Roles of the Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase, Plasma Membrane Ca2+-ATPase and Na+/Ca2+ Exchanger in Regulation of Heart Rate in Larval Drosophila

We investigated the roles of three regulatory proteins that impact [Ca2+]i within cardiac myocytes of Drosophila melanogaster. The NCX (Na+/Ca2+ exchanger), PMCA (plasma membrane Ca2+-ATPase) and SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) were compromised by ionic, pharmacological, mutationalmanipulation, and with a combination of approaches, while heart rate (HR) was monitored. A decrease in SERCA function reduced HR more for intact larva in comparison to a dissected larva. Dissected preparations were used to expose the heart directly to agents. A compromised PMCA also reduced HR; however, attenuated NCX function by low [Na+]○ increased HR. KBR7943, a blocker of Ca2+ entry via NCX, exposure increased HR. A combined loss of function in all three channels did not show a significant change in HR. The results indicate that NCX and PMCA are important in regulating HR, whereas SERCA does not have as pronounced role for dissected preparations. However, with intact preparations the loss of SERCA function by a mutation does have a significant impact on HR. Pharmacological approaches to alter PMCA and SERCA paralleled the results obtained by ionic and mutational approaches. To further understand the pacemaker activity, intracellular recordings were obtained. Mapping of action-potentials in myocytes revealed that the caudal region of the heart has large amplitude potentials and is likely to contain the pacemaker cells. The Drosophila heart can serve as a genetic model in understanding regulation of ionic currents for pacing cells of various types

Genome Rearrangements Detected by SNP Microarrays in Individuals with Intellectual Disability Referred with Possible Williams Syndrome

Intellectual disability (ID) affects 2-3% of the population and may occur with or without multiple congenital anomalies (MCA) or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for approximately 50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challenge. With the advent of microarray techniques, submicroscopic genome alterations not associated with known syndromes are emerging as a significant cause of ID and MCA.High-density SNP microarrays were used to determine genome wide copy number in 42 individuals: 7 with confirmed alterations in the WS region but atypical clinical phenotypes, 31 with ID and/or MCA, and 4 controls. One individual from the first group had the most telomeric gene in the WS critical region deleted along with 2 Mb of flanking sequence. A second person had the classic WS deletion and a rearrangement on chromosome 5p within the Cri du Chat syndrome (OMIM:123450) region. Six individuals from the ID/MCA group had large rearrangements (3 deletions, 3 duplications), one of whom had a large inversion associated with a deletion that was not detected by the SNP arrays.Combining SNP microarray analyses and qPCR allowed us to clone and sequence 21 deletion breakpoints in individuals with atypical deletions in the WS region and/or ID or MCA. Comparison of these breakpoints to databases of genomic variation revealed that 52% occurred in regions harboring structural variants in the general population. For two probands the genomic alterations were flanked by segmental duplications, which frequently mediate recurrent genome rearrangements; these may represent new genomic disorders. While SNP arrays and related technologies can identify potentially pathogenic deletions and duplications, obtaining sequence information from the breakpoints frequently provides additional information

In silico approaches to study mass and energy flows in microbial consortia: a syntrophic case study

<p>Abstract</p> <p>Background</p> <p>Three methods were developed for the application of stoichiometry-based network analysis approaches including elementary mode analysis to the study of mass and energy flows in microbial communities. Each has distinct advantages and disadvantages suitable for analyzing systems with different degrees of complexity and <it>a priori </it>knowledge. These approaches were tested and compared using data from the thermophilic, phototrophic mat communities from Octopus and Mushroom Springs in Yellowstone National Park (USA). The models were based on three distinct microbial guilds: oxygenic phototrophs, filamentous anoxygenic phototrophs, and sulfate-reducing bacteria. Two phases, day and night, were modeled to account for differences in the sources of mass and energy and the routes available for their exchange.</p> <p>Results</p> <p>The <it>in silico </it>models were used to explore fundamental questions in ecology including the prediction of and explanation for measured relative abundances of primary producers in the mat, theoretical tradeoffs between overall productivity and the generation of toxic by-products, and the relative robustness of various guild interactions.</p> <p>Conclusion</p> <p>The three modeling approaches represent a flexible toolbox for creating cellular metabolic networks to study microbial communities on scales ranging from cells to ecosystems. A comparison of the three methods highlights considerations for selecting the one most appropriate for a given microbial system. For instance, communities represented only by metagenomic data can be modeled using the pooled method which analyzes a community's total metabolic potential without attempting to partition enzymes to different organisms. Systems with extensive <it>a priori </it>information on microbial guilds can be represented using the compartmentalized technique, employing distinct control volumes to separate guild-appropriate enzymes and metabolites. If the complexity of a compartmentalized network creates an unacceptable computational burden, the nested analysis approach permits greater scalability at the cost of more user intervention through multiple rounds of pathway analysis.</p

Radioactive 26Al and massive stars in the Galaxy

Gamma-rays from radioactive 26Al (half life ~7.2 10^5 yr) provide a 'snapshot' view of ongoing nucleosynthesis in the Galaxy. The Galaxy is relatively transparent to such gamma-rays, and emission has been found concentrated along the plane of the Galaxy. This led to the conclusion1 that massive stars throughout the Galaxy dominate the production of 26Al. On the other hand, meteoritic data show locally-produced 26Al, perhaps from spallation reactions in the protosolar disk. Furthermore, prominent gamma-ray emission from the Cygnus region suggests that a substantial fraction of Galactic 26Al could originate in localized star-forming regions. Here we report high spectral resolution measurements of 26Al emission at 1808.65 keV, which demonstrate that the 26Al source regions corotate with the Galaxy, supporting its Galaxy-wide origin. We determine a present-day equilibrium mass of 2.8 (+/-0.8) M_sol of 26Al. We use this to estimate that the frequency of core collapse (i.e. type Ib/c and type II) supernovae to be 1.9(+/- 1.1) events per century.Comment: accepted for publication in Nature, 24 pages including Online Supplements, 11 figures, 1 tabl

The Effect of Male Incarceration on Rape Myth Acceptance: Application of Propensity Score Matching Technique

The aim is to assess the effect of imprisonment on rape myth acceptance. The research used a sample of male prisoners incarcerated for non-sexual crimes (n = 98) and a sample of males drawn from the general population (n = 160). Simple linear regression did not indicate a significant effect of incarceration on rape myth acceptance. After controlling for background covariates using propensity score matching, analysis revealed a positive significant effect of incarceration on rape myth acceptance. Although further research is required, results indicate that being subject to incarceration has a significant positive effect on stereotypical thinking about rape