Rapid diversification of sexual signals in Hawaiian Nesosydne planthoppers (Hemiptera: Delphacidae): the relative role of neutral and selective forces

Changes in sexual signals have the potential to promote rapid divergence and reproductive isolation among populations of animals. Thus, identifying processes contributing to variation in signals is key to understanding the drivers of speciation. However, it is difficult to identify the processes initiating changes in signals in empirical systems because (1) the demographic history of populations under study is usually unclear, and (2) there is no unified hypothesis‐testing framework for evaluating the simultaneous contribution of multiple processes. A unique system for study in the Hawaiian Islands, the planthopper species Nesosydne chambersi, offers a clear demographic context to disentangle these factors. By measuring variation in male vibratory sexual signals across different genetic populations on the island of Hawaii, we found that that multiple signal traits varied significantly between populations. We developed a mixed modelling framework to simultaneously test competing hypotheses about which processes contribute to changes in signal traits: genetic drift, sensory drive or reproductive character displacement. Our findings suggest that signal divergence proceeds along different axes for different signal traits under the influence of both neutral and selective processes. They are the first, to our knowledge, to document the relative importance of multiple processes on divergence in sexual signals.     

Assessment of regional and local biodiversity in tropical and subtropical coastal habitats in the East African Marine Ecoregion

The transboundary networks of Marine Protected Areas (MPAs) project, TRANSMAP, assessed local turnover and regional biodiversity across the East African Marine Ecoregion, where inter-governmental co-operation has been working to connect local MPAs. The benthic fauna in the three most dominant habitats on this coastline??beaches, mangroves and seagrasses??were studied in two Regions (Northern Region, 10?C13°S; Southern Region, 25?C28°S). Meiofaunal taxa were used as the model faunal group owing to their diversity and abundance across habitat types and environmental conditions. Meiofaunal abundance averaged 2,500 individuals 10 cm^?2 and was generally higher in mangrove and seagrass sediments than on the beaches, and was significantly different between habitats × Regions. In total, 18 taxa were recorded with highest diversity in the beach samples. Diversity indices and assemblage structure were significantly different between habitats, but also Regions. Specific granulometric 1?? size classes, shore-height and number of rain days were the factors most significantly correlating with the observed assemblage patterns. Additionally, the size of a MPA and latitude (which correlated with MPA age, but not number of rain days), were the factors fitting best with meiofaunal assemblage patterns across the beaches, the habitat for which the most comprehensive data were generated. Sample diversity was higher in the Southern Region, and although within- and across-habitats diversity were similar across the Regions, the two Regions appeared to provide complementary habitats and supported different assemblages. Within the Regions, beaches (the only habitat for which more than one location was sampled) were significantly different between Locations, supporting the establishment of multiple protected locations of the same habitat within each transboundary MPA.     

Acylideneoxoindoles: a new class of reversible inhibitors of human transglutaminase 2

Inhibitors of human transglutaminase 2 (TG2) are anticipated to be useful in the therapy of a variety of diseases including celiac sprue as well as certain CNS disorders and cancers. A class of 3-acylidene-2-oxoindoles was identified as potent reversible inhibitors of human TG2. Structure-activity relationship analysis of a lead compound led to the generation of several potent, competitive inhibitors. Analogs with significant non-competitive character were also identified, suggesting that the compounds bind at one or more allosteric regulatory sites on this multidomain enzyme. The most active compounds had K_i values below 1.0 μM in two different kinetic assays for human TG2, and may therefore be suitable for investigations into the role of TG2 in physiology and disease in animals.     

First crystal structures of Na+,K+-ATPase: new light on the oldest ion pump

Na(+),K(+)-adenosine triphosphatase (NKA) is the first P-type ion translocating adenosine triphosphatase (ATPase) ever identified, and the significance of this class of proteins was highlighted by the 1997 Nobel Prize in Chemistry awarded to Jens C. Skou for the discovery in 1957. More than half a century passed between the initial identification and the publication of a high-resolution crystal structure of NKA. Although the new crystal structures provided many surprises and insights, structural biology on this system remains challenging, as NKA is a very difficult protein to crystallize. Here we explain the reasons behind the challenges, introduce a mechanism that governs the function, and summarize current knowledge of NKA structure in comparison with another member of the P-type ATPase family, Ca(2+)-ATPase.     

A pilot randomised trial of induced blood-stage Plasmodium falciparum infections in healthy volunteers for testing efficacy of new antimalarial drugs

Background

Critical to the development of new drugs for treatment of malaria is the capacity to safely evaluate their activity in human subjects. The approach that has been most commonly used is testing in subjects with natural malaria infection, a methodology that may expose symptomatic subjects to the risk of ineffective treatment. Here we describe the development and pilot testing of a system to undertake experimental infection using blood stage Plasmodium falciparum parasites (BSP). The objectives of the study were to assess the feasibility and safety of induced BSP infection as a method for assessment of efficacy of new drug candidates for the treatment of P. falciparum infection.

Methods and Findings

A prospective, unblinded, Phase IIa trial was undertaken in 19 healthy, malaria-naïve, male adult volunteers who were infected with BSP and followed with careful clinical and laboratory observation, including a sensitive, quantitative malaria PCR assay. Volunteers were randomly allocated to treatment with either of two licensed antimalarial drug combinations, artemether–lumefantrine (A/L) or atovaquone-proguanil (A/P). In the first cohort (n = 6) where volunteers received ∼360 BSP, none reached the target parasitemia of 1,000 before the day designated for antimalarial treatment (day 6). In the second and third cohorts, 13 volunteers received 1,800 BSP, with all reaching the target parasitemia before receiving treatment (A/L, n = 6; A/P, n = 7) The study demonstrated safety in the 19 volunteers tested, and a significant difference in the clearance kinetics of parasitemia between the drugs in the 13 evaluable subjects, with mean parasite reduction ratios of 759 for A/L and 17 for A/P (95% CI 120–4786 and 7–40 respectively; p<0.01).

Conclusions

This system offers a flexible and safe approach to testing the in vivo activity of novel antimalarials.

Trial Registration:

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01055002","term_id":"NCT01055002"}}NCT01055002     

The effect of ozone on the yellowing process of magnesium-deficient clonal Norway spruce grown under defined conditions

During two vegetation periods, young clonal spruce trees (Picea abies (L.) Karst.) with sufficient and poor magnesium (Mg) supply were exposed in the environmental chambers of the GSF phytotron to three levels of ozone (daily means: 18-22, 88-130, and 135-190 microg m(-3); 10% reduction at night). Previous year's needles were examined at 4-week intervals with respect to their contents of Mg, Ca, K, Mn, N, P, and chlorophyll (Chl), various parameters of Chl fluorescence, and the stability of the isolated light-harvesting Chl-a/b-protein complex LHC II. The needles of the two nutrition variants contained more than 0.53 or less than 0.27mg Mg g(-1) needle dry matter, respectively. The ratio of variable to maximal Chl-a fluorescence of the dark-adapted needles, Fv/Fm, and the photoinhibitory quenching of Fv after light treatment, SVi.v, were affected by the Mg content of the needles rather than the ozone levels. Changes of the Chl content and the behavior of the LHC II allowed differentiating between a slow process of needle yellowing occurring under Mg deficiency only, and a rapid process of needle yellowing occurring under the combined action of Mg deficiency and ozone pollution. Only the rapid yellowing process was accompanied by destabilization of the LHC II, and the degree of destabilization was correlated with the ozone concentration present in the days before sampling. The results are consistent with observations obtained at a research site in the Central Black Forest (J Plant Physiol 161 (2004) 423).     

High-throughput aggregate culture system to assess the chondrogenic potential of mesenchymal stem cells

We have developed an improved method for preparing cell aggregates for in vitro chondrogenesis studies. This method is a modification of a previously developed conical tube-based culture system that replaces the original 15-mL polypropylene tubes with 96-well plates. These modifications allow a high-throughput approach to chondrogenic cultures, which reduces both the cost and time to produce chondrogenic aggregates, with no detrimental effects on the histological and histochemical qualities of the aggregates. We prepared aggregates in both systems with human bone marrow-derived mesenchymal stem cells (hMSC). The aggregates were harvested after 2 and 3 weeks in chondrogenic culture and analyzed for their ability to differentiate along the chondrogenic pathway in a defined in vitro environment. Chondrogenic differentiation was assessed biochemically by DNA and glycosaminoglycan (GAG) quantification assays and by histological and immunohistologic assessment. The chondrogenic cultures produced in the 96-well plates appear to be slightly larger in size and contain more DNA and GAG than the aggregates made in tubes. When analyzed histologically, both systems demonstrate morphological characteristics that are consistent with chondrogenic differentiation and cartilaginous extracellular matrix production.     

Contribution of Archaea to total prokaryotic production in the deep Atlantic Ocean

Fluorescence in situ hybridization (FISH) in combination with polynucleotide probes revealed that the two major groups of planktonic Archaea (Crenarchaeota and Euryarchaeota) exhibit a different distribution pattern in the water column of the Pacific subtropical gyre and in the Antarctic Circumpolar Current system. While Euryarchaeota were found to be more dominant in nearsurface waters, Crenarchaeota were relatively more abundant in the mesopelagic and bathypelagic waters. We determined the abundance of archaea in the mesopelagic and bathypelagic North Atlantic along a south-north transect of more than 4,000 km. Using an improved catalyzed reporter deposition-FISH (CARD-FISH) method and specific oligonucleotide probes, we found that archaea were consistently more abundant than bacteria below a 100-m depth. Combining microautoradiography with CARD-FISH revealed a high fraction of metabolically active cells in the deep ocean. Even at a 3,000-m depth, about 16% of the bacteria were taking up leucine. The percentage of Euryarchaeota and Crenarchaeaota taking up leucine did not follow a specific trend, with depths ranging from 6 to 35% and 3 to 18%, respectively. The fraction of Crenarchaeota taking up inorganic carbon increased with depth, while Euryarchaeota taking up inorganic carbon decreased from 200 m to 3,000 m in depth. The ability of archaea to take up inorganic carbon was used as a proxy to estimate archaeal cell production and to compare this archaeal production with total prokaryotic production measured via leucine incorporation. We estimate that archaeal production in the mesopelagic and bathypelagic North Atlantic contributes between 13 to 27% to the total prokaryotic production in the oxygen minimum layer and 41 to 84% in the Labrador Sea Water, declining to 10 to 20% in the North Atlantic Deep Water. Thus, planktonic archaea are actively growing in the dark ocean although at lower growth rates than bacteria and might play a significant role in the oceanic carbon cycle.