R-Ras regulates β1-integrin trafficking via effects on membrane ruffling and endocytosis

<p>Abstract</p> <p>Background</p> <p>Integrin-mediated cell adhesion and spreading is dramatically enhanced by activation of the small GTPase, R-Ras. Moreover, R-Ras localizes to the leading edge of migrating cells, and regulates membrane protrusion. The exact mechanisms by which R-Ras regulates integrin function are not fully known. Nor is much known about the spatiotemporal relationship between these two molecules, an understanding of which may provide insight into R-Ras regulation of integrins.</p> <p>Results</p> <p>GFP-R-Ras localized to the plasma membrane, most specifically in membrane ruffles, in Cos-7 cells. GFP-R-Ras was endocytosed from these ruffles, and trafficked via multiple pathways, one of which involved large, acidic vesicles that were positive for Rab11. Cells transfected with a dominant negative form of GFP-R-Ras did not form ruffles, had decreased cell spreading, and contained numerous, non-trafficking small vesicles. Conversely, cells transfected with the constitutively active form of GFP-R-Ras contained a greater number of ruffles and large vesicles compared to wild-type transfected cells. Ruffle formation was inhibited by knock-down of endogenous R-Ras with siRNA, suggesting that activated R-Ras is not just a component of, but also an architect of ruffle formation. Importantly, β₁-integrin co-localized with endogenous R-Ras in ruffles and endocytosed vesicles. Expression of dominant negative R-Ras or knock down of R-Ras by siRNA prevented integrin accumulation into ruffles, impaired endocytosis of β₁-integrin, and decreased β₁-integrin-mediated adhesion. Knock-down of R-Ras also perturbed the dynamics of another membrane-localized protein, GFP-VSVG, suggesting a more global role for R-Ras on membrane dynamics. However, while R-Ras co-internalized with integrins, it did not traffic with VSVG, which instead moved laterally out of ruffles within the plane of the membrane, suggesting multiple levels of regulation of and by R-Ras.</p> <p>Conclusions</p> <p>Our results suggest that integrin function involves integrin trafficking via a cycle of membrane protrusion, ruffling, and endocytosis regulated by R-Ras, providing a novel mechanism by which integrins are linked to R-Ras through control of membrane dynamics.</p

Influence de la saison sur l’ecodistribution des glossines, tabanides, stomoxes du Baï de Momba Makokou, Gabon

Dans un souci de valorisation écotouristique du baï de Momba, la dynamique saisonnière des glossines, tabanidés et stomoxes a été évaluée. Dix pièges Vavoua ont été utilisés durant 7 j consécutifs soit un effort de piégeage de 70 pièges-j. Un total de 2 641 stomoxes (57 %), 1 680 glossines (36 %) et 325 tabanidés (7 %) ont été capturés pendant la saison des pluies et la saison sèche. La plus forte densité a été obtenueavec les glossines indépendamment des saisons, soit une DAP = 5,91 glossines/piège/j en saison des pluies et DAP = 6,09 glossine/piège/jour en saison sèche. L’indice de Shannon a montré que la plus forte diversité spécifique de glossines a été observée en saison sèche (0,58) et la plus faible en saison des pluies (0,48). Les tabanidés ont une DAP de 2,02 tabanidés/piège/j et une DAP de 0,3 tabanidé/piège/j respectivement en saison des pluies et en saison sèche. L’indice de Shannon est de 0,69 en saison des pluies et de 0,68 en saison sèche. Tandis que les stomoxes ont une DAP de 18,69 stomoxes/piège/j en saison des pluies et une DAP de 0,18 stomoxe/piège/j en saison sèche. L’indice de Shannon de ces espèces est de 0,4 en saison des pluies et de 0,23 en saison sèche. La présence de vecteurs de trypanosomoses et de filarioses dans ce milieu écologique très particulier suggère d’inclure des stratégies de lutte contre ces insectes dans le processus de valorisation du baï de Momba en termes d’écotourisme.Mots clés : Glossines, tabanidés, stomoxes, baï de Momba, Gabon

Etude préliminaire de l’infestation des glossines par les trypanosomes dans le baï de Momba (Nord-Est Gabon)

Une étude préliminaire entomo-parasitologique a été effectuée pendant la grande saison sèche à l’interieur et autour du baï de Momba (nord-est Gabon) pour examiner les espèces de Trypanosomes transmises par les glossines. Ces dernières ont été capturées à l’aide des pièges vavoua et nzi. Les infections par les trypanosomes chez ces glossines ont été recherchées à l’aide d’un microscope au niveau des glandes salivaires, proboscis et intestins moyens des glossines. Ainsi, une infection du proboscis seul correspond à T. vivax, celles des glandes salivaires à T. brucei et celle du proboscis et de l’intestin moyen à T. congolense. Au total six espèces de glossines ont été identifiées : Glossina palpalis palpalis, G. nashi, G. fusca congolensis, G. tachinoides, G. frezili et G. fuscipes fuscipes. Le taux global d’infestation des glossines disséquées et observées au microscope a été estimé à 30 %. L’infestation des glossines par les trypanosomes témoigne de l’existence d’un risque trypanosomien dans le baï de Momba et suggère ainsi l’établissement d’un cycle de transmission Animal-Glossine-Homme dans ce milieu.Mots clés: Glossina, T. vivax, T. congolense, baï de Momba, trypanosomes. Preliminary study of infection of tsetse by trypanosomes in the baï of Momba North East GabonA preliminary study are insect parasitology was carried out during the long dry season in and around the baï of Momba (north-east Gabon) to examine the species of trypanosomes transmitted by tsetse flies. The flies were captured using traps and Vavoua nzi. Infections by trypanosomes were investigated using a microscope in the salivary glands and the proboscis intestines means tsetse. In total six tsetse species were identified : Glossina palpalis palpalis, G. nashi, G. fusca congolensis, G. tachinoides, G. frezili and G. fuscipes fuscipes. The overall rate of infestation of flies dissected and observed under the microscope is estimated at 30 %. The infestation of Bai Momba by flies carrying trypanosomes demonstrates the existence of a trypanosome risk and thus suggests the establishment of a transmission cycle Human-Animal-Glossina in this environment.Keywords: tsetse flies, T. vivax, T. congolense, baï of Momba, trypanosome

Inventory of potential vectors of trypanosoma and infection rate of the Tsetse fly in the National Park of Ivindo, Gabon.

Background: Trypanosoma\u2019s vectors distribution is poorly investigated in Gabon, where Trypanosomiasis historical foci exist. Thus, an active detection of Trypanosoma sp transmission needs to be assessed. Objectives: The present study aims to identify potential vectors of Trypanosoma sp and to evaluate the infection rate of the Tsetse fly in an area of Gabon. Methods: An entomological survey was conducted in the National Park of Ivindo in May 2012 using Vavoua traps. All captured insects were identified. Tsetse were dissected and organs were microscopically observed to detect the presence of Trypanosoma sp. Results: 247 biting flies known as vectors of Trypanosomiasis were caught including 189 tsetse flies, 32 Tabanid and 26 Stomoxys . Tsetse flies had the highest bulk densities per trap per day (ADT = 3 tsetse / trap / day), while the lowest density was found among Stomoxys (ADT= 0.41 Stomoxys / trap / day). The infection rate of flies was 6.3%. Infectious organs were midguts and to a lesser extent salivary glands and proboscis. Conclusion: The presence of Tsetse infected by Trypanosoma highlights an existing risk of trypanosomiasis infection in the National Park of Ivindo

The impact of Loa loa microfilaraemia on research subject retention during a whole sporozoite malaria vaccine trial in Equatorial Guinea

Loa loa microfilariae were found on thick blood smears (TBSs) from 8 of 300 (2.7%) residents of Bioko Island, Equatorial Guinea, during a Plasmodium falciparum sporozoite malaria vaccine clinical trial. Only one subject was found to have microfilaraemia on his first exam; parasites were not discovered in the other seven until subsequent TBSs were performed, at times many weeks into the study. All infected individuals were asymptomatic, and were offered treatment with diethylcarbamazine, per national guidelines. L. loa microfilaraemia complicated the enrolment or continued participation of these eight trial subjects, and only one was able to complete all study procedures. If ruling out loiasis is deemed to be important during clinical trials, tests that are more sensitive than TBSs should be performed

Trade-offs in linking adaptation and mitigation in the forests of the Congo Basin

Recent discussions on forests and climate change have highlighted the potential for conservation of tropical forests to contribute synergistically to both mitigation (reducing emissions of greenhouse gases) and adaptation (increasing capacity to cope with changing climate conditions). Key mechanisms through which adaptive advantages might be gained include the potential for forest resources to support livelihoods in the context of climatic strains on agriculture and the protection that intact forest ecosystems might provide against landslides, flash floods and other hazards related to extreme weather. This paper presents findings from field research with forest communities in three areas of the Congo Basin in Central Africa, in which the adaptive role and potential of forests in these respects is critically analysed. The investigation was carried out through a combination of structured and semi-structured qualitative techniques within six villages in Cameroon, Equatorial Guinea and Rwanda. The findings of the research highlight the need to understand both the limits of synergy, and the constraints and trade-offs for rural livelihoods that may be associated with a forest conservation agenda driven by the additional impetus of carbon sequestration. The search for synergy may be conceptually laudable, but if forest management actions do not take account of on-the-ground contexts of constraints and social trade-offs then the result of those actions risks undermining wider livelihood resilience

Safety and immunogenicity of radiation-attenuated PfSPZ vaccine in equatoguinean infants, children, and adults

The radiation-attenuated Plasmodium falciparum sporozoites (PfSPZ) Vaccine has demonstrated safety and immunogenicity in 5-month-old to 50-year-old Africans in multiple trials. Except for one, each trial has restricted enrollment to either infants and children or adults /= 0.17). There were no significant differences between vaccinees and controls with respect to the rates or severity of unsolicited AEs or laboratory abnormalities. Development of antibodies to P. falciparum circumsporozoite protein occurred in 67/69 vaccinees (97%) and 0/15 controls. Median antibody levels were highest in infants and 1-5-year-olds and declined progressively with age. Antibody responses in children were greater than in adults protected against controlled human malaria infection. Robust immunogenicity, combined with a benign AE profile, indicates children are an ideal target for immunization with PfSPZ Vaccine

Re-emergence of dengue virus serotype 3 infections in Gabon in 2016?2017, and evidence for the risk of repeated dengue virus infections

Objectives: Dengue outbreaks, mainly caused by dengue virus serotype 2 (DENV-2), occurred in 2007 and in 2010 in Gabon, Central Africa. However, information on DENV infections has been insufficient since 2010. The aim of this study was to investigate the current DENV infection scenario and the risk of repeated infections in Gabon. Methods: During 2015?2017, serum samples were collected from enrolled febrile participants and were tested for DENV infection using RT-qPCR. DENV-positive samples were analyzed for a history of previous DENV infection(s) using ELISA. The complete DENV genome was sequenced to analyze the phylogeny of Gabonese DENV strains. Results: DENV-3 was exclusively detected, with a high rate of anti-DENV IgG seropositivity among DENV-3-positive participants. DENV-3 showed higher infection rates in adults and the infection was seasonal with peaks in the rainy seasons. Phylogenetic analysis revealed that Gabonese DENV-3 originated from West African strains and has been circulating continuously in Gabon since at least 2010, when the first DENV-3 case was reported. Conclusions: These findings indicate stable DENV-3 circulation and the risk of repeated DENV infections in Gabon, highlighting the need for continuous monitoring to control DENV infections

Aprendizaje virtual de las matemáticas utilizando distintas TICs

Proyecto para ayudar al estudiantado en el aprendizaje de las Matemáticas y promover su aprendizaje autónomo. Todo ello, con materiales más visuales como vídeos, píldoras educativas, clases en modo síncrono, ejemplos con GeoGebra y cuestionarios

Taller de matemáticas básicas, aprendizaje semipresencial

El Taller de Matemáticas Básicas, aprendizaje semipresencial sirve para ayudar a los estudiantes de nuevo ingreso a repasar, reforzar y/o aprender conceptos matemáticos para afrontar con éxito el estudio de un grado universitario