Constitutive activation of zebrafish Stat5 expands hematopoietic cell populations in vivo

Objective
Constitutive activation of Stat5 has been observed in a variety of malignancies, particularly myeloid leukemias. To directly investigate the in vivo consequences of Stat5 perturbation, we expressed constitutively active forms in zebrafish.
Methods
We generated mutants of the zebrafish stat5.1 protein (N646H, H298R/N714F, and N714F) based on previously identified constitutively active mutants of murine Stat5a. The in vitro properties of these mutants were determined using phosphorylation-specific antibodies and luciferase reporter assays, and their in vivo effects were analyzed through microinjection of zebrafish embryos.
Results
Two of these stat5.1 mutants (N646H and H298R/N714F) showed increased tyrosine phosphorylation and transactivation activity compared to the wild-type protein. Expression of either mutant led to a range of hematological perturbations, which were more pronounced for the H298R/N714F mutant. Interestingly, expression of wild-type also produced generally similar phenotypes. Further analysis showed that expression of the H298R/N714F mutant led to increased numbers of early and late myeloid cells, erythrocytes, and B cells. Some nonhematopoietic developmental perturbations were also observed, but these were equally prominent with wild-type or mutant forms.
Conclusion
These data implicate Stat5 activity as a direct critical regulator of hematological cell proliferation, suggesting a causal role for constitutively-active Stat5 in the etiology of hematological malignancies.

Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies

A WHO expert consultation addressed the debate about interpretation of recommended body-mass index (BMI) cut-off points for determining overweight and obesity in Asian populations, and considered whether population-specific cut-off points for BMI are necessary. They reviewed scientific evidence that suggests that Asian populations have different associations between BMI, percentage of body fat, and health risks than do European populations. The consultation concluded that the proportion of Asian people with a high risk of type 2 diabetes and cardiovascular disease is substantial at BMIs lower than the existing WHO cut-off point for overweight (25 kg/m2). However, available data do not necessarily indicate a clear BMI cut-off point for all Asians for overweight or obesity. The cut-off point for observed risk varies from 22kg/m2 to 25kg/m2 in different Asian populations; for high risk it varies from 26kg/m2 to 31kg/m2. No attempt was made, therefore, to redefine cut-off points for each population separately. The consultation also agreed that the WHO BMI cut-off points should be retained as international classifications. The consultation identified further potential public health action points (23·0, 27·5, 32·5, and 37·5 kg/m2) along the continuum of BMI, and proposed methods by which countries could make decisions about the definitions of increased risk for their population.

Intervening early to reduce developmentally harmful substance use among youth populations

Early-onset or frequent substance use during adolescence increases the risk of developing mental health problems, as well as a range of other adverse outcomes (eg, alcohol or drug dependence, educational underachievement, health problems, social difficulties) during late adolescence and early adulthood.

Increases in rates of risky drinking among young people are particularly concerning, suggesting that an effective, evidence-based alcohol policy and preventive framework needs to be developed.

Restricting the supply of licit and illicit substances to adolescents, delaying the age that licit substances can be legally purchased, reducing positive media portrayals of substance use, and banning targeted promotions, should be universal, public prevention priorities.

Mass-media campaigns need to deliver coherent and credible evidence-based messages to young people, utilising a broad array of dissemination strategies.

Clear policy and guidelines for parents regarding appropriate alcohol use for adolescents also need to be developed.

Prevention programs should target children and adolescents in families with parents who use drugs, young people who have been suspended from school, or those with mental health problems.

Preventive screening and targeted brief interventions can be effectively delivered in a variety of settings by a range of health professionals.

Medically Underserved Areas and Populations in Maine 2008

http://digitalcommons.colby.edu/atlasofmaine2009/1022/thumbnail.jpg

Burden of disease and injury in Aboriginal and non-Aboriginal populations in the Northern Territory

Objective:
To quantify the burden of disease and injury for the Aboriginal and non-Aboriginal populations in the Northern Territory.

Design and setting:
Analysis of Northern Territory data for 1 January 1994 to 30 December 1998 from multiple sources.

Main outcome measures:
Disability-adjusted life-years (DALYs), by age, sex, cause and Aboriginality.

Results:
Cardiovascular disease was the leading contributor (14.9%) to the total burden of disease and injury in the NT, followed by mental disorders (14.5%) and malignant neoplasms (11.2%). There was also a substantial contribution from unintentional injury (10.4%) and intentional injury (4.9%). Overall, the NT Aboriginal population had a rate of burden of disease 2.5 times higher than the non-Aboriginal population; in the 35-54-year age group their DALY rate was 4.1 times higher. The leading causes of disease burden were cardiovascular disease for both Aboriginal men (19.1%) and women (15.7%) and mental disorders for both non-Aboriginal men (16.7%) and women (22.3%).

Conclusions:
A comprehensive assessment of fatal and non-fatal conditions is important in describing differentials in health status of the NT population. Our study provides comparative data to identify health priorities and facilitate a more equitable distribution of health funding.

Promotion of exercise prescriptions in general practice for older populations

Regular physical activity in older populations reduces the risks of cardiovascular diseases, diabetes, osteoporosis and falls and also improves mental health. Some programs of written exercise prescriptions by general practitioners have been shown to significantly increase physical activity levels over the medium-term (six to 12 months). Increasing the confidence and skills of general practitioners to prescribe and monitor exercise programs is important. However, the more challenging barriers to the widespread uptake of exercise prescription programs are the structural and economic constraints within general practice, as well as the competing promotion of prescribing pharmaceutical products. Implementation research on overcoming these barriers is urgently needed.

Is water extraction a threat to insect populations in intermittently-flowing streams?

Stream insects use a variety of refuges to survive drought that vary in their vulnerability to water extraction. We surveyed drought refuges in 16 ephemeral streams with different flow regimes. Perennial sections were the most important drought refuge, but are the most likely to disappear when water is extracted.

Variation in gametophyte dominance in populations of Chondrus verrucosus (Gigartinaceae, Rhodophyta)

We describe the abundance, including spatial and temporal variability, of phases of the isomorphic Chondrus verrucosus Mikami from Japan. Chondrus verrucosus occurred in a dense (∼90% cover) and temporally stable bed on a small, isolated rocky outcrop (Oyakoiwa) in Shizuoka Prefecture. Small vegetative fronds were always much more abundant than large vegetative and fertile fronds over the spring to late summer periods in 1999 and 2000. Over the same period, fertile carposporophytic fronds were generally more abundant than fertile tetrasporophytic fronds, and fertile male fronds appeared infrequently at low densities. Using the resorcinol-acetal test, we determined the proportion of gametophytes and tetrasporophytes in three populations of C. verrucosus: Oyakoiwa and Noroshi (Shizuoka) in the summers of 1999 and 2000 and Kamehana Point (Miyagi) in autumn 2000. All populations had a significantly higher proportion of gametophytes than tetrasporophytes in both years, although gametophytic proportions were lower at Noroshi (∼70%) than at Oyakoiwa (∼80%) and Kamehana Point (∼97%). However, examination of all isolated individuals sampled on Noroshi showed equal proportions of each phase in 1999, but gametophyte dominance (74%) in 2000. Differences in dispersal and spore production between phases are discussed as mechanisms potentially contributing to variation in gametophyte dominance.

Barriers to cross-fertilization between populations of a widely dispersed Polychaete species are unlikely to have arisen through gametic compatibility arms-races

Although there are theoretical reasons to suspect that gametic incompatibility may develop readily among populations of broadcast spawning marine invertebrates, there have been very few studies documenting geographic patterns of interpopulation incompatibility for any species. To address this we determined how successfully individuals of the intertidal serpulid polychaete, Galeolaria caespitosa, can cross-fertilize within and among populations from across temperate Australia. Fertilization assays revealed asymmetrical differences between very distantly located populations from different coasts, with near-complete incompatibility between eggs from Sydney with sperm from Adelaide, but the reverse cross (Adelaide eggs, Sydney sperm) was reasonably compatible. Although that pattern was congruent with a clear difference in Cytochrome B sequences between worms on the south and east coasts of Australia, we also detected some indication of interpopulation incompatibility within the genetic grouping on east coast, between two populations separated by only 220 km. We then assessed whether commonly proposed gametic compatibility arms-races could account for these patterns. Our results suggest reduced gametic compatibility may reduce a female's maximum fertilization potential, resulting in a cost to this potential mechanism for reducing polyspermy. Consequently, the apparently rapid development of reproductive barriers here seems unlikely to have been driven by arms-races involving sexual conflict over fertilization rate.

Factors influencing population dynamics in island and mainland populations of the Swamp Antechinus (Antechinus minimus)

Simultaneously analysing demographic processes of small mammals living in different ecological contexts may help to understand mechanisms that influence the growth and decline of these populations. The size and demography of swamp antechinus (Antechinus minimus) populations located in a coastal mainland habitat and on a small offshore island in south-eastern Australia were investigated. Large demographic differences occurred between the two ecosystems, with the island population density often 100 times greater than that on the mainland. The swamp antechinus in the mainland habitat was influenced by extrinsic climatic forces, with juvenile recruitment, individual body mass and overall population size being affected by rainfall, a factor likely to influence food availability for the species. However, the island population did not appear to be affected by drought to the same degree where allochthonous marine nutrient inputs may have offset any drought-induced reduction in primary production. Significantly greater juvenile recruitment in the island habitats combined with restricted emigration and potentially reduced predation and interspecific competition are likely to be responsible for the high population densities on the island. Although island populations appear robust, future conservation efforts should focus on mainland populations given the genetic deficiencies in the island populations.