Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension

Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%–2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5′ region of Uromodulin (UMOD; rs13333226, combined P value of 3.6×10⁻¹¹). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84–0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860–0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83–0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83–0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.     

A Sarcocystid Misidentified as Hepatozoon didelphydis: Molecular Data from a Parasitic Infection in the Blood of the Southern Mouse Opossum (Thylamys elegans) from Chile

ABSTRACT. The blood of 21 adult South American mouse opossums (Thylamys elegans) captured from April through August of 2005 in central Chile was examined for parasites. Light microscopic analysis of blood smears initially suggested that a highly pleomorphic Hepatozoon species typical of American opossums was infecting erythrocytes. Unexpectedly, amplification by PCR and sequencing of a DNA fragment of the small subunit rDNA combined with phylogenetic analyses indicated that the parasite is not a member of the suborder Adeleorina, which includes the Haemogregarina and Hepatozoon species, but that it is a clearly distinct member of the suborder Eimeriorina, which includes the cyst‐forming family Sarcocystidae. Therefore, a reclassification of this unusual intraerythrocytic apicomplexan will require additional life cycle, microscopic, and molecular analyses.     

Impaired associative learning in schizophrenia: behavioral and computational studies

Associative learning is a central building block of human cognition and in large part depends on mechanisms of synaptic plasticity, memory capacity and fronto–hippocampal interactions. A disorder like schizophrenia is thought to be characterized by altered plasticity, and impaired frontal and hippocampal function. Understanding the expression of this dysfunction through appropriate experimental studies, and understanding the processes that may give rise to impaired behavior through biologically plausible computational models will help clarify the nature of these deficits. We present a preliminary computational model designed to capture learning dynamics in healthy control and schizophrenia subjects. Experimental data was collected on a spatial-object paired-associate learning task. The task evinces classic patterns of negatively accelerated learning in both healthy control subjects and patients, with patients demonstrating lower rates of learning than controls. Our rudimentary computational model of the task was based on biologically plausible assumptions, including the separation of dorsal/spatial and ventral/object visual streams, implementation of rules of learning, the explicit parameterization of learning rates (a plausible surrogate for synaptic plasticity), and learning capacity (a plausible surrogate for memory capacity). Reductions in learning dynamics in schizophrenia were well-modeled by reductions in learning rate and learning capacity. The synergy between experimental research and a detailed computational model of performance provides a framework within which to infer plausible biological bases of impaired learning dynamics in schizophrenia.     

Notch signaling specifies megakaryocyte development from hematopoietic stem cells

In the hematopoietic system, Notch signaling specifies T cell lineage fate, in part through negative regulation of B cell and myeloid lineage development. However, we unexpectedly observed the development of megakaryocytes when using heterotypic cocultures of hematopoietic stem cells with OP9 cells expressing Delta-like1, but not with parental OP9 cells. This effect was abrogated by inhibition of Notch signaling either with gamma-secretase inhibitors or by expression of the dominant-negative Mastermind-like1. The importance of Notch signaling for megakaryopoietic development in vivo was confirmed by using mutant alleles that either activate or inhibit Notch signaling. These findings indicate that Notch is a positive regulator of megakaryopoiesis and plays a more complex role in cell-fate decisions among myeloid progenitors than previously appreciated.     

Comparative algological and bacteriological examinations on biofilms developed on different substrata in a shallow soda lake

According to the European Water Framework Directives, benthic diatoms of lakes are a tool for ecological status assessment. In this study, we followed an integrative sample analysis approach, in order to find an appropriate substratum for the water qualification-oriented biomonitoring of a shallow soda lake, Lake Velencei. Six types of substrata (five artificial and one natural), i.e., andesite, granite, polycarbonate, old reed stems, Plexiglass discs and green reed, were sampled in May and in November. We analysed total alga and diatom composition, chlorophyll a content of the periphyton, surface tension and roughness of the substrata and carbon source utilisation of microbial communities. Water quality index was calculated based on diatom composition. Moreover, using a novel statistical tool, a self-organising map, we related algal composition to substratum types. Biofilms on plastic substrates deviated to a great extent from the stone and reed substrata, with regard to the parameters measured, whereas the biofilms developing on reed and stone substrata were quite similar. We conclude that for water quality monitoring purposes, sampling from green reed during springtime is not recommended, since this is the colonization time of periphyton on the newly growing reed, but it may be appropriate from the second half of the vegetation period. Stone and artificially placed old reed substrata may be appropriate for biomonitoring of shallow soda lakes in both spring and autumn since they showed in both seasons similar results regarding all measured features.     

Quantity versus quality: Endemism and protected areas in the temperate forest of South America

Abstract Identification of biodiversity hotspots is essential to conservation strategies aimed at minimizing the possibility of losing half of the world's species in the next 50 years. The aims of the present study were: (i) to locate and designate zones of endemism in the temperate forest of South America; and (ii) to compare the distribution of these areas with the distribution of existing protected areas in this habitat type. Endemism areas were determined by using parsimonious analysis of endemism, which identified zones of endemism on the basis of sets of endemic species that were restricted to two or more study areas. We used distribution information for five unrelated taxa (ferns, trees, reptiles, birds and mammals) to provide more reliable results and patterns than would work with only a single taxon or related taxa. The northern part of this region has high endemism for all of the taxa considered in this study. We demonstrate that although the temperate forest of South America has more than 30% of its area under some type of protection, correlation between protected areas and the areas of endemism is remarkably low. In fact, less than 10% of protected areas are situated in areas that have the greatest value for conservation (i.e. high endemism). Under the current strategy, biodiversity within South America's temperate forest is in danger despite the large amount of protected area for this forest type.     

Ant diversity in an Amazonian savanna: Relationship with vegetation structure,disturbance by fire,and dominant ants

Abstract The savannas of South America support a relatively diverse ant fauna, but little is known about the factors that influence the structure and dynamics of these assemblages. In 1998 and 2002, we surveyed the ground‐dwelling ant fauna and the fauna associated with the woody vegetation (using baits and direct sampling) from an Amazonian savanna. The aim was to evaluate the influence of vegetation structure, disturbance by fire and dominant ants on patterns of ant species richness and composition. Variations in the incidence of fires among our 39 survey plots had no or only limited influence on these patterns. In contrast, spatial variations in tree cover and cover by tall grasses (mostly Trachypogon plumosus), significantly affected ant species composition. Part of the variation in species richness among the study plots correlated with variations in the incidence of a dominant species (Solenopsis substituta) at baits. Ant species richness and composition also varied through time, possibly as an indirect effect of changes in vegetation cover. In many plots, and independently of disturbance by fire, there was a major increase in cover by tall grasses, which occupied areas formerly devoid of vegetation. Temporal changes in vegetation did not directly explain the observed increase in the number of ant species per plot. However, the incidence of S. substituta at baits declined sharply in 2002, especially in plots where changes in vegetation cover were more dramatic, and that decline was correlated with an increase in the number of ground‐dwelling species, a greater turnover of bait‐recruiting species and the appearance of the little fire ant Wasmannia auropunctata. The extent to which these changes in fact resulted from the relaxation of dominance by S. substituta is not clear. However, our results strongly suggest that the ant fauna of Amazonian savannas is affected directly and indirectly by the structure of the vegetation.     

Leishmania infection can hamper immune recovery in virologically suppressed HIV-infected patients

An HIV-infected patient started combination antiretroviral therapy with 13 CD4+ cells/microL. Despite sustained virological suppression over the following four years, the anemia did not resolve, and the CD4+ cell counts always remained below 200/microL until co-infection with Leishmania was diagnosed in October 2006 when the patient started complaining of persistent mild fever and asthenia. Once treatment for leishmaniasis was started with miltefosine, CD4+ cell count rose above 400/microL. A new drop in CD4+ cell count was observed when Leishmania DNA turned out again to be positive, but treatment with liposomal amphotericin-B restored immune recovery.     

Polyploid evolution and plastid DNA variation in the Dactylorhiza incarnata/maculata complex (Orchidaceae) in Scandinavia

The Dactylorhiza incarnata/maculata complex (Orchidaceae) was used as a model system to understand genetic differentiation processes in a naturally occurring polyploid complex with much of ongoing diversification and wide distribution in recently glaciated areas in northern Europe. Data were obtained for 12 hypervariable regions in the plastid DNA genome. A total of 166 haplotypes were found in a sample of 1099 plants. Allopolyploid taxa have inherited their plastid genomes from D. maculata s.l. Overall haplotype diversity of the combined group of allopolyploid taxa was comparable to that of maternal D. maculata s.l., but populations of allopolyploids were also more strongly differentiated from each other and contained lower numbers of haplotypes than populations of D. maculata s.l. In addition to haplotypes found in extant D. maculata s.l., the allopolyploids also contained several distinct and widespread haplotypes that were not found in any of the parental lineages. Some of these haplotypes were shared between widespread allopolyploids. Divergent allopolyploids with small distributions did not seem to originate from local polyploidization events, but rather as segregates of already existing allopolyploids. Genetic diversification of allopolyploid Dactylorhiza is the result of repeated polyploid formation, secondary hybridization and introgression between already existing polyploids and extant representatives of parental lineages, hybridization between independently derived polyploid lineages, and phyletic diversification in the group of allopolyploids. Although some polyploid taxa must have evolved after the last glaciation, genetic material from the parental lineages has been transferred continuously for longer periods of time. This combination of processes may explain the taxonomic complexity encountered in Dactylorhiza and other polyploid complexes distributed in previously glaciated parts of Europe.