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VAMP721 and VAMP722, play crucial roles in membrane fusion at post-Golgi compartments. They are involved in cell plate formation, recycling, endocytosis, and secretion. While individual SNARE actors and regulators exhibit significant overlap, specificity is achieved through distinct combinations of these components. Cytokinesis-related SNAREs traffic as preformed CIS-complexes, which require disassembly by the NSF/αSNAP chaperoning complex to facilitate subsequent homotypic fusion at the cell plate. Recent findings suggest a similar mechanism may operate during secretion. Regulation of VAMP721 activity involves interactions with tethers, GTPases, and Sec1/Munc18 proteins, along with a newly discovered phosphorylation at Tyrosine residue 57. These advances provide valuable insights into the fascinating world of cellular trafficking and membrane fusion.
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Transporte Proteico , Proteínas R-SNARE , Proteínas R-SNARE/metabolismo , Proteínas R-SNARE/genética , Fusão de MembranaRESUMO
Cold resection of colonic polyps is an important tool that reduces the incidence of colon cancer. Cold loop polypectomy is a safe and effective technique in colonic lesions smaller than 10 mm and cold mucosectomy with submucosal injection is a growing technique for the resection of non-pedunculated lesions between 10 and 19 mm. Post polypectomy bleeding is an infrequent complication in cold resection, but its recognition is key to reduce the impact of its consequences. The use of hemostatic clips is one of the methods preferred by endoscopists for the management of immediate post polypectomy bleeding, however its usefulness in the prevention of late bleeding is uncertain. In recent years, both meta-analysis and cost- effectiveness studies have concluded that the use of hemoclips does not reduce the incidence of late post-polypectomy bleeding, so their use should be reserved only for high-risk patients.
La resección fría de pólipos colónicos es una importante herramienta que reduce la incidencia de cáncer de colon. La polipectomía con asa fría es una técnica segura y efectiva en lesiones colónicas menores de 10 mm y la mucosectomía fría con inyección submucosa es una técnica en auge para la resección de lesiones no pediculadas entre 10 a 19 mm. El sangrado pospolipectomía es una complicación infrecuente en la resección fría, pero su reconocimiento es clave para disminuir el impacto de sus consecuencias. El uso de clips hemostáticos es uno de los método preferidos por los endoscopistas para el manejo del sangrado inmediato pospolipectomía, no obstante su utilidad en la prevención del sangrado tardío es incierto. En los últimos años, tanto metaanálisis como estudios de costo efectividad concluyen que el uso de hemoclips no reduce la incidencia de sangrado tardío pospolipectomía por lo que su uso debería reservarse sólo a pacientes de alto riesgo.
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Instrumentos Cirúrgicos , Pólipos do Colo/cirurgia , Colonoscopia/métodos , Colonoscopia/efeitos adversos , Hemostasia Cirúrgica/instrumentação , Hemostasia Cirúrgica/métodosRESUMO
ABSTRACT Background: Polypectomy is an important treatment option for preventing colorectal cancer. Incomplete polyp resection (IPR) is recognized as a risk factor for interval cancer. Objective: The primary objective was to evaluate the complete polyp resection (CPR) rate for cold snare polypectomy (CSP) in small non-pedunculated polyps and, secondarily, specimen retrieval and complication rates. Methods: We prospectively evaluated 479 polyps <10 mm removed by CSP in 276 patients by an inexperienced endoscopist. Results: A total of 476 polyps (99.4%) were resected en bloc. A negative margin (classified as CPR) was observed in 435 polyps (90.8%). An unclear or positive margin (classified as IPR) was observed in 43 cases (9.0%) and 1 case (0.2%), respectively, for an overall IPR rate of 9.2% (44/479). The IPR rate was 12.2% in the first half of cases and 5.9% in the second half (P=0.02). Dividing into tertiles, the IPR rate was 15.0% in the first tertile, 6.9% in the second tertile, and 5.7% in the third tertile (P=0.01). Dividing into quartiles, the IPR rate was 15.8% in the first quartile and 5.9% in the fourth quartile (P=0.03). The IPR rate was 6.3% for type 0-IIa lesions and 14.1% for type 0-Is lesions (P=0.01). For serrated and adenomatous lesions, the IPR rate was 9.2%. Specimen retrieval failed in 3.6% of cases. Immediate bleeding (>30 s) occurred in 1 case (0.2%), treated with argon plasma coagulation. No delayed bleeding or perforation occurred. Conclusion: CSP is a safe technique that provides good results for the resection of small non-pedunculated polyps, with a short learning curve.
RESUMO Contexto: A polipectomia é uma importante opção terapêutica na prevenção do câncer colorretal (CCR). A ressecção incompleta do pólipo (RIP) é reconhecida como fator de risco para o câncer de intervalo. Objetivo: O principal objetivo foi avaliar o índice de ressecção completa da polipectomia a frio (PF) em pequenos pólipos não pediculados e, secundariamente, a recuperação do espécime e índice de complicações. Métodos: Avaliamos prospectivamente 479 pólipos <10 mm removidos por PF em 276 pacientes, por um endoscopista sem experiência com este método. Resultados: Foram ressecados em bloco 476 pólipos (99,4%). Tivemos margem negativa, considerada ressecção completa do pólipo (RCP), em 435 (90,8%) casos. Margem indefinida ou positiva (classificada como RIP) foi observada em 43 (9,0%) casos e em 1 (0,2%) caso, respectivamente, com um índice global de RIP de 9,2% (44/479). O índice de RIP foi de 12,5% na primeira metade dos casos e 5,9% na última metade (P=0,02). Dividindo em tercis, o índice de RIP foi de 15,0% no primeiro terço, 6,9% no segundo terço e 5,7% no terceiro quarto, P=0,01. Dividindo em quartis, o índice de RIP foi de 15,8% no primeiro quarto, enquanto o último quarto foi de 5,9%, P=0,03. O índice de RIP foi de 6,3% para lesões tipo 0-IIa e de 14,1% para lesões tipo 0-Is, P=0,01. O índice de RIP foi de 9,2% para lesões serrilhadas e adenomatosas. Houve falha na recuperação dos espécimes em 3,6% dos casos. Sangramento imediato (>30 s) ocorreu em um caso (0,2%), controlado com plasma de argônio. Sem sangramento tardio e perfuração. Conclusão: PF é uma técnica segura que apresenta bons resultados para a ressecção de pequenas lesões não pediculadas, com uma curta curva aprendizado.
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Intracellular vesicular trafficking ensures the exchange of lipids and proteins between endomembrane compartments. This is relevant under high salinity conditions, since both the removal of transporters and ion channels from the plasma membrane and the compartmentalization of toxic ions require the formation of vesicles, which can be maintained as multivesicular bodies or be fused to the central vacuole. SNARE proteins (Soluble N-ethylmaleimide-sensitive factor attachment receptor) participate in the vesicle fusion process and give specificity to their destination. Plant genome studies have revealed a superfamily of genes that encode for proteins called SNARE-like. These proteins appear to be participating in vesicular trafficking with similar functions to those of SNARE proteins. A SNARE-like, named SlSLSP6, in Solanum lycopersicum plants has been shown to be induced under high salinity conditions. A phylogenetic relationship of SlSLSP6 with SNARE-like proteins of salinity-tolerant plants, including Salicornia brachiata, Zostera marina and Solanum pennelli, was determined. Considering its amino acid sequence, a putative clathrin adapter complex domain and palmitoylation site was predicted. Subcellular localization analysis evidenced that SlSLSP6 is mostly localized in the plasma membrane. Using transgenic tomato plants, we identified that overexpression of SlSLSP6 increased tolerance to salt stress. This tolerance was evident when we quantified an improvement in physiological and biochemical parameters, such as higher chlorophyll content, performance index, efficiency of photosystem II and relative water content, and lower malondialdehyde content, compared to control plants. At the subcellular level, the overexpression of SlSLSP6 reduced the presence of H2O2 in roots and increased the compartmentalization of sodium in vacuoles during salt stress. These effects appear to be associated with the higher endocytic rate of FM4-64, determined in the plant root cells. Taken together, these results indicate that SlSLSP6 increases tolerance to salt stress by modulating vesicular trafficking through over-induction of the endocytic pathway. This work contributes to understanding the role of this type of SNARE-like protein during salt stress and could be a potential candidate in breeding programs for tolerance to salt stress in tomato plants.
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Antigen cross-presentation is a vital mechanism of dendritic cells and other antigen presenting cells to orchestrate the priming of cytotoxic responses towards killing of infected or cancer cells. In this process, exogenous antigens are internalized by dendritic cells, processed, loaded onto MHC class I molecules and presented to CD8+ T cells to activate them. Sec22b is an ER-Golgi Intermediate Compartment resident SNARE protein that, in partnership with sintaxin4, coordinates the recruitment of the transporter associated with antigen processing protein and the peptide loading complex to phagosomes, where antigenic peptides that have been proteolyzed in the cytosol are loaded in MHC class I molecules and transported to the cell membrane. The silencing of Sec22b in dendritic cells primary cultures and conditionally in dendritic cells of C57BL/6 mice, critically impairs antigen cross-presentation, but neither affects other antigen presentation routes nor cytokine production and secretion. Mice with Sec22b conditionally silenced in dendritic cells (Sec22b-/-) show deficient priming of CD8+ T lymphocytes, fail to control tumor growth, and are resistant to anti-checkpoint immunotherapy. In this work, we show that Sec22b-/- mice elicit a deficient specific CD8+ T cell response when challenged with sublethal doses of Trypanosoma cruzi trypomastigotes that is associated with increased blood parasitemia and diminished survival.
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Resumen El implante percutáneo de un electrodo de estimulación ventricular izquierdo a través del seno coronario para resincronización cardiaca siempre ha implicado un reto y más aún en pacientes con anatomía venosa coronaria compleja. Este caso demuestra cómo una técnica de doble canulación del seno coronario con uso de catéter multi-snare permite la colocación exitosa de un electrodo de estimulación ventricular izquierdo mediante acceso retrógrado a una vena posterolateral estenótica.
Abstract The percutaneous implantation of a left ventricular pacing electrode through the coronary sinus for cardiac resynchronization has always been a challenge, especially in patients with a complex coronary venous anatomy. This case shows how double cannulation of the coronary sinus using a multisnare catheter allows a left ventricular pacing electrode to be placed through retrograde access to a stenotic posterolateral vein, with a good clinical outcome.
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In plants, vesicular trafficking is crucial for the response and survival to environmental challenges. The active trafficking of vesicles is essential to maintain cell homeostasis during salt stress. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are regulatory proteins of vesicular trafficking. They mediate membrane fusion and guarantee cargo delivery to the correct cellular compartments. SNAREs from the Qbc subfamily are the best-characterized plasma membrane SNAREs, where they control exocytosis during cell division and defense response. The Solanum lycopersicum gene SlSNAP33.2 encodes a Qbc-SNARE protein and is induced under salt stress conditions. SlSNAP33.2 localizes on the plasma membrane of root cells of Arabidopsis thaliana. In order to study its role in endocytosis and salt stress response, we overexpressed the SlSNAP33.2 cDNA in a tomato cultivar. Constitutive overexpression promoted endocytosis along with the accumulation of sodium (Na+) in the vacuoles. It also protected the plant from cell damage by decreasing the accumulation of hydrogen peroxide (H2O2) in the cytoplasm of stressed root cells. Subsequently, the higher level of SlSNAP33.2 conferred tolerance to salt stress in tomato plants. The analysis of physiological and biochemical parameters such as relative water content, the efficiency of the photosystem II, performance index, chlorophyll, and MDA contents showed that tomato plants overexpressing SlSNAP33.2 displayed a better performance under salt stress than wild type plants. These results reveal a role for SlSNAP33.2 in the endocytosis pathway involved in plant response to salt stress. This research shows that SlSNAP33.2 can be an effective tool for the genetic improvement of crop plants.
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Fusion of cortical granules with oocyte plasma membrane is one of the most significant secretory events to prevent polyspermy during oocyte activation. Cortical granule exocytosis (CGE) is distinct from most other exocytosis because cortical granules are not renewed after secretion. However, it is thought to be mediated by SNARE complex, which mediates membrane fusion in other exocytoses. SNAREs proteins are divided into Q (glutamine)- and R (arginine)-SNAREs. Q-SNAREs include Syntaxins and SNAP25 family, and R-SNAREs include VAMPs family. In mouse oocytes, Syntaxin4 and SNAP23 have been involved in CGE; nevertheless, it is unknown if VAMP is required. Here, we demonstrated by RT-PCR and immunoblotting that VAMP1 and VAMP3 are expressed in mouse oocyte, and they localized in the cortical region of this cell. Using a functional assay to quantify CGE, we showed that tetanus toxin -which specifically cleavages VAMP1, VAMP2 or VAMP3- inhibited CGE suggesting that at least one VAMP was necessary. Function blocking assays demonstrated that only the microinjection of anti-VAMP1 or anti-VAMP3 antibodies abolished CGE in activated oocytes. These findings demonstrate that R-SNAREs sensitive to tetanus toxin, VAMP1 and VAMP3 -but not VAMP2-, are required for CGE and demonstrate that CGE is mediated by the SNARE complex.
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Grânulos Citoplasmáticos/fisiologia , Exocitose , Regulação da Expressão Gênica/efeitos dos fármacos , Oócitos/fisiologia , Proteínas SNARE/metabolismo , Toxina Tetânica/farmacologia , Animais , Grânulos Citoplasmáticos/efeitos dos fármacos , Feminino , Camundongos , Neurotoxinas/farmacologia , Oócitos/citologia , Oócitos/efeitos dos fármacos , Proteínas SNARE/genéticaRESUMO
Degranulation, a fundamental effector response from mast cells (MCs) and platelets, is an example of regulated exocytosis. This process is mediated by SNARE proteins and their regulators. We have previously shown that several of these proteins are essential for exocytosis in MCs and platelets. Here, we assessed the role of the SNARE protein SNAP23 using conditional knockout mice, in which SNAP23 was selectively deleted from either the megakaryocyte/platelet or connective tissue MC lineages. We found that removal of SNAP23 in platelets results in severe defects in degranulation of all three platelet secretory granule types, i.e., alpha, dense, and lysosomal granules. The mutation also induces thrombocytopenia, abnormal platelet morphology and activation, and reduction in the number of alpha granules. Therefore, the degranulation defect might not be secondary to an intrinsic failure of the machinery mediating regulated exocytosis in platelets. When we removed SNAP23 expression in MCs, there was a complete developmental failure in vitro and in vivo. The developmental defects in platelets and MCs and the abnormal translocation of membrane proteins to the surface of platelets indicate that SNAP23 is also involved in constitutive exocytosis in these cells. The MC conditional deletant animals lacked connective tissue MCs, but their mucosal MCs were normal and expanded in response to an antigenic stimulus. We used this mouse to show that connective tissue MCs are required and mucosal MCs are not sufficient for an anaphylactic response.
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Anafilaxia/imunologia , Plaquetas/imunologia , Tecido Conjuntivo/imunologia , Mastócitos/imunologia , Proteínas Qb-SNARE/imunologia , Proteínas Qc-SNARE/imunologia , Anafilaxia/genética , Anafilaxia/patologia , Animais , Plaquetas/patologia , Tecido Conjuntivo/patologia , Exocitose/genética , Exocitose/imunologia , Mastócitos/patologia , Camundongos , Camundongos Knockout , Proteínas Qb-SNARE/genética , Proteínas Qc-SNARE/genética , Vesículas Secretórias/genética , Vesículas Secretórias/imunologiaRESUMO
Insulin stimulates glucose uptake in muscle cells by rapidly redistributing vesicles containing GLUT4 glucose transporters from intracellular compartments to the plasma membrane (PM). GLUT4 vesicle fusion requires the formation of SNARE complexes between vesicular VAMP and PM syntaxin4 and SNAP23. SNARE accessory proteins usually regulate vesicle fusion processes. Complexins aide in neuro-secretory vesicle-membrane fusion by stabilizing trans-SNARE complexes but their participation in GLUT4 vesicle fusion is unknown. We report that complexin-2 is expressed and homogeneously distributed in L6 rat skeletal muscle cells. Upon insulin stimulation, a cohort of complexin-2 redistributes to the PM. Complexin-2 knockdown markedly inhibited GLUT4 translocation without affecting proximal insulin signalling of Akt/PKB phosphorylation and actin fiber remodelling. Similarly, complexin-2 overexpression decreased maximal GLUT4 translocation suggesting that the concentration of complexin-2 is finely tuned to vesicle fusion. These findings reveal an insulin-dependent regulation of GLUT4 insertion into the PM involving complexin-2.
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Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Insulina/farmacologia , Mioblastos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Transportador de Glucose Tipo 4/genética , Insulina/genética , Insulina/metabolismo , Músculo Esquelético/citologia , Mioblastos/efeitos dos fármacos , Proteínas do Tecido Nervoso/genética , Transporte Proteico/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais , Proteínas rac1 de Ligação ao GTP/metabolismoRESUMO
The SNP rs2251214 of the SYT1 gene was recently associated with externalizing phenotypes, including ADHD and cocaine use disorder (CUD). Here, we investigated whether SYT1-rs2251214 could also be implicated with cognitive performance variations among women with CUD. Results showed that G homozygous (n = 146) have lower cognitive performance in the Stroop, Trail Making and Matrix Reasoning tests compared with A-allele carriers (n = 64), suggesting that rs2251214 may influence the severity of cognitive impairments in CUD.
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Transtornos Relacionados ao Uso de Cocaína/complicações , Disfunção Cognitiva/genética , Sinaptotagmina I/genética , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
N-ethylmaleimide-sensitive factor (NSF) disassembles fusion-incompetent cis soluble-NSF attachment protein receptor (SNARE) complexes making monomeric SNAREs available for subsequent trans pairing and fusion. In most cells the activity of NSF is constitutive, but in Jurkat cells and sperm it is repressed by tyrosine phosphorylation; the phosphomimetic mutant NSF-Y83E inhibits secretion in the former. The questions addressed here are if and how the NSF mutant influences the configuration of the SNARE complex. Our model is human sperm, where the initiation of exocytosis (acrosome reaction (AR)) de-represses the activity of NSF through protein tyrosine phosphatase 1B (PTP1B)-mediated dephosphorylation. We developed a fluorescence microscopy-based method to show that capacitation increased, and challenging with an AR inducer decreased, the number of cells with tyrosine-phosphorylated PTP1B substrates in the acrosomal domain. Results from bioinformatic and biochemical approaches using purified recombinant proteins revealed that NSF-Y83E bound PTP1B and thereupon inhibited its catalytic activity. Mutant NSF introduced into streptolysin O-permeabilized sperm impaired cis SNARE complex disassembly, blocking the AR; subsequent addition of PTP1B rescued exocytosis. We propose that NSF-Y83E prevents endogenous PTP1B from dephosphorylating sperm NSF, thus maintaining NSF's activity in a repressed mode and the SNARE complex unable to dissociate. The contribution of this paper to the sperm biology field is the detection of PTP1B substrates, one of them likely being NSF, whose tyrosine phosphorylation status varies during capacitation and the AR. The contribution of this paper to the membrane traffic field is to have generated direct evidence that explains the dominant-negative role of the phosphomimetic mutant NSF-Y83E.
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Proteínas Sensíveis a N-Etilmaleimida/metabolismo , Fosforilação/fisiologia , Proteínas SNARE/metabolismo , Reação Acrossômica/fisiologia , Western Blotting , Catálise , Biologia Computacional , Exocitose/fisiologia , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Masculino , Plasmídeos , Ligação Proteica , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Espermatozoides/metabolismo , Tirosina/metabolismoRESUMO
Synaptotagmin-1 is an essential regulator of synaptic vesicle exocytosis, and its encoding gene (SYT1) is a genome and transcriptome-wide association hit in cognitive performance, personality and cocaine use disorder (CUD) studies. Additionally, in candidate gene studies the specific variant rs2251214 has been associated with attention-deficit/hyperactivity disorder (ADHD), antisocial personality disorder and other externalizing phenotypes in adults with ADHD, as well as with response to methylphenidate (MPH) treatment. In this context, we sought to evaluate, in an independent sample, the association of this variant with CUD, a phenotype that shares common biological underpinnings with the previously associated traits. We tested the association between SYT1-rs2251214 and CUD susceptibility and severity (addiction severity index) in a sample composed by 315 patients addicted to smoked cocaine and 769 non-addicted volunteers. SYT1-rs2251214 was significantly associated with susceptibility to CUD, where the G allele presented increased risk for the disorder in the genetic models tested (Pâ¯=â¯0.0021, ORâ¯=â¯1.44, allelic; Pâ¯=â¯0.0012, ORâ¯=â¯1.48, additive; Pâ¯=â¯0.0127, ORâ¯=â¯1.41, dominant). This is the same allele that was associated with increased risk for ADHD and other externalizing behaviors, as well as poor response to MPH treatment in previous studies. These findings suggest that the neurotransmitter exocytosis pathway might play a critical role in the liability for psychiatric disorders, especially externalizing behaviors and CUD.
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Transtornos Relacionados ao Uso de Cocaína/genética , Predisposição Genética para Doença/genética , Sinaptotagmina I/genética , Adulto , Estudos de Casos e Controles , Cocaína Crack , Feminino , Estudos de Associação Genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Adulto JovemRESUMO
NEW FINDINGS: What is the central question of this study? Does protein restriction in early life modify glucose-induced insulin secretion by altering [Ca2+ ]i and the expression of SNARE proteins in pancreatic islets from pregnant rats? What is the main finding and its importance? Protein restriction in early life increased the first phase of glucose-induced insulin secretion and [Ca2+ ]i without altering the expression of SNARE proteins during pregnancy. This finding contributes to our understanding of the mechanisms of altered insulin secretion and might provide new perspectives for the development of therapeutic tools for gestational diabetes. ABSTRACT: We investigated the kinetics of glucose-induced insulin secretion and their relationship with [Ca2+ ]i and the expression of protein from exocytotic machinery in islets from recovered pregnant and long-term protein-deficient pregnant rats. Isolated islets were evaluated from control-fed pregnant (CP), protein-deficient pregnant (DP), control-fed non-pregnant (CNP) and protein-deficient non-pregnant (DNP) female adult rats, and from protein-deficient pregnant (RP) and non-pregnant (RNP) rats that were recovered after weaning. The insulin responses to glucose during the first phase of secretion were higher in RP than in CP groups, and both were higher than in the DP group. Islets from RP rats displayed a rapid increase in insulin release (first phase), followed by a plateau that was maintained thereafter. The [Ca2+ ]i in islets from the protein-deficient groups was lower than in the control groups, and both were lower than in the RP and RNP groups. SNAP-25 was increased in islets from pregnant rats independently of their nutritional status, and the syntaxin-1A content was reduced in islets from the RP rats compared with the RNP rats. The VAMP2 content was similar among the groups. Thus, protein restriction during intrauterine life and lactation increased insulin secretion during pregnancy, attributable, in part, to increased [Ca2+ ]i , and independent of an alteration of expression of SNARE proteins.
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Cálcio/metabolismo , Dieta com Restrição de Proteínas/tendências , Regulação da Expressão Gênica no Desenvolvimento , Secreção de Insulina/fisiologia , Líquido Intracelular/metabolismo , Proteínas SNARE/biossíntese , Animais , Glicemia/metabolismo , Feminino , Ilhotas Pancreáticas/metabolismo , Masculino , Gravidez , Ratos , Ratos Wistar , Proteínas SNARE/genéticaRESUMO
PURPOSE: To describe a novel endovascular bailout technique for successful completion of target vessel stenting during branched stent-graft repair of thoracoabdominal aortic aneurysms (TAAA) after encountering difficulties with standard catheterization techniques. TECHNIQUE: Technical difficulties when using fenestrated and branched grafts should be expected, especially in difficult anatomy or when an off-the-shelf device (eg, standard 4-branch device) is used that does not perfectly "match" the anatomy. The "snare-ride technique" facilitates antegrade transaxillary side branch catheterization and stent placement during TAAA branched grafting using a snare via a transfemoral approach. The branch of the graft is catheterized from an axillary access. The respective target vessel is then catheterized via a femoral access. An Indy snare is advanced over the transfemoral wire and positioned near the entrance of the target vessel. The transaxillary wire inside the branch of the graft is then advanced, snared, and pushed inside the target vessel with the snare. The procedure is thereafter continued with antegrade bridging of the target vessel in routine fashion. CONCLUSION: The snare-ride technique can be a useful maneuver to catheterize target vessels with difficult anatomy in TAAA branched stent-graft repair. Early experience shows safety and feasibility.
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Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/métodos , Cateterismo Periférico/métodos , Procedimentos Endovasculares/métodos , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/fisiopatologia , Aortografia , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/instrumentação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Humanos , Desenho de Prótese , Stents , Fatores de Tempo , Resultado do Tratamento , Dispositivos de Acesso VascularRESUMO
Attention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric disorder, affecting both children and adults. The Soluble N-ethylmaleimide sensitive factor Attachment REceptors (SNARE) complex has been implicated in ADHD pathophysiology since it is a key component of neurotransmitter release events and neurodevelopment processes, and SNPs in this complex have been associated with ADHD. Here we aim to analyze the effects of SNARE complex variants on ADHD susceptibility and its clinical heterogeneity in affected adults. We tested the association between ADHD and polymorphisms on the SNARE genes STX1A (rs2228607), SYT1 (rs1880867 and rs2251214), VAMP2 (26bp Ins/Del) and SNAP25 (rs6108461 and rs8636) on a sample comprised of 548 adults with ADHD and 644 non-affected controls. Regarding clinical heterogeneity, we further investigated the effects of associated SNPs on age at onset of impairment due to ADHD and on relevant externalizing behaviors (i.e. school suspensions/expulsions and problems with law/authority) and comorbidities (i.e. Substance Use Disorder, Oppositional Defiant Disorder, Conduct Disorder and Antisocial Personality Disorder). We replicated a previously reported association between SYT1-rs2251214 and ADHD in adulthood. This SNP was also associated with age at onset of impairment due to ADHD symptoms and with a range of externalizing phenotypes. These findings involving SYT1 suggest that variation in neurotransmitter exocytosis mechanisms may represent an underlying genetic factor shared by a spectrum of externalizing behaviors and disorders, including - but not restricted to - ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtornos Mentais/etiologia , Polimorfismo de Nucleotídeo Único/genética , Sinaptotagmina I/genética , Transtorno da Personalidade Antissocial/etiologia , Estudos de Casos e Controles , Criança , Transtorno da Conduta/etiologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , MasculinoRESUMO
Unsustainable hunting outside protected areas is threatening tropical biodiversity worldwide and requires conservationists to engage increasingly in antipoaching activities. Following the example of ecocertified logging companies, we argue that other extractive industries managing large concessions should engage in antipoaching activities as part of their environmental management plans. Onshore hydrocarbon concessions should also adopt antipoaching protocols as a standard because they represent a biodiversity threat comparable to logging. We examined the spatiotemporal patterns of small- and large-mammal poaching in an onshore oil concession in Gabon, Central Africa, with a Bayesian occupancy model based on signs of poaching collected from 2010 to 2015 on antipoaching patrols. Patrol locations were initially determined based on local intelligence and past patrol successes (adaptive management) and subsequently with a systematic sampling of the concession. We generated maps of poaching probability in the concession and determined the temporal trends of this threat over 5 years. The spatiotemporal patterns of large- and small-mammal poaching differed throughout the concession, and likely these groups will need different management strategies. By elucidating the relationship between site-specific sampling effort and detection probability, the Bayesian method allowed us to set goals for future antipoaching patrols. Our results indicate that a combination of systematic sampling and adaptive management data is necessary to infer spatiotemporal patterns with the statistical method we used. On the basis of our case study, we recommend hydrocarbon companies interested in implementing efficient antipoaching activities in their onshore concessions to lay the foundation of long-needed industry standards by: adequately measuring antipoaching effort; mixing adaptive management and balanced sampling; setting goals for antipoaching effort; pairing patrols with large-mammal monitoring; supporting antipoaching patrols across the landscape; restricting access to their concessions; performing random searches for bushmeat and mammal products at points of entry; controlling urban and agricultural expansion; supporting bushmeat alternatives; and supporting land-use planning.
Assuntos
Conservação dos Recursos Naturais , Hidrocarbonetos , Agricultura , Animais , Teorema de Bayes , Biodiversidade , Agricultura Florestal , Gabão , MamíferosRESUMO
Multiple biological processes throughout development require intracellular vesicular trafficking, where the SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors) complex plays a major role. The core proteins forming the SNARE complex are SNAP-25 (synaptosomal-associated protein 25), VAMP (vesicle-associated membrane protein) and Syntaxins, besides its regulatory proteins, such as Synaptotagmin. Genes encoding these proteins (SNAP25, VAMP1, VAMP2, STX1A, SYT1 and SYT2) have been studied in relation to psychiatric disorders susceptibility. Here, we review physiological aspects of SNARE complex and genetic association results reported for attention deficit hyperactivity disorder, both in children and adults, autism spectrum disorders, major depressive disorder, bipolar disorder and schizophrenia. Moreover, we included findings from expression, pharmacogenetics and animal model studies regarding these clinical phenotypes. The overall scenario depicted here suggests that the SNARE complex may exert distinct roles throughout development, with age-specific effects of genetic variants in psychiatric disorders. Such perspective should be considered in future studies regarding SNARE complex genes.
Assuntos
Exocitose/fisiologia , Transtornos Mentais , Neurotransmissores/metabolismo , Proteínas SNARE/metabolismo , Humanos , Transtornos Mentais/genética , Transtornos Mentais/metabolismo , Transtornos Mentais/patologia , Farmacogenética , Processamento de Proteína Pós-Traducional , Transporte Proteico/fisiologia , Proteínas SNARE/genéticaRESUMO
We have previously demonstrated that hypercholesterolemic LDL receptor knockout (LDLr(-/-)) mice secrete less insulin than wild-type mice. Removing cholesterol from isolated islets using methyl-beta-cyclodextrin reversed this defect. In this study, we hypothesized that in vivo treatment of LDLr(-/-) mice with the HMGCoA reductase inhibitor pravastatin would improve glucose-stimulated insulin secretion. Female LDLr(-/-) mice were treated with pravastatin (400mg/L) for 1-3 months. Isolated pancreatic islets were assayed for insulin secretion rates, intracellular calcium oscillations, cholesterol levels, NAD(P)H and SNARE protein levels, apoptosis indicators and lipidomic profile. Two months pravastatin treatment reduced cholesterol levels in plasma, liver and islets by 35%, 25% and 50%, respectively. Contrary to our hypothesis, pravastatin treatment increased fasting and fed plasma levels of glucose and decreased markedly (40%) fed plasma levels of insulin. In addition, ex vivo glucose stimulated insulin secretion was significantly reduced after two and three months (36-48%, p<0.05) of pravastatin treatment. Although reducing insulin secretion and insulinemia, two months pravastatin treatment did not affect glucose tolerance because it improved global insulin sensitivity. Pravastatin induced islet dysfunction was associated with marked reductions of exocytosis-related SNARE proteins (SNAP25, Syntaxin 1A, VAMP2) and increased apoptosis markers (Bax/Bcl2 protein ratio, cleaved caspase-3 and lower NAD(P)H production rates) observed in pancreatic islets from treated mice. In addition, several oxidized phospholipids, tri- and diacylglycerols and the proapoptotic lipid molecule ceramide were identified as markers of pravastatin-treated islets. Cell death and oxidative stress (H2O2 production) were confirmed in insulin secreting INS-1E cells treated with pravastatin. These results indicate that chronic treatment with pravastatin impairs the insulin exocytosis machinery and increases ß-cell death. These findings suggest that prolonged use of statins may have a diabetogenic effect.
Assuntos
Exocitose/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/toxicidade , Hipercolesterolemia/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Pravastatina/toxicidade , Animais , Esquema de Medicação , Exocitose/fisiologia , Feminino , Hipercolesterolemia/genética , Hipercolesterolemia/patologia , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de LDL/deficiência , Receptores de LDL/genéticaRESUMO
The organophosphate and carbamate pesticides methyl-parathion and carbaryl have a common action mechanism: they inhibit acetylcholinesterase enzyme by blocking the transmission of nerve impulses. However, they can alter the expression of exocytotic membrane proteins (SNARE), by modifying release of neurotransmitters and other substances. This study evaluated the adverse effects of the pesticides methyl-parathion and carbaryl on expression of SNARE proteins: Syntaxin-1, Syntaxin-4 and SNAP-23 in freshwater rotifer Brachionus calyciflorus. Protein expression of these three proteins was analyzed before and after exposure to these two pesticides by Western Blot. The expression of Syntaxin-1, Syntaxin-4 and SNAP-23 proteins in B. calyciflorussignificantly decreases with increasing concentration of either pesticides. This suggests that organophosphates and carbamates have adverse effects on expression of membrane proteins of exocytosis by altering the recognition, docking and fusion of presynaptic and vesicular membranes involved in exocytosis of neurotransmitters. Our results demonstrate that the neurotoxic effect of anticholinesterase pesticides influences the interaction of syntaxins and SNAP-25 and the proper assembly of the SNARE complex.(AU)
Os pesticidas organofosforados e carbamatos metil- paration e carbaril tem um mecanismo de ação comum: eles inibem a enzima acetilcolinesterase, bloqueando a transmissão dos impulsos nervosos. No entanto, eles podem alterar a expressão de proteínas de membrana de exocitose (SNARE), através da modificação da libertação de neurotransmissores e outras substâncias. Este estudo avaliou os efeitos adversos dos pesticidas metil- paration e carbaril sobre a expressão de proteínas SNARE: Sintaxina -1, Sintaxina-4 e SNAP-23 em rotíferos de água doce Brachionus calyciflorus. A expressão destas três proteínas foi analisada antes e depois da exposição a estes dois pesticidas por Western Blot. A expressão das proteínas Sintaxina-1, Sintaxina-4 e SNAP-23 em B. calyciflorus diminui significativamente com o aumento da concentração de ambos os pesticidas. Isto sugere que os organofosfatos e carbamatos têm efeitos adversos sobre a expressão de proteínas de membrana de exocitose, alterando o reconhecimento, de encaixe e fusão de membranas pré-sinápticas e vesiculares envolvidas na exocitose de neurotransmissores. Nossos resultados demonstram que o efeito neurotóxico de pesticidas anticolinesterásicos influencia a interação de sintaxinas e SNAP-25 e a montagem correta do complexo SNARE.(AU)