Attenuation of dengue virus infection by adeno-associated virus-mediated siRNA delivery

BACKGROUND: The need for safe and effective treatment of dengue virus (DEN), a class A agent that causes dengue hemorrhagic fever/dengue shock syndrome, has been a critical global priority. An effective vaccine for DEN is not yet available. In this study the possibility of attenuating DEN infection using adeno-associated virus (AAV)-encoded short interfering RNAs (siRNA) was examined in Vero cells and human dendritic cells (DCs). METHODS: A cassette encoding siRNA targeted to a 3' untranslated sequence common to all DEN serotypes was designed and tested for its ability to attenuate DEN infection by use of AAV delivery. RESULTS: Vero cells or DCs infected with AAV-siRNA showed a significant, dose-dependent reduction in DEN infection. Treatment of DCs with AAV-siRNA also decreased the DEN-induced apoptosis of DCs and did not induce significant inflammation. CONCLUSION: These results demonstrate that AAV-mediated siRNA delivery is capable of reducing DEN infection in cells and may be useful in decreasing DEN replication in humans.     

Differential accumulation and pigmenting ability of dietary carotenoids in colorful finches

Many animals develop bright red, orange, or yellow carotenoid pigmentation that they use to attract mates. Colorful carotenoid pigments are acquired from the diet and are either directly incorporated as integumentary colorants or metabolized into other forms before deposition. Because animals often obtain several different carotenoids from plant and animal food sources, it is possible that these pigments are accumulated at different levels in the body and may play unique roles in shaping the ultimate color expression of individuals. We studied patterns of carotenoid accumulation and integumentary pigmentation in two colorful finch species--the American goldfinch (Carduelis tristis) and the zebra finch (Taeniopygia guttata). Both species acquire two main hydroxycarotenoids, lutein and zeaxanthin, from their seed diet but transform these into a series of metabolites that are used as colorful pigments in the plumage (goldfinches only) and beak (both species). We conducted a series of carotenoid-supplementation experiments to investigate the relative extent to which lutein and zeaxanthin are accumulated in blood and increase carotenoid coloration in feathers and bare parts. First, we supplemented the diets of both species with either lutein or zeaxanthin and measured plasma pigment status, feather carotenoid concentration (goldfinches only), and integumentary color. Zeaxanthin-supplemented males grew more colorful feathers and beaks than lutein-supplemented males, and in goldfinches incorporated a different ratio of carotenoids in feathers (favoring the accumulation of canary xanthophyll B). We also fed goldfinches different concentrations of a standard lutein-zeaxanthin mix and found that at physiologically normal and high concentrations, birds circulated proportionally more zeaxanthin over lutein than occurred in the diet. Collectively, these results demonstrate that zeaxanthin is preferentially accumulated in the body and serves as a more potent substrate for pigmentation than lutein in these finches.     

Beyond prostate-specific antigen: new serologic biomarkers for improved diagnosis and management of prostate cancer

The use of total prostate-specific antigen (tPSA) measurement has dramatically improved the ability to detect prostate cancer at earlier stages. However, as the number of men presenting with advanced disease (and high tPSA levels) has decreased, and given the fact that tPSA is highly reflective of benign prostatic hyperplasia, the need has emerged for novel biomarkers specifically associated with prostate cancer in order to improve predictive models. Several new biomarkers have shown promise, and studies continue to investigate the role of these markers in the detection, staging, and prognosis of prostate cancer. As new useful biomarkers continue to emerge, guidelines for their employment, as well as coordination of further research studies, are needed; a systematic, phased, nomogram-based model is a rational way to manage these efforts.     

Endothermy in African platypleurine cicadas: the influence of body size and habitat (Hemiptera: Cicadidae)

The platypleurine cicadas have a wide distribution across Africa and southern Asia. We investigate endothermy as a thermoregulatory strategy in 11 South African species from five genera, with comparisons to the lone ectothermic platypleurine we found, in an attempt to ascertain any influence that habitat and/or body size have on the expression of endothermy in the platypleurine cicadas. Field measurements of body temperature (T(b)) show that these animals regulate T(b) through endogenous heat production. Heat production in the laboratory elevated T(b) to the same range as in animals active in the field. Maximum T(b) measured during calling activity when there was no access to solar radiation ranged from 13.2 degrees to 22.3 degrees C above ambient temperature in the five species measured. The mean T(b) during activity without access to solar radiation did not differ from the mean T(b) during diurnal activity. All platypleurines exhibit a unique behavior for cicadas while warming endogenously, a temperature-dependent telescoping pulsation of the abdomen that probably functions in ventilation. Platypleurines generally call from trunks and branches within the canopy and appear to rely on endothermy even when the sun is available to elevate T(b), in contrast to the facultative endothermy exhibited by New World endothermic species. The two exceptions to this generalization we found within the platypleurines are Platypleura wahlbergi and Albanycada albigera, which were the smallest species studied. The small size of P. wahlbergi appears to have altered their thermoregulatory strategy to one of facultative endothermy, whereby they use the sun when it is available to facilitate increases in T(b). Albanycada albigera is the only ectothermic platypleurine we found. The habitat and host plant association of A. albigera appear to have influenced the choice of ectothermy as a thermoregulatory strategy, as the species possesses the metabolic machinery to elevate to the T(b) range observed in the endothermic species. Therefore, size and habitat appear to influence the expression of thermoregulatory strategies in African platypleurine cicadas.     

Pattern and process in Amazon tree turnover, 1976-2001

Previous work has shown that tree turnover, tree biomass and large liana densities have increased in mature tropical forest plots in the late twentieth century. These results point to a concerted shift in forest ecological processes that may already be having significant impacts on terrestrial carbon stocks, fluxes and biodiversity. However, the findings have proved controversial, partly because a rather limited number of permanent plots have been monitored for rather short periods. The aim of this paper is to characterize regional-scale patterns of 'tree turnover' (the rate with which trees die and recruit into a population) by using improved datasets now available for Amazonia that span the past 25 years. Specifically, we assess whether concerted changes in turnover are occurring, and if so whether they are general throughout the Amazon or restricted to one region or environmental zone. In addition, we ask whether they are driven by changes in recruitment, mortality or both. We find that: (i) trees 10 cm or more in diameter recruit and die twice as fast on the richer soils of southern and western Amazonia than on the poorer soils of eastern and central Amazonia; (ii) turnover rates have increased throughout Amazonia over the past two decades; (iii) mortality and recruitment rates have both increased significantly in every region and environmental zone, with the exception of mortality in eastern Amazonia; (iv) recruitment rates have consistently exceeded mortality rates; (v) absolute increases in recruitment and mortality rates are greatest in western Amazonian sites; and (vi) mortality appears to be lagging recruitment at regional scales. These spatial patterns and temporal trends are not caused by obvious artefacts in the data or the analyses. The trends cannot be directly driven by a mortality driver (such as increased drought or fragmentation-related death) because the biomass in these forests has simultaneously increased. Our findings therefore indicate that long-acting and widespread environmental changes are stimulating the growth and productivity of Amazon forests.     

The brain and the law

Much has been written about how law as an institution has developed to solve many problems that human societies face. Inherent in all of these explanations are models of how humans make decisions. This article discusses what current neuroscience research tells us about the mechanisms of human decision making of particular relevance to law. This research indicates that humans are both more capable of solving many problems than standard economic models predict, but also limited in ways those models ignore. This article discusses how law is both shaped by our cognitive processes and also shapes them. The article considers some of the implications of this research for improving our understanding of how our current legal regimes operate and how the law can be structured to take advantage of our neural mechanisms to improve social welfare.     

Structure of the species--energy relationship

The relationship between energy availability and species richness (the species-energy relationship) is one of the best documented macroecological phenomena. However, the structure of species distribution along the gradient, the proximate driver of the relationship, is poorly known. Here, using data on the distribution of birds in southern Africa, for which species richness increases linearly with energy availability, we provide an explicit determination of this structure. We show that most species exhibit increasing occupancy towards more productive regions (occurring in more grid cells within a productivity class). However, average reporting rates per species within occupied grid cells, a correlate of local density, do not show a similar increase. The mean range of used energy levels and the mean geographical range size of species in southern Africa decreases along the energy gradient, as most species are present at high productivity levels but only some can extend their ranges towards lower levels. Species turnover among grid cells consequently decreases towards high energy levels. In summary, these patterns support the hypothesis that higher productivity leads to more species by increasing the probability of occurrence of resources that enable the persistence of viable populations, without necessarily affecting local population densities.     

Synthesis and X-ray crystal structure of [Ag(phendio)<Subscript>2</Subscript>]ClO<Subscript>4</Subscript> (phendio = 1,10-phenanthroline-5,6-dione) and its effects on fungal and mammalian cells

The Cu(II) and Ag(I) complexes, [Cu(phendio)₃](ClO₄)₂4H₂O and [Ag(phendio)₂]ClO₄ (phendio = 1,10-phenanthroline-5,6-dione), are prepared in good yield by reacting phendio with the appropriate metal perchlorate salt. The X-ray crystal structure of the Ag(I) complex shows it to have a pseudo tetrahedral structure. `Metal-free' phendio and the Cu(II) and Ag(I) phendio complexes strongly inhibit the growth of the fungal pathogen Candida albicans, and are more active than their 1,10-phenanthroline analogues. The simple Ag(I) salts, AgCH<sub>3</sub>CO<sub>2</sub>, AgNO<sub>3</sub> and AgClO<sub>4</sub>.H<sub>2</sub>O display superior anti-fungal properties compared to analogous simple Cu(II) and Mn(II) salts, suggesting that the nature of the metal ion strongly influences activity. Exposing C. albicans to `metal-free' phendio, simple Ag(I) salts and [Ag(phendio)₂]ClO₄ causes extensive, non-specific DNA cleavage. `Metal-free' phendio and [Ag(phendio)₂]ClO₄ induce gross distortions in fungal cell morphology and there is evidence for disruption of cell division. Both drugs also exhibit high anti-cancer activity when tested against cultured mammalian cells.