Big flies, small repeats: the "Thr-Gly" region of the period gene in Diptera

The region of the clock gene period (per) that encodes a repetitive tract of threonine-glycine (Thr-Gly) pairs has been compared between Dipteran species both within and outside the Drosophilidae. All the non- Drosophilidae sequences in this region are short and present a remarkably stable picture compared to the Drosophilidae, in which the region is much larger and extremely variable, both in size and composition. The accelerated evolution in the repetitive region of the Drosophilidae appears to be mainly due to an expansion of two ancestral repeats, one encoding a Thr-Gly dipeptide and the other a pentapeptide rich in serine, glycine, and asparagine or threonine. In some drosophilids the expansion involves a duplication of the pentapeptide sequence, but in Drosophila pseudoobscura both the dipeptide and the pentapeptide repeats are present in larger numbers. In the nondrosophilids, however, the pentapeptide sequence is represented by one copy and the dipeptide by two copies. These observations fulfill some of the predictions of recent theoretical models that have simulated the evolution of repetitive sequences.      

Thermal variation near the thermal optimum does not affect the growth,metabolism or swimming performance in wild Atlantic salmon Salmo salar

Typically, laboratory studies on the physiological effects of temperature are conducted using stable acclimation temperatures. Nonetheless, information extrapolated from these studies may not accurately represent wild populations living in thermally variable environments. The aim of this study was to compare the growth rate, metabolism and swimming performance of wild Atlantic salmon exposed to cycling temperatures, 16–21°C, and stable acclimation temperatures, 16, 18.5, 21°C. Growth rate, metabolic rate, swimming performance and anaerobic metabolites did not change among acclimation groups, suggesting that within Atlantic salmon's thermal optimum range, temperature variation has no effect on these physiological properties.     

Precise genetic mapping and haplotype analysis of the familial dysautonomia gene on human chromosome 9q31

Familial dysautonomia (FD) is an autosomal recessive disorder characterized by developmental arrest in the sensory and autonomic nervous systems and by Ashkenazi Jewish ancestry. We previously had mapped the defective gene (DYS) to an 11-cM segment of chromosome 9q31-33, flanked by D9S53 and D9S105. By using 11 new polymorphic loci, we now have narrowed the location of DYS to <0.5 cM between the markers 43B1GAGT and 157A3. Two markers in this interval, 164D1 and D9S1677, show no recombination with the disease. Haplotype analysis confirmed this candidate region and revealed a major haplotype shared by 435 of 441 FD chromosomes, indicating a striking founder effect. Three other haplotypes, found on the remaining 6 FD chromosomes, might represent independent mutations. The frequency of the major FD haplotype in the Ashkenazim (5 in 324 control chromosomes) was consistent with the estimated DYS carrier frequency of 1 in 32, and none of the four haplotypes associated with FD was observed on 492 non-FD chromosomes from obligatory carriers. It is now possible to provide accurate genetic testing both for families with FD and for carriers, on the basis of close flanking markers and the capacity to identify >98% of FD chromosomes by their haplotype.     

Dissection of a metastatic gene expression signature into distinct components

Background

Metastasis, the process whereby cancer cells spread, is in part caused by an incompletely understood interplay between cancer cells and the surrounding stroma. Gene expression studies typically analyze samples containing tumor cells and stroma. Samples with less than 50% tumor cells are generally excluded, thereby reducing the number of patients that can benefit from clinically relevant signatures.

Results

For a head-neck squamous cell carcinoma (HNSCC) primary tumor expression signature that predicts the presence of lymph node metastasis, we first show that reduced proportions of tumor cells results in decreased predictive accuracy. To determine the influence of stroma on the predictive signature and to investigate the interaction between tumor cells and the surrounding microenvironment, we used laser capture microdissection to divide the metastatic signature into six distinct components based on tumor versus stroma expression and on association with the metastatic phenotype. A strikingly skewed distribution of metastasis associated genes is revealed.

Conclusion

Dissection of predictive signatures into different components has implications for design of expression signatures and for our understanding of the metastatic process. Compared to primary tumors that have not formed metastases, primary HNSCC tumors that have metastasized are characterized by predominant down-regulation of tumor cell specific genes and exclusive up-regulation of stromal cell specific genes. The skewed distribution agrees with poor signature performance on samples that contain less than 50% tumor cells. Methods for reducing tumor composition bias that lead to greater predictive accuracy and an increase in the types of samples that can be included are presented.     

Teesside coronary survey: an epidemiological study of acute attacks of myocardial infarction.

A 12-month epidemiological survey of attacks of acute myocardial infarction was carried out in a large urban population. The incidence and mortality at all ages and in both sexes were examined. Altogether, 1938 attacks were diagnosed--an overall incidence of 4-89 per 1000 population. The 28-day fatality rate was 50-5%. A third of the patients were treated at home and these patients had a lower fatality rate than those in hospital, a difference that could not be attributed to age, sex, or severity of attack. Half of the deaths that were witnessed occurred suddenly and a further 21% occurred within the next two hours. The median time to patients coming under care was about three hours. As used at present, coronary care units are unlikely to improve fatality rates. Future advances in treatment must take place outside hospital and will require re-education of the public and the general practitioner.     

Acclimation to hypercarbia protects cardiac contractility and alters tissue carbohydrate metabolism in the Amazonian armored catfish <Emphasis Type="Italic">Pterygoplichthys pardalis</Emphasis>

The armored catfish Pterygoplichthys pardalis tolerates environmental hypercarbia, high partial pressures of CO₂ (\(P_{{{\text{CO}}_{ 2} }}\)), by preferentially protecting intracellular pH (pHi) in the face of extracellular acidosis. This response is associated with ionic changes which may disrupt contractility in cardiac muscle, and it is not known whether acclimation to hypercarbia provides protection against these changes. We studied the influence of different \(P_{{{\text{CO}}_{ 2} }}\) acclimation histories on cardiac muscle function using isometrically contracting ventricular strip preparations. Fish were held for >4 months at 21 mmHg \(P_{{{\text{CO}}_{ 2} }}\) and then exposed to normocarbia (6 mmHg \(P_{{{\text{CO}}_{ 2} }}\)) for either 15 h or 5–6 days. Acclimation to chronic hypercarbia eliminated the negative inotropic effects of in vitro hypercarbia, decreased extracellular Ca²⁺ sensitivity, and reduced maximum pacing frequency in ventricular strip preparations. Fish acclimated to chronic hypercarbia also exhibited hepatic glycogen and plasma glucose accumulation, and lower plasma lactate levels compared to fish acclimated to normocarbia for 5–6 days. We suggest chronic hypercarbia may induce cardiac remodeling to protect contractility and reduce the energetic demands of pHi regulation. The activation of HCO₃ ^? synthesis pathways may decrease glucose utilization and enhance carbohydrate stores, potentially providing protection against hypoxia, a stressor frequently encountered in conjunction with hypercarbia in the Amazon.