Patterns of trace metal accumulation in Swedish marine nemerteans

Total body burdens of Zn, Pb, Al and Cu were measured in Swedish marine nemerteans sampled from an area close to a major source of pollution. Accumulation patterns varied both seasonally and spatially. The results suggest that nemerteans may be useful bioindicator species in environmental monitoring programmes.     

Comparison of effects of sustained isocapnic hypoxia on ventilation in men and women

Sajkov, Dimitar, Alister Neill, Nicholas A. Saunders, and R. Douglas McEvoy. Comparison of the effects of sustained isocapnichypoxia on ventilation in men and women. J. Appl.Physiol. 83(2): 599-607, 1997.Sleep-relatedrespiratory disturbances are more common in men than in premenopausalwomen. This might, in part, be due to different susceptibilities to therespiratory depressant effects of hypoxia. Therefore, we comparedventilation during 10 min of baseline room-air breathing and 20-minsustained isocapnic hypoxia (fractional inspiredO₂ = 11%, arterial saturation ofO₂  80%) followed by 10 min ofbreathing 100% O₂ in 10 normal men and in 10 women in the follicular phase of the menstrual cycle. Control measurements were made during two transitions from room air (10 min) to 100% O₂ (10 min) andaveraged. Inspired minute ventilation(I) after2 min of hypoxia was the same in men and women [131 ± 6.1%baseline for men, 136 ± 7.7% baseline for women; not significant(NS)] and declined to the same level after 20 min (115 ± 5.0% baseline for men, 116 ± 6.6% baseline for women; NS)associated with a similar decline in inspiratory time and tidal volume.Breathing frequency did not change.I decreased transiently during subsequent 100%O₂ breathing in both men and women, associated with reduced frequency and duty cycle and increased expiratory time. The fall inI wassignificantly greater than that observed during control hyperoxiaexperiments in men but not in women. We conclude that ventilatoryresponses to sustained isocapnic hypoxia do not differ between awakehealthy men and women in the follicular phase of their menstrual cycle.However, after termination of isocapnic hypoxia, men appear to depress their ventilation to a greater degree than women.

     

Fetal rat pancreas in organ culture: effects of serum on the development of the endocrine cells

Eighteen-day-old rat fetal pancreas was grown in organ culture for four days on medium consisting of tissue culture Medium 199 and varying concentrations of chicken serum. The glucagon and somatostatin concentration of the explants was decreased when the serum concentration of the medium was reduced from 50 to 10%. There was a further reduction in these hormones when the explants were cultured on Medium 199 alone. Explant insulin content was reduced only when serum was omitted from the medium. A "serum factor" tripeptide was not able to substitute for this serum requirement. Heat-inactivation of the serum resulted in a significant increase in medium insulin content and an increase in both the insulin and glucagon contents of the explants. This increase in hormone content was directly correlated with increases in the beta and alpha cell volumes of the explants. There was no change in the somatostatin content or delta cell volume of the explants grown on heat-inactivated medium. It is suggested that the serum is an important component of the culture media and is apparently required in high concentration for the development of the islet cells in vitro. The islet cell types differ in their requirement for serum. The alpha and delta a higher concentration than do the beta cells.     

Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics

There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease.     

Improved Detection of Common Variants Associated with Schizophrenia by Leveraging Pleiotropy with Cardiovascular-Disease Risk Factors

Several lines of evidence suggest that genome-wide association studies (GWASs) have the potential to explain more of the “missing heritability” of common complex phenotypes. However, reliable methods for identifying a larger proportion of SNPs are currently lacking. Here, we present a genetic-pleiotropy-informed method for improving gene discovery with the use of GWAS summary-statistics data. We applied this methodology to identify additional loci associated with schizophrenia (SCZ), a highly heritable disorder with significant missing heritability. Epidemiological and clinical studies suggest comorbidity between SCZ and cardiovascular-disease (CVD) risk factors, including systolic blood pressure, triglycerides, low- and high-density lipoprotein, body mass index, waist-to-hip ratio, and type 2 diabetes. Using stratified quantile-quantile plots, we show enrichment of SNPs associated with SCZ as a function of the association with several CVD risk factors and a corresponding reduction in false discovery rate (FDR). We validate this “pleiotropic enrichment” by demonstrating increased replication rate across independent SCZ substudies. Applying the stratified FDR method, we identified 25 loci associated with SCZ at a conditional FDR level of 0.01. Of these, ten loci are associated with both SCZ and CVD risk factors, mainly triglycerides and low- and high-density lipoproteins but also waist-to-hip ratio, systolic blood pressure, and body mass index. Together, these findings suggest the feasibility of using genetic-pleiotropy-informed methods for improving gene discovery in SCZ and identifying potential mechanistic relationships with various CVD risk factors.