A team effort: natural killer cells on the first leg of the tumor immunity relay race

Recent work by Böttcher and colleagues defines a new role for Natural Killer cells in the anti-tumor immune response, arriving early into the tumor microenvironment before passing the baton to DC1 dendritic cells. DC1 dendritic cells subsequently activate CD8+ T cells resulting in effective anti-tumor immunity. This work highlights the cooperative nature of anti-tumor immunity set in motion by Natural Killer cells, and immune evasion by tumors through their exclusion.National Cancer Institute (U.S.) (R00CA204595

Global assessment of nitrogen deposition effects on terrestrial plant diversity : a synthesis

Atmospheric nitrogen (N) deposition is it recognized threat to plant diversity ill temperate and northern parts of Europe and North America. This paper assesses evidence from field experiments for N deposition effects and thresholds for terrestrial plant diversity protection across a latitudinal range of main categories of ecosystems. from arctic and boreal systems to tropical forests. Current thinking on the mechanisms of N deposition effects on plant diversity, the global distribution of G200 ecoregions, and current and future (2030) estimates of atmospheric N-deposition rates are then used to identify the risks to plant diversity in all major ecosystem types now and in the future. This synthesis paper clearly shows that N accumulation is the main driver of changes to species composition across the whole range of different ecosystem types by driving the competitive interactions that lead to composition change and/or making conditions unfavorable for some species. Other effects such its direct toxicity of nitrogen gases and aerosols long-term negative effects of increased ammonium and ammonia availability, soil-mediated effects of acidification, and secondary stress and disturbance are more ecosystem, and site-specific and often play a supporting role. N deposition effects in mediterranean ecosystems have now been identified, leading to a first estimate of an effect threshold. Importantly, ecosystems thought of as not N limited, such as tropical and subtropical systems, may be more vulnerable in the regeneration phase. in situations where heterogeneity in N availability is reduced by atmospheric N deposition, on sandy soils, or in montane areas. Critical loads are effect thresholds for N deposition. and the critical load concept has helped European governments make progress toward reducing N loads on sensitive ecosystems. More needs to be done in Europe and North America. especially for the more sensitive ecosystem types. including several ecosystems of high conservation importance. The results of this assessment Show that the Vulnerable regions outside Europe and North America which have not received enough attention are ecoregions in eastern and Southern Asia (China, India), an important part of the mediterranean ecoregion (California, southern Europe). and in the coming decades several subtropical and tropical parts of Latin America and Africa. Reductions in plant diversity by increased atmospheric N deposition may be more widespread than first thought, and more targeted Studies are required in low background areas, especially in the G200 ecoregions

Dietary patterns and type 2 diabetes among Ghanaian migrants in Europe and their compatriots in Ghana: the RODAM study.

BACKGROUND/OBJECTIVES: We aimed to study the associations of dietary patterns (DPs) with type 2 diabetes (T2D) among Ghanaian adults. SUBJECTS/METHODS: In the multi-centre, cross-sectional RODAM (Research on Obesity and Diabetes among African Migrants) study (n = 4543), three overall DPs ("mixed", "rice, pasta, meat and fish," and "roots, tubers and plantain") and two site-specific DPs per study site (rural Ghana, urban Ghana and Europe) were identified by principal component analysis. The DPs-T2D associations were calculated by logistic regression models. RESULTS: Higher adherence to the "rice, pasta, meat and fish" DP (characterized by legumes, rice/pasta, meat, fish, cakes/sweets, condiments) was associated with decreased odds of T2D, adjusted for socio-demographic factors, total energy intake and adiposity measures (odds ratio (OR)per 1 SD = 0.80; 95% confidence interval (CI) = 0.70-0.92). Similar DPs and T2D associations were discernible in urban Ghana and Europe. In the total study population, neither the "mixed" DP (whole grain cereals, sweet spreads, dairy products, potatoes, vegetables, poultry, coffee/tea, sodas/juices, olive oil) nor the "roots, tubers and plantain" DP (refined cereals, fruits, nuts/seeds, roots/tubers/plantain, fermented maize products, legumes, palm oil, condiments) was associated with T2D. Yet, after the exclusion of individuals with self-reported T2D, the "roots, tubers and plantain" DP was inversely associated with T2D (ORper 1 SD = 0.88; 95% CI = 0.69-1.12). CONCLUSION: In this Ghanaian population, DPs characterized by the intake of legumes, fish, meat and confectionery were inversely associated with T2D. The effect of a traditional-oriented diet (typical staples, vegetables and legumes) remains unclear

Peripheral insulin resistance rather than beta cell dysfunction accounts for geographical differences in impaired fasting blood glucose among sub-Saharan African individuals: findings from the RODAM study.

AIMS/HYPOTHESIS: The aim of this study was to assess the extent to which insulin resistance and beta cell dysfunction account for differences in impaired fasting blood glucose (IFBG) levels in sub-Saharan African individuals living in different locations in Europe and Africa. We also aimed to identify determinants associated with insulin resistance and beta cell dysfunction among this population. METHODS: Data from the cross-sectional multicentre Research on Obesity and Diabetes among African Migrants (RODAM) study were analysed. Participants included Ghanaian individuals without diabetes, aged 18-96 years old, who were residing in Amsterdam (n = 1337), Berlin (n = 502), London (n = 961), urban Ghana (n = 1309) and rural Ghana (n = 970). Glucose and insulin were measured in fasting venous blood samples. Anthropometrics were assessed during a physical examination. Questionnaires were used to assess demographics, physical activity, smoking status, alcohol consumption and energy intake. Insulin resistance and beta cell function were determined using homeostatic modelling (HOMA-IR and HOMA-B, respectively). Logistic regression analysis was used to study the contribution of HOMA-IR and inverse HOMA-B (beta cell dysfunction) to geographical differences in IFBG (fasting glucose 5.6-6.9 mmol/l). Multivariate linear regression analysis was used to identify determinants associated with HOMA-IR and inverse HOMA-B. RESULTS: IFBG was more common in individuals residing in urban Ghana (OR 1.41 [95% CI 1.08, 1.84]), Amsterdam (OR 3.44 [95% CI 2.69, 4.39]) and London (OR 1.58 [95% CI 1.20 2.08), but similar in individuals living in Berlin (OR 1.00 [95% CI 0.70, 1.45]), compared with those in rural Ghana (reference population). The attributable risk of IFBG per 1 SD increase in HOMA-IR was 69.3% and in inverse HOMA-B was 11.1%. After adjustment for HOMA-IR, the odds for IFBG reduced to 0.96 (95% CI 0.72, 1.27), 2.52 (95%CI 1.94, 3.26) and 1.02 (95% CI 0.78, 1.38) for individuals in Urban Ghana, Amsterdam and London compared with rural Ghana, respectively. In contrast, adjustment for inverse HOMA-B had very minor impact on the ORs of IFBG. In multivariate analyses, BMI (β = 0.17 [95% CI 0.11, 0.24]) and waist circumference (β = 0.29 [95%CI 0.22, 0.36]) were most strongly associated with higher HOMA-IR, whereas inverse HOMA-B was most strongly associated with age (β = 0.20 [95% CI 0.16, 0.23]) and excess alcohol consumption (β = 0.25 [95% CI 0.07, 0.43]). CONCLUSIONS/INTERPRETATION: Our findings suggest that insulin resistance, rather than beta cell dysfunction, is more important in accounting for the geographical differences in IFBG among sub-Saharan African individuals. We also show that BMI and waist circumference are important factors in insulin resistance in this population

Food variety, dietary diversity, and type 2 diabetes in a multi-center cross-sectional study among Ghanaian migrants in Europe and their compatriots in Ghana: the RODAM study.

PURPOSE: The importance of dietary diversification for type 2 diabetes (T2D) risk remains controversial. We investigated associations of between- and within-food group variety with T2D, and the role of dietary diversification for the relationships between previously identified dietary patterns (DPs) and T2D among Ghanaian adults. METHODS: In the multi-center cross-sectional Research on Obesity and Diabetes among African Migrants (RODAM) Study (n = 3810; Ghanaian residence, 56%; mean age, 46.2 years; women, 63%), we constructed the Food Variety Score (FVS; 0-20 points), the Dietary Diversity Score (DDS; 0-7 points), and the Diet Quality Index-International (DQI-I) variety component (0-20 points). The associations of these scores, of a "rice, pasta, meat and fish" DP, of a "mixed" DP, and of a "roots, tubers and plantain" DP with T2D were calculated by logistic regression. RESULTS: The FVS was inversely associated with T2D, adjusted for socio-demographic, lifestyle, and anthropometric factors [odds ratio (OR) for T2D per 1 standard deviation (SD) increase: 0.81; 95% confidence interval (CI) 0.71-0.93]. The DDS and the DQI-I variety component were not associated with T2D. There was no association of the "mixed" DP and the "roots, tubers and plantain" DP with T2D. Yet, the "rice, pasta, meat and fish" DP is inversely associated with T2D (OR for T2D per 1 SD increase: 0.82; 95% CI 0.71-0.95); this effect was slightly attenuated by the FVS. CONCLUSIONS: In this Ghanaian population, between-food group variety may exert beneficial effects on glucose metabolism and partially explains the inverse association of the "rice, pasta, meat and fish" DP with T2D

The Discovery Potential of a Super B Factory

The Proceedings of the 2003 SLAC Workshops on flavor physics with a high luminosity asymmetric e+e- collider. The sensitivity of flavor physics to physics beyond the Standard Model is addressed in detail, in the context of the improvement of experimental measurements and theoretical calculations.Comment: 476 pages. Printed copies may be obtained by request to [email protected] . arXiv admin note: v2 appears to be identical to v

An epigenome-wide association study in whole blood of measures of adiposity among Ghanaians: the RODAM study

Background: Epigenome-wide association studies (EWAS) have identified DNA methylation loci involved in adiposity. However, EWAS on adiposity in sub- Saharan Africans are lacking despite the high burden of adiposity among African populations. We undertook an EWAS for anthropometric indices of adiposity among Ghanaians aiming to identify DNA methylation loci that are significantly associated. Methods: The Illumina 450k DNA methylation array was used to profile DNA methylation in whole blood samples of 547 Ghanaians from the Research on Obesity and Diabetes among African Migrants (RODAM) study. Differentially methylated positions (DMPs) and differentially methylation regions (DMRs) were identified for BMI and obesity (BMI ≥ 30 kg/m2), as well as for waist circumference (WC) and abdominal obesity (WC ≥ 102 cm in men, ≥88 cm in women). All analyses were adjusted for age, sex, blood cell distribution estimates, technical covariates, recruitment site and population stratification. We also did a replication study of previously reported EWAS loci for anthropometric indices in other populations. Results: We identified 18 DMPs for BMI and 23 for WC. For obesity and abdominal obesity, we identified three and one DMP, respectively. Fourteen DMPs overlapped between BMI and WC. DMP cg00574958 annotated to gene CPT1A was the only DMP associated with all outcomes analysed, attributing to 6.1 and 5.6% of variance in obesity and abdominal obesity, respectively. DMP cg07839457 (NLRC5) and cg20399616 (BCAT1) were significantly associated with BMI, obesity and with WC and had not been reported by previous EWAS on adiposity. Conclusions: This first EWAS for adiposity in Africans identified three epigenome-wide significant loci (CPT1A, NLRC5 and BCAT1) for both general adiposity and abdominal adiposity. The findings are a first step in understanding the role of DNA methylation in adiposity among sub-Saharan Africans. Studies on other sub-Saharan African populations as well as translational studies are needed to determine the role of these DNA methylation variants in the high burden of adiposity among sub- Saharan Africans

Obesity and type 2 diabetes in sub-Saharan Africans - Is the burden in today's Africa similar to African migrants in Europe? The RODAM study.

BACKGROUND: Rising rates of obesity and type 2 diabetes (T2D) are impending major threats to the health of African populations, but the extent to which they differ between rural and urban settings in Africa and upon migration to Europe is unknown. We assessed the burden of obesity and T2D among Ghanaians living in rural and urban Ghana and Ghanaian migrants living in different European countries. METHODS: A multi-centre cross-sectional study was conducted among Ghanaian adults (n = 5659) aged 25-70 years residing in rural and urban Ghana and three European cities (Amsterdam, London and Berlin). Comparisons between groups were made using prevalence ratios (PRs) with adjustments for age and education. RESULTS: In rural Ghana, the prevalence of obesity was 1.3 % in men and 8.3 % in women. The prevalence was considerably higher in urban Ghana (men, 6.9 %; PR: 5.26, 95 % CI, 2.04-13.57; women, 33.9 %; PR: 4.11, 3.13-5.40) and even more so in Europe, especially in London (men, 21.4 %; PR: 15.04, 5.98-37.84; women, 54.2 %; PR: 6.63, 5.04-8.72). The prevalence of T2D was low at 3.6 % and 5.5 % in rural Ghanaian men and women, and increased in urban Ghanaians (men, 10.3 %; PR: 3.06; 1.73-5.40; women, 9.2 %; PR: 1.81, 1.25-2.64) and highest in Berlin (men, 15.3 %; PR: 4.47; 2.50-7.98; women, 10.2 %; PR: 2.21, 1.30-3.75). Impaired fasting glycaemia prevalence was comparatively higher only in Amsterdam, and in London, men compared with rural Ghana. CONCLUSION: Our study shows high risks of obesity and T2D among sub-Saharan African populations living in Europe. In Ghana, similarly high prevalence rates were seen in an urban environment, whereas in rural areas, the prevalence of obesity among women is already remarkable. Similar processes underlying the high burden of obesity and T2D following migration may also be at play in sub-Saharan Africa as a consequence of urbanisation

Cardiovascular disease risk prediction in sub-Saharan African populations - Comparative analysis of risk algorithms in the RODAM study.

BACKGROUND: Validated absolute risk equations are currently recommended as the basis of cardiovascular disease (CVD) risk stratification in prevention and control strategies. However, there is no consensus on appropriate equations for sub-Saharan African populations. We assessed agreement between different cardiovascular risk equations among Ghanaian migrant and home populations with no overt CVD. METHODS: The 10-year CVD risks were calculated for 3586 participants aged 40-70years in the multi-centre RODAM study among Ghanaians residing in Ghana and Europe using the Framingham laboratory and non-laboratory and Pooled Cohort Equations (PCE) algorithms. Participants were classified as low, moderate or high risk, corresponding to 20% respectively. Agreement between the risk algorithms was assessed using kappa and correlation coefficients. RESULTS: 19.4%, 12.3% and 5.8% were ranked as high 10-year CVD risk by Framingham non-laboratory, Framingham laboratory and PCE, respectively. The median (25th-75th percentiles) estimated 10-year CVD risk was 9.5% (5.4-15.7), 7.3% (3.9-13.2) and 5.0% (2.3-9.7) for Framingham non-laboratory, Framingham laboratory and PCE, respectively. The concordance between PCE and Framingham non-laboratory was better in the home Ghanaian population (kappa=0.42, r=0.738) than the migrant population (kappa=0.24, r=0.732) whereas concordance between PCE and Framingham laboratory was better in migrant Ghanaians (kappa=0.54, r=0.769) than the home population (kappa=0.51, r=0.758). CONCLUSION: CVD prediction with the same algorithm differs for the migrant and home populations and the interchangeability of Framingham laboratory and non-laboratory algorithms is limited. Validation against CVD outcomes is needed to inform appropriate selection of risk algorithms for use in African ancestry populations