Genome sequence, population history, and pelage genetics of the endangered African wild dog (Lycaon pictus)

BACKGROUND: The African wild dog (Lycaon pictus) is an endangered sub-Saharan canid threatened by severe habitat fragmentation, human-wildlife conflict, and infectious disease. A highly specialized carnivore, it is distinguished by its social structure, dental morphology, absence of dewclaws, and colorful pelage. RESULTS: We sequenced the genomes of two individuals from populations representing two distinct ecological histories (Laikipia County, Kenya and KwaZulu-Natal Province, South Africa). We reconstructed population demographic histories for the two individuals and scanned the genomes for evidence of selection. CONCLUSIONS: We show that the African wild dog has undergone at least two effective population size reductions in the last one million years. We found evidence of Lycaon individual-specific regions of low diversity, suggestive of inbreeding or population-specific selection. Further research is needed to clarify whether these population reductions and low diversity regions are characteristic of the species as a whole. We documented positive selection on the Lycaon mitochondrial genome. Finally, we identified several candidate genes (ASIP, MITF, MLPH, PMEL) that may play a role in the characteristic Lycaon pelage

Interchain interaction and fractionally charged solitons in a commensurate charge-density-wave system

AbstractA novel MEMS based drug delivery device has been developed, consisting of an array of metallic contacts. The meander structured device created a uniform electric field which stimulates drug releases. An electro-active hydrogel based polymer matrix responds to an electrical stimulus and shrinks or de-swells on application of an electric field from the fabricated device. Different drug candidates can be encapsulated within the polymer matrix. The de-swelling of the polymer enables the encapsulated drug to be released from the matrix. The gel is able to recover its original size once electric stimulation has been stopped. By controlling the voltage and time, the drug release rate and dose can be precisely controlled. Controlled drug delivery devices may be integrated with sensor technology in combined diagnostic / therapeutic point of care devices

Testing the paradox of enrichment along a land use gradient in a multitrophic aboveground and belowground community

In the light of ongoing land use changes, it is important to understand how multitrophic communities perform at different land use intensities. The paradox of enrichment predicts that fertilization leads to destabilization and extinction of predator-prey systems. We tested this prediction for a land use intensity gradient from natural to highly fertilized agricultural ecosystems. We included multiple aboveground and belowground trophic levels and land use-dependent searching efficiencies of insects. To overcome logistic constraints of field experiments, we used a successfully validated simulation model to investigate plant responses to removal of herbivores and their enemies. Consistent with our predictions, instability measured by herbivore-induced plant mortality increased with increasing land use intensity. Simultaneously, the balance between herbivores and natural enemies turned increasingly towards herbivore dominance and natural enemy failure. Under natural conditions, there were more frequently significant effects of belowground herbivores and their natural enemies on plant performance, whereas there were more aboveground effects in agroecosystems. This result was partly due to the “boom-bust” behavior of the shoot herbivore population. Plant responses to herbivore or natural enemy removal were much more abrupt than the imposed smooth land use intensity gradient. This may be due to the presence of multiple trophic levels aboveground and belowground. Our model suggests that destabilization and extinction are more likely to occur in agroecosystems than in natural communities, but the shape of the relationship is nonlinear under the influence of multiple trophic interactions.

Common ADRB2 Haplotypes Derived from 26 Polymorphic Sites Direct β2-Adrenergic Receptor Expression and Regulation Phenotypes

The beta2-adrenergic receptor (beta2AR) is expressed on numerous cell-types including airway smooth muscle cells and cardiomyocytes. Drugs (agonists or antagonists) acting at these receptors for treatment of asthma, chronic obstructive pulmonary disease, and heart failure show substantial interindividual variability in response. The ADRB2 gene is polymorphic in noncoding and coding regions, but virtually all ADRB2 association studies have utilized the two common nonsynonymous coding SNPs, often reaching discrepant conclusions.We constructed the 8 common ADRB2 haplotypes derived from 26 polymorphisms in the promoter, 5'UTR, coding, and 3'UTR of the intronless ADRB2 gene. These were cloned into an expression construct lacking a vector-based promoter, so that beta2AR expression was driven by its promoter, and steady state expression could be modified by polymorphisms throughout ADRB2 within a haplotype. "Whole-gene" transfections were performed with COS-7 cells and revealed 4 haplotypes with increased cell surface beta2AR protein expression compared to the others. Agonist-promoted downregulation of beta2AR protein expression was also haplotype-dependent, and was found to be increased for 2 haplotypes. A phylogenetic tree of the haplotypes was derived and annotated by cellular phenotypes, revealing a pattern potentially driven by expression.Thus for obstructive lung disease, the initial bronchodilator response from intermittent administration of beta-agonist may be influenced by certain beta2AR haplotypes (expression phenotypes), while other haplotypes may influence tachyphylaxis during the response to chronic therapy (downregulation phenotypes). An ideal clinical outcome of high expression and less downregulation was found for two haplotypes. Haplotypes may also affect heart failure antagonist therapy, where beta2AR increase inotropy and are anti-apoptotic. The haplotype-specific expression and regulation phenotypes found in this transfection-based system suggest that the density of genetic information in the form of these haplotypes, or haplotype-clusters with similar phenotypes can potentially provide greater discrimination of phenotype in human disease and pharmacogenomic association studies

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

The Patriarchal Bargain in a Context of Rapid Changes to Normative Gender Roles: Young Arab Women’s Role Conflict in Qatar

Social norms in patriarchal countries in the Middle East are changing at differing rates. In Qatar, expectations about education have shifted, and women’s participation in higher education is normative. However, women’s participation in the workforce remains relatively low, and women still are expected to perform all household and child-rearing activities. Interviews with 27 18–25 year-old Qatari women enrolled in college in Qatar are used to illustrate the conflict between norms about education, workforce, and family. Many young women resolve this normative conflict by giving preference to family over work and education. Other women hold conflicting norms and goals for their future without acknowledging the normative conflict. Overall, young women in this sample feared divorce, were uncertain about customary family safety nets, and thus desired financial independence so they would be able to support themselves if they were left alone later in life due to divorce, or the death of their husband. The Qatari government should revisit the appropriateness of continuing to emphasize the patriarchal family structure and socially conservative family norms, if they desire to advance women in their society

Are time-trends of smoking among pregnant immigrant women in Sweden determined by cultural or socioeconomic factors?

<p>Abstract</p> <p>Background</p> <p>The widening socioeconomic gap in smoking during pregnancy remains a challenge to the Swedish antenatal care services. However, the influence of cultural factors in explaining the socioeconomic differences in smoking during pregnancy is not clear among the immigrant women. The aim of this study was to investigate whether the development of smoking prevalence among pregnant immigrant women in Sweden followed the trajectory which could be expected from the stages of the global smoking epidemic model in the women's countries of origin, or not.</p> <p>Methods</p> <p>Delivery data on pregnancies in Sweden from 1982 to 2001 was collected from the Swedish Medical Birth Registry. From a total of 2,224,469 pregnant women during this period, all immigrant pregnant women (n = 234,731) were selected to this study. A logistic regression analysis and attributable fraction were used to investigate the association between smoking during pregnancy and the socioeconomic differences among immigrant women.</p> <p>Results</p> <p>Overall, the prevalence of smoking among pregnant immigrant women decreased from 30.3% in 1982 to 11.0% in 2001, albeit with remarkable differences between educational levels and country of origin. The greatest decline of absolute prevalence was recorded among low educated women (27,9%) and among other Nordic countries (17,9%). In relative terms, smoking inequalities increased between educational levels regardless of country of origin. The odds ratios for low educational level for women from other Nordic countries increased from 4.9 (95% CI 4.4-5.4) in 1982 to 13.4 (95% CI 11.2-16.2) in 2001, as compared to women with high education in the same group. Further, the total attributable fraction for educational difference increased from 55% in 1982 to 62% in 2001, demonstrating the strong effect of educational attainment.</p> <p>Conclusions</p> <p>Our hypothesis that the socioeconomic time trend of smoking based on the stage of the world wide tobacco epidemic model related to country of origin of the immigrant women was not supported by our analyses. Our findings does not support a call for specific "culture sensitive" antismoking policies or interventions in Sweden or similar countries, but reinforce the existing evidence with a focus on women with a low educational level, regardless of cultural background.</p

Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae

The benzylisoquinoline alkaloids (BIAs) are a diverse class of metabolites that exhibit a broad range of pharmacological activities and are synthesized through plant biosynthetic pathways comprised of complex enzyme activities and regulatory strategies. We have engineered yeast to produce the key intermediate reticuline and downstream BIA metabolites from a commercially available substrate. An enzyme tuning strategy was implemented that identified activity differences between variants from different plants and determined optimal expression levels. By synthesizing both stereoisomer forms of reticuline and integrating enzyme activities from three plant sources and humans, we demonstrated the synthesis of metabolites in the sanguinarine/berberine and morphinan branches. We also demonstrated that a human P450 enzyme exhibits a novel activity in the conversion of (R)-reticuline to the morphinan alkaloid salutaridine. Our engineered microbial hosts offer access to a rich group of BIA molecules and associated activities that will be further expanded through synthetic chemistry and biology approaches

The use of the SF-36 questionnaire in adult survivors of childhood cancer: evaluation of data quality, score reliability, and scaling assumptions

BACKGROUND: The SF-36 has been used in a number of previous studies that have investigated the health status of childhood cancer survivors, but it never has been evaluated regarding data quality, scaling assumptions, and reliability in this population. As health status among childhood cancer survivors is being increasingly investigated, it is important that the measurement instruments are reliable, validated and appropriate for use in this population. The aim of this paper was to determine whether the SF-36 questionnaire is a valid and reliable instrument in assessing self-perceived health status of adult survivors of childhood cancer. METHODS: We examined the SF-36 to see how it performed with respect to (1) data completeness, (2) distribution of the scale scores, (3) item-internal consistency, (4) item-discriminant validity, (5) internal consistency, and (6) scaling assumptions. For this investigation we used SF-36 data from a population-based study of 10,189 adult survivors of childhood cancer. RESULTS: Overall, missing values ranged per item from 0.5 to 2.9 percent. Ceiling effects were found to be highest in the role limitation-physical (76.7%) and role limitation-emotional (76.5%) scales. All correlations between items and their hypothesised scales exceeded the suggested standard of 0.40 for satisfactory item-consistency. Across all scales, the Cronbach's alpha coefficient of reliability was found to be higher than the suggested value of 0.70. Consistent across all cancer groups, the physical health related scale scores correlated strongly with the Physical Component Summary (PCS) scale scores and weakly with the Mental Component Summary (MCS) scale scores. Also, the mental health and role limitation-emotional scales correlated strongly with the MCS scale score and weakly with the PCS scale score. Moderate to strong correlations with both summary scores were found for the general health perception, energy/vitality, and social functioning scales. CONCLUSION: The findings presented in this paper provide support for the validity and reliability of the SF-36 when used in long-term survivors of childhood cancer. These findings should encourage other researchers and health care practitioners to use the SF-36 when assessing health status in this population, although it should be recognised that ceiling effects can occur

Consistent phenological shifts in the making of a biodiversity hotspot: the Cape flora

Background The best documented survival responses of organisms to past climate change on short (glacial-interglacial) timescales are distributional shifts. Despite ample evidence on such timescales for local adaptations of populations at specific sites, the long-term impacts of such changes on evolutionary significant units in response to past climatic change have been little documented. Here we use phylogenies to reconstruct changes in distribution and flowering ecology of the Cape flora - South Africa's biodiversity hotspot - through a period of past (Neogene and Quaternary) changes in the seasonality of rainfall over a timescale of several million years. Results Forty-three distributional and phenological shifts consistent with past climatic change occur across the flora, and a comparable number of clades underwent adaptive changes in their flowering phenology (9 clades; half of the clades investigated) as underwent distributional shifts (12 clades; two thirds of the clades investigated). Of extant Cape angiosperm species, 14-41% have been contributed by lineages that show distributional shifts consistent with past climate change, yet a similar proportion (14-55%) arose from lineages that shifted flowering phenology. Conclusions Adaptive changes in ecology at the scale we uncover in the Cape and consistent with past climatic change have not been documented for other floras. Shifts in climate tolerance appear to have been more important in this flora than is currently appreciated, and lineages that underwent such shifts went on to contribute a high proportion of the flora's extant species diversity. That shifts in phenology, on an evolutionary timescale and on such a scale, have not yet been detected for other floras is likely a result of the method used; shifts in flowering phenology cannot be detected in the fossil record