Segmental copy number variation shapes tissue transcriptomes

Abstract : Copy number variation (CNV) of DNA segments has recently gained considerable interest as a source of genetic variation likely to play a role in phenotypic diversity and evolution. Much effort has been put into the identification and mapping of regions that vary in copy number among seemingly normal individuals, both in humans and in a number of model organisms, using both bioinformatic and hybridization-based methods. Synteny studies suggest the existence of CNV hotspots in mammalian genomes, often in connection with regions of segmental duplication. CNV alleles can be in equilibrium within a population, but can also arise de novo between generations, illustrating the highly dynamic nature of these regions. A small number of studies have assessed the effect of CNV on single loci, however, at the genome-wide scale, the functional impact of CNV remains poorly studied. We have explored the influence of CNV on gene expression, first using the Williams-Beuren syndrome (WBS) associated deletion as a model, and second at the genome-wide scale in inbred mouse strains. We found that the WBS deletion influences the expression levels not only of the hemizygous genes, but also affects the euploid genes mapping nearby. Consistently, on a genome wide scale we observe that CNV genes are expressed at more variable levels than genes that do not vary in copy number. Likewise, CNVs influence the relative expression levels of genes that map to the flank of the genome rearrangements, thus globally influencing tissue transcriptomes. Further studies are warranted to complete cataloguing and fine mapping of CNV regions, as well as to elucidate the different mechanisms by which CNVs influence gene expression. Résumé : La variation en nombre de copies (copy number variation ou CNV) de segments d'ADN suscite un intérêt en tant que variation génétique susceptible de jouer un r81e dans la diversité phénotypique et l'évolution. Les régions variables en nombre de copies parmi des individus apparemment normaux ont été cartographiées et cataloguées au moyen de puces à ADN et d'analyse bioinformatique. L'étude de la synténie entre plusieurs espèces de mammifères laisse supposer l'existence de régions à haut taux de variation, souvent liées à des duplications segmentaires. Les allèles CNV peuvent être en équilibre au sein d'une population ou peuvent apparaître de novo. Ces faits illustrent la nature hautement dynamique de ces régions. Quelques études se sont penchées sur l'effet de la variation en nombre de copies de loci isolés, cependant l'impact de ce phénomène n'a pas été étudié à l'échelle génomique. Nous avons examiné l'influence des CNV sur l'expression des gènes. Dans un premier temps nous avons utilisé la délétion associée au syndrome de Williams-Beuren (WBS), puis, dans un second temps, nous avons poursuivi notre étude à l'échelle du génome, dans des lignées consanguines de souris. Nous avons établi que la délétion WBS influence l'expression non seulement des gènes hémizygotes, mais également celle des gènes euploïdes voisins. A l'échelle génomique, nous observons des phénomènes concordants. En effet, l'expression des gènes variant en nombre de copies est plus variable que celles des gènes ne variant pas. De plus, à l'instar de la délétion WBS, les CNV influencent l'expression des gènes adjacents, exerçant ainsi un impact global sur les profils d'expression dans les tissus. Résumé pour un large public : De nombreuses maladies ont pour cause un défaut génétique. Parmi les types de mutations, on compte la disparition (délétion) d'une partie de notre génome ou sa duplication. Bien que l'on connaisse les anomalies associées à certaines maladies, les mécanismes moléculaires par lesquels ces réarrangements de notre matériel génétique induisent les maladies sont encore méconnus. C'est pourquoi nous nous sommes intéressés à la régulation des gènes dans les régions susceptibles à délétion ou duplication. Dans ce travail, nous avons démontré que les délétions et les duplications influencent la régulation des gènes situés à proximité, et que ces changements interviennent dans plusieurs organes.

Estudio comparativo de conocimientos y percepciones ambientales sobre la Reserva de la Biosfera de Sian Ka'an entre estudiantes de primaria de comunidades maya, México

El estudio analiza y compara las percepciones y conocimientos ambientales que estudiantes de primaria del municipio maya de Felipe Carrillo Puerto tienen sobre la vecina Reserva de la Biósfera de Sian Ka’an (RBSK) en términos de biodiversidad, con el fin de evaluar y elaborar programas de Educación Ambiental (EA) dirigidos a promover la protección de este espacio natural. Se analizan dibujos, cuestionarios y encuestas recogidos en tres comunidades maya que difieren en su proximidad a la RBSK y en su nivel de urbanización. Los resultados indican que los niños en general desconocen la RBSK y la biodiversidad de la zona. Para aumentar el conocimiento ambiental de los alumnos se propone potenciar el conocimiento vivencial, mantener la lengua y cultura maya y el contacto de ésta con la naturaleza y potenciar la afinidad del maestro por la temática ambiental y por la RBSK.

Descripción socioambiental y análisis de las fuentes de agua de la microcuenca La Jabonera (Estelí, Nicaragua)

El objetivo principal de este proyecto es la caracterización de la microcuenca la Jabonera (Estelí, Nicaragua) enfatizando el agua como factor clave que conecta todos los elementos que interaccionan en la microcuenca y que, además delimita el área de estudio. El trabajo de campo ha consistido básicamente en la georeferenciación de los puntos de interés, la realización de encuestas a la población y la evaluación de las fuentes de agua y del agua del río mediante análisis fisicoquímicos. En el procesamiento de la información se ha elaborado cartografía temática mediante la herramienta SIG que ha servido de soporte para la interpretación de los resultados. Las características morfométricas y biofísicas favorecen que el agua precipitada se pierda rápidamente por escorrentía superficial con una tendencia moderada a crecidas e inundaciones. El agua infiltrada circula rápidamente por fracturas del material geológico con tiempos de tránsito cortos, y además, el área de recarga de los nacientes es local por lo que las fuentes son especialmente vulnerables a períodos de sequía y a la contaminación en su entorno cercano. El estudio de usos del suelo junto con la realización de análisis del agua ha permitido determinar que los agroquímicos son la principal fuente potencial de contaminación del agua en la microcuenca. Los resultados obtenidos muestran la necesidad de llevar a cabo una gestión integrada del territorio que garantice un desarrollo socioambiental sostenible.

Contribution to the sand fly fauna (Diptera: Phlebotominae) of Rio Grande do Sul, Brazil and Leishmania (Viannia) infections

American cutaneous leishmaniasis (ACL) is endemic in the State of Rio Grande do Sul, Brazil. As reports of nearby hospitals suggest, the Parque Estadual do Turvo seems to serve as a source for the disease. During three months from November 1996 to February 1997 we collected, in this park, 2,228 sandflies (10 Lutzomyia species and 2 6species). We applied the polymerase chain reaction to 920 females which belong to the following species: Lutzomyia migonei, Lu. pessoai, Lu. fischeri, Lu. misionensis, Lu. lanei, Lu. neivai, Lu. shannoni, and Lu. monticola, in an attempt to verify natural infection by Leishmania (Viannia), the causative agent of ACL. Le. (Viannia) infections were demonstrated by DNA amplification from two Lu. pessoai and one Lu. misionensis female. Lu. pessoai have been found with leptomonas in the gut believed to be Le. (V.) braziliensis in other endemic areas of northeastern and southeastern Brazil. However, Lu. misionensis has never been found carrying a natural infection of Le. (Viannia).

Microhabitat preferences of Biomphalaria pfeifferi and Lymnaea natalensis in a natural and a man-made habitat in Southeastern Tanzania

Schistosoma mansoni is an important human parasitic disease which is widespread throughout Africa. As Biomphalaria pfeifferi snails act as intermediate host, knowledge of their population ecology is an essential prerequisite towards understanding disease transmission. We conducted a field study and assessed the density and microhabitat preferences of B.pfeifferi in a natural habitat which was a residual pool of a river. Repeated removal collecting revealed a density of 26.6 [95% confidence interval (CI): 24.9-28.3] snails/m2. B.pfeifferi showed microhabitat preferences for shallow water (depths: 0-4cm). They were found most abundantly close to the shoreline (distances: 0-40cm), and preferred either plant detritus or bedrock as substratum. Lymnaea natalensis, a snail which may act as a host for human Fasciola gigantica, also occurred in this habitat with a density of 34.0 (95% CI: 24.7-43.3) snails/m2, and preferred significantly different microhabitats when compared to B.pfeifferi. Microhabitat selection by these snail species was also investigated in a man-made habitat nearby, which consisted of a flat layer of concrete fixed on the riverbed, covered by algae. Here, B.pfeifferi showed no preference for locations close to the shoreline, probably because the habitat had a uniform depth. We conclude that repeated removal collecting in shallow habitats provides reliable estimates of snail densities and that habitat changes through constructions may create favourable microhabitats and contribute to additional disease transmission.

Triatoma sordida Stål 1859 (Hemiptera, Reduviidae: Triatominae) in palms of northeastern Argentina

Several palms species provide an important habitat for triatomines and associate vertebrates in tropical America. The objective of this work is to identify the triatomine species living in the palms of rural areas in the Province of Corrientes, and to estimate the potential epidemiological risk they represent for the residents of nearby houses. The survey was carried out in a palm community in Colonia Laurel, Department San Roque, Province of Corrientes, Argentina. Samplings were performed in October, November and December 1998; January, February and March 1999; May and June 1999. Thirty palms: 27 (90%) Butia yatay (Mart.) Becc. and 3 Acrocomia aculeata (Jacq.) Lodd ex Mart. were dissected. Triatoma sordida Stål 1859 was found in 96.2% of B. yatay and in all the A. aculeata palms. A total of 272 live T. sordida was collected; 36 of them (13.2%) were found in bird nests in the frond and the remainder in other locations of the tree. The mean number of triatomines per palm was 9.6 (range 1-60, mode 2). T. sordida was collected during all the sampling months and all stages were present at all seasons. The highest population density was reached in spring and the lowest in autumn. Trypanosoma cruzi was detected in 38.5% in feces of 174 examined insects and identified as such, both by microscopical examination and PCR. This is the first finding of T. sordida populations in B. yatay, an endemic palm of South America distributed in southern Brazil, Uruguay and northeastern Argentina. The high infection prevalence found in this work suggests that T. sordida plays an essential role in the maintenance of the wild T. cruzi transmission cycle in northeastern Argentina.

Triatomines Involved in Domestic and Wild Trypanosoma cruzi Transmission in Concepción, Corrientes, Argentina

An entomological and serological survey was performed in three localities of the Department of Concepción, Province of Corrientes, Argentina in 1998 and 1999, to identify triatomines species involved in domestic and wild transmission of Chagas disease. Triatomines were collected by man/hour capture in 32 houses randomly selected and 44 nearby outdoor ecotopes. Trypanosoma cruzi infection in triatomines was assessed by direct microscopic observation (400x) of feces and polymerase chain reaction. Serological techniques used for people were Indirect Hemagglutination Test and Indirect Fluorescent Test. Triatomines were collected in 28.1% of the houses and 31.8% of the wild biotopes. Triatoma infestans (Klug 1834) was exclusively found indoors and T. cruzi infected 60% of them. Triatoma sordida (Stål 1859) was mainly found in extradomestic ecotopes where trypanosome infection rate reached 12.7%. Serological study of 98 local people showed that 29.6% were seroreactive; most of their houses were closed to wild biotopes colonized by T. sordida. Results indicate that there is an active T. infestans mediated transmission of Chagas disease in this zone that yields important human prevalence and that the populations of T. sordida in wild biotopes not only sustain the wild T. cruzi cycle but also represent an actual risk for people living in the area.

Acute schistosomiasis outbreak in the metropolitan area of Belo Horizonte, Minas Gerais: alert about the risk of unnoticed transmission increased by growing rural tourism

The present article describes the occurrence of 17 cases of acute schistosomiasis in the metropolitan area of Belo Horizonte, state of Minas Gerais, Brazil. All individuals affected took a bath in a swimming pool of a holiday resort that was provided with water from a nearby brook. The apparently clean water and the absence of snails in the pool gave the wrong impression that there was no risk for infection. During a malacological survey at the site snails of the species Biomphalaria glabrata were found and tested positive for Schistosoma mansoni. All the patients live in the middle-class area of Barreiro, metropolitan area of Belo Horizonte and have medium grade school education. The difficulties in establishing the right diagnosis is expressed by the search for medical attention in 17 different medical facilities, the wide range of laboratory test and the inadequate treatment administration. A lack of knowledge about the disease was found in all groups studied. The booming rural tourism in endemic areas is identified as a probable risk factor for infection, especially for individuals of the non-immune middle and upper class parts of the society in urban centers. Special attention is given to a multidisciplinary approach to the complex issue of disease control and prevention.

Blackflies (Diptera: Simuliidae) of Southern Guyana with keys for the identification of adults and pupae: a review

A revision is made of the previously poorly studied blackfly fauna from the south-western border of Guyana with Brazil. Notes on the biosystematics of the species found are provided, together with keys and illustrations based on their morphology. Of the 14 species recorded, eight are anthropophilic and two of these (Simulium oyapockense s.l. and S. guianense s.l.) are proven vectors of human onchocerciasis in the nearby Amazonia focus of the disease in neighbouring Brazil.

Distribution and pathogenicity of Trypanosoma cruzi isolated from peridomestic populations of Triatoma infestans and Triatoma guasayana from rural Western Argentina

We assessed the distribution of Trypanosoma cruzi infection in peridomestic triatomines collected manually at a district-wide scale in rural villages around Olta, Western Argentina, and typed the isolated strains according to their pathogenicity to laboratory mice. Of 1623 triatomines examined, only 14 (0.9%) were infected with T. cruzi based on microscopical examination of feces. The prevalence of T. cruzi infection was 0.8% in Triatoma infestans, 2.3% in T. guasayana, and nil in T. garciabesi, T. platensis, and T. eratyrusiformis. Local transmission occurred in kitchens, store-rooms and goat corrals or nearby, though at very low levels. T. cruzi was detected by at least one parasitological method in 11 (79%) of 14 microscope-positive bugs. Hemoculture was the most sensitive method (67%) followed by culture of organ homogenates, histopathology or xenodiagnosis of inoculated suckling mice (55-58%), and culture of microscope-positive bug feces (46%). The evidence suggests that most of the isolated T. cruzi strains would be myotropic type III. Our study establishes for the first time that peridomestic, microscope-positive T. guasayana nymphs were actually infected with T. cruzi, and may be implicated as a putative secondary vector of T. cruzi in domestic or peridomestic sites.

Palaeoenvironment and palaeoclimate of the Middle Miocene lake in the Steinheim basin, SW Germany: A reconstruction from C, O, and Sr isotopes of fossil remains

A differentiated reconstruction of palaeolimnologic, -environmental, and -climatic conditions is presented for the Middle Miocene long-term freshwater lake (14.3 to 13.5 Ma) of the Steinheim basin, on the basis of a combined C, 0, and Sr isotope study of sympatric skeletal fossils of aquatic and terrestrial organisms from the lake sediments. The oxygen isotope composition for lake water of the Steinheim basin (delta O-18(H2O) = +2.0 +/- 0.4 parts per thousand VSMOW, n = 6) was reconstructed from measurements of delta O-18(PO4) of aquatic turtle bones. The drinking water calculated from the enamel of large mammals (proboscideans, rhinocerotids, equids, cervids, suids) has delta O-18(H2O) values (delta(OH2O)-O-18 = -5.9 +/- 1.7 parts per thousand VSMOW, n = 31) typical for Middle Miocene meteoric water of the area. This delta O-18(H2O) value corresponds to a mean annual air temperature (MAT) of 18.8 +/- 3.8 degrees C, calculated using a modem-day delta(OH2O)-O-18-MAT relation. Hence, large mammals did not use the lake water as principal drinking water. In contrast, small mammals, especially the then abundant pika Prolagus oeningensis drank from O-18-enriched water sources (delta O-18(H2O) = +2.7 +/- 2.3 parts per thousand VSMOW, n = 7), such as the lake water. Differences in Sr and 0 isotopic compositions between large and small mammal teeth indicate different home ranges and drinking behaviour and support migration of some large mammals between the Swabian Alb plateau and the nearby Molasse basin, while small mammals ingested their food and water locally. Changes in the lake level, water chemistry, and temperature were inferred using isotopic compositions of ostracod and gastropod shells from a composite lake sediment profile. Calcitic ostracod valves (Ilyocypris binocularis; delta O-18 = +1.7 +/- 1.2 parts per thousand VPDB, delta C-18 = -0.5 +/- 0.9 parts per thousand, VPDB, n = 68) and aragonitic, gastropod shells (Gyraulus spp.; delta O-18 = +2.0 +/- 13 parts per thousand VPDB, delta C-13 = -1.1 +/- 1.3 parts per thousand VPDB, n = 89) have delta O-18 and delta C-13 values similar to or even higher than those of marine, carbonates. delta C-13 values:of the biogenic carbonates parallel lake level fluctuations while delta O-18 values scatter around +2 +/- 2 parts per thousand and reflect the short term variability of meteoric water inflow vs. longer term evaporation. Sr-87/Sr-86 ratios of aragonitic Gyraulus spp. gastropod shells parallel the lake level fluctuations, reflecting variable inputs of groundwater and surface waters. Using a water delta O-18(H2O) value of +2.0 parts per thousand VSMOW, water temperatures calculated from skeletal tissue delta O-18 values of ostracods are 16.7 +/- 5.0 degrees C, gastropods 20.6 +/- 5.6 degrees C, otoliths 21.8 +/- 1.4 degrees C, and fish teeth 17.0 +/- 2.7 degrees C. The calculated MAT (similar to 19 degrees C), lake water temperatures (similar to 17 to 22 degrees C) and the O-18-enriched water compositions are indicative of warm-temperate climatic conditions, possibly with a high humidity during this period. Vegetation in the area surrounding the basin was largely of the C-3-type, as indicated by carbon isotopic compositions of tooth enamel from large mammals (delta C-13 = -11.1 +/- 1.1 parts per thousand VPDB, n = 40). (c) 2006 Elsevier B.V. All rights reserved.

Managing microglia in Alzheimer's

Microglia are often found near damaged tissue in Alzheimer's disease patients, but whether the brain's innate immune cells are helpful or harmful in the disease has been an open question. Now, German researchers have evidence that both camps got it right. A pair of studies reveals that microglia play opposing roles in AD pathogenesis: they not only eliminate �_-amyloid aggregates via phagocytosis but also kill nearby neurons by causing inflammation and the release of neurotoxic proteases.Importantly, the reports suggest that the two functions of microglia are controlled by different cell-surface receptors, thus providing a road map for how to clear �_-amyloid (A�_) plaques without destroying healthy neurons that are in close proximity. A full report is available here

Ecological components and evolution of selfing in the freshwater snail Galba truncatula.

The reproductive assurance hypothesis emphasizes that self-fertilization should evolve in species with reduced dispersal capability, low population size or experiencing recurrent bottlenecks. Our work investigates the ecological components of the habitats colonized by the snail, Galba truncatula, that may influence the evolution of selfing. Galba truncatula is a preferential selfer inhabiting freshwater habitats, which vary with respect to the degree of permanence. We considered with a population genetic approach the spatial and the temporal degree of isolation of populations of G. truncatula. We showed that patches at distances of only a few meters are highly structured. The effective population sizes appear quite low, in the order of 10 individuals or less. This study indicates that individuals of the species G. truncatula are likely to be alone in a site and have a low probability of finding a partner from a nearby site to reproduce. These results emphasize the advantage of selfing in this species.

Technical note: Implementation of a geodatabase of published and unpublished data on the catastrophic Vaiont landslide

On 9 October 1963 a catastrophic landslide suddenly occurred on the southern slope of the Vaiont dam reservoir. A mass of approximately 270 million m3 collapsed into the reservoir generating a wave that overtopped the dam and hit the town of Longarone and other villages nearby. Several investigations and interpretations of the slope collapse have been carried out during the last 45 years, however, a comprehensive explanation of both the triggering and the dynamics of the phenomenon has yet to be provided. In order to re-evaluate the currently existing information on the slide, an electronic bibliographic database and an ESRI-geodatabase have been developed. The chronology of the collected documentation showed that most of the studies for re-evaluating the failure mechanisms were conducted in the last decade, as a consequence of knowledge, methods and techniques recently acquired. The current contents of the geodatabase will improve definition of the structural setting that influenced the slide and led to the the propagation of the displaced rock mass. The objectives, structure and contents of the e-bibliography and Geodatabase are indicated, together with a brief description on the possible use of the alphanumeric and spatial contents of the databases.

Search for dark matter using VHE gamma-ray telescopes

One of the unresolved questions of modern physics is the nature of Dark Matter. Strong experimental evidences suggest that the presence of this elusive component in the energy budget of the Universe is quite significant, without, however, being able to provide conclusive information about its nature. The most plausible scenario is that of weakly interacting massive particles (WIMPs), that includes a large class of non-baryonic Dark Matter candidates with a mass typically between few tens of GeV and few TeVs, and a cross section of the order of weak interactions. Search for Dark Matter particles using very high energy gamma-ray Cherenkov telescopes is based on the model that WIMPs can self-annihilate, leading to production of detectable species, like photons. These photons are very energetic, and since unreflected by the Universe's magnetic fields, they can be traced straight to the source of their creation. The downside of the approach is a great amount of background radiation, coming from the conventional astrophysical objects, that usually hides clear signals of the Dark Matter particle interactions. That is why good choice of the observational candidates is the crucial factor in search for Dark Matter. With MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov Telescopes), a two-telescope ground-based system located in La Palma, Canary Islands, we choose objects like dwarf spheroidal satellite galaxies of the Milky Way and galaxy clusters for our search. Our idea is to increase chances for WIMPs detection by pointing to objects that are relatively close, with great amount of Dark Matter and with as-little-as-possible pollution from the stars. At the moment, several observation projects are ongoing and analyses are being performed.