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

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

The Effects of Supply Chain Finance on Organizational Performance: A Moderated and Mediated Model

Abstract Purpose- This paper draws on the dynamic capabilities approach, and aims to empirically investigate the impact of supply chain finance (SCF) on firm performance (e.g. operational risk and operational performance), the critical effect of environmental dynamism (ED) as moderator and supply chain risk (SCR) and a mediator in the relationship between SCF and OP. Design/methodology/approach –This study is based on empirical data collected from a survey of 210 companies and their supply chains in mainland China. Structural equation modeling is used to test our proposed relationships. Findings – The findings show that SCF significantly mitigates the SCR, which subsequently has a significant positive effect on organizational performance (e.g., cost performance and operational performance). The findings also show that when environmental dynamism (ED) is high, the relationship between SCF and SCR is stronger and vice versa. Moreover, supply chain risk (SCR) mediates the relationship between supply chain finance (SCF) and organizational performance (OP). Hypothesis regarding the moderating effect of environmental dynamism (ED) on the paths joining supply chain finance (SCF) and supply chain risk (SCR) was also supported. Supply chain risk (SCR) has a significant negative effect on organizational performance (OP). However, hypothesis regarding the effect of environmental dynamism (ED) on supply chain risk (SCR) was not supported. Research limitations/implications- This study has some limitations. First, we conducted our research with Chinese organizations. This may result in low generalizability in other contexts. In addition, we employed survey method and cross-sectional data design in this study, which may generate the potential issue of common method bias (CMB). However, the findings of this study will help organizations across China and other emerging economies to adopt SCF as a secure financing mechanism to enhance working capital and mitigate risk. In addition, our paper provides some new managerial insights for decision makers in organizations, while exploring different factors such as supply chain finance (SCF), supply chain risk (SCR), and environmental dynamism (ED), and their effect on organizational. Originality/value- This study has greatly developed a general SCF adoption model that helps to guide empirical research investigating the critical impact of SCF on firm performance

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