Software quality assurance plan for GCS

The software quality assurance (SQA) function for the Guidance and Control Software (GCS) project which is part of a software error studies research program is described. The SQA plan outlines all of the procedures, controls, and audits to be carried out by the SQA organization to ensure adherence to the policies, procedures, and standards for the GCS project

Pedometer-determined physical activity and active transport in girls

<p>Abstract</p> <p>Background</p> <p>It is well established that the risk of insufficient physical activity is greater in girls than in boys, especially during the adolescent years. The promotion of active transport (AT) to and from school has been posited as a practical and convenient solution for increasing girls' total daily activity. However, there is limited information describing the associations between AT choices and girls' physical activity across a range of age, ethnic, and socioeconomic groups. The objectives of this study were to (1) investigate physical activity patterns in a large multiethnic sample of female children and adolescents, and to (2) estimate the physical activity associated with AT to and from school.</p> <p>Methods</p> <p>A total of 1,513 girls aged 5–16 years wore sealed multiday memory (MDM) pedometers for three weekdays and two weekend days. The ethnic composition of this sample was 637 European (42.1%), 272 Pacific Island (18.0%), 207 East Asian (13.7%), 179 Maori (11.8%), 142 South Asian (9.4%), and 76 from other ethnic groups (5%). Pedometer compliance and school-related AT were assessed by questionnaire.</p> <p>Results</p> <p>Mean weekday step counts (12,597 ± 3,630) were higher and less variable than mean weekend steps (9,528 ± 4,407). A consistent decline in daily step counts was observed with age: after adjustment for ethnicity and SES, girls in school years 9–10 achieved 2,469 (weekday) and 4,011 (weekend) fewer steps than girls in years 1–2. Daily step counts also varied by ethnicity, with Maori girls the most active and South Asian girls the least active. Overall, 44.9% of participants used AT for school-related travel. Girls who used AT to and from school averaged 1,052 more weekday steps than those who did not use AT. However, the increases in steps associated with AT were significant only in older girls (school years 5–10) and in those of Maori or European descent.</p> <p>Conclusion</p> <p>Our data suggest that adolescent-aged girls and girls of Asian descent are priority groups for future physical activity interventions. While the apparent benefits of school-related AT vary among demographic groups, promoting AT in girls appears to be a worthwhile strategy.</p

Set1 Targets Genes with Essential Identity and Tumor-Suppressing Functions in Planarian Stem Cells

Tumor suppressor genes (TSGs) are essential for normal cellular function in multicellular organisms, but many TSGs and tumor-suppressing mechanisms remain unknown. Planarian flatworms exhibit particularly robust tumor suppression, yet the specific mechanisms underlying this trait remain unclear. Here, we analyze histone H3 lysine 4 trimethylation (H3K4me3) signal across the planarian genome to determine if the broad H3K4me3 chromatin signature that marks essential cell identity genes and TSGs in mammalian cells is conserved in this valuable model of in vivo stem cell function. We find that this signature is indeed conserved on the planarian genome and that the lysine methyltransferase Set1 is largely responsible for creating it at both cell identity and putative TSG loci. In addition, we show that depletion of set1 in planarians induces stem cell phenotypes that suggest loss of TSG function, including hyperproliferation and an abnormal DNA damage response (DDR). Importantly, this work establishes that Set1 targets specific gene loci in planarian stem cells and marks them with a conserved chromatin signature. Moreover, our data strongly suggest that Set1 activity at these genes has important functional consequences both during normal homeostasis and in response to genotoxic stress

Evolutionary origin and genomic organisation of runt-domain containing genes in arthropods

<p>Abstract</p> <p>Background</p> <p>Gene clusters, such as the <it>Hox </it>gene cluster, are known to have critical roles in development. In eukaryotes gene clusters arise primarily by tandem gene duplication and divergence. Genes within a cluster are often co-regulated, providing selective pressure to maintain the genome organisation, and this co-regulation can result in temporal or spatial co-linearity of gene expression. It has been previously noted that in <it>Drosophila melanogaster</it>, three of the four runt-domain (RD) containing genes are found in a relatively tight cluster on chromosome 1, raising the possibility of a putative functional RD gene cluster in <it>D. melanogaster</it>.</p> <p>Results</p> <p>To investigate the possibility of such a gene cluster, orthologues of the <it>Drosophila melanogaste</it>r RD genes were identified in several endopterygotan insects, two exopterygotan insects and two non-insect arthropods. In all insect species four RD genes were identified and orthology was assigned to the <it>Drosophila </it>sequences by phylogenetic analyses. Although four RD genes were found in the crustacean <it>D. pulex</it>, orthology could not be assigned to the insect sequences, indicating independent gene duplications from a single ancestor following the split of the hexapod lineage from the crustacean lineage.</p> <p>In insects, two chromosomal arrangements of these genes was observed; the first a semi-dispersed cluster, such as in <it>Drosophila</it>, where <it>lozenge </it>is separated from the core cluster of three RD genes often by megabases of DNA. The second arrangement was a tight cluster of the four RD genes, such as in <it>Apis mellifera</it>.</p> <p>This genomic organisation, particularly of the three core RD genes, raises the possibility of shared regulatory elements. <it>In situ </it>hybridisation of embryonic expression of the four RD genes in <it>Drosophila melanogaster </it>and the honeybee <it>A. mellifera </it>shows no evidence for either spatial or temporal co-linearity of expression during embryogenesis.</p> <p>Conclusion</p> <p>All fully sequenced insect genomes contain four RD genes and orthology can be assigned to these genes based on similarity to the <it>D. melanogaster </it>protein sequences. Examination of the genomic organisation of these genes provides evidence for a functional RD gene cluster. RD genes from non-insect arthropods are also clustered, however the lack of orthology between these and insect RD genes suggests this cluster is likely to have resulted from a duplication event independent from that which created the insect RD gene cluster. Analysis of embryonic RD gene expression in two endopterygotan insects, <it>A. mellifera </it>and <it>D. melanogaster</it>, did not show evidence for coordinated gene expression, therefore while the functional significance of this gene cluster remains unknown its maintenance during insect evolution implies some functional significance to the cluster.</p

Core transcriptional regulatory circuitry in human hepatocytes

We mapped the transcriptional regulatory circuitry for six master regulators in human hepatocytes using chromatin immunoprecipitation and high-resolution promoter microarrays. The results show that these regulators form a highly interconnected core circuitry, and reveal the local regulatory network motifs created by regulator–gene interactions. Autoregulation was a prominent theme among these regulators. We found that hepatocyte master regulators tend to bind promoter regions combinatorially and that the number of transcription factors bound to a promoter corresponds with observed gene expression. Our studies reveal portions of the core circuitry of human hepatocytes

Core transcriptional regulatory circuitry in human hepatocytes

We mapped the transcriptional regulatory circuitry for six master regulators in human hepatocytes using chromatin immunoprecipitation and high-resolution promoter microarrays. The results show that these regulators form a highly interconnected core circuitry, and reveal the local regulatory network motifs created by regulator–gene interactions. Autoregulation was a prominent theme among these regulators. We found that hepatocyte master regulators tend to bind promoter regions combinatorially and that the number of transcription factors bound to a promoter corresponds with observed gene expression. Our studies reveal portions of the core circuitry of human hepatocytes

A biophysical model of prokaryotic diversity in geothermal hot springs

Recent field investigations of photosynthetic bacteria living in geothermal hot spring environments have revealed surprisingly complex ecosystems, with an unexpected level of genetic diversity. One case of particular interest involves the distribution along hot spring thermal gradients of genetically distinct bacterial strains that differ in their preferred temperatures for reproduction and photosynthesis. In such systems, a single variable, temperature, defines the relevant environmental variation. In spite of this, each region along the thermal gradient exhibits multiple strains of photosynthetic bacteria adapted to several distinct thermal optima, rather than the expected single thermal strain adapted to the local environmental temperature. Here we analyze microbiology data from several ecological studies to show that the thermal distribution field data exhibit several universal features independent of location and specific bacterial strain. These include the distribution of optimal temperatures of different thermal strains and the functional dependence of the net population density on temperature. Further, we present a simple population dynamics model of these systems that is highly constrained by biophysical data and by physical features of the environment. This model can explain in detail the observed diversity of different strains of the photosynthetic bacteria. It also reproduces the observed thermal population distributions, as well as certain features of population dynamics observed in laboratory studies of the same organisms