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911.
Selective recapture of secretory granule components after full collapse exocytosis in neuroendocrine chromaffin cells 总被引:1,自引:0,他引:1
Ceridono M Ory S Momboisse F Chasserot-Golaz S Houy S Calco V Haeberlé AM Demais V Bailly Y Bader MF Gasman S 《Traffic (Copenhagen, Denmark)》2011,12(1):72-88
In secretory cells, calcium-regulated exocytosis is rapidly followed by compensatory endocytosis. Neuroendocrine cells secrete hormones and neuropeptides through various modes of exo-endocytosis, including kiss-and-run, cavicapture and full-collapse fusion. During kiss-and-run and cavicapture modes, the granule membrane is maintained in an omega shape, whereas it completely merges with the plasma membrane during full-collapse mode. As the composition of the granule membrane is very different from that of the plasma membrane, a precise sorting process of granular proteins must occur. However, the fate of secretory granule membrane after full fusion exocytosis remains uncertain. Here, we investigated the mechanisms governing endocytosis of collapsed granule membranes by following internalization of antibodies labeling the granule membrane protein, dopamine-β-hydroxylase (DBH) in cultured chromaffin cells. Using immunofluorescence and electron microscopy, we observed that after full collapse, DBH remains clustered on the plasma membrane with other specific granule markers and is subsequently internalized through vesicular structures composed mainly of granule components. Moreover, the incorporation of this recaptured granule membrane into an early endosomal compartment is dependent on clathrin and actin. Altogether, these results suggest that after full collapse exocytosis, a selective sorting of granule membrane components is facilitated by the physical preservation of the granule membrane entity on the plasma membrane. 相似文献
912.
Background
Many individuals diagnosed with Multiple Sclerosis (MS) are sensitive to increased body temperature, which has been recognized as correlating with the symptom of fatigue. The need to explore this association has been highlighted. The aim of this study was to investigate the occurrence of heat sensitivity and its relations to disease course, disability, common MS-related symptoms and ongoing immunosuppressive treatments among individuals 65 years of age or younger diagnosed with MS. 相似文献913.
The morphology of β-lactoglobulin structures inside droplets was studied during aggregation and gelation using confocal laser scanning microscopy (CLSM) equipped with a temperature stage and transmission electron microscopy (TEM). The results showed that there is a strong driving force for the protein to move to the interface between oil and water in the droplet, and the β-lactoglobulin formed a dense shell around the droplet built up from the inside of the droplets. Less protein was found inside the droplets. The longer the β-lactoglobulin was allowed to aggregate prior to gel formation, the larger the part of the protein went to the interface, resulting in a thicker shell and very little material being left inside the droplets. The droplets were easily deformed because no network stabilizes them. When 0.5% emulsifier, polyglycerol polyresinoleat (PGPR), was added to the oil phase, the β-lactoglobulin was situated both inside the droplets and at the interface between the droplets and the oil phase; when 2% PGPR was added, the β-lactoglobulin structure was concentrated to the inside of the droplets. The possibility to use the different morphological structures of β-lactoglobulin in droplets to control the diffusion rate through a β-lactoglobulin network was evaluated by fluorescence recovery after photobleaching (FRAP). The results show differences in the diffusion rate due to heterogeneities in the structure: the diffusion of a large water-soluble molecule, FITC-dextran, in a dense particulate gel was 1/4 of the diffusion rate in a more open particulate β-lactoglobulin gel in which the diffusion rate was similar to that in pure water. 相似文献
914.
Corinne Génu-Dellac Gilles Gosselin Frédéric Puech Jean-Claude Henry Anne-Marie Aubertin Georges Obert 《Nucleosides, nucleotides & nucleic acids》2013,32(6):1345-1376
Abstract The α-L-arabinofuranosyl and 2′-deoxy-α-L-erythro-pentofuranosyl analogues of the naturally occurring nucleosides have been synthesized and their antiviral properties examined. The α-L-arabinofuranosyl nucleosides were prepared by glycosylation of purine and pyrimidine aglycons with a suitably peracyl-α-L-arabinose, followed by removal of the protecting groups. Their 2′-deoxy derivatives were obtained by sequential selective 2′-O-deacylation and deoxygenation. All the prepared compounds were tested for their activity against a variety of RNA and DNA viruses, but they did not show significant antiviral activity. 相似文献
915.
Katarzyna J. Maresz Annelie Hellvard Aneta Sroka Karina Adamowicz Ewa Bielecka Joanna Koziel Katarzyna Gawron Danuta Mizgalska Katarzyna A. Marcinska Malgorzata Benedyk Krzysztof Pyrc Anne-Marie Quirke Roland Jonsson Saba Alzabin Patrick J. Venables Ky-Anh Nguyen Piotr Mydel Jan Potempa 《PLoS pathogens》2013,9(9)
Rheumatoid arthritis and periodontitis are two prevalent chronic inflammatory diseases in humans and are associated with each other both clinically and epidemiologically. Recent findings suggest a causative link between periodontal infection and rheumatoid arthritis via bacteria-dependent induction of a pathogenic autoimmune response to citrullinated epitopes. Here we showed that infection with viable periodontal pathogen Porphyromonas gingivalis strain W83 exacerbated collagen-induced arthritis (CIA) in a mouse model, as manifested by earlier onset, accelerated progression and enhanced severity of the disease, including significantly increased bone and cartilage destruction. The ability of P. gingivalis to augment CIA was dependent on the expression of a unique P. gingivalis peptidylarginine deiminase (PPAD), which converts arginine residues in proteins to citrulline. Infection with wild type P. gingivalis was responsible for significantly increased levels of autoantibodies to collagen type II and citrullinated epitopes as a PPAD-null mutant did not elicit similar host response. High level of citrullinated proteins was also detected at the site of infection with wild-type P. gingivalis. Together, these results suggest bacterial PAD as the mechanistic link between P. gingivalis periodontal infection and rheumatoid arthritis. 相似文献
916.
Annie M. Bérard Aurélie Bedel Rémi Le Trequesser Geneviève Freyburger Alan Nurden Sylvie Colomer Viviane Guérin Marie-Christine Vergnes Fran?ois Becker Gabriel Camelot Luc Bressolette Philippe Lacroix Jean-Pierre Cambou Alessandra Bura-Rivière Joseph Emmerich Michel Darmon Anne-Marie Deletraz Samir Mesli Brigitte Colombies Virginie Vanbrugghe Claude Conri Jo?l Constans 《PloS one》2013,8(3)
Background
This study aimed to determine the prevalence of genetic and environmental vascular risk factors in non diabetic patients with premature peripheral arterial disease, either peripheral arterial occlusive disease or thromboangiitis obliterans, the two main entities of peripheral arterial disease, and to established whether some of them are specifically associated with one or another of the premature peripheral arterial disease subgroups.Methods and Results
This study included 113 non diabetic patients with premature peripheral arterial disease (diagnosis <45-year old) presenting either a peripheral arterial occlusive disease (N = 64) or a thromboangiitis obliterans (N = 49), and 241 controls matched for age and gender. Both patient groups demonstrated common traits including cigarette smoking, low physical activity, decreased levels of HDL-cholesterol, apolipoprotein A–I, pyridoxal 5′-phosphate (active form of B6 vitamin) and zinc. Premature peripheral arterial occlusive disease was characterized by the presence of a family history of peripheral arterial and carotid artery diseases (OR 2.3 and 5.8 respectively, 95% CI), high lipoprotein (a) levels above 300 mg/L (OR 2.3, 95% CI), the presence of the factor V Leiden (OR 5.1, 95% CI) and the glycoprotein Ia807T,837T,873A allele (OR 2.3, 95% CI). In thromboangiitis obliterans group, more patients were regular consumers of cannabis (OR 3.5, 95% CI) and higher levels in plasma copper has been shown (OR 6.5, 95% CI).Conclusions
According to our results from a non exhaustive list of study parameters, we might hypothesize for 1) a genetic basis for premature peripheral arterial occlusive disease development and 2) the prevalence of environmental factors in the development of thromboangiitis obliterans (tobacco and cannabis). Moreover, for the first time, we demonstrated that the 807T/837T/873A allele of platelet glycoprotein Ia may confer an additional risk for development of peripheral atherosclerosis in premature peripheral arterial occlusive disease. 相似文献917.
Manish A. Shah Zev A. Wainberg Daniel V. T. Catenacci Howard S. Hochster James Ford Pamela Kunz Fa-Chyi Lee Howard Kallender Fabiola Cecchi Daniel C. Rabe Harold Keer Anne-Marie Martin Yuan Liu Robert Gagnon Peter Bonate Li Liu Tona Gilmer Donald P. Bottaro 《PloS one》2013,8(3)
Purpose
The receptors for hepatocyte and vascular endothelial cell growth factors (MET and VEGFR2, respectively) are critical oncogenic mediators in gastric adenocarcinoma. The purpose is to examine the safety and efficacy of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2, and VEGFR2 receptors, for the treatment of metastatic gastric adenocarcinoma.Patients and Methods
Foretinib safety and tolerability, and objective response rate (ORR) were evaluated in patients using intermittent (240 mg/day, for 5 days every 2 weeks) or daily (80 mg/day) dosing schedules. Thirty evaluable patients were required to achieve alpha = 0.10 and beta = 0.2 to test the alternative hypothesis that single-agent foretinib would result in an ORR of ≥25%. Up to 10 additional patients could be enrolled to ensure at least eight with MET amplification. Correlative studies included tumor MET amplification, MET signaling, pharmacokinetics and plasma biomarkers of foretinib activity.Results
From March 2007 until October 2009, 74 patients were enrolled; 74% male; median age, 61 years (range, 25–88); 93% had received prior therapy. Best response was stable disease (SD) in 10 (23%) patients receiving intermittent dosing and five (20%) receiving daily dosing; SD duration was 1.9–7.2 months (median 3.2 months). Of 67 patients with tumor samples, 3 had MET amplification, one of whom had SD. Treatment-related adverse events occurred in 91% of patients. Rates of hypertension (35% vs. 15%) and elevated aspartate aminotransferase (23% vs. 8%) were higher with intermittent dosing. In both patients with high baseline tumor phospho-MET (pMET), the pMET:total MET protein ratio decreased with foretinib treatment.Conclusion
These results indicate that few gastric carcinomas are driven solely by MET and VEGFR2, and underscore the diverse molecular oncogenesis of this disease. Despite evidence of MET inhibition by foretinib, single-agent foretinib lacked efficacy in unselected patients with metastatic gastric cancer.Trial Registration
ClinicalTrials.gov NCT00725712相似文献918.
Maximilien Barret Christian Boustiere Jean-Marc Canard Jean-Pierre Arpurt David Bernardini Philippe Bulois Stanislas Chaussade Denis Heresbach Isabelle Joly Jean Lapuelle René Laugier Gilles Lesur Patrice Pienkowski Thierry Ponchon Bertrand Pujol Bruno Richard-Molard Michel Robaszkiewicz Rémi Systchenko Fatima Abbas Anne-Marie Schott-Pethelaz Christophe Cellier for the Société Fran?aise d'Endoscopie Digestive 《PloS one》2013,8(7)
Introduction
Colonoscopy can prevent deaths due to colorectal cancer (CRC) through early diagnosis or resection of colonic adenomas. We conducted a prospective, nationwide study on colonoscopy practice in France.Methods
An online questionnaire was administered to 2,600 French gastroenterologists. Data from all consecutive colonoscopies performed during one week were collected. A statistical extrapolation of the results to a whole year was performed, and factors potentially associated with the adenoma detection rate (ADR) or the diagnosis of polyps or cancer were assessed.Results
A total of 342 gastroenterologists, representative of the overall population of French gastroenterologists, provided data on 3,266 colonoscopies, corresponding to 1,200,529 (95% CI: 1,125,936-1,275,122) procedures for the year 2011. The indication for colonoscopy was CRC screening and digestive symptoms in 49.6% and 38.9% of cases, respectively. Polypectomy was performed in 35.5% of cases. The ADR and prevalence of CRC were 17.7% and 2.9%, respectively. The main factors associated with a high ADR were male gender (p=0.0001), age over 50 (p=0.0001), personal or family history of CRC or colorectal polyps (p<0.0001 and p<0.0001, respectively), and positive fecal occult blood test (p=0.0005). The prevalence of CRC was three times higher in patients with their first colonoscopy (4.2% vs. 1.4%; p<0.0001).Conclusions
For the first time in France, we report nationwide prospective data on colonoscopy practice, including histological results. We found an average ADR of 17.7%, and observed reduced CRC incidence in patients with previous colonoscopy. 相似文献919.
Sai V. Vemula Yadvinder S. Ahi Anne-Marie Swaim Jacqueline M. Katz Ruben Donis Suryaprakash Sambhara Suresh K. Mittal 《PloS one》2013,8(4)
Recurrent outbreaks of H5, H7 and H9 avian influenza viruses in domestic poultry accompanied by their occasional transmission to humans have highlighted the public health threat posed by these viruses. Newer vaccine approaches for pandemic preparedness against these viruses are needed, given the limitations of vaccines currently approved for H5N1 viruses in terms of their production timelines and the ability to induce protective immune responses in the absence of adjuvants. In this study, we evaluated the feasibility of an adenovirus (AdV)-based multivalent vaccine approach for pandemic preparedness against H5, H7 and H9 avian influenza viruses in a mouse model. Replication-defective AdV vectors expressing hemagglutinin (HA) from different subtypes and nucleoprotein (NP) from one subtype induced high levels of humoral and cellular immune responses and conferred protection against virus replication following challenge with H5, H7 and H9 avian influenza virus subtypes. Inclusion of HA from the 2009 H1N1 pandemic virus in the vaccine formulation further broadened the vaccine coverage. Significantly high levels of HA stalk-specific antibodies were observed following immunization with the multivalent vaccine. Inclusion of NP into the multivalent HA vaccine formulation resulted in the induction of CD8 T cell responses. These results suggest that a multivalent vaccine strategy may provide reasonable protection in the event of a pandemic caused by H5, H7, or H9 avian influenza virus before a strain-matched vaccine can be produced. 相似文献