Lactation-associated redistribution of the glial fibrillary acidic protein within the supraoptic nucleus

Summary Three clones of myeloproliferative virus (MPV)-transformed rat fibroblasts (NRK) with different growth properties and morphology were transplanted to athymic nude mice. Presence of carbohydrate-binding proteins was inferred by fluorescence microscopy using fluorescent, glycosylated markers. Salt and detergent extracts of tumors from this model system were fractionated under identical conditions on different sets of Sepharose columns, to which lactose, asialofetuin, melibiose, mannan and fucose had been covalently linked. Successive elution by chelating reagent and specific sugar resulted in isolation of the different Ca²⁺-dependent and Ca²⁺-independent endogenous carbohydrate-binding proteins that were assayable as agglutinins. In comparison, the different tumors displayed a pattern with qualitative and quantitative alterations. Since protein-carbohydrate interaction mediated by carbohydrate-binding proteins (lectins) is of importance for cognitive processes, it is remarkable that the pattern of membrane glycoproteins, isolated by affinity chromatography on resins with immobilized plant lectins, had also been found to reveal certain individual properties for receptors specific for peanut agglutinin (PNA) and Ulex europaeus agglutinin (UEA). These demonstrated differences within the system of protein-carbohydrate interaction suggest that endogenous lectins and their ligands have potential significance as markers defining a certain phenotype within this tumor model system.Dedicated to Prof. Dr. W. Lamprecht on the occasion of his 60th birthday     

Signatures of diversifying selection at EST‐SSR loci and association with climate in natural Eucalyptus populations

Understanding the environmental parameters that drive adaptation among populations is important in predicting how species may respond to global climatic changes and how gene pools might be managed to conserve adaptive genetic diversity. Here, we used Bayesian F_ST outlier tests and allele–climate association analyses to reveal two Eucalyptus EST‐SSR loci as strong candidates for diversifying selection in natural populations of a southwestern Australian forest tree, Eucalyptus gomphocephala (Myrtaceae). The Eucalyptus homolog of a CONSTANS‐like gene was an F_ST outlier, and allelic variation showed significant latitudinal clinal associations with annual and winter solar radiation, potential evaporation, summer precipitation and aridity. A second F_ST outlier locus, homologous to quinone oxidoreductase, was significantly associated with measures of temperature range, high summer temperature and summer solar radiation, with important implications for predicting the effect of temperature on natural populations in the context of climate change. We complemented these data with investigations into neutral population genetic structure and diversity throughout the species range. This study provides an investigation into selection signatures at gene‐homologous EST‐SSRs in natural Eucalyptus populations, and contributes to our understanding of the relationship between climate and adaptive genetic variation, informing the conservation of both putatively neutral and adaptive components of genetic diversity.     

Epidermal growth factor receptor and notch pathways participate in the tumor suppressor function of gamma-secretase

Gamma-secretase, a unique aspartyl protease, is required for the regulated intramembrane proteolysis of Notch and APP, pathways that are implicated, respectively, in the pathogenesis of cancer and Alzheimer disease. However, the mechanism whereby reduction of gamma-secretase causes tumors such as squamous cell carcinoma (SCC) remains poorly understood. Here, we demonstrate that gamma-secretase functions in epithelia as a tumor suppressor in an enzyme activity-dependent manner. Notch signaling is down-regulated and epidermal growth factor receptor (EGFR) is activated in SCC caused by genetic reduction of gamma-secretase. Moreover, the level of EGFR is inversely correlated with the level of gamma-secretase in fibroblasts, suggesting that the up-regulation of EGFR stimulates hyperproliferation in epithelia of mice with genetic reduction of gamma-secretase. Supporting this notion is our finding that the proliferative response of fibroblasts lacking gamma-secretase activity is more sensitive when challenged by either EGF or an inhibitor of EGFR as ompared with wild type cells. Interestingly, the up-regulation of EGFR is independent of Notch signaling, suggesting that the EGFR pathway functions in parallel with Notch in the tumorigenesis of SCC. Collectively, our results establish a novel mechanism linking the EGFR pathway to the tumor suppressor role of gamma-secretase and that mice with genetic reduction of gamma-secretase represent an excellent rodent model for clarifying pathogenesis of SCC and for testing therapeutic strategy to ameliorate this type of human cancer.     

The consequences of rewardlessness in orchids: reward-supplementation experiments with Anacamptis morio (Orchidaceae)

Pollinators are expected to respond to low reward availability in an inflorescence by visiting fewer flowers before departure, thus potentially causing reduced visitation, but also reduced geitonogamous selfing. I tested this hypothesis using Anacamptis morio, an orchid that does not reward its pollinators. Supplementation of inflorescences with artificial nectar did not result in an increase in fruit set on supplemented inflorescences compared to control inflorescences and tended to reduce pollinia removal. Supplementation resulted in reduced fruit quality, but there was no evidence that this was as a result of inbreeding depression. Behavioral experiments showed that pollinating bumble bees, as predicted, visited more flowers on supplemented inflorescences. Bumble bees also deposited more self-pollen on supplemented inflorescences, but this was marginally significant. Bumble bee queens removed significantly more pollinia from control inflorescences, while Bombus terrestris and B. lucorum workers did not. I conclude that while pollinators behaved as predicted, there was weak evidence that pollinia removal, pollen deposition, and fruit set followed the predictions of the hypothesis. I argue that this was probably because some pollinators were more efficient at removing and depositing pollen on control inflorescences, while others were not.     

Soil phosphorus fractions and adsorption as affected by organic and inorganic sources

The effect of organic and inorganic sources of phosphorus (P) on soil P fractions and P adsorption was studied in a field without plant growth on a Kandiudalf in western Kenya. A high-quality organic source, Tithonia diversifolia (Hemsley) A. Gray leaves, and a low-quality source, maize (Zea mays L.) stover, were applied alone or in combination with triple superphosphate (TSP). The P rate was kept constant at 15 kg P ha^-1. Soil extractable P (resin, bicarbonate and sodium hydroxide), microbial biomass P and C and P adsorption isotherms were determined during 16 weeks after application of treatments. Application of tithonia either alone or with TSP increased resin P, bicarbonate P, microbial P, and sodium hydroxide inorganic P. Tithonia alone reduced P adsorption at 2–16 weeks. Maize stover had no effect on any of the P fractions or P adsorption. At 8 weeks, the application of tithonia reduced microbial C-to-P ratio (20) as compared to maize stover, TSP and the control (31–34). The reduction in P adsorption by tithonia was accompanied by increases in all measured P fractions, the sum of P in those fractions (resin, bicarbonate and sodium hydroxide) being larger than the P added. The reduction in P adsorption apparently resulted from competition for adsorption sites, probably by organic anions produced during decomposition of the high quality tithonia. Integration of inorganic P (TSP) with organic materials had little added benefit compared to sole application of TSP, except that combination of tithonia with TSP increased microbial biomass. The results indicate that a high quality organic input can be comparable to or more effective than inorganic P in increasing P availability in the soil.     

Discovery of halo-nitrobenzamides with potential application against human African trypanosomiasis

A series of halo-nitrobenzamide were synthesized and evaluated for their ability to block proliferation of Trypanosoma brucei brucei. A number of these compounds had significant activity against the parasite, particularly 2-chloro-N-(4-chlorophenyl)-5-nitrobenzamide 17 which exhibited low micromolar inhibitory potency against T. brucei and selectivity towards both malaria and mammalian cells.     

When Is Group Membership Zero-Sum? Effects of Ethnicity,Threat, and Social Identity on Dual National Identity

This paper presents an investigation into marginalizing racism, a form of prejudice whereby ingroup members claim that specific individuals belong to their group, but also exclude them by not granting them all of the privileges of a full ingroup member. One manifestation of this is that perceived degree of outgroup membership will covary negatively with degree of ingroup membership. That is, group membership may be treated as a zero-sum quantity (e.g., one cannot be both Australian and Iraqi). Study 1 demonstrated that judges allocate more zero-sum membership assignments and lower combined membership in their country of origin and their adopted country to high-threat migrants than low-threat migrants. Study 2 identified a subtle type of zero-sum reasoning which holds that stronger degree of membership in one’s original nationality constrains membership in a new nationality to a greater extent than stronger membership in the new nationality constrains membership in one’s original nationality. This pattern is quite general, being replicated in large samples from four nations (USA, UK, India, and China). Taken together, these studies suggest that marginalizing racism is more than a belief that people retain a “stain” from membership in their original group. Marginalizing racism also manifests itself as conditional zero-sum beliefs about multiple group memberships.     

Impact of Malaria Control on Mortality and Anemia among Tanzanian Children Less than Five Years of Age, 1999–2010

Background

Mainland Tanzania scaled up multiple malaria control interventions between 1999 and 2010. We evaluated whether, and to what extent, reductions in all-cause under-five child mortality (U5CM) tracked with malaria control intensification during this period.

Methods

Four nationally representative household surveys permitted trend analysis for malaria intervention coverage, severe anemia (hemoglobin <8 g/dL) prevalence (SAP) among children 6–59 months, and U5CM rates stratified by background characteristics, age, and malaria endemicity. Prevalence of contextual factors (e.g., vaccination, nutrition) likely to influence U5CM were also assessed. Population attributable risk percentage (PAR%) estimates for malaria interventions and contextual factors that changed over time were used to estimate magnitude of impact on U5CM.

Results

Household ownership of insecticide-treated nets (ITNs) rose from near zero in 1999 to 64% (95% CI, 61.7–65.2) in 2010. Intermittent preventive treatment of malaria in pregnancy reached 26% (95% CI, 23.6–28.0) by 2010. Sulfadoxine-pyrimethamine replaced chloroquine in 2002 and artemisinin-based combination therapy was introduced in 2007. SAP among children 6–59 months declined 50% between 2005 (11.1%; 95% CI, 10.0–12.3%) and 2010 (5.5%; 95% CI, 4.7–6.4%) and U5CM declined by 45% between baseline (1995–9) and endpoint (2005–9), from 148 to 81 deaths/1000 live births, respectively. Mortality declined 55% among children 1–23 months of age in higher malaria endemicity areas. A large reduction in U5CM was attributable to ITNs (PAR% = 11) with other malaria interventions adding further gains. Multiple contextual factors also contributed to survival gains.

Conclusion

Marked declines in U5CM occurred in Tanzania between 1999 and 2010 with high impact from ITNs and ACTs. High-risk children (1–24 months of age in high malaria endemicity) experienced the greatest declines in mortality and SAP. Malaria control should remain a policy priority to sustain and further accelerate progress in child survival.     

Effects of inhaled corticosteroids on sputum cell counts in stable chronic obstructive pulmonary disease: a systematic review and a meta-analysis

Background

Whether inhaled corticosteroids suppress airway inflammation in chronic obstructive pulmonary disease (COPD) remains controversial. We sought to determine the effects of inhaled corticosteroids on sputum indices of inflammation in stable COPD.

Methods

We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Databases for randomized, controlled clinical trials that used induced sputum to evaluate the effect of inhaled corticosteroids in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of sputum cells before and after treatment in both intervention and control groups. These values were then converted into standardized mean differences to accommodate the differences in patient selection, clinical treatment, and biochemical procedures that were employed across original studies. If significant heterogeneity was present (p < 0.10), then a random effects model was used to pool the original data. In the absence of significant heterogeneity, a fixed effects model was used.

Results

We identified six original studies that met the inclusion criteria (N = 162 participants). In studies with higher cumulative dose (≥ 60 mg) or longer duration of therapy (≥ 6 weeks), inhaled corticosteroids were uniformly effective in reducing the total cell, neutrophil, and lymphocyte counts. In contrast, studies with lower cumulative dose (< 60 mg) or shorter duration of therapy (< 6 weeks) did not demonstrate a favorable effect of inhaled corticosteroids on these sputum indices.

Conclusions

Our study suggests that prolonged therapy with inhaled corticosteroids is effective in reducing airway inflammation in stable COPD.