Caenorhabditis elegans Operons Contain a Higher Proportion of Genes with Multiple Transcripts and Use 3′ Splice Sites Differentially

RNA splicing generates multiple transcript isoforms from a single gene and enhances the complexity of eukaryotic gene expression. In some eukaryotes, operon exists as an ancient regulatory mechanism of gene expression that requires strict positional and regulatory relationships among its genes. It remains unknown whether operonic genes generate transcript isoforms in a similar manner as non-operonic genes do, the expression of which is less likely limited by their positions and relationships with surrounding genes. We analyzed the number of transcript isoforms of Caenorhabditis elegans operonic genes and found that C. elegans operons contain a much higher proportion of genes with multiple transcript isoforms than non-operonic genes do. For genes that express multiple transcript isoforms, there is no apparent difference between the number of isoforms in operonic and non-operonic genes. C. elegans operonic genes also have a different preference of the 20 most common 3′ splice sites compared to non-operonic genes. Our analyses suggest that C. elegans operons enhance expression complexity by increasing the proportion of genes that express multiple transcript isoforms and maintain splicing efficiency by differential use of common 3′ splice sites

Synthesis and Detection of Oxygen-18 Labeled Phosphate

Phosphorus (P) has only one stable isotope and therefore tracking P dynamics in ecosystems and inferring sources of P loading to water bodies have been difficult. Researchers have recently employed the natural abundance of the ratio of 18O/16O of phosphate to elucidate P dynamics. In addition, phosphate highly enriched in oxygen-18 also has potential to be an effective tool for tracking specific sources of P in the environment, but has so far been used sparingly, possibly due to unavailability of oxygen-18 labeled phosphate (OLP) and uncertainty in synthesis and detection. One objective of this research was to develop a simple procedure to synthesize highly enriched OLP. Synthesized OLP is made up of a collection of species that contain between zero and four oxygen-18 atoms and, as a result, the second objective of this research was to develop a method to detect and quantify each OLP species. OLP was synthesized by reacting either PCl5 or POCl3 with water enriched with 97 atom % oxygen-18 in ambient atmosphere under a fume hood. Unlike previous reports, we observed no loss of oxygen-18 enrichment during synthesis. Electrospray ionization mass spectrometertry (ESI-MS) was used to detect and quantify each species present in OLP. OLP synthesized from POCl3 contained 1.2% P18O16O3, 18.2% P18O216O2, 67.7% P18O316O, and 12.9% P18O4, and OLP synthesized from PCl5 contained 0.7% P16O4, 9.3% P18O316O, and 90.0% P18O4. We found that OLP can be synthesized using a simple procedure in ambient atmosphere without the loss of oxygen-18 enrichment and ESI-MS is an effective tool to detect and quantify OLP that sheds light on the dynamics of synthesis in ways that standard detection methods cannot

Uses of population census data for monitoring geographical imbalance in the health workforce: snapshots from three developing countries

BACKGROUND: Imbalance in the distribution of human resources for health (HRH), eventually leading to inequities in health services delivery and population health outcomes, is an issue of social and political concern in many countries. However, the empirical evidence to support decision-making is often fragmented, and many standard data sources that can potentially produce statistics relevant to the issue remain underused, especially in developing countries. This study investigated the uses of demographic census data for monitoring geographical imbalance in the health workforce for three developing countries, as a basis for formulation of evidence-based health policy options. METHODS: Population-based indicators of geographical variations among HRH were extracted from census microdata samples for Kenya, Mexico and Viet Nam. Health workforce statistics were matched against international standards of occupational classification to control for cross-national comparability. Summary measures of inequality were calculated to monitor the distribution of health workers across spatial units and by occupational group. RESULTS: Strong inequalities were found in the geographical distribution of the health workforce in all three countries, with the highest densities of HRH tending to be found in the capital areas. Cross-national differences were found in the magnitude of distributional inequality according to occupational group, with health professionals most susceptible to inequitable distribution in Kenya and Viet Nam but less so in Mexico compared to their associate professional counterparts. Some discrepancies were suggested between mappings of occupational information from the raw data with the international system, especially for nursing and midwifery specializations. CONCLUSIONS: The problem of geographical imbalance among HRH across countries in the developing world holds important implications at the local, national and international levels, in terms of constraints for the effective deployment, management and retention of HRH, and ultimately for the equitable delivery of health services. A number of advantages were revealed of using census data in health research, notably the potential for producing detailed statistics on health workforce characteristics at the sub-national level. However, lack of consistency in the compilation and processing of occupational information over time and across countries continues to hamper comparative analyses for HRH policy monitoring and evaluation

Effectiveness of temozolomide for primary glioblastoma multiforme in routine clinical practice

Temozolomide has been used as a standard therapy for the treatment of newly diagnosed glioblastoma multiforme since 2005. To assess the effectiveness of temozolomide in routine clinical practice, we conducted an observational study at Maastricht University Medical Centre (MUMC). Data of patients receiving radiotherapy and temozolomide between January 2005 and January 2008 were retrieved from a clinical database (radiochemotherapy group), as were data of patients in a historical control group from the period before 2005 treated with radiotherapy only (radiotherapy group). The primary endpoint was overall survival. A total of 125 patients with GBM were selected to form the study cohort. Median survival benefit was 4 months: the median overall survival was 12 months (95% CI, 9.7–14.3) in the group with radiochemotherapy with temozolomide, versus 8 months (95% CI, 5.3–10.7) in the group with only radiotherapy. Progression-free survival was 7 months (95% CI, 5.5–8.5) in the radiochemotherapy group and 4 months (95% CI, 2.9-5.1) in the group with only radiotherapy. The two-year survival rate was 18% with radiochemotherapy with temozolomide against 4% with radiotherapy alone. Concomitant treatment with radiotherapy and temozolomide followed by adjuvant temozolomide resulted in grade III or IV haematological toxic effects in 9% of patients. The addition of temozolomide to radiotherapy in routine clinical practice for newly diagnosed glioblastoma resulted in a clinically meaningful survival benefit with minimal haematological toxicity, which confirms the experience of previous trials and justifies the continued use of temozolomide in routine clinical practice

The stellar and sub-stellar IMF of simple and composite populations

The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-

The Genomic Distribution and Function of Histone Variant HTZ-1 during C. elegans Embryogenesis

In all eukaryotes, histone variants are incorporated into a subset of nucleosomes to create functionally specialized regions of chromatin. One such variant, H2A.Z, replaces histone H2A and is required for development and viability in all animals tested to date. However, the function of H2A.Z in development remains unclear. Here, we use ChIP-chip, genetic mutation, RNAi, and immunofluorescence microscopy to interrogate the function of H2A.Z (HTZ-1) during embryogenesis in Caenorhabditis elegans, a key model of metazoan development. We find that HTZ-1 is expressed in every cell of the developing embryo and is essential for normal development. The sites of HTZ-1 incorporation during embryogenesis reveal a genome wrought by developmental processes. HTZ-1 is incorporated upstream of 23% of C. elegans genes. While these genes tend to be required for development and occupied by RNA polymerase II, HTZ-1 incorporation does not specify a stereotypic transcription program. The data also provide evidence for unexpectedly widespread independent regulation of genes within operons during development; in 37% of operons, HTZ-1 is incorporated upstream of internally encoded genes. Fewer sites of HTZ-1 incorporation occur on the X chromosome relative to autosomes, which our data suggest is due to a paucity of developmentally important genes on X, rather than a direct function for HTZ-1 in dosage compensation. Our experiments indicate that HTZ-1 functions in establishing or maintaining an essential chromatin state at promoters regulated dynamically during C. elegans embryogenesis

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Decreased startle modulation during anticipation in the postpartum period in comparison to late pregnancy

Knowledge about healthy women’s psychophysiological adaptations during the large neuroendocrine changes of pregnancy and childbirth is essential in order to understand why these events have the potential to disrupt mental health in vulnerable individuals. This study aimed to compare startle response modulation, an objective psychophysiological measure demonstrated to be influenced by anxiety and depression, longitudinally across late pregnancy and the postpartum period. The acoustic startle response modulation was assessed during anticipation of affective images and during image viewing in 31 healthy women during gestational weeks 36–39 and again at 4 to 6 weeks postpartum. No startle modulation by affective images was observed at either time point. Significant modulation during anticipation stimuli was found at pregnancy assessment but was reduced in the postpartum period. The women rated the unpleasant images more negative and more arousing and the pleasant images more positive at the postpartum assessment. Self-reported anxiety and depressive symptoms did not change between assessments. The observed postpartum decrease in modulation of startle by anticipation suggests a relatively deactivated defense system in the postpartum period

Pre-surgical depression and anxiety and recovery following coronary artery bypass graft surgery

We aimed to explore the combined contribution of pre-surgical depression and anxiety symptoms for recovery following coronary artery bypass graft (CABG) using data from 251 participants. Participants were assessed prior to surgery for depression and anxiety symptoms and followed up at 12 months to assess pain and physical symptoms, while hospital emergency admissions and death/major adverse cardiac events (MACE) were monitored on average 2.68 years after CABG. After controlling for covariates, baseline anxiety symptoms, but not depression, were associated with greater pain (β = 0.231, p = 0.014) and greater physical symptoms (β = 0.194, p = 0.034) 12 months after surgery. On the other hand, after controlling for covariates, baseline depression symptoms, but not anxiety, were associated with greater odds of having an emergency admission (OR 1.088, CI 1.010–1.171, p = 0.027) and greater hazard of death/MACE (HR 1.137, CI 1.042–1.240, p = 0.004). These findings point to different pathways linking mood symptoms with recovery after CABG surgery

Stimulant Reduction Intervention using Dosed Exercise (STRIDE) - CTN 0037: Study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study.</p> <p>Methods/Design</p> <p>STRIDE is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. This study will evaluate individuals diagnosed with stimulant abuse or dependence who are receiving treatment in a residential setting. Three hundred and thirty eligible and interested participants who provide informed consent will be randomized to one of two treatment arms: Vigorous Intensity High Dose Exercise Augmentation (DEI) or Health Education Intervention Augmentation (HEI). Both groups will receive TAU (i.e., usual care). The treatment arms are structured such that the quantity of visits is similar to allow for equivalent contact between groups. In both arms, participants will begin with supervised sessions 3 times per week during the 12-week acute phase of the study. Supervised sessions will be conducted as one-on-one (i.e., individual) sessions, although other participants may be exercising at the same time. Following the 12-week acute phase, participants will begin a 6-month continuation phase during which time they will attend one weekly supervised DEI or HEI session.</p> <p>Clinical Trials Registry</p> <p>ClinicalTrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01141608">NCT01141608</a></p> <p><url>http://clinicaltrials.gov/ct2/show/NCT01141608?term=Stimulant+Reduction+Intervention+using+Dosed+Exercise&rank=1</url></p