrition bias may obscure significant clinical change over time. The current study sought to examine the presence and magnitude of practice effects and the role of attrition bias in a sample of cognitively normal older men enrolled in a prevention trial.
Participants were grouped according to whether they completed five years of follow-up (n = 182) or less (n = 126). Practice effects were examined in these participants as a whole (n = 308) and by group.
Findings indicate that moderate practice effects exist in both groups on the CERAD T-score and that attrition bias likely does not play a contributing role in improved scores over time.
The current study provides additional evidence and support for previous findings that repeated cognitive assessment results in rising test scores in longitudinally collected data and demonstrates that these findings are unlikely to be due to attrition.
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