Screening for Parkinson’s Disease with Response Time Barriers: A Pilot Study

Background: Although significant response time deficits (both reaction time and movement time) have been identified in numerous studies of patients with Parkinson’s disease (PD), few attempts have been made to evaluate the use of these measures in screening for PD. Methods: Receiver operator characteristic curves were used to identify cutoff scores for a unitweighted composite of two choice response tasks in a sample of 40 patients and 40 healthy participants. These scores were then cross-validated in an independent sample of 20 patients and 20 healthy participants. Results: The unit-weighted movement time composite demonstrated high sensitivity (90%) and specificity (90%) in the identification of PD. Movement time was also significantly correlated (r = 0.59, p \u3c 0.025) with the motor score of the Unified Parkinson’s Disease Rating Scale (UPDRS). Conclusions: Measures of chronometric speed, assessed without the use of biomechanically complex movements, have a potential role in screening for PD. Furthermore, the significant correlation between movement time and UPDRS motor score suggests that movement time may be useful in the quantification of PD severity

Genetic and environmental contributions to population group differences on the Raven's Progressive Matrices estimated from twins reared together and apart

We carried out two studies to test the hypothesis that genetic and environmental influences explain population group differences in general mental ability just as they do individual differences within a group. We estimated the heritability and environmentality of scores on the diagrammatic puzzles of the Raven's Coloured and/or Standard Progressive Matrices (CPM/SPM) from two independent twin samples and correlated these estimates with group differences on the same items. In Study 1, 199 pairs of 5- to 7-year-old monozygotic (MZ) and dizygotic (DZ) twins reared together provided estimates of heritability and environmentality for 36 puzzles from the CPM. These estimates correlated with the differences between the twins and 94 Serbian Roma (both rs=0.32; Ns=36; ps<0.05). In Study 2, 152 pairs of adult MZ and DZ twins reared apart provided estimates of heritability and environmentality for 58 puzzles from the SPM. These estimates correlated with the differences among 11 diverse samples including (i) the reared-apart twins, (ii) another sample of Serbian Roma, and (iii) East Asian, White, South Asian, Coloured and Black high school and university students in South Africa. In 55 comparisons, group differences were more pronounced on the more heritable and on the more environmental items (mean rs=0.40 and 0.47, respectively; Ns=58; ps<0.05). After controlling for measurement reliability and variance in item pass rates, the heritabilities still correlated with the group differences, although the environmentalities did not. Puzzles found relatively difficult (or easy) by the twins were those found relatively difficult (or easy) by the others (mean r=0.87). These results suggest that population group differences are part of the normal variation expected within a universal human cognition

No evidence that polymorphisms of brain regulator genes Microcephalin and ASPM are associated with general mental ability, head circumference or altruism

We test the hypothesis that polymorphisms of the brain regulator genes MCPH1 and ASPM contribute to variations in human brain size and its correlates. We measured general mental ability, head circumference and social intelligence in 644 Canadian adults (496 Caucasians, 36 Orientals, 84 Mixed Race/Other and 28 Blacks; 257 men and 387 women). The gene polymorphisms were assessed from buccal DNA; mental ability by Wonderlic Personnel Test and Multidimensional Aptitude Battery; head circumference by stretchless tape; and social intelligence by prosocial attitude questionnaires. Although all measures were construct valid and the allele frequencies showed expected population differences, no relationship was found between the genes and any of the criteria. Among Caucasian 18–25 year olds, for example, the two mental ability tests correlated with each other (r=0.78, N=476, p<0.001), with head circumference (r=0.17, N=182, p<0.05) and with prosocial attitudes (r=0.23, N=182, p<0.001)

Finger-length ratios show evidence of prenatal hormone-transfer between opposite-sex twins

Finger-length ratio (second to fourth finger; 2D:4D) has been associated with various measures thought to be related to prenatal androgens. In addition, hormone-transfer theory posits that hormones can transfer between twins. We examined 2D:4D in same-sex (SS) and opposite-sex (OS) dizygotic twins to test both propositions. Results show that 2D:4D is masculinized in OS females compared to SS females. This provides strong evidence that 2D:4D is laid down prenatally, and that hormones (likely androgens) can transfer from male to female fetuses. Implications for developmental timeframes for both hormone-transfer and 2D:4D are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83921/1/finger_length_ratios_show_evidence_of_prenatal_hormone-transfer_between_opposite-sex_twins.pd

Human Neurobehavioral Effects of Long-Term Exposure to Styrene: A Meta-Analysis

Many reports in the literature suggest that long-term exposure to styrene may exert a variety of effects on the nervous system, including increased choice reaction time and decreased performance of color discrimination and color arrangement tasks. Sufficient information exists to perform a meta-analysis of these observations quantifying the relationships between exposure (estimated from biomarkers) and effects on two measures of central nervous system function: reaction time and color vision. To perform the meta-analysis, we pooled data into a single database for each end point. End-point data were transformed to a common metric of effect magnitude (percentage of baseline). We estimated styrene concentration from biomarkers of exposure and fitted linear least-squares equations to the pooled data to produce dose–effect relationships. Statistically significant relationships were demonstrated between cumulative styrene exposure and increased choice reaction time as well as increased color confusion index. Eight work-years of exposure to 20 ppm styrene was estimated to produce a 6.5% increase in choice reaction time, which has been shown to significantly increase the probability of automobile accidents. The same exposure history was predicted to increase the color confusion index as much as 1.7 additional years of age in men

A Behavior Genetic Study of the Connection Between Social Values and Personality

The present research examined the extent to which relations between social values and personality are due to shared genetic or environmental factors. Using the Rokeach (1973) Value Survey and a scoring key from Schwartz and Bilsky (1990), seven value scores (enjoyment, achievement, self-direction, maturity, prosocial, security, and restrictive conformity) were derived in a sample of twins. As expected, all of the value scales were found to have a significant genetic component, with values ranging from 36% for enjoyment to 63% for prosocial, and there were numerous significant phenotypic correlations found between the value scales and personality scores. Most important, bivariate genetic analyses revealed that some of these phenotypic correlations could be attributed to common genetic or environmental factors

A Whole-Transcriptome Approach to Evaluating Reference Genes for Quantitative Gene Expression Studies: A Case Study in Mimulus

While quantitative PCR (qPCR) is widely recognized as being among the most accurate methods for quantifying gene expression, it is highly dependent on the use of reliable, stably expressed reference genes. With the increased availability of high-throughput methods for measuring gene expression, whole-transcriptome approaches may be increasingly utilized for reference gene selection and validation. In this study, RNA-seq was used to identify a set of novel qPCR reference genes and evaluate a panel of traditional housekeeping reference genes in two species of the evolutionary model plant genus Mimulus. More broadly, the methods proposed in this study can be used to harness the power of transcriptomes to identify appropriate reference genes for qPCR in any study organism, including emerging and nonmodel systems. We find that RNA-seq accurately estimates gene expression means in comparison to qPCR, and that expression means are robust to moderate environmental and genetic variation. However, measures of expression variability were only in agreement with qPCR for samples obtained from a shared environment. This result, along with transcriptome-wide comparisons, suggests that environmental changes have greater impacts on expression variability than on expression means. We discuss how this issue can be addressed through experimental design, and suggest that the ever-expanding pool of published transcriptomes represents a rich and low-cost resource for developing better reference genes for qPCR

Prolonged and tunable residence time using reversible covalent kinase inhibitors.

Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrated biochemical residence times spanning from minutes to 7 d. An inverted cyanoacrylamide with prolonged residence time in vivo remained bound to BTK for more than 18 h after clearance from the circulation. The inverted cyanoacrylamide strategy was further used to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating the generalizability of the approach. Targeting of noncatalytic cysteines with inverted cyanoacrylamides may serve as a broadly applicable platform that facilitates 'residence time by design', the ability to modulate and improve the duration of target engagement in vivo