Mitochondrial haplogroups, control region polymorphisms and malignant melanoma: a study in middle European Caucasians

Background

Because mitochondria play an essential role in energy metabolism, generation of reactive oxygen species (ROS), and apoptosis, sequence variation in the mitochondrial genome has been postulated to be a contributing factor to the etiology of multifactorial age-related diseases, including cancer. The aim of the present study was to compare the frequencies of mitochondrial DNA (mtDNA) haplogroups as well as control region (CR) polymorphisms of patients with malignant melanoma (n = 351) versus those of healthy controls (n = 1598) in Middle Europe.

Methodology and Principal Findings

Using primer extension analysis and DNA sequencing, we identified all nine major European mitochondrial haplogroups and known CR polymorphisms. The frequencies of the major mitochondrial haplogroups did not differ significantly between patients and control subjects, whereas the frequencies of the one another linked CR polymorphisms A16183C, T16189C, C16192T, C16270T and T195C were significantly higher in patients with melanoma compared to the controls. Regarding clinical characteristics of the patient cohort, none of the nine major European haplogroups was associated with either Breslow thickness or distant metastasis. The CR polymorphisms A302CC-insertion and T310C-insertion were significantly associated with mean Breslow thickness, whereas the CR polymorphism T16519C was associated with metastasis.

Conclusions and Significance

Our results suggest that mtDNA variations could be involved in melanoma etiology and pathogenesis, although the functional consequence of CR polymorphisms remains to be elucidated.     

Cross-species comparison of Drosophila male accessory gland protein genes

Drosophila melanogaster males transfer seminal fluid proteins along with sperm during mating. Among these proteins, ACPs (Accessory gland proteins) from the male's accessory gland induce behavioral, physiological, and life span reduction in mated females and mediate sperm storage and utilization. A previous evolutionary EST screen in D. simulans identified partial cDNAs for 57 new candidate ACPs. Here we report the annotation and confirmation of the corresponding Acp genes in D. melanogaster. Of 57 new candidate Acp genes previously reported in D. melanogaster, 34 conform to our more stringent criteria for encoding putative male accessory gland extracellular proteins, thus bringing the total number of ACPs identified to 52 (34 plus 18 previously identified). This comprehensive set of Acp genes allows us to dissect the patterns of evolutionary change in a suite of proteins from a single male-specific reproductive tissue. We used sequence-based analysis to examine codon bias, gene duplications, and levels of divergence (via dN/dS values and ortholog detection) of the 52 D. melanogaster ACPs in D. simulans, D. yakuba, and D. pseudoobscura. We show that 58% of the 52 D. melanogaster Acp genes are detectable in D. pseudoobscura. Sequence comparisons of ACPs shared and not shared between D. melanogaster and D. pseudoobscura show that there are separate classes undergoing distinctly dissimilar evolutionary dynamics.     

Enhanced cognitive control in young people with Tourette's syndrome

Tourette's syndrome (TS) is a neurodevelopmental disorder characterized by the presence of chronic vocal and motor tics. Tics are sudden, highly stereotyped, movements that can be simple or complex in appearance. Since patients with TS have difficulties preventing unwanted movements, one might expect that their ability to voluntarily control goal-directed movements would be similarly poor. Indeed, it has been suggested that TS sufferers are impaired at inhibiting reflexively triggered movements and in rapidly selecting or switching between different motor sets. This idea is consistent with current views on the neurological basis of TS that posit a dysfunction of the neural circuits linking the frontal lobes and the striatum. These circuits are known to be involved in the voluntary control of action. By using an oculomotor switching task, we show for the first time that young people with TS exhibit paradoxically greater levels of cognitive control over their movements than their age-matched controls. This finding is consistent with an increased need to monitor and control movements and may indicate a subcortical locus for the triggering of tics. It also suggests that the constant need to suppress tics could have resulted in an enhancement of the executive processes involved in inhibitory control.     

Evaluation of c-erbB-2 overexpression and Her-2/neu gene copy number heterogeneity in Barrett's adenocarcinoma.

Amplification of the Her-2/neu gene is accompanied by overexpression of its cell surface receptor product, c-erbB-2 protein. To investigate the degree of intratumoural heterogeneity we applied immunohistochemistry in primary Barrett's adenocarcinoma (BCA) (n = 6) and dysplasia adjacent to the carcinoma (n = 4). In addition, fluorescence in situ hybridisation (FISH) was performed in primary BCA (n = 5) and dysplastic areas (n = 4). For an objective evaluation digital image analysis and laser scanning microscopy were used. Five of six BCA showed a marked intratumoral heterogeneous staining pattern ranging from areas in which the tumour cells were negative or faintly positive to tumour areas with a strong staining of the entire membrane. Among the two dysplastic areas also a heterogeneous staining pattern was observed. FISH analysis revealed marked heterogeneity of intratumoral gene copy number changes in all BCA showing populations with different fractions of cells with polysomy, low level amplification and high level amplification. One dysplasia showed a minor population with Her-2/neu signal clusters. In conclusion, we observed marked intratumoural heterogeneity of c-erbB-2 protein overexpression and Her-2/neu gene copy number in the majority of the primary BCA analyzed. Digital image analysis and laser scanning microscopy were helpful in quantifying the variations in protein expression and DNA copy number in individual tumour cells. The observed heterogeneity could hamper the exact diagnostic determination of the c-erbB-2 status in small biopsies and possibly influence the effectiveness of a potential c-erbB-2 targeting therapy. Figures on http://www.esacp.org/acp/2000/20-1/walch.htm+ ++.     

Phosphorylation of histone H1 through the cell cycle of Physarum polycephalum. 24 sites of phosphorylation at metaphase

H1 phosphorylation has been studied through the precise nuclear division cycle of Physarum polycephalum. The number of sites of phosphorylation of Physarum H1 is very much larger than the number of sites reported for mammalian H1 molecules which is consistent with the larger molecular weight of Physarum H1. At metaphase all of the Physarum H1 molecules contain 20-24 phosphates. Immediately following metaphase, these metaphase-phosphorylated H1 molecules undergo rapid dephosphorylation to give an intermediate S phase set of phosphorylated H1 molecules containing 9-16 phosphates. Progressing into S phase newly synthesized H1 is phosphorylated and eventually merges with the old dephosphorylated H1 to give a ladder of bands 1-20. By the end of S phase or early G2 phase, there is a ladder of bands 1-16 all of which undergo phosphate turnover. Further into G2 phase the bands move to higher states of phosphorylation, and by prophase all of the H1 molecules contain 15-24 phosphates which increases to 20-24 phosphates at metaphase. These results support the proposals that H1 phosphorylation is an important factor in the process of chromosome condensation through G2 phase, prophase to metaphase.     

First experimental evidence of corals feeding on seagrass matter

We present the first experimental evidence of a coral (Oulastrea crispata) ingesting and assimilating seagrass material. Tropical seagrass meadows export a substantial portion of their productivity and can provide an important source of nutrients to neighbouring systems such as coral reefs; however, little is known about the mechanisms of this link. To investigate whether seagrass nutrient uptake via coral heterotrophy is possible, we conducted a feeding experiment with seagrass particulate and dissolved organic matter. Using gut extractions and stable isotope analyses, we determined that O. crispata ingested ¹⁵N-enriched seagrass particles and assimilated the nitrogen into its tissue at a rate of 0.75 μg N cm^?2 h^?1. Corals took up nitrogen from dissolved matter at a comparable rate of 0.98 μg N cm^?2 h^?1. While other ecological connections between seagrass meadows and reef ecosystems are well known, our results suggest a previously unstudied direct nutritional link between seagrasses and corals.     

Respiratory muscle reserve in rats during heavy exercise

Gosselin, Luc E., David Megirian, Joshua Rodman, DonnaMueller, and Gaspar A. Farkas. Respiratory muscle reserve in ratsduring heavy exercise. J. Appl.Physiol. 83(4): 1405-1409, 1997.The extent towhich the respiratory pump muscles limit maximal aerobic capacity inquadrupeds is not entirely clear. To examine the effect of reducedrespiratory muscle reserve on aerobic capacity, whole bodypeak oxygen consumption(O_{2 peak}) wasmeasured in healthy Sprague-Dawley rats before and after Sham,unilateral, or bilateral hemidiaphragm denervation (Dnv) surgery.O_{2 peak} wasdetermined by using a graded treadmill running test.Hemidiaphragm paralysis was verified after testing byrecording the absence of electromyographic activity duringinspiration. Before surgery, O_{2 peak} averaged 86, 87, and 92 ml · kg¹ · min¹for the Sham, unilateral, and bilateral Dnv groups, respectively. Twoweeks after surgery, there was no significant change inO_{2 peak} foreither the Sham or unilateral Dnv group. However,O_{2 peak} decreased~19% in the bilateral Dnv group 2 wk after surgery. These findingsstrongly suggest that the pulmonary system in rats is designed suchthat during heavy exercise, the remaining respiratory pump muscles areable to compensate for the loss of one hemidiaphragm, but not of both.