Germline mutations in TMEM127 confer susceptibility to pheochromocytoma

Pheochromocytomas, which are catecholamine-secreting tumors of neural crest origin, are frequently hereditary(1). However, the molecular basis of the majority of these tumors is unknown(2). We identified the transmembrane-encoding gene TMEM127 on chromosome 2q11 as a new pheochromocytoma susceptibility gene. In a cohort of 103 samples, we detected truncating germline TMEM127 mutations in approximately 30% of familial tumors and about 3% of sporadic-appearing pheochromocytomas without a known genetic cause. The wild-type allele was consistently deleted in tumor DNA, suggesting a classic mechanism of tumor suppressor gene inactivation. Pheochromocytomas with mutations in TMEM127 are transcriptionally related to tumors bearing NF1 mutations and, similarly, show hyperphosphorylation of mammalian target of rapamycin (mTOR) effector proteins. Accordingly, in vitro gain-of-function and loss-of-function analyses indicate that TMEM127 is a negative regulator of mTOR. TMEM127 dynamically associates with the endomembrane system and colocalizes with perinuclear (activated) mTOR, suggesting a subcompartmental-specific effect. Our studies identify TMEM127 as a tumor suppressor gene and validate the power of hereditary tumors to elucidate cancer pathogenesis.

Experimental infection of Crested Caracara (Caracara plancus) with Toxoplasma gondu simulating natural conditions

Toxoplasma gondu affects mainly warm-blooded animals including birds Even though previous experimental data indicate that raptors are resistant to clinical infection there is no information regarding the susceptibility of Brazilian birds of prey to T gondii The present study aimed to observe how the crested caracara a common raptor in Brazil Interacts with T gondu, using an experimental model Seven crested caracaras seronegative for T gondu were separated into infected (n = 5) and control groups (n = 2) Birds from the infected group were fed T gondu-Infected Calomys callosus a rodent present in Brazilian savanna and described as highly susceptible to infection by the parasite for three consecutive days while control animals were fed non-Infected rodents All Infected birds produced T gondu-specific IgG antibodies that were firstly detected at day 7 post-Infection with peak production detected between 15 and 30 dpi No significant alterations in clinical and hematological parameters were observed throughout the experimental period and parasites were sparsely found in muscular tissues after the birds were euthanized In conclusion our results demonstrated that crested caracaras are resistant to oral infection with T gondu suggesting that the host-parasite relationship between both species has reached a remarkable equilibrium (C) 2010 Elsevier B V All rights reserved

Codificación a nivel de paquete para comunicaciones móviles por satélite

Una de les opcions que es contemplen per transmetre continguts multimèdia i proporcionar accés a Internet a grups de usuaris mòbils és fer servir satèl·lits. Les condiciones de propagació del canal mòbil impliquen que d'una manera o altra haurem de garantir la qualitat de servei. Això té fins i tot més importància si tenim en compte que, en el cas d'accés a Internet, no es té la capacitat d'assumir cert percentatge de pèrdua de dades que tenim, per exemple, en la transmissió de so o vídeo (rebaixant la qualitat). Entre les principals alternatives per a aquesta classe d’entorns es troba la inclusió de codificacions a nivell de paquet. El funcionament d'aquesta tècnica es basa en incloure a la transmissió paquets redundants, obtinguts mitjançant un determinat algoritme. El receptor podrà recuperar la informació original que es volia enviar, sempre que hagi rebut una certa quantitat de paquets, similar a la quantitat de paquets originals. A aquest mecanisme se'l coneix com Forward Error Correction (FEC) a nivell de paquet. En aquesta memòria es valoren breument les alternatives existents i s'expliquen algunes de les codificacions per a FEC més importants. A continuació es realitza un estudi compartiu d’algunes d'elles: les variants de LDPC (Low Density Parity Check) conegudes com LDGM (Low Density Generator Matrix), i la codificació Raptor

PGE2-induced colon cancer growth is mediated by mTORC1.

The inflammatory prostaglandin E2 (PGE2) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE2 directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE2-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE2 increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE2 EP4 receptor was responsible for transducing the signal to mTORC1. Moreover, PGE2 increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE2-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE2 increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE2 mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth.

mTORC2 regulates PGE2-mediated endothelial cell survival and migration.

Prostaglandin E(2) (PGE(2)) promotes angiogenesis by in part inducing endothelial cell survival and migration. The present study examined the role of mTOR and its two complexes, mTORC1 and mTORC2, in PGE(2)-mediated endothelial cell responses. We used small interfering RNA (siRNA) to raptor or rictor to block mTORC1 or mTORC2, respectively. We observed that down-regulation of mTORC2 but not mTORC1 reduced baseline and PGE(2)-induced endothelial cell survival and migration. At the molecular level, we found that knockdown of mTORC2 inhibited PGE(2)-mediated Rac and Akt activation two important signaling intermediaries in endothelial cell migration and survival, respectively. In addition, inhibition of mTORC2 by prolonged exposure of endothelial cells to rapamycin also prevented PGE(2)-mediated endothelial cell survival and migration confirming the results obtained with the siRNA approach. Taken together these results show that mTORC2 but not mTORC1 is an important signaling intermediary in PGE(2)-mediated endothelial cell responses.

Partitioning of genetic (Rapd) variability among sexes and populations of the Barn Owl (Tyto alba) in Europe

The white Barn Owl subspecies (Tyto alba alba) is found in southern Europe and the reddish-brown subspecies (T a. guttata) in northern and eastern Europe. In central Europe, the two subspecies interbreed producing a large range of phenotypic variants. Because of the different ratios of the subspecies in different geographic regions, we predict that genetic variation should be greater in Switzerland than in Hungary. We tested this hypothesis by measuring genetic variation with the RAPD method. As predicted, the genetic differentiation within a Swiss population of Barn Owls was significantly greater than the variation within a Hungarian population. This suggests that gene flow is greater in central Europe than at the eastern limit of the Barn Owl distribution in Hungary. In both countries genetic variation was more pronounced in females than in males. As in other birds, this is probably because female Barn Owls are less philopatric than males. The number of migrants between Hungary and Switzerland is ca. 1 individual per generation; if calculated separately for the sexes, then 0.525 for males and ca. I for females (Nm values). The difference in the number of migrants between genders again is likely a consequence of higher male philopatry. The sexual differentiation is greater in the Swiss population than in the Hungarian and the genetic substructuring of the populations of the species is substantial. The reason for the considerable population substructuring could be the nonmigratory behavior and socially monogamous pairing of the species, as well as the geographical barriers (Alps) between the populations examined.

Role of mTOR, Bad, and Survivin in RasGAP Fragment N-Mediated Cell Protection.

Partial cleavage of p120 RasGAP by caspase-3 in stressed cells generates an N-terminal fragment, called fragment N, which activates an anti-apoptotic Akt-dependent survival response. Akt regulates several effectors but which of these mediate fragment N-dependent cell protection has not been defined yet. Here we have investigated the role of mTORC1, Bad, and survivin in the capacity of fragment N to protect cells from apoptosis. Neither rapamycin, an inhibitor of mTORC1, nor silencing of raptor, a subunit of the mTORC1 complex, altered the ability of fragment N from inhibiting cisplatin- and Fas ligand-induced death. Cells lacking Bad, despite displaying a stronger resistance to apoptosis, were still protected by fragment N against cisplatin-induced death. Fragment N was also able to protect cells from Fas ligand-induced death in conditions where Bad plays no role in apoptosis regulation. Fragment N expression in cells did neither modulate survivin mRNA nor its protein expression. Moreover, the expression of cytoplasmic survivin, known to exert anti-apoptotic actions in cells, still occurred in UV-B-irradiated epidermis of mouse expressing a caspase-3-resistant RasGAP mutant that cannot produce fragment N. Additionally, survivin function in cell cycle progression was not affected by fragment N. These results indicate that, taken individually, mTOR, Bad, or Survivin are not required for fragment N to protect cells from cell death. We conclude that downstream targets of Akt other than mTORC1, Bad, or survivin mediate fragment N-induced protection or that several Akt effectors can compensate for each other to induce the pro-survival fragment N-dependent response.

Isolation and characterization of 21 microsatellite markers in the barn owl (Tyto alba).

We report 21 new polymorphic microsatellite markers in the European barn owl (Tyto alba). The polymorphism of the reported markers was evaluated in a population situated in western Switzerland and in another from Tenerife, Canary Islands. The number of alleles per locus varies between two and 31, and expected heterozygosity per population ranges from 0.16 to 0.95. All loci are in Hardy-Weinberg equilibrium and no linkage disequilibrium was detected. Two loci exhibit a null allele in the Tenerife population.

Mammalian target of rapamycin complex 1 orchestrates invariant NKT cell differentiation and effector function.

Invariant NKT (iNKT) cells play critical roles in bridging innate and adaptive immunity. The Raptor containing mTOR complex 1 (mTORC1) has been well documented to control peripheral CD4 or CD8 T cell effector or memory differentiation. However, the role of mTORC1 in iNKT cell development and function remains largely unknown. By using mice with T cell-restricted deletion of Raptor, we show that mTORC1 is selectively required for iNKT but not for conventional T cell development. Indeed, Raptor-deficient iNKT cells are mostly blocked at thymic stage 1-2, resulting in a dramatic decrease of terminal differentiation into stage 3 and severe reduction of peripheral iNKT cells. Moreover, residual iNKT cells in Raptor knockout mice are impaired in their rapid cytokine production upon αGalcer challenge. Bone marrow chimera studies demonstrate that mTORC1 controls iNKT differentiation in a cell-intrinsic manner. Collectively, our data provide the genetic evidence that iNKT cell development and effector functions are under the control of mTORC1 signaling.

Autophagy defect is associated with low glucose-induced apoptosis in 661W photoreceptor cells.

Glucose is an important metabolic substrate of the retina and diabetic patients have to maintain a strict normoglycemia to avoid diabetes secondary effects, including cardiovascular disease, nephropathy, neuropathy and retinopathy. Others and we recently demonstrated the potential role of hypoglycemia in diabetic retinopathy. We showed acute hypoglycemia to induce retinal cell death both in vivo during an hyperinsulinemic/hypoglycemic clamp and in vitro in 661W photoreceptor cells cultured at low glucose concentration. In the present study, we showed low glucose to induce a decrease of BCL2 and BCL-XL anti-apoptotic proteins expression, leading to an increase of free pro-apoptotic BAX. In parallel, we showed that, in retinal cells, low glucose-induced apoptosis is involved in the process of autophagosomes formation through the AMPK/RAPTOR/mTOR pathway. Moreover, the decrease of LAMP2a expression led to a defect in the autophagosome/lysosome fusion process. Specific inhibition of autophagy, either by 3-methyladenine or by down-regulation of ATG5 or ATG7 proteins expression, increased caspase 3 activation and 661W cell death. We show that low glucose modifies the delicate equilibrium between apoptosis and autophagy. Cells struggled against low nutrient condition-induced apoptosis by starting an autophagic process, which led to cell death when inhibited. We conclude that autophagy defect is associated with low glucose-induced 661W cells death that could play a role in diabetic retinopathy. These results could modify the way of addressing negative effects of hypoglycemia. Short-term modulation of autophagy could be envisioned to treat diabetic patients in order to avoid secondary complications of the disease.

Macbride nature recreation area : environmental education, 1989.

This brochure contains information on the environmental information available at the Macbride Nature Recreation Area including programs on cycles and inter-relationships in nature, wildlife adaptations and survival, life in the forest community, patterns and changes in autumn, flowers insects and the renewal of spring, lives of birds and raptor information geared for elementary aged children.

mTORC2 regulates PGE(2)-mediated endothelial cell survival and migration

Prostaglandin E-2 (PGE(2)) promotes angiogenesis by in part inducing endothelial cell survival and migration. The present study examined the role of mTOR and its two complexes, mTORC1 and mTORC2, in PGE(2)-mediated endothelial cell responses. We used small interfering RNA (siRNA) to raptor or rictor to block mTORC1 or mTORC2, respectively. We observed that down-regulation of mTORC2 but not mTORC1 reduced baseline and PGE(2)-induced endothelial cell survival and migration. At the molecular level, we found that knockdown of mTORC2 inhibited PGE2-mediated Rac and Akt activation two important signaling intermediaries in endothelial cell migration and survival, respectively. In addition, inhibition of mTORC2 by prolonged exposure of endothelial cells to rapamycin also prevented PGE2-mediated endothelial cell survival and migration confirming the results obtained with the siRNA approach. Taken together these results show that mTORC2 but not mTORC1 is an important signaling intermediary in PGE2-mediated endothelial cell responses.

Multi-scale effects of nestling diet on breeding performance in a terrestrial top predator inferred from stable isotope analysis

Inter-individual diet variation within populations is likely to have important ecological and evolutionary implications. The diet-fitness relationships at the individual level and the emerging population processes are, however, poorly understood for most avian predators inhabiting complex terrestrial ecosystems. In this study, we use an isotopic approach to assess the trophic ecology of nestlings in a long-lived raptor, the Bonelli"s eagle Aquila fasciata, and investigate whether nestling dietary breath and main prey consumption can affect the species" reproductive performance at two spatial scales: territories within populations and populations over a large geographic area. At the territory level, those breeding pairs whose nestlings consumed similar diets to the overall population (i.e. moderate consumption of preferred prey, but complemented by alternative prey categories) or those disproportionally consuming preferred prey were more likely to fledge two chicks. An increase in the diet diversity, however, related negatively with productivity. The age and replacements of breeding pair members had also an influence on productivity, with more fledglings associated to adult pairs with few replacements, as expected in long-lived species. At the population level, mean productivity was higher in those population-years with lower dietary breadth and higher diet similarity among territories, which was related to an overall higher consumption of preferred prey. Thus, we revealed a correspondence in diet-fitness relationships at two spatial scales: territories and populations. We suggest that stable isotope analyses may be a powerful tool to monitor the diet of terrestrial avian predators on large spatio-temporal scales, which could serve to detect potential changes in the availability of those prey on which predators depend for breeding. We encourage ecologists and evolutionary and conservation biologists concerned with the multi-scale fitness consequences of inter-individual variation in resource use to employ similar stable isotope-based approaches, which can be successfully applied to complex ecosystems such as the Mediterranean.

Uuden sukupolven taistelukoneiden suorituskyky ja kehitysnäkymät

Tutkielma käsittelee uuden sukupolven taistelukoneita, niiden suorituskykyä ja kehitysnäkymiä. Tutkimus kohdentuu uusimpien sukupolvien kiinteäsiipisiin ilma-aluksiin. Kiinteäsiipi-sellä ilma-aluksella tarkoitetaan monitoimihävittäjää, joka edustaa sotilasilmailun kehit-tyneintä teknologiaa. Kohdevaltioina tutkielmassa on Venäjä ja Yhdysvallat. Tämä tutkielma on luonteeltaan kvalitatiivinen eli laadullinen tutkimus. Tutkielmassa käytetään tiedonkeruumenetelmänä asiakirja- ja tekstianalyysia. Tutkimusongelmana ja tavoitteena on selvittää mitkä ovat uuden sukupolven taistelukoneiden kehityksen suuntaviivat. Tutkimusongelman tueksi on asetettu alakysymyksiä, joiden avulla pyritään helpottamaan varsinaisen tutkimusongelman selvittelyä ja käsittelyä. Alatutkimusongelmat: - Minkälainen on uuden sukupolven monitoimihävittäjä? - Mikä on kohdevaltioiden hävittäjäsuunnittelun tämän hetkinen tila? - Millä tavalla kohdevaltioiden konekalusto eroaa toisistaan? Tutkimusaineistona on käytetty mielipidekirjoituksia, asiantuntijalähteitä, eri toimijoiden sotilasaikakausijulkaisuja ja eri yhteisöjen internet-sivustoja. Tutkielmassa on määritetty kohdevaltioiden tulevaisuuden kehitystrendejä. Yhdysvaltain so-takoneistolla on käytössään ainoa uuden sukupolven monitoimihävittäjä F-22A Raptor. Lisäksi testi- ja koelentovaihetta läpikäyvä F-35 Lightning II saataneen operatiiviseen käyttöön vuonna 2012. Yhdysvallat onkin asettamassa tavoitteita seuraavan sukupolven ilma-alukselle, joka nykyisten suuntaviivojen mukaisesti on todennäköisesti miehittämätön. Yhdysvaltojen suunnatessa katsettaan jo seuraavan sukupolven ilma-alukseen kehittää Venä-jä omaa uuden sukupolven monitoimihävittäjää tavoitteena sen tuotannon aloittaminen aikaisintaan vuonna 2015. Venäjän sotilasilmailun uusimmat modernisoinnit toimivat testialustoina uuden sukupolven monitoimihävittäjälle. Lisäksi niillä on tarkoitus täyttää vanhan kalus-ton ja uuden sukupolven monitoimihävittäjän väliin jäävä aukko. Venäjän sotilasilmailuteollisuuden tulevaisuus riippuu suuresti uuden sukupolven monitoimihävittäjästä. Mikäli se operatiiviseen käyttöön tullessa pystyy täyttämään sille asetetut vaatimukset pystyy Venäjän so-tilasilmailu mahdollisesti siirtämään katsettaan kohti seuraavaa hävittäjäsukupolvea.

Viidennen sukupolven hävittäjien häiveteknologia

Tämän tutkielman tarkoituksena on selvittää viidennen sukupolven hävittäjien häiveteknologian toteutusratkaisuja. On käsitelty miksi häiveteknologiaa tarvitaan sekä vertailtu miten häiveteknologia toteutetaan viidennen sukupolven hävittäjissä. Suomen ilmavoimien päähävittäjäkalusto F/A-18 Hornet edustaa neljättä sukupolvea ja saavuttaa elinkaarensa lopun 2020-luvun lopussa, joten seuraajasta on lähivuosina tehtävä päätös. On siis mahdollista, että seuraajaksi hankitaan jokin viidennen sukupolven hävittäjä häiveteknologialla varustettuna. Viidennen sukupolven hävittäjiä kehitellään ainakin Yhdysvalloissa, Venäjällä, Kiinassa, Intiassa ja Japanissa, mutta tässä tutkielmassa on vertailtu vain Yhdysvaltojen, Venäjän ja Kiinan viidennen sukupolven hävittäjiä. Yhdysvalloilla on tällä hetkellä ainut operaatiokäytössä oleva viidennen sukupolven hävittäjä, Lockheed Martin F-22 Raptor. Raptorin lisäksi Yhdysvalloilla on kehitysvaiheessa oleva Lockheed Martin F-35 Lightning II. Venäjällä on myös kehitysvaiheessa oleva Suhoi PAK FA samoin kuin Kiinalla on Chengdu J-20. Nämä kolme kehitysvaiheessa olevaa viidennen sukupolven hävittäjää on tarkoitus ottaa palveluskäyttöön ennen 2020-lukua. Tutkielman päätutkimuskysymys on, miten häiveteknologia toteutetaan viidennen sukupolven hävittäjissä. Lisäksi tutkielmassa on kaksi alakysymystä. Nämä ovat seuraavat: Miksi häiveteknologiaa tarvitaan? Miten häiveteknologian toteutus eroaa viidennen sukupolven hävittäjissä? Tutkimusmenetelmänä on käytetty kvalitatiivista kirjallisuustutkimusta ja vertailua julkisista lähteistä. Häiveteknologia ei ole mikään uusi innovaatio. Teknologiaa on kehitelty aina 1940-luvulta asti ja yksi tunnetuimmista häivepommikoneista, Lockheed Martinin F-117 Nighthawk, on jo poistunut palvelukäytöstä. Tuolloin häiveominaisuuksien ylläpito ja huolto aiheuttivat merkittäviä kustannuksia tutkasignaalia absorboivien maalien ja materiaalien takia. Viidennen sukupolven hävittäjissä on pyritty vähentämään näiden maalien ja materiaalien käyttöä, jotta käyttökustannukset saataisiin pienennettyä. On panostettu enemmän hävittäjien muodon antamaan suojaan tutkasignaalia vastaan maalien ja materiaalien sijaan. Tämä on nykyaikana mahdollista kehittyneiden tietokoneiden avulla, jotka pystyvät laskemaan optimaalisen muodon hävittäjälle sekä häive- että aerodynaamisten ominaisuuksien kannalta. Tutkasignaalia absorboivia maaleja ja materiaaleja on kuitenkin pakko käyttää erilaisten luukkujen ympärillä sekä muissa reunoissa, joissa muodolla ei saada riittävää vaikutusta.