Interactions between Endothelin Receptor B and Transcription Factors Sox10 and Pax3 in the Melanocyte Lineage

Genetic interactions that underlie developmental processes such as cell differentiation and pattern formation are complex and difficult to elucidate. Neural Crest (NC) cells and their derivatives offer an optimal system in which to probe for these complex interactions as they acquire different cell fates and constitute a variety of structures. The transcription factors Sox10 and Pax3 as well as the transmembrane receptor Endothelin receptor b (Ednrb) are temporally and spatially co-expressed early in NC cells and mutations in these genes lead to similar hypopigmentation phenotypes due to a reduced number of NC-derived melanocyte precursors, the melanoblasts. The goal of this study was to establish whether Sox10 and Ednrb or Pax3 and Ednrb interact to promote normal murine melanocyte development. Crosses of Sox10 or Pax3 with Ednrb heterozygous mutants showed that the double heterozygous hypopigmentation phenotype was significantly more pronounced than phenotypes of single heterozygotes, implying that a synergistic interaction exists between Sox10 and Ednrb and Pax3 and Ednrb. This interaction was further explored by the attempt to rescue the Sox10 and Pax3 hypopigmentation phenotypes by the transgenic addition of Ednrb to melanoblasts. Pigmentation was completely restored in the Sox10 and partially restored in the Pax3 mutant mice. The comparison of the number of melanoblasts in transgenic and non-transgenic Sox10 mutant embryos showed that the transgenic rescue occurred as early as E11.5, a critical time for melanoblast population expansion. Cell survival assays indicated that the rescue was not due to an effect of the transgene on melanoblast survival. A novel phenotype arose when studying the interaction between Ednrb and Pax3. Newborns appeared normal but by 3.5 weeks of age, the affected pups were smaller than normal littermates and developed a dome-shaped head; some also developed thoracic kyphosis. Affected pups were dead by 4 weeks of age: 80% were Pax3Sp/+ and 75% were female. When compared to normal littermates, affected mice had brains with enlarged 4th ventricles and more glia while skeletal staining showed kyphosis, wider rib cages and pelvic differences. An epistatic interaction resulting from the mixing of genetic backgrounds that is exacerbated in the presence of Pax3 heterozygosity is suspected.

Examination of Personality, Social and Cognitive Factors on the Co-Occurrence of Health Risk Behaviors among Multi-Problem Youth: The Utility of An Integrative Framework

Research has identified a number of putative risk factors that places adolescents at incrementally higher risk for involvement in alcohol and other drug (AOD) use and sexual risk behaviors (SRBs). Such factors include personality characteristics such as sensation-seeking, cognitive factors such as positive expectancies and inhibition conflict as well as peer norm processes. The current study was guided by a conceptual perspective that support the notion that an integrative framework that includes multi-level factors has significant explanatory value for understanding processes associated with the co-occurrence of AOD use and sexual risk behavior outcomes. This study evaluated simultaneously the mediating role of AOD-sex related expectancies and inhibition conflict on antecedents of AOD use and SRBs including sexual sensation-seeking and peer norms for condom use. The sample was drawn from the Enhancing My Personal Options While Evaluating Risk (EMPOWER: Jonathan Tubman, PI), data set (N = 396; aged 12-18 years). Measures used in the study included Sexual Sensation-Seeking Scale, Inhibition Conflict for Condom Use, Risky Sex Scale. All relevant measures had well-documented psychometric properties. A global assessment of alcohol, drug use and sexual risk behaviors was used. Results demonstrated that AOD-sex related expectancies mediated the influence of sexual sensation-seeking on the co-occurrence of alcohol and other drug use and sexual risk behaviors. The evaluation of the integrative model also revealed that sexual sensation-seeking was positively associated with peer norms for condom use. Also, peer norms predicted inhibition conflict among this sample of multi-problem youth. This dissertation research identified mechanisms of risk and protection associated with the co-occurrence of AOD use and SRBs among a multi-problem sample of adolescents receiving treatment for alcohol or drug use and related problems. This study is informative for adolescent-serving programs that address those individual and contextual characteristics that enhance treatment efficacy and effectiveness among adolescents receiving substance use and related problems services.

Risk and resilience factors associated with delinquent behavior among African American adolescent males

Juvenile crime is a social problem of increasing concern to many citizens in the United States. In 2000, there were an estimated 2.4 million juvenile arrests for a variety of crimes ranging from misdemeanors to violent felony offenses. African American males are disproportionately represented among juvenile offenders in the United States. In 2000, black youth were approximately 16% of the U.S. population between the ages of 10-17; however, they accounted for 42% of juvenile arrests for violent crime. This study explored putative factors associated with juvenile offending among a sample of African American adolescent males. The independent variables in this study were academic achievement, religiosity, parenting styles and discrimination. The dependent variables were delinquent behavior and arrest. The data used in this study were from a larger NIDA funded longitudinal study that included approximately 425 African American youths. The data collection method involved structured interviews and questionnaires. The participants for the original study were selected via random sampling from all students attending middle school in Miami-Dade County. The study examined the hypotheses that African American males retrospectively reporting (a) high academic achievement, (b) high religiosity, (c) authoritarian parenting and (d) low perceptions of discrimination are less likely to be involved in delinquent behavior and are also less likely to be arrested. Results indicated that among African American adolescent males, delinquent behavior had a significant relationship (p The findings indicated that experimental studies are needed to clarify cause and effect relationship among the variables associated with juvenile offending among African American males, which may differ from those associated with juvenile offending among other groups.

Assessing Administrative and Political Factors in Implementing a Living Wage Ordinance

Since 2000, the number of living wage ordinances has steadily increased throughout the country. While most of the current research has focused on the beneficial outcomes of living wages, little has been published on their administrative practices. To address this shortcoming, this study focused on the identification of key administrative and political factors involved impacting the implementation of living wage ordinances in Miami-Dade and Broward Counties. The study utilized a triangulation of interviews, surveys, and direct observation. The author conducted interviews of administrators and members of the living wage oversight boards in both counties and observed the monthly meetings held by each county’s oversight board from January 2006 to June 2007. These findings were buttressed with a national survey of senior staff in other living wage communities. The study utilized descriptive statistics, Chi Square, Cronbach’s Alpha, and Spearman’s Rank Correlation Coefficient (Spearman’s rho). Interviews indicated that administrators in Dade and Broward are seriously under-staffed and budgeted. Ambiguities in the enabling ordinances have lead to loopholes that undermine implementation and accountability for participating contractors. Survey results showed that policy ambiguity, organizational politics, and a lack of organizational capacity were significant negative factors in the implementation process while an organizational culture emphasizing consistent enforcement was a positive factor. Without the proper inputs, an organization hinders itself from meeting its outputs and outcomes. This study finds that Broward and Miami-Dade Counties do not provide the necessary administrative support to implement a living wage effectively – in stark contrast to the high hopes and strong political support behind their passage. For a living wage to succeed, it first needs an organizational culture committed to providing the necessary resources for implementation as well as transparent, consistent accountability mechanisms.

(Table 1) TOC, d13C, and preservation factors of turbidite sediments

In ocean margin sediments both marine and terrestrial organic matter (OM) are buried but the factors governing their relative preservation and degradation are not well understood. In this study, we analysed the degree of preservation of marine isoprenoidal and soil-derived branched glycerol dialkyl glycerol tetraethers (GDGTs) upon long-term oxygen exposure in OM-rich turbidites from the Madeira Abyssal Plain by analyzing GDGT concentrations across oxidation fronts. Relative to the anoxic part of the turbidites ca. 7-20% of the soil-derived branched GDGTs were preserved in the oxidized part while only 0.2-3% of the marine isoprenoid GDGT crenarchaeol was preserved. Due to these different preservation factors the Branched Isoprenoid Tetraether (BIT) index, a ratio between crenarchaeol and the major branched GDGTs that is used as a tracer for soil-derived organic matter, substantially increases from 0.02 to 0.4. Split Flow Thin Cell (SPLITT) separation of turbidite sediments showed that the enhanced preservation of soil-derived carbon was a general phenomenon across the fine particle size ranges (<38 ?m). Calculations reveal that, despite their relatively similar chemical structures, degradation rates of crenarchaeol are 2-fold higher than those of soil-derived branched GDGTs, suggesting preferential soil OM preservation possibly due to matrix protection.

Risk and protective factors in the mental health of adolescents living with HIV in Namibia

"Introducción": A pesar de que el 90% de los adolescentes con VIH en el mundo viven en África subsahariana, pocos estudios han examinado el impacto que tiene el hecho de estar infectados por VIH sobre su salud mental en este región. Además, los adolescentes con VIH en contextos de escasos recursos se enfrentan con factores de riesgo adicionales, como la pobreza, la falta de apoyo social y el estigma relacionado con el VIH. Este estudio examina la salud mental de los adolescentes que viven con el VIH en Namibia, un país con una de las prevalencias de VIH más altas del mundo. El estudio examina si estos adolescentes muestran mayores problemas de salud mental respecto a un grupo de comparación de la comunidad. Asimismo, el estudio evalúa los factores que predicen problemas de salud mental con el fin de identificar las potenciales áreas de intervención que permitan mejorar dichos problemas. Métodos: En una fase piloto, se organizan grupos de discusión con 34 adolescentes y entrevistas con ocho informantes clave para explorar las percepciones locales sobre los problemas de salud mental, así como sus factores de riesgo y factores de proteccion. Dado que las propiedades psicométricas del instrumento seleccionado para medir salud mental, el cuestionario Strengths and Difficulties Questionnaire/ Cuestionario de Capacidades y Dificultades (SDQ), nunca habían sido exploradas antes en Namibia, se decidió administrarlo a 236 participantes con edades comprendidas entre 12 y 18 años en una fase piloto cuantitativa...

Patterns of local R&D cooperation of foreign subsidiaries in an intermediate country: innovative and structural factors

We attempt to contribute to a better understanding of cooperative innovation patterns of foreign subsidiaries (FS) in Spain as a representative intermediate country, going deeply into three main aspects: firstly, a sectoral taxonomy which combines international technological dynamism and revealed technological advantage as a way to understand such patterns. Secondly we focus our attention on innovative intensive subsidiaries, assuming they are the most important ones for hosting countries. Thirdly, we combine innovation and structural-competitive variables to explain local cooperation. We found more intense cooperation of FS with local agents in dynamic specialization sectors, as well as the fact that this is mostly carried out in a complementary mode with inner knowledge capabilities of the companies. Cooperative activities are influenced by economicstructural factors of the Spanish economy, particularly in highly innovative companies. Cooperative strategies of domestic firms might also have an influence on those of foreign subsidiaries.

Reconstructing direct and indirect interactions in networked public goods game

W.-X.W. was supported by NNSFC under Grant No. 61573064 and Grant No. 61074116, Beijing Nova Programme, China, and the Fundamental Research Funds for the Central Universities. Y.-C.L. was supported by ARO under Grant W911NF-14-1-0504.

Identifying and exploring factors influencing career choice, recruitment and retention of anaesthesia trainees in the UK

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Direct and indirect genetic and fine-scale location effects on breeding date in song sparrows

Peer reviewed

"Cruising" film demonstration and rally in Sheridan Square

General note: Title and date provided by Bettye Lane.

Biological and Physical Factors Affecting the Natural History and Evolution of Encapsulated Development

The evolution of reproductive strategies involves a complex calculus of costs and benefits to both parents and offspring. Many marine animals produce embryos packaged in tough egg capsules or gelatinous egg masses attached to benthic surfaces. While these egg structures can protect against environmental stresses, the packaging is energetically costly for parents to produce. In this series of studies, I examined a variety of ecological factors affecting the evolution of benthic development as a life history strategy. I used marine gastropods as my model system because they are incredibly diverse and abundant worldwide, and they exhibit a variety of reproductive and developmental strategies.

The first study examines predation on benthic egg masses. I investigated: 1) behavioral mechanisms of predation when embryos are targeted (rather than the whole egg mass); 2) the specific role of gelatinous matrix in predation. I hypothesized that gelatinous matrix does not facilitate predation. One study system was the sea slug Olea hansineensis, an obligate egg mass predator, feeding on the sea slug Haminoea vesicula. Olea fed intensely and efficiently on individual Haminoea embryos inside egg masses but showed no response to live embryos removed from gel, suggesting that gelatinous matrix enables predation. This may be due to mechanical support of the feeding predator by the matrix. However, Haminoea egg masses outnumber Olea by two orders of magnitude in the field, and each egg mass can contain many tens of thousands of embryos, so predation pressure on individuals is likely not strong. The second system involved the snail Nassarius vibex, a non-obligate egg mass predator, feeding on the polychaete worm Clymenella mucosa. Gel neither inhibits nor promotes embryo predation for Nassarius, but because it cannot target individual embryos inside an egg mass, its feeding is slow and inefficient, and feeding rates in the field are quite low. However, snails that compete with Nassarius for scavenged food have not been seen to eat egg masses in the field, leaving Nassarius free to exploit the resource. Overall, egg mass predation in these two systems likely benefits the predators much more than it negatively affects the prey. Thus, selection for environmentally protective aspects of egg mass production may be much stronger than selection for defense against predation.

In the second study, I examined desiccation resistance in intertidal egg masses made by Haminoea vesicula, which preferentially attaches its flat, ribbon-shaped egg masses to submerged substrata. Egg masses occasionally detach and become stranded on exposed sand at low tide. Unlike adults, the encased embryos cannot avoid desiccation by selectively moving about the habitat, and the egg mass shape has high surface-area-to-volume ratio that should make it prone to drying out. Thus, I hypothesized that the embryos would not survive stranding. I tested this by deploying individual egg masses of two age classes on exposed sand bars for the duration of low tide. After rehydration, embryos midway through development showed higher rates of survival than newly-laid embryos, though for both stages survival rates over 25% were frequently observed. Laboratory desiccation trials showed that >75% survival is possible in an egg mass that has lost 65% of its water weight, and some survival (<25%) was observed even after 83% water weight lost. Although many surviving embryos in both experiments showed damage, these data demonstrate that egg mass stranding is not necessarily fatal to embryos. They may be able to survive a far greater range of conditions than they normally encounter, compensating for their lack of ability to move. Also, desiccation tolerance of embryos may reduce pressure on parents to find optimal laying substrata.

The third study takes a big-picture approach to investigating the evolution of different developmental strategies in cone snails, the largest genus of marine invertebrates. Cone snail species hatch out of their capsules as either swimming larvae or non-dispersing forms, and their developmental mode has direct consequences for biogeographic patterns. Variability in life history strategies among taxa may be influenced by biological, environmental, or phylogenetic factors, or a combination of these. While most prior research has examined these factors singularly, my aim was to investigate the effects of a host of intrinsic, extrinsic, and historical factors on two fundamental aspects of life history: egg size and egg number. I used phylogenetic generalized least-squares regression models to examine relationships between these two egg traits and a variety of hypothesized intrinsic and extrinsic variables. Adult shell morphology and spatial variability in productivity and salinity across a species geographic range had the strongest effects on egg diameter and number of eggs per capsule. Phylogeny had no significant influence. Developmental mode in Conus appears to be influenced mostly by species-level adaptations and niche specificity rather than phylogenetic conservatism. Patterns of egg size and egg number appear to reflect energetic tradeoffs with body size and specific morphologies as well as adaptations to variable environments. Overall, this series of studies highlights the importance of organism-scale biotic and abiotic interactions in evolutionary patterns.

Understanding Antenatal Genetics Services in Sri Lanka: Current Landscape of Screening and Diagnostic Services and Contextual Factors Influencing Their Availability and Uptake

Background: Too little information is available on Sri Lanka’s current capacity to provide community genetic services—antenatal genetic services in particular—to understand whether building that capacity could further improve and reduce disparity in maternal and child health. This qualitative research project seeks to gather information on congenital disorders, routine antenatal care, and the current state of antenatal screening testing services within that routine antenatal to assess the feasibility of and the need for scaling up antenatal genetics services in Sri Lanka. Methods: Nineteen key informant (KI) interviews were conducted with stakeholders in antenatal care and genetic services. Seven focus group discussions were held with a total of 56 Public Health Midwives (PHMs), the health workers responsible for antenatal care at the field level. Transcripts for all interviews and FGDs were analyzed for key themes, and themes were categorized to address the specific aims of the project. Results: Antenatal genetic services play a minor role in antenatal care, with screening and diagnostic procedures available in the private sector and paid for out-of-pocket. KIs and PHMs expect that demand for antenatal genetic services will increase as patients’ purchasing power and knowledge grow but note that prohibitive abortion laws limit the ability of patients to act on test results. Genetic services compete for limited financial and human resources in the free public health system, and inadequate information on the prevalence of congenital disorders limits the ability to understand whether funding for services related to those disorders should be increased. A number of alternatives to scaling up antenatal genetic services within the free health system might be better suited to the Sri Lankan structural and social context. Conclusions: Scaling up antenatal genetic services within the public health system is not feasible in the current financial, legal, and human resource context. Yet current availability and utilization patterns contribute to regional and economic disparities, suggesting that stasis will not bring continued improvements in maternal and child health. More information on the burden of congenital disorders is necessary to fully understand if and how antenatal genetic service availability should be increased in Sri Lanka, but even before that information is gathered, examination of policies for patient referral, termination of pregnancy, and government support for individuals with genetic disease are steps that might bring extend improvements and reduce disparity in maternal and child health.