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Teresa Daraio, Ismael Valladolid-Acebes, Kerstin Brismar, Christina Bark
SNAP-25 is a protein involved in regulated membrane fusion and part of the SNARE complex. It exists as two splicing variants, SNAP-25a and SNAP-25b, which differ in 9 out of 206 amino acids. SNAP-25 together with Syntaxin 1 and VAMP-2 forms the ternary SNARE complex essential for mediating activity-dependent release of hormones and neurotransmitters. The functional difference between SNAP-25a and SNAP-25b is poorly understood as both can participate in SNARE complexes and mediate membrane fusion. However, we recently demonstrated that SNAP-25b-deficiency results in metabolic disease and increased insulin secretion...
March 13, 2018: Neuroscience Letters
Benedikt Hacker, Christoph Schultheiß, Michael Döring, Ursula Kurzik-Dumke
This study provides first insights into the involvement of hNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, in various putative molecular networks. HNOT/ALG3 encodes two translated transcripts encoding precursor proteins differing in their N-terminus and showing 33% identity with the yeast asparagine-linked glycosylation 3 (ALG3) protein. Experimental evidence for the functional homology of the proteins of fly and man in the N-glycosylation has still to be provided. In this study, using the yeast two-hybrid technique we identify 17 molecular partners of hNOT-1/ALG3-1...
March 14, 2018: Human Molecular Genetics
Geoffrey Masuyer, Sicai Zhang, Sulyman Barkho, Yi Shen, Linda Henriksson, Sara Košenina, Min Dong, Pål Stenmark
Botulinum neurotoxins (BoNTs) are among the most potent toxins known and are also used to treat an increasing number of medical disorders. There are seven well-established serotypes (BoNT/A-G), which all act as zinc-dependent endopeptidases targeting specific members of the SNARE proteins required for synaptic vesicle exocytosis in neurons. A new toxin serotype, BoNT/X, was recently identified. It cleaves not only the canonical targets, vesicle associated membrane proteins (VAMP) 1/2/3 at a unique site, but also has the unique ability to cleave VAMP4/5 and Ykt6...
March 14, 2018: Scientific Reports
Emanuele Felice Osimo, Katherine Beck, Tiago Reis Marques, Oliver D Howes
Although synaptic loss is thought to be core to the pathophysiology of schizophrenia, the nature, consistency and magnitude of synaptic protein and mRNA changes has not been systematically appraised. Our objective was thus to systematically review and meta-analyse findings. The entire PubMed database was searched for studies from inception date to the 1st of July 2017. We selected case-control postmortem studies in schizophrenia quantifying synaptic protein or mRNA levels in brain tissue. The difference in protein and mRNA levels between cases and controls was extracted and meta-analysis conducted...
March 6, 2018: Molecular Psychiatry
Alfredo Ramos-Miguel, Andrea A Jones, Ken Sawada, Alasdair M Barr, Thomas A Bayer, Peter Falkai, Sue E Leurgans, Julie A Schneider, David A Bennett, William G Honer
The molecular underpinnings associated with cognitive reserve remain poorly understood. Because animal models fail to fully recapitulate the complexity of human brain aging, postmortem studies from well-designed cohorts are crucial to unmask mechanisms conferring cognitive resistance against cumulative neuropathologies. We tested the hypothesis that functionality of the SNARE protein interactome might be an important resilience factor preserving cognitive abilities in old age. Cognition was assessed annually in participants from the Rush "Memory and Aging Project" (MAP), a community-dwelling cohort representative of the overall aging population...
February 26, 2018: Neurobiology of Disease
B Gray, V Cadd, M Elliott, M Beard
The in vitro potency of botulinum neurotoxin (BoNT) serotypes is often measured by monitoring cleavage of their soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein substrates. A frequently used method is Western blot, whereby the full-length protein and cleaved form migrate at different molecular weights. Until now, it has been extremely difficult to detect the cleaved cellular form of the SNARE protein vesicle associated membrane protein 1, 2 or 3 (VAMP1, 2 or 3) by Western blot...
January 23, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Chong Ding, Xin Cong, Yan Zhang, Sheng-Lin Li, Li-Ling Wu, Guang-Yan Yu
Autologous submandibular gland transplantation is an effective treatment for severe dry eye syndrome. However, the protein secretion in transplanted gland is altered by a mechanism that remains to be elucidated. In the present study, we found that β1-adrenoceptor (b1-AR) and β2-AR expression and the phosphorylation of the downstream molecule protein kinase A (PKA) were elevated in transplanted submandibular glands obtained from epiphora patients. Synaptobrevin/vesicle-associated membrane protein 2 (VAMP-2) interacted with syntaxin-4 and actin in human submandibular gland...
January 22, 2018: Bioscience Reports
Fabio L Urbina, Shawn M Gomez, Stephanie L Gupton
Neurite elongation and branching in developing neurons requires plasmalemma expansion, hypothesized to occur primarily via exocytosis. We posited that exocytosis in developing neurons and nonneuronal cells would exhibit distinct spatiotemporal organization. We exploited total internal reflection fluorescence microscopy to image vesicle-associated membrane protein (VAMP)-pHluorin-mediated exocytosis in mouse embryonic cortical neurons and interphase melanoma cells, and developed computer-vision software and statistical tools to uncover spatiotemporal aspects of exocytosis...
January 19, 2018: Journal of Cell Biology
Víctor Martín-Granado, Sara Ortiz-Rivero, Rita Carmona, Sara Gutiérrez-Herrero, Mario Barrera, Laura San-Segundo, Celia Sequera, Pedro Perdiguero, Francisco Lozano, Francisco Martín-Herrero, José Ramón González-Porras, Ramón Muñoz-Chápuli, Almudena Porras, Carmen Guerrero
Previous observations indicated that C3G (RAPGEF1) promotes α-granule release, evidenced by the increase in P-selectin exposure on the platelet surface following its activation. The goal of the present study is to further characterize the potential function of C3G as a modulator of the platelet releasate and its implication in the regulation of angiogenesis. Proteomic analysis revealed a decreased secretion of anti-angiogenic factors from activated transgenic C3G and C3G∆Cat platelets. Accordingly, the secretome from both transgenic platelets had an overall pro-angiogenic effect as evidenced by an in vitro capillary-tube formation assay with HUVECs (human umbilical vein endothelial cells) and by two in vivo models of heterotopic tumor growth...
December 19, 2017: Oncotarget
Guannan Wang, Xiaosan Fang, Meng Han, Xiaoming Wang, Qiang Huang
The aim of the present study was to explore the role of miR‑493-5p in liver cancer tissues and cell lines, and its effect on cell behavioral characteristics. The expression of miR-493-5p was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in liver cancer tissues and cell lines (hepatic cell line HL-7702 and the liver cancer cell lines HCCC-9810, HuH-7 and HepG2). In addition, the mechanism by which miR-493-5p mediates its effects was analyzed via the transfection of miR-493-5p mimic and negative control miRNA into HepG2 cells...
January 2, 2018: International Journal of Molecular Medicine
Andreas Mardt, Luca Pasquali, Hao Wu, Frank Noé
There is an increasing demand for computing the relevant structures, equilibria, and long-timescale kinetics of biomolecular processes, such as protein-drug binding, from high-throughput molecular dynamics simulations. Current methods employ transformation of simulated coordinates into structural features, dimension reduction, clustering the dimension-reduced data, and estimation of a Markov state model or related model of the interconversion rates between molecular structures. This handcrafted approach demands a substantial amount of modeling expertise, as poor decisions at any step will lead to large modeling errors...
January 2, 2018: Nature Communications
Charles J Lowenstein
No abstract text is available yet for this article.
December 28, 2017: Blood
Mohit S Verma, Alar Ainla, Dian Yang, Daniel Harburg, George M Whitesides
This article demonstrates a pneumatically actuated soft robot capable of navigating the inside of a tube. This robot was built using buckling pneumatic actuators (vacuum-actuated muscle-inspired pneumatic structures, or VAMPs). The tube climber can navigate through a tube with turns, inclines, and varying diameters. The robot is also able to remove obstacles (of more than 10 times its own weight) from tubes to perform a clearing function. It maintains climbing and clearing performance in wet conditions and under water...
November 30, 2017: Soft Robotics
Javier Encinar Del Dedo, Fatima-Zahra Idrissi, Isabel María Fernandez-Golbano, Patricia Garcia, Elena Rebollo, Marek K Krzyzanowski, Helga Grötsch, Maria Isabel Geli
Oxysterol binding protein-related proteins (ORPs) are conserved lipid binding polypeptides, enriched at ER contacts sites. ORPs promote non-vesicular lipid transport and work as lipid sensors in the context of many cellular tasks, but the determinants of their distinct localization and function are not understood. Here, we demonstrate that the yeast endocytic invaginations associate with the ER and that this association specifically requires the ORPs Osh2 and Osh3, which bridge the endocytic myosin-I Myo5 to the ER integral-membrane VAMP-associated protein (VAP) Scs2...
December 4, 2017: Developmental Cell
Aleksander Rust, Ciara Doran, Rosalyn Hart, Thomas Binz, Paul Stickings, Dorothea Sesardic, Andrew A Peden, Bazbek Davletov
Botulinum neurotoxins (BoNTs) type A and type B are commonly used as biopharmaceutics for neurological diseases, uniquely allowing months-long paralysis of target muscles. Their exquisite neuronal specificity is conferred by a multistep process of binding, internalization, cytosolic escape and cleavage of the neuron-specific proteins, SNAP-25 and vesicle-associated membrane proteins (VAMPs), ultimately to inhibit secretion of neurotransmitters. Currently the mouse lethality bioassay is the only available method for quality control testing of VAMP-cleaving botulinum products...
2017: Frontiers in Pharmacology
Masaki Fukui, Yoko Ogawa, Shin Mukai, Mizuka Kamoi, Teru Asato, Yutaka Kawakami, Kazuo Tsubota
Purpose: To investigate whether the SNARE protein vesicle-associated membrane protein 8 (VAMP8) was implicated in the development of chronic ocular graft-versus-host disease (GVHD). Methods: Firstly, the chronic GVHD (cGVHD) and Sjögren's syndrome (SS)-impaired lacrimal gland (LG) tissue sections from humans for diagnostic purpose were evaluated for VAMP8 expression by histopathology and immunohistochemistry. Next, serial changes of tear secretion and VAMP8 expression at both protein and mRNA level of LG in an animal cGVHD model compared with the syngeneic control...
2017: Journal of Ophthalmology
Mark Elliott, Jacquie Maignel, Sai Man Liu, Christine Favre-Guilmard, Imran Mir, Paul Farrow, Fraser Hornby, Sandra Marlin, Shilpa Palan, Matthew Beard, Johannes Krupp
Botulinum neurotoxins (BoNTs) are used extensively as therapeutic agents. Serotypes A and B are available as marketed products. Higher doses of BoNT/B are required to reach an efficacy similar to that of products containing BoNT/A. Advances in our understanding of BoNT/B mechanism of action have afforded the opportunity to make rational modifications to the toxin aimed at increasing its activity. Recently, a mutation in the light chain of BoNT/B (S201P) was described that increases the catalytic activity of the isolated BoNT/B light chain in biochemical assays...
2017: PloS One
Carolyn McIntosh, Jean Patterson, Suzanne Miller
Studying undergraduate midwifery at a distance has advantages in terms of accessibility and community support but presents challenges for practice based competence assessment. Student -recorded videos provide opportunities for completing the assigned skills, self-reflection, and assessment by a lecturer. This research asked how midwifery students experienced the process of completing the Video Assessment of Midwifery Practice Skills (VAMPS) in 2014 and 2015. The aim of the survey was to identify the benefits and challenges of the VAMPS assessment and to identify opportunities for improvement from the students' perspective...
September 20, 2017: Nurse Education in Practice
Qin Xu, Chuanben Chen, An Lin, Yunqing Xie
OBJECTIVE: To investigate the role of endoplasmic reticulum (ER) stress-mediated CRT/ERp57 complex expression underlying the mechanism of resistance to doxorubicin (DOX) in endometrial carcinoma (EC) in vivo and in vitro. METHODS: The expression of CRT, ERp57, p-PERK, eIF2α, p-eIF2α in EC patients and EC cells was detected by Western blots and by immunofluorescence assay. MTT assay was used to determine the LC50 of EC cells to DOX and cell viability. Apoptosis was assayed using flow cytometer...
August 29, 2017: Oncotarget
Meenakshi Banerjee, Smita Joshi, Jinchao Zhang, Carole L Moncman, Shilpi Yadav, Beth A Bouchard, Brian Storrie, Sidney W Whiteheart
Endocytosis is key to fibrinogen (Fg) uptake, trafficking of integrins (αIIbβ3, αvβ3) and purinergic receptors (P2Y1, P2Y12), and thus for normal platelet function. However, the molecular machinery required and possible trafficking routes are still ill-defined. To further identify elements of the platelet endocytic machinery, we examined the role of a vesicle-residing, Soluble N-ethylmaleimide Factor Attachment Protein Receptor (v-SNARE) called Cellubrevin/Vesicle-Associated Membrane Protein-3 (VAMP-3) in platelet function...
September 20, 2017: Blood
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