Global biodiversity patterns of marine phytoplankton and zooplankton

Although the oceans cover 70% of the Earth's surface, our knowledge of biodiversity patterns in marine phytoplankton and zooplankton is very limited compared to that of the biodiversity of plants and herbivores in the terrestrial world. Here, we present biodiversity data for marine plankton assemblages from different areas of the world ocean. Similar to terrestrial vegetation, marine phytoplankton diversity is a unimodal function of phytoplankton biomass, with maximum diversity at intermediate levels of phytoplankton biomass and minimum diversity during massive blooms. Contrary to expectation, we did not find a relation between phytoplankton diversity and zooplankton diversity. Zooplankton diversity is a unimodal function of zooplankton biomass. Most strikingly, these marine biodiversity patterns show a worldwide consistency, despite obvious differences in environmental conditions of the various oceanographic regions. These findings may serve as a new benchmark in the search for global biodiversity patterns of plants and herbivores.     

An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus

Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at risk of developing significant morbidity and mortality. Current interferon-based therapies are suboptimal especially in patients infected with HCV genotype 1, and they are poorly tolerated, highlighting the unmet medical need for new therapeutics. The HCV-encoded NS3 protease is essential for viral replication and has long been considered an attractive target for therapeutic intervention in HCV-infected patients. Here we identify a class of specific and potent NS3 protease inhibitors and report the evaluation of BILN 2061, a small molecule inhibitor biologically available through oral ingestion and the first of its class in human trials. Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 protease inhibitor. Our results further illustrate the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics.     

The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria

Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity--including haemolysins, phospholipases and iron acquisition functions--and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis.     

Structure of a nanobody-stabilized active state of the β(2) adrenoceptor

G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β(2) adrenergic receptor (β(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11?? outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation.     

Estimation procedures for understory biomass and fuel loads in sagebrush steppe invaded by woodlands

Regression equations were developed to predict biomass for 9 shrubs, 9 grasses, and 10 forbs that generally dominate sagebrush ecosystems in central Nevada. Independent variables included percent cover, average height, and plant volume. We explored 2 ellipsoid volumes: one with maximum plant height and 2 crown diameters and another with live crown height and 2 crown diameters. Dependent variables were total, live, leaf, and dead biomass. Simple, multiple, linear, and power equations were investigated. Models were chosen based on scatter plots, residual plots, and R 2 and SEE values. In general, simple power equations provided the best-fit regressions. For shrubs, the ellipsoid volume computed with maximum plant height best predicted total plant weight, and the ellipsoid volume computed with the live crown height best predicted shrub foliage weight. In addition to regression equations for biomass, ratios for division of that biomass into 1-, 10-, 100-, and 1000-hour fuels were derived for common large shrubs. Regression equations were also derived to relate litter mat sizes of major shrub species to litter weights. The equations in this paper could be used to predict biomass in other areas of the Great Basin if training data were taken to validate or adjust these models.     

The Children's Planning Initiative: Researching Decision-Making for Children

This paper recounts the story of how a number of workers involved in the care of children decided that they needed to do more than improve their skills and began instead to question some of the assumptions on which child care planning processes are built. The paper records a growing consciousness about the value of action research in developing alternative models of decision-making. It leads us from early questioning, through model creation, and on into testing the model in a new and complex organizational setting. While other voices are quoted, the paper recounts the story from the viewpoint of two actors, practitioner/manager and consultant.     

Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes

Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes.     

Common variation at 10p12.31 near MLLT10 influences meningioma risk

To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 × 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.