A Cross-Sectional Characterization of Insulin Resistance by Phenotype and Insulin Clamp in East Asian Americans with Type 1 and Type 2 Diabetes

Classic features of type 1 and type 2 diabetes may not apply in Asian Americans, due to shared absence of common HLA DR-DQ genotype, low prevalence of positive anti-islet antibodies and low BMI in both types of diabetes. Our objective was to characterize diabetic phenotypes in Asian Americans by clamp and clinical features.This was a cross-sectional study conducted in a referral center. Thirty East young Asian American adult volunteers (27.6±5.5 years) with type 1, type 2 diabetes or controls underwent hyperinsulinemic euglycemic clamp to assess insulin resistance and DEXA to assess adiposity.Gender, BMI, waist/hip ratio, leptin, LDL, anti-GAD, anti-IA2 antibodies and C-reactive protein were similar among three groups. Serum C-peptide, adiponectin, free fatty acid, HDL concentrations and truncal fat by DEXA, were different between diabetic groups. Glucose disposal rate by clamp was lowest in type 2 diabetes, followed by type 1 diabetes and controls (5.43±2.70, 7.62±2.59, 8.61±2.37 mg/min/kg, respectively, p = 0.001). Free fatty acid concentration universally plummeted during steady state of the clamp procedure regardless of diabetes types in all three groups. Adipocyte fatty acid binding protein in the entire cohort (r = -0.625, p = 0.04) and controls (r = -0.869, p = 0.046) correlated best with insulin resistance, independent of BMI.Type 2 diabetes in Asian Americans was associated with insulin resistance despite having low BMI as type 1 diabetes, suggesting a potential role for targeting insulin resistance apart from weight loss. Adipocyte fatty acid binding protein, strongly associated with insulin resistance, independent of adiposity in the young Asian American population, may potentially serve as a biomarker to identify at-risk individuals. Larger studies are needed to confirm this finding

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)

Heritability of Self-reported Phobic Fear

Twin studies on fear and phobia suggest moderate genetic effects. However, results are inconclusive regarding the presence of dominant genetic effects and sex differences. Using an extended twin design, including male and female twins (n = 5,465) and their siblings (n = 1,624), we examined the genetic and environmental influences on blood-injury, social, and agoraphobic fear and investigated their interaction with sex and age. Data of spouses (n = 708) of twins were used to evaluate assortative mating for the three fear dimensions. Results showed that there was no assortative mating for blood-injury, social and agoraphobic fear. Resemblance between biological relatives could be explained by additive and non-additive genetic effects for blood-injury and agoraphobic fear in all participants, and social fear in participants aged 14–25 years. For social fear in participants aged 26–65 only additive genetic effects were detected. Broad-sense heritability estimates ranged from 36 to 51% and were similar for men and women

Semantic Knowledge Influences Prewired Hedonic Responses to Odors

Background Odor hedonic perception relies on decoding the physicochemical properties of odorant molecules and can be influenced in humans by semantic knowledge. The effect of semantic knowledge on such prewired hedonic processing over the life span has remained unclear. Methodology/Principal Findings The present study measured hedonic response to odors in different age groups (children, teenagers, young adults, and seniors) and found that children and seniors, two age groups characterized by either low level of (children) or weak access to (seniors) odor semantic knowledge, processed odor hedonics more on the basis of their physicochemical properties. In contrast, in teenagers and young adults, who show better levels of semantic odor representation, the role of physicochemical properties was less marked. Conclusions/Significance These findings demonstrate for the first time that the biological determinants that make an odor pleasant or unpleasant are more powerful at either end of the life span

Post-meiotic transcription of phosphoglycerate-kinase 2 in mouse testes

We have used a human phosphoglycerate kinase-1 (PGK-1) cDNA clone to study expression of PGK-2 during mouse spermatogenesis. Hybrid selection, in vitro translation with product identification by 2-D gel electrophoresis demon-strated that the PGK-1 cDNA clone hybridized to PGK-2 mRNA in mouse testes. Northern analyses of RNA purified from separated spermatogenic cells demonstrated a large increase in abundance of PGK-2 mRNA in post-meiotic cells. Thus, post-meiotic transcription of PGK-2 mRNA is demonstrable with cloned DNA probes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44192/1/10540_2005_Article_BF01119630.pd

Stable Genetic Effects on Symptoms of Alcohol Abuse and Dependence from Adolescence into Early Adulthood

Relatively little is known about how genetic influences on alcohol abuse and dependence (AAD) change with age. We examined the change in influence of genetic and environmental factors which explain symptoms of AAD from adolescence into early adulthood. Symptoms of AAD were assessed using the four AAD screening questions of the CAGE inventory. Data were obtained up to six times by self-report questionnaires for 8,398 twins from the Netherlands Twin Register aged between 15 and 32 years. Longitudinal genetic simplex modeling was performed with Mx. Results showed that shared environmental influences were present for age 15–17 (57%) and age 18–20 (18%). Unique environmental influences gained importance over time, contributing 15% of the variance at age 15–17 and 48% at age 30–32. At younger ages, unique environmental influences were largely age-specific, while at later ages, age-specific influences became less important. Genetic influences on AAD symptoms over age could be accounted for by one factor, with the relative influence of this factor differing across ages. Genetic influences increased from 28% at age 15–17 to 58% at age 21–23 and remained high in magnitude thereafter. These results are in line with a developmentally stable hypothesis that predicts that a single set of genetic risk factors acts on symptoms of AAD from adolescence into young adulthood

Post-meiotic transcription in mouse testes detected with spermatid cDNA clones

cDNA clones to poly(A) + mRNA from spermatids have been obtained to study gene transcription in post-meiotic germ cells. Four cDNA clones detect mRNAs that increase in abundance in post-meiotic germ cells. One clone, pPM459, was shown to correspond to an mRNA that is transcribed after meiosis. Pulse-labelling experiments demonstrate transcription o5 the message in spermatids. These data constitute further evidence for post-meiotic gene transcription in spermatids.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44190/1/10540_2005_Article_BF01116696.pd

The peroxisome: still a mysterious organelle

More than half a century of research on peroxisomes has revealed unique features of this ubiquitous subcellular organelle, which have often been in disagreement with existing dogmas in cell biology. About 50 peroxisomal enzymes have so far been identified, which contribute to several crucial metabolic processes such as β-oxidation of fatty acids, biosynthesis of ether phospholipids and metabolism of reactive oxygen species, and render peroxisomes indispensable for human health and development. It became obvious that peroxisomes are highly dynamic organelles that rapidly assemble, multiply and degrade in response to metabolic needs. However, many aspects of peroxisome biology are still mysterious. This review addresses recent exciting discoveries on the biogenesis, formation and degradation of peroxisomes, on peroxisomal dynamics and division, as well as on the interaction and cross talk of peroxisomes with other subcellular compartments. Furthermore, recent advances on the role of peroxisomes in medicine and in the identification of novel peroxisomal proteins are discussed