Diversification of the Caenorhabditis heat shock response by Helitron transposable elements.

Heat Shock Factor 1 (HSF-1) is a key regulator of the heat shock response (HSR). Upon heat shock, HSF-1 binds well-conserved motifs, called Heat Shock Elements (HSEs), and drives expression of genes important for cellular protection during this stress. Remarkably, we found that substantial numbers of HSEs in multiple Caenorhabditis species reside within Helitrons, a type of DNA transposon. Consistent with Helitron-embedded HSEs being functional, upon heat shock they display increased HSF-1 and RNA polymerase II occupancy and up-regulation of nearby genes in C. elegans. Interestingly, we found that different genes appear to be incorporated into the HSR by species-specific Helitron insertions in C. elegans and C. briggsae and by strain-specific insertions among different wild isolates of C. elegans. Our studies uncover previously unidentified targets of HSF-1 and show that Helitron insertions are responsible for rewiring and diversifying the Caenorhabditis HSR

Specialized foster care and group home care: Similarities and differences in the characteristics of children in care

Until recently, foster children who presented special medical or behavioral problems were largely served in group care environments. Specialized (or "treatment") foster care has recently been developed to serve some of these challenging children. Although growing evidence points to the special needs of children in foster care, much is still unknown about how children placed in various out-of-home care settings differ from one another. The growth of specialized foster care as an alternative placement to group care, calls for examination of how children in these settings compare on demographic, educational, health, and behavioral characteristics. A cross-sectional mailed survey was distributed to all group care and specialized foster care agencies in a large state to address topics related to children's characteristics. Comparisons point to two groups of very difficult children, with unique mental health and health needs. © 1993

Binding Site Turnover Produces Pervasive Quantitative Changes in Transcription Factor Binding between Closely Related Drosophila Species

Genome-wide comparison of transcription factor binding between related Drosophila species highlights how sequence changes affect the biochemical events that underlie animal development

Transcription Factors Bind Thousands of Active and Inactive Regions in the Drosophila Blastoderm

Identifying the genomic regions bound by sequence-specific regulatory factors is central both to deciphering the complex DNA cis-regulatory code that controls transcription in metazoans and to determining the range of genes that shape animal morphogenesis. We used whole-genome tiling arrays to map sequences bound in Drosophila melanogaster embryos by the six maternal and gap transcription factors that initiate anterior–posterior patterning. We find that these sequence-specific DNA binding proteins bind with quantitatively different specificities to highly overlapping sets of several thousand genomic regions in blastoderm embryos. Specific high- and moderate-affinity in vitro recognition sequences for each factor are enriched in bound regions. This enrichment, however, is not sufficient to explain the pattern of binding in vivo and varies in a context-dependent manner, demonstrating that higher-order rules must govern targeting of transcription factors. The more highly bound regions include all of the over 40 well-characterized enhancers known to respond to these factors as well as several hundred putative new cis-regulatory modules clustered near developmental regulators and other genes with patterned expression at this stage of embryogenesis. The new targets include most of the microRNAs (miRNAs) transcribed in the blastoderm, as well as all major zygotically transcribed dorsal–ventral patterning genes, whose expression we show to be quantitatively modulated by anterior–posterior factors. In addition to these highly bound regions, there are several thousand regions that are reproducibly bound at lower levels. However, these poorly bound regions are, collectively, far more distant from genes transcribed in the blastoderm than highly bound regions; are preferentially found in protein-coding sequences; and are less conserved than highly bound regions. Together these observations suggest that many of these poorly bound regions are not involved in early-embryonic transcriptional regulation, and a significant proportion may be nonfunctional. Surprisingly, for five of the six factors, their recognition sites are not unambiguously more constrained evolutionarily than the immediate flanking DNA, even in more highly bound and presumably functional regions, indicating that comparative DNA sequence analysis is limited in its ability to identify functional transcription factor targets

Comparing population health in the United States and Canada

<p>Abstract</p> <p>Background</p> <p>The objective of the paper is to compare population health in the United States (US) and Canada. Although the two countries are very similar in many ways, there are potentially important differences in the levels of social and economic inequality and the organization and financing of and access to health care in the two countries.</p> <p>Methods</p> <p>Data are from the Joint Canada/United States Survey of Health 2002/03. The Health Utilities Index Mark 3 (HUI3) was used to measure overall health-related quality of life (HRQL). Mean HUI3 scores were compared, adjusting for major determinants of health, including body mass index, smoking, education, gender, race, and income. In addition, estimates of life expectancy were compared. Finally, mean HUI3 scores by age and gender and Canadian and US life tables were used to estimate health-adjusted life expectancy (HALE).</p> <p>Results</p> <p>Life expectancy in Canada is higher than in the US. For those < 40 years, there were no differences in HRQL between the US and Canada. For the 40+ group, HRQL appears to be higher in Canada. The results comparing the white-only population in both countries were very similar. For a 19-year-old, HALE was 52.0 years in Canada and 49.3 in the US.</p> <p>Conclusions</p> <p>The population of Canada appears to be substantially healthier than the US population with respect to life expectancy, HRQL, and HALE. Factors that account for the difference may include access to health care over the full life span (universal health insurance) and lower levels of social and economic inequality, especially among the elderly.</p

Three-tier regulation of cell number plasticity by neurotrophins and Tolls in Drosophila

Cell number plasticity is coupled to circuitry in the nervous system, adjusting cell mass to functional requirements. In mammals, this is achieved by neurotrophin (NT) ligands, which promote cell survival via their Trk and p75 receptors and cell death via p75 and Sortilin. NTs (DNTs) bind Toll receptors instead to promote neuronal survival, but whether they can also regulate cell death is unknown. In this study, we show that DNTs and Tolls can switch from promoting cell survival to death in the central nervous system (CNS) via a three-tier mechanism. First, DNT cleavage patterns result in alternative signaling outcomes. Second, different Tolls can preferentially promote cell survival or death. Third, distinct adaptors downstream of Tolls can drive either apoptosis or cell survival. Toll-6 promotes cell survival via MyD88-NF-κB and cell death via Wek-Sarm-JNK. The distribution of adaptors changes in space and time and may segregate to distinct neural circuits. This novel mechanism for CNS cell plasticity may operate in wider contexts

Knowledge of the childhood immunization schedule and of contraindications to vaccinate by private and public providers in Los Angeles

BACKGROUND METHODS RESULTS CONCLUSION