High variability and non-neutral evolution of the mammalian avpr1a gene

<p>Abstract</p> <p>Background</p> <p>The arginine-vasopressin 1a receptor has been identified as a key determinant for social behaviour in <it>Microtus </it>voles, humans and other mammals. Nevertheless, the genetic bases of complex phenotypic traits like differences in social and mating behaviour among species and individuals remain largely unknown. Contrary to previous studies focusing on differences in the promotor region of the gene, we investigate here the level of functional variation in the coding region (exon 1) of this locus.</p> <p>Results</p> <p>We detected high sequence diversity between higher mammalian taxa as well as between species of the genus <it>Microtus</it>. This includes length variation and radical amino acid changes, as well as the presence of distinct protein variants within individuals. Additionally, negative selection prevails on most parts of the first exon of the <it>arginine-vasopressin receptor 1a (avpr1a) </it>gene but it contains regions with higher rates of change that harbour positively selected sites. Synonymous and non-synonymous substitution rates in the <it>avpr1a </it>gene are not exceptional compared to other genes, but they exceed those found in related hormone receptors with similar functions.</p> <p>Discussion</p> <p>These results stress the importance of considering variation in the coding sequence of <it>avpr1a </it>in regards to associations with life history traits (e.g. social behaviour, mating system, habitat requirements) of voles, other mammals and humans in particular.</p

Many-to-One Boundary Labeling with Backbones

In this paper we study \emph{many-to-one boundary labeling with backbone leaders}. In this new many-to-one model, a horizontal backbone reaches out of each label into the feature-enclosing rectangle. Feature points that need to be connected to this label are linked via vertical line segments to the backbone. We present dynamic programming algorithms for label number and total leader length minimization of crossing-free backbone labelings. When crossings are allowed, we aim to obtain solutions with the minimum number of crossings. This can be achieved efficiently in the case of fixed label order, however, in the case of flexible label order we show that minimizing the number of leader crossings is NP-hard.Comment: 23 pages, 10 figures, this is the full version of a paper that is about to appear in GD'1

Genomic Scans Support Repetitive Continental Colonization Events during the Rapid Radiation of Voles (Rodentia: Microtus): the Utility of AFLPs versus Mitochondrial and Nuclear Sequence Markers

Single locus studies might not resolve phylogenetic relationships and the evolutionary history of taxa. The analysis of multiple markers promises higher resolution, and congruence among loci may indicate that the phylogenies represent the underlying species history. Here, we examine the utility of a genome-wide approach based on amplified fragment length polymorphisms (AFLP) and several DNA sequence markers in resolving phylogenetic signals in the rapidly radiating rodent genus Microtus which produced about 70 vole species within the last 1.2-2 myr. The current Holarctic distribution of Microtus is assumed to have resulted from three independent colonization events out of Asia to North America, Europe, and northern Asia without subsequent colonization, which would have led to deep splits between species from different continents. We investigated this hypothesis of three single colonization events by reconstructing the phylogenetic relationships among species from all three continents based on data from the first exon of the nuclear arginine vasopressin receptor 1a gene (EXON1), an adjacent noncoding region and the mitochondrial cytochrome b gene. The phylogenetic patterns obtained from these sequence markers are contrasted to genome-wide data on more than 1800 amplified fragment length polymorphisms (AFLP) analyzed for the same samples. Our results show that the single sequence markers partially resolve the phylogenetic relationships within Microtus, but with some incongruence mostly between EXON1 and the other loci. However, deeper nodes of the radiation are only weakly supported and neither the combination of the markers nor additional nuclear sequences improved the resolution significantly. AFLPs provided much stronger support for major continent-specific clades, and show also that reciprocal monophyly of American and European voles is incomplete. Our results demonstrate that Microtus voles colonized the American and European continents each repeatedly in several independent events on similar colonization routes during their radiation. More generally, this study supports the suitability of AFLPs as an alternative to sequence markers to resolve the evolutionary history of rapidly radiating tax

Gene flow in a pioneer plant metapopulation (Myricaria germanica) at the catchment scale in a fragmented alpine river system

River alterations for natural hazard mitigation and land reclamation result in habitat decline and fragmentation for riparian plant species. Extreme events such as floods are responsible for additional local species loss or population decline. Tributaries might provide refugia and subsequent source populations for the colonization of downstream sites in connected riverine networks with metapopulations of plant species. In this study, we analyzed the metapopulation structure of the endangered riparian shrub species Myricaria germanica along the river Isel, Austria, which is part of the Natura 2000 network, and its tributaries. The use of 22 microsatellite markers allowed us to assess the role of tributaries and single populations as well as gene flow up- and downstream. The analysis of 1307 individuals from 45 sites shows the influence of tributaries to the genetic diversity at Isel and no overall isolation by distance pattern. Ongoing bidirectional gene flow is revealed by the detection of first-generation migrants in populations of all tributaries as well as the river Isel, supporting upstream dispersal by wind (seeds) or animals (seeds and pollen). However, some populations display significant population declines and high inbreeding, and recent migration rates are non-significant or low. The genetic pattern at the mouth of river Schwarzach into Isel and shortly thereafter river Kalserbach supports the finding that geographically close populations remain connected and that tributaries can form important refugia for M. germanica in the dynamic riverine network. Conservation and mitigation measures should therefore focus on providing sufficient habitat along tributaries of various size allowing pioneer plants to cope with extreme events in the main channel, especially as they are expected to be more frequent under changing climate

Genomic scans support repetitive continental colonization events during the rapid radiation of voles (Rodentia: Microtus): the utility of AFLPs versus mitochondrial and nuclear sequence markers

Background According to the World Health Organization position paper, immunodeficiency such as human immunodeficiency virus (HIV) infection is a relative contraindication for specific immunotherapy (SIT). Since the introduction of highly active antiretroviral therapy, a significant reconstitution of immune competence in individuals with HIV is possible.Case Report In a 52-year-old man, HIV infection was diagnosed in 1987. Antiretroviral therapy was started in 1998. He presented himself in July 2001 because of an increasingly severe seasonal rhinoconjunctivitis. Symptoms were not sufficiently alleviated by various antiallergic drugs.Results The investigations showed a relevant sensitization to tree pollens. Specific immunotherapy with a tree pollen mix (hazel, birch, ash, and alder, 25% each) was started in November 2001. Viral load at this time was less than 50 copies/mL, the CD4+ cell count was 307/μL. Therapy was given in monthly intervals until mid-April 2005 without any side effects. Viral load and CD4+ cell counts did not change during SIT. Clinically, rhinoconjunctivitis was experienced only intermittently and symptom relief was almost 90%.Conclusions This report indicates that in patients with well-controlled HIV infection on highly active antiretroviral therapy, SIT with pollen extracts is a potential and successful therapeutic option. Keywords: human immunodeficiency virus, pollen allergy, respiratory allergy, allergy treatment, specific immunotherap

Assessing the impact of the physical properties of industrially produced carbon nanotubes on their interaction with human primary macrophages in vitro

Currently it is not fully understood how carbon nanotubes (CNTs) may affect human health. Despite this, CNTs are produced at a tonne mass scale yearly. Due to their large production and intended use within a variety of applications it is imperative that a clear understanding of the hazard potential of CNTs is gained. The aim of this study therefore was to assess the impact of five different industrially produced CNTs which varied in their physical properties on the viability of human monocyte derived macrophages (MDM), and subsequently, at sub-lethal concentrations (0.005-0.02 mg/mL), their ability to cause oxidative stress and a pro-inflammatory response in these important immune cells over a 24-h period. None of the CNTs caused significant cytotoxicity up to 0.02 mg/mL after 24 h. Only the long multi-walled CNTs (MWNCTs) caused a significant, dose-dependent (0.005-0.02 mg/mL) reactive oxygen species production, whilst bundled MWCNTs showed a significant tumor necrosis factor alpha release after 24 h exposure at 0.02 mg/mL. No effects were observed for either tangled MWCNTs or short MWCNTs. It can be concluded from the findings of the present study that the industrially produced CNTs studied can cause hazardous effects in vitro that may be associated with their physical propertie

Ultrathin ceramic membranes as scaffolds for functional cell coculture models on a biomimetic scale

Epithelial tissue serves as an interface between biological compartments. Many in vitro epithelial cell models have been developed as an alternative to animal experiments to answer a range of research questions. These in vitro models are grown on permeable two-chamber systems; however, commercially available, polymer-based cell culture inserts are around 10 μm thick. Since the basement membrane found in biological systems is usually less than 1 μm thick, the 10-fold thickness of cell culture inserts is a major limitation in the establishment of realistic models. In this work, an alternative insert, accommodating an ultrathin ceramic membrane with a thickness of only 500 nm (i.e., the Silicon nitride Microporous Permeable Insert [SIMPLI]-well), was produced and used to refine an established human alveolar barrier coculture model by both replacing the conventional inserts with the SIMPLI-well and completing it with endothelial cells. The structural–functional relationship of the model was evaluated, including the translocation of gold nanoparticles across the barrier, revealing a higher translocation if compared to corresponding polyethylene terephthalate (PET) membranes. This study demonstrates the power of the SIMPLI-well system as a scaffold for epithelial tissue cell models on a truly biomimetic scale, allowing construction of more functionally accurate models of human biological barriers