Successive Increases in the Resistance of Drosophila to Viral Infection through a Transposon Insertion Followed by a Duplication

To understand the molecular basis of how hosts evolve resistance to their parasites, we have investigated the genes that cause variation in the susceptibility of Drosophila melanogaster to viral infection. Using a host-specific pathogen of D. melanogaster called the sigma virus (Rhabdoviridae), we mapped a major-effect polymorphism to a region containing two paralogous genes called CHKov1 and CHKov2. In a panel of inbred fly lines, we found that a transposable element insertion in the protein coding sequence of CHKov1 is associated with increased resistance to infection. Previous research has shown that this insertion results in a truncated messenger RNA that encodes a far shorter protein than the susceptible allele. This resistant allele has rapidly increased in frequency under directional selection and is now the commonest form of the gene in natural populations. Using genetic mapping and site-specific recombination, we identified a third genotype with considerably greater resistance that is currently rare in the wild. In these flies there have been two duplications, resulting in three copies of both the truncated allele of CHKov1 and CHKov2 (one of which is also truncated). Remarkably, the truncated allele of CHKov1 has previously been found to confer resistance to organophosphate insecticides. As estimates of the age of this allele predate the use of insecticides, it is likely that this allele initially functioned as a defence against viruses and fortuitously “pre-adapted” flies to insecticides. These results demonstrate that strong selection by parasites for increased host resistance can result in major genetic changes and rapid shifts in allele frequencies; and, contrary to the prevailing view that resistance to pathogens can be a costly trait to evolve, the pleiotropic effects of these changes can have unexpected benefits

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

The linked units of 5S rDNA and U1 snDNA of razor shells (Mollusca: Bivalvia: Pharidae)

[Abstract] The linkage between 5S ribosomal DNA and other multigene families has been detected in many eukaryote lineages, but whether it provides any selective advantage remains unclear. In this work, we report the occurrence of linked units of 5S ribosomal DNA (5S rDNA) and U1 small nuclear DNA (U1 snDNA) in 10 razor shell species (Mollusca: Bivalvia: Pharidae) from four different genera. We obtained several clones containing partial or complete repeats of both multigene families in which both types of genes displayed the same orientation. We provide a comprehensive collection of razor shell 5S rDNA clones, both with linked and nonlinked organisation, and the first bivalve U1 snDNA sequences. We predicted the secondary structures and characterised the upstream and downstream conserved elements, including a region at −25 nucleotides from both 5S rDNA and U1 snDNA transcription start sites. The analysis of 5S rDNA showed that some nontranscribed spacers (NTSs) are more closely related to NTSs from other species (and genera) than to NTSs from the species they were retrieved from, suggesting birth-and-death evolution and ancestral polymorphism. Nucleotide conservation within the functional regions suggests the involvement of purifying selection, unequal crossing-overs and gene conversions. Taking into account this and other studies, we discuss the possible mechanisms by which both multigene families could have become linked in the Pharidae lineage. The reason why 5S rDNA is often found linked to other multigene families seems to be the result of stochastic processes within genomes in which its high copy number is determinan

Evaluating Patterns of a White-Band Disease (WBD) Outbreak in Acropora palmata Using Spatial Analysis: A Comparison of Transect and Colony Clustering

. Likewise, there is little known about the spatiality of outbreaks. We examined the spatial patterns of WBD during a 2004 outbreak at Buck Island Reef National Monument in the US Virgin Islands. colonies with and without WBD.As the search for causation continues, surveillance and proper documentation of the spatial patterns may inform etiology, and at the same time assist reef managers in allocating resources to tracking the disease. Our results indicate that the spatial scale of data collected can drastically affect the calculation of prevalence and spatial distribution of WBD outbreaks. Specifically, we illustrate that higher resolution sampling resulted in more realistic disease estimates. This should assist in selecting appropriate sampling designs for future outbreak investigations. The spatial techniques used here can be used to facilitate other coral disease studies, as well as, improve reef conservation and management

A quantitative synthesis of the medicinal ethnobotany of the Malinké of Mali and the Asháninka of Peru, with a new theoretical framework

<p>Abstract</p> <p>Background</p> <p>Although ethnomedically and taxonomically guided searches for new medicinal plants can improve the percentage of plants found containing active compounds when compared to random sampling, ethnobotany has fulfilled little of its promise in the last few decades to deliver a bounty of new, laboratory-proven medicinal plants and compounds. It is quite difficult to test, isolate, and elucidate the structure and mechanism of compounds from the plethora of new medicinal plant uses described each year with limited laboratory time and resources and the high cost of clinical trials of new drug candidates.</p> <p>Methods</p> <p>A new quantitative theoretical framework of mathematical formulas called "relational efficacy" is proposed that should narrow down this search for new plant-derived medicines based on the hypothesis that closely related plants used to treat closely related diseases in distantly related cultures have a higher probability of being effective because they are more likely to be independent discoveries of similar plant compounds and disease mechanisms. A prerequisite to this hypothesis, the idea that empirical testing in traditional medicine will lead to choosing similar medicinal plants and therefore the medicinal flora of two distant cultures will prove to be more similar than their general flora, is tested using resampling statistics on cross-cultural field data of the plants used by the Malinké of Mali and the Asháninka of Peru to treat the diseases malaria, African sleeping sickness, Chagas' disease, leishmaniasis, diabetes, eczema, asthma, and uterine fibroids.</p> <p>Results</p> <p>In this case, the similarity of the medicinal floras is found to be significantly greater than the similarity of the general floras, but only when the diseases in question are grouped into the categories of parasitic and autoimmune diseases.</p> <p>Conclusion</p> <p>If the central theoretical framework of this hypothesis is shown to be true, it will allow the synthesis of medicinal plant information from around the world to pinpoint the species with the highest potential efficacy to take into the laboratory and analyze further, ultimately saving much field and laboratory time and resources.</p> <p><b>Spanish abstract</b></p> <p>Las búsquedas que utilizan la etnomedicina y la taxonomía para descubrir nuevas plantas medicinales, pueden aumentar la probabilidad de éxito de encontrar compuestos químicos activos en plantas, en comparación con las búsquedas aleatorias. A pesar de lo anterior, en las últimas décadas, la etnobotánica no ha cumplido con las expectativas de proveer numerosas plantas medicinales y químicos nuevos una vez examinados en el laboratorio. Cada año se describen una plétora de plantas medicinales y sus usos, sin embargo las limitaciones de tiempo y recursos en los laboratorios, unidos al alto coste de los ensayos clínicos de las drogas potenciales, hacen muy difícil probar, aislar, y elucidar la estructura y el mecanismo de los compuestos de estas plantas. Se propone un nuevo marco teórico cuantitativo cuyo fin es focalizar la búsqueda de nueva plantas medicinales. Este marco teórico está basado en la hipótesis que las plantas cercanamente relacionadas, usadas para tratar enfermedades cercanamente relacionadas en culturas distantemente relacionadas, tienen una eficacia potencial más alta, debido a que es más probable que estos hallazgos sean descubrimientos independientes de compuestos químicos similares. Parte de esta hipótesis, que las escogencias racionales se hacen para elegir plantas medicinales similares y que la flora medicinal de dos culturas distantes es más similar que su flora general, se probó usando métodos estadísticos de remuestreo con datos de campo de la comunidad Malinké de Malí y de la Asháninka de Perú, y las enfermedades de paludismo, enfermedad africana del sueño, enfermedad de Chagas, leishmania, diabetes, eczema, asma, y fibromas uterinos. Se encontró, en este caso, que la similitud de las floras medicinales es significativamente mayor a la similitud de las floras generales, solamente cuando las enfermedades analizadas se agruparon en las categorías de enfermedades parasitarias y enfermedades autoinmunes. Si se demostrara que las otras partes de esta hipótesis son ciertas, se podría sintetizar la información sobre plantas medicinales alrededor del mundo, para establecer así las plantas potencialmente más eficaces para llevarlas al laboratorio y analizarlas más profundamente.</p> <p><b>French abstract</b></p> <p>Par rapport aux recherches menées de façon aléatoire, les recherches effectuées par des critères ethnobotaniques et taxonomiques ont de meilleures chances à découvrir de nouvelles plantes médicinales à produit chimique actifs. Pendant les dernières décennies pourtant, l'ethnobotanique a réalisé peu de ces promesses à révéler un grand nombre de plantes médicinales et de nouveaux produits chimiques, testés au laboratoire. Avec les ressources limitées pour la recherche au laboratoire et le coût élevé des épreuves cliniques pour trouver de nouveaux candidats aux médicaments, il est difficile d'étudier, d'isoler et d'élucider la structure et le mécanisme des produits chimiques de chacune des nombreuses plantes médicinales (et les utilisations de ces plantes) décrites chaque année. Nous proposons une nouvelle technique théorique et quantitative pour préciser la recherche de nouvelles plantes médicinales; elle est basée sur l'hypothèse que les plantes étroitement apparentées, employées pour traiter les maladies étroitement apparentées dans les cultures très éloignées les unes des autres, ont une potentialité d'efficacité supérieure parce qu'elles représentent la découverte indépendante des propriétés chimiques semblables des plantes. Une partie de cette hypothèse-qui démontre que la sélection des plantes médicinales semblables est un choix rationnel et qu'il y a davantage de ressemblance dans la flore médicinale de deux cultures éloignées que dans leur flore générale-est examinée par un re-échantillonnage des données de recherches effectuées parmi les Malinké au Mali et les Asháninka au Pérou, en particulier sur la malaria, la maladie africaine du sommeil, la maladie de Chagas, la leishmania, le diabète, l'eczéma, l'asthme et les fibromes utérins. Dans ces cas précis, la similitude de la flore médicinale s'avère sensiblement plus grande que la similitude de la flore générale, mais seulement quand les maladies en question sont regroupées ensemble comme maladies parasitaires et auto-immunitaires. Si cette hypothèse est prouvée, elle permettra la synthèse des informations recueillies sur les plantes médicinales du monde entier pour en sélectionner de façon plus précise celles qui sont les plus efficaces et qui méritent analyse plus approfondie au laboratoire.</p> <p><b>Asháninka abstract</b></p> <p>Aayiantyarori iròpero aavintane, ontzimatye ancovacovatero ayotero ovaqueraripaye incashi iyoyetziri ashaninka, ayotzityaro aajatzi iyotane viracocha paitachari "quimica" ancantero aaca oshintsinka inchashipaye. Atziri yotacotzirori cametsa, ishtoriajacotzirori iyotane ashaninkapaye te iroñàrantero maaroni ocaratzi yamenacotaqueri laboratorioki. Aaviantyarori cametsa, ayotacotero aavintarontsiyetatsiri osamani antzimaventero ishtoriatacotaro, aajatzi osheki opinata ampinaventero aparopaye inchashi, acoviriqui ayotacotero, osaretsikipaye. Tzimatsi ovaquerari quenquishiriantsitatsiri ero opinata osheki ashitoriatacotero aparopaye inchashi, asampiyetatyrey pashinipaye atziri saicatsiri intaina puitarika inchasshi yavintari, ajatzirica oshiyaro ayotzi aaca, quemetachari atziri saikatsiri nampitsiki malinke aajatzi ishiyari ashaninka saicatsiri peruki, tzimatsi inchashi aajatzi yaavintari osheki okamètsatzi aririka anteri mantsiyarentsi icantaitziri ompetarentsi catsirentsi, pochokirentsi, patsarontsi(matatsi) ashipetate maaroni, ampochavathate, ancainikentsite, oncatsithakite tsinani. Aririka añaker aajatzi ahiyaro inchashi yaavintayetari pashinipaye atziri intainasatzi irdotake ahitoriatacoperoteri anàashityard aavintarontsi ovamairiri shithanentsi, onàshitaavintarontsi tzicaacoventairi ero antane mantsiyarentsi. Omanperotatyarica iròperotzi avintarontsi, oshitovake laboratorioki aritaque iyoitanaquero maaroni quipatsiki iroperori avintarontsi.</p

Circulating microparticles: square the circle

Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes

White matter measures are near normal in controlled HIV infection except in those with cognitive impairment and longer HIV duration

The objective of the current study was to quantify the degree of white matter (WM) abnormalities in chronic and virally suppressed HIV-infected (HIV+) persons while carefully taking into account demographic and disease factors. Diffusion tensor imaging (DTI) was conducted in 40 HIV- and 82 HIV+ men with comparable demographics and life style factors. The HIV+ sample was clinically stable with successful viral control. Diffusion was measured across 32 non-colinear directions with a b-value of 1000 s/mm2; fractional anisotropy (FA) and mean diffusivity (MD) maps were quantified with Itrack IDL. Using the ENIGMA DTI protocol, FA and MD values were extracted for each participant and in 11 skeleton regions of interest (SROI) from standard labels in the JHU ICBM-81 atlas covering major striato-frontal and parietal tracks. We found no major differences in FA and MD values across the 11 SROI between study groups. Within the HIV+ sample, we found that a higher CNS penetrating antiretroviral treatment, higher current CD4+ T cell count, and immune recovery from the nadir CD4+ T cell count were associated with increased FA and decreased MD (p &lt; 0.05-0.006), while HIV duration, symptomatic, and asymptomatic cognitive impairment were associated with decreased FA and increased MD (p &lt; 0.01-0.004). Stability of HIV treatment and antiretroviral CNS penetration efficiency in addition to current and historical immune recovery were related to higher FA and lower MD (p = 0.04-p &lt; 0.01). In conclusion, WM DTI measures are near normal except for patients with neurocognitive impairment and longer HIV disease duration