ICAM G241A polymorphism and soluble ICAM-1 serum levels: Evidence for an active immune process in schizophrenia

Objectives: We have previously reported reduced serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) in schizophrenic patients. A single-nucleotide polymorphism ( SNP) of the ICAM-1 gene was described at position 241. The G --> A SNP results in a nonsynonymous amino acid exchange of the ICAM-1 protein, and the A allele was shown to be also associated with several immunological disorders like rheumatoid arthritis. Methods: We investigated 70 schizophrenic patients and 128 unrelated healthy control persons regarding the relationship between the serum levels of sICAM-1 and the ICAM-1 G214A polymorphism. Results: We were able to replicate our previous finding of reduced sICAM-1 levels in schizophrenia. Healthy control persons carrying the polymorphic A allele showed markedly lower sICAM-1 serum levels than carriers of the homozygous GG wild type ( p < 0.004). In contrast, no significant difference in the sICAM-1 serum levels were seen regarding the G241A genotype distribution in schizophrenic patients. Conclusion: We hypothesize that the biochemical effect of the G241A SNP is masked in schizophrenic patients, indicating a disease-related mechanism leading to reduced levels of sICAM-1 in schizophrenia. Copyright (C) 2005 S. Karger AG, Basel

Specification of primordial germ cells in medaka (Oryzias latipes)

BACKGROUND: Primordial germ cells (PGCs) give rise to gametes that are responsible for the development of a new organism in the next generation. Two modes of germ line specification have been described: the inheritance of asymmetrically-localized maternally provided cytoplasmic determinants and the induction of the PGC fate by other cell types. PGCs specification in zebrafish appears to depend on inheritance of germ plasm in which several RNA molecules such as vasa and nanos reside. Whether the specification mode of PGCs found in zebrafish is general for other fish species was brought into question upon analysis of olvas expression – the vasa homologue in another teleost, medaka (Oryzias latipes). Here, in contrast to the findings in zebrafish, the PGCs are found in a predictable position relative to a somatic structure, the embryonic shield. This finding, coupled with the fact that vasa mRNA, which is localized to the germ plasm of zebrafish but does not label a similar structure in medaka opened the possibility of fundamentally different mechanisms governing PGC specification in these two fish species. RESULTS: In this study we addressed the question concerning the mode of PGC specification in medaka using embryological experiments, analysis of RNA stability in the PGCs and electron microscopy observations. Dramatic alterations in the somatic environment, i.e. induction of a secondary axis or mesoderm formation alteration, did not affect the PGC number. Furthermore, the PGCs of medaka are capable of protecting specific RNA molecules from degradation and could therefore exhibit a specific mRNA expression pattern controlled by posttrancriptional mechanisms. Subsequent analysis of 4-cell stage medaka embryos using electron microscopy revealed germ plasm-like structures located at a region corresponding to that of zebrafish germ plasm. CONCLUSION: Taken together, these results are consistent with the idea that in medaka the inheritance of maternally provided asymmetrically-localized cytoplasmic determinants directs cells to assume the germ line fate similar to zebrafish PGCs

Differences in BMI z-Scores between Offspring of Smoking and Nonsmoking Mothers: A Longitudinal Study of German Children from Birth through 14 Years of Age

BACKGROUND: Children of mothers who smoked during pregnancy have a lower birth weight but have a higher chance to become overweight during childhood. OBJECTIVES: We followed children longitudinally to assess the age when higher body mass index (BMI) z-scores became evident in the children of mothers who smoked during pregnancy, and to evaluate the trajectory of changes until adolescence. METHODS: We pooled data from two German cohort studies that included repeated anthropometric measurements until 14 years of age and information on smoking during pregnancy and other risk factors for overweight. We used longitudinal quantile regression to estimate age-and sex-specific associations between maternal smoking and the 10th, 25th, 50th, 75th, and 90th quantiles of the BMI z-score distribution in study participants from birth through 14 years of age, adjusted for potential confounders. We used additive mixed models to estimate associations with mean BMI z-scores. Results: Mean and median (50th quantile) BMI z-scores at birth were smaller in the children of mothers who smoked during pregnancy compared with children of nonsmoking mothers, but BMI z-scores were significantly associated with maternal smoking beginning at the age of 4-5 years, and differences increased over time. For example, the difference in the median BMI z-score between the daughters of smokers versus nonsmokers was 0.12 (95% CI: 0.01, 0.21) at 5 years, and 0.30 (95% CI: 0.08, 0.39) at 14 years of age. For lower BMI z-score quantiles, the association with smoking was more pronounced in girls, whereas in boys the association was more pronounced for higher BMI z-score quantiles. CONCLUSIONS: A clear difference in BMI z-score (mean and median) between children of smoking and nonsmoking mothers emerged at 4-5 years of age. The shape and size of age-specific effect estimates for maternal smoking during pregnancy varied by age and sex across the BMI z-score distribution

Metabolic Rearrangements Causing Elevated Proline and Polyhydroxybutyrate Accumulation During the Osmotic Adaptation Response of Bacillus megaterium

For many years now, Bacillus megaterium serves as a microbial workhorse for the high-level production of recombinant proteins in the g/L-scale. However, efficient and stable production processes require the knowledge of the molecular adaptation strategies of the host organism to establish optimal environmental conditions. Here, we interrogated the osmotic stress response of B. megaterium using transcriptome, proteome, metabolome, and fluxome analyses. An initial transient adaptation consisted of potassium import and glutamate counterion synthesis. The massive synthesis of the compatible solute proline constituted the second longterm adaptation process. Several stress response enzymes involved in iron scavenging and reactive oxygen species (ROS) fighting proteins showed higher levels under prolonged osmotic stress induced by 1.8 M NaCl. At the same time, the downregulation of the expression of genes of the upper part of glycolysis resulted in the activation of the pentose phosphate pathway (PPP), generating an oversupply of NADPH. The increased production of lactate accompanied by the reduction of acetate secretion partially compensate for the unbalanced (NADH/NAD+) ratio. Besides, the tricarboxylic acid cycle (TCA) mainly supplies the produced NADH, as indicated by the higher mRNA and protein levels of involved enzymes, and further confirmed by 13C flux analyses. As a consequence of the metabolic flux toward acetyl-CoA and the generation of an excess of NADPH, B. megaterium redirected the produced acetyl-CoA toward the polyhydroxybutyrate (PHB) biosynthetic pathway accumulating around 30% of the cell dry weight (CDW) as PHB. This direct relation between osmotic stress and intracellular PHB content has been evidenced for the first time, thus opening new avenues for synthesizing this valuable biopolymer using varying salt concentrations under non-limiting nutrient conditions

Overweight in Adolescence Can Be Predicted at Age 6 Years: A CART Analysis in German Cohorts

Objective: To examine, whether overweight in adolescents can be predicted from the body mass index (BMI) category, at the age of 6, the mother's education level and mother's obesity and to quantify the proportion of overweight at the age of 14 that can be explained by these predictors. Method: Pooled data from three German cohorts providing anthropometric and other relevant data to a total of 1 287 children. We used a classification and regression tree (CART) approach to identify the contribution of BMI category at the age of 6 (obese: BMI>97th percentile (P97);overweight: P90P90) at the age of 14. Results: While 4.8% [95% CI: 3.2;7.0] of 651 boys and 4.1% [95% CI: 2.6;6.2] of 636 girls with a BMI= P75. The lowest prevalence was 1.9% [95% CI: 0.8;3.8] in boys with a BMI P97 (similar results for girls). BMI >= P75 at the age of 6 explained 63.5% [95% CI: 51.1;74.5]) and 72.0% [95% CI: 60.4;81.8] of overweight/obesity at the age of 14 in boys and girls, respectively. Conclusions: Overweight/obesity in adolescence can be predicted by BMI category at the age of 6 allowing for parent counselling or risk guided interventions in children with BMI >= P75, who accounted for >2/3 of overweight/obesity in adolescents