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https://www.readbyqxmd.com/read/29166604/capture-of-dense-core-vesicles-at-synapses-by-jnk-dependent-phosphorylation-of-synaptotagmin-4
#1
Vinita Bharat, Michael Siebrecht, Katja Burk, Saheeb Ahmed, Carsten Reissner, Mahdokht Kohansal-Nodehi, Vicky Steubler, Markus Zweckstetter, Jonathan T Ting, Camin Dean
Delivery of neurotrophins and neuropeptides via long-range trafficking of dense core vesicles (DCVs) from the cell soma to nerve terminals is essential for synapse modulation and circuit function. But the mechanism by which transiting DCVs are captured at specific sites is unknown. Here, we discovered that Synaptotagmin-4 (Syt4) regulates the capture and spatial distribution of DCVs in hippocampal neurons. We found that DCVs are highly mobile and undergo long-range translocation but switch directions only at the distal ends of axons, revealing a circular trafficking pattern...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166573/interaction-of-hsp90-with-phospholipid-model-membranes
#2
Muhan Zhang, Daoying Wang, Pengpeng Li, Chong Sun, Rong Xu, Zhiming Geng, Weimin Xu, Zhaoqi Dai
Heat shock protein 90 (Hsp90) is an essential molecular chaperone with versatile functions in cell homeostatic control under both normal and stress conditions. Hsp90 has been found to be expressed on the cell surface, but the mechanism of Hsp90 association to the membrane remains obscure. In this study, the direct interaction of Hsp90 and phospholipid vesicles was characterized, and the role of Hsp90 on membrane physical state was explored. Using surface plasmon resonance (SPR), we observed a strong interaction between Hsp90 and different compositions of lipid...
November 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29166241/two-classes-of-secreted-synaptic-organizers-in-the-central-nervous-system
#3
Michisuke Yuzaki
Research in the last two decades has identified many synaptic organizers in the central nervous system that directly regulate the assembly of preand/ or postsynaptic molecules, such as synaptic vesicles, active zone proteins, and neurotransmitter receptors. They are classified into secreted factors and cell adhesion molecules, such as neurexins and neuroligins. Certain secreted factors are termed extracellular scaffolding proteins (ESPs) because they are components of the synaptic extracellular matrix and serve as a scaffold at the synaptic cleft...
November 20, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/29166098/pulling-force-and-surface-tension-drive-membrane-fusion
#4
Xuejuan Liu, Falin Tian, Tongtao Yue, Xianren Zhang, Chongli Zhong
Despite catalyzed by fusion proteins of quite different molecular architectures, intracellular, viral, and cell-to-cell fusions are found to have the essential common features and the nearly same nature of transition states. The similarity inspires us to find a more general catalysis mechanism for membrane fusion that minimally depends on the specific structures of fusion proteins. In this work, we built a minimal model for membrane fusion, and by using dissipative particle dynamics simulations, we propose a mechanism that the pulling force generated by fusion proteins initiates the fusion process and the membrane tension regulates the subsequent fusion stages...
November 21, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29165341/extracellular-vesicles-released-by-oxidatively-injured-or-intact-c2c12-myotubes-promote-distinct-responses-converging-toward-myogenesis
#5
Michele Guescini, Serena Maggio, Paola Ceccaroli, Michela Battistelli, Giosuè Annibalini, Giovanni Piccoli, Piero Sestili, Vilberto Stocchi
Myogenic differentiation is triggered, among other situations, in response to muscle damage for regenerative purposes. It has been shown that during myogenic differentiation, myotubes release extracellular vesicles (EVs) which participate in the signalling pattern of the microenvironment. Here we investigated whether EVs released by myotubes exposed or not to mild oxidative stress modulate the behaviour of targeted differentiating myoblasts and macrophages to promote myogenesis. We found that EVs released by oxidatively challenged myotubes (H₂O₂-EVs) are characterized by an increased loading of nucleic acids, mainly DNA...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29165099/recent-patents-and-formulation-of-nanopharmaceuticals-using-ultrasonication-technique
#6
Nidhi Saiwal, Mandeep Dahiya, Harish Dureja
BACKGROUND: Ultrasound (US) has the ever-rising role in the delivery of therapeutic agents that includes chemotherapeutic agents, proteins, and genetic material. The microbubbles are the cavitating gas bodies that act as the mediators through which the energy of relatively non-interactive pressure waves is accumulated to produce forces that can permeabilize cell membranes and disrupt the vesicles that carry the therapeutic agent. This shows that the microbubbles greatly enhance the delivery of smaller chemical agents, proteins and genetic material...
November 19, 2017: Recent Patents on Nanotechnology
https://www.readbyqxmd.com/read/29164996/cptp-a-sphingolipid-transfer-protein-that-regulates-autophagy-and-inflammasome-activation
#7
Shrawan Kumar Mishra, Yong-Guang Gao, Yibin Deng, Charles E Chalfant, Edward H Hinchcliffe, Rhoderick E Brown
The macroautophagy/autophagy and inflammasome pathways are linked through their roles in innate immunity and chronic inflammatory disease. Ceramide-1-phosphate (C1P) is a bioactive sphingolipid that regulates pro-inflammatory eicosanoid production. Whether C1P also regulates autophagy and inflammasome assembly/activation is not known. Here we show that CPTP (a protein that traffics C1P from its site of phosphorylation in the trans-Golgi to target membranes) regulates both autophagy and inflammasome activation...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29164874/combined-reflectometric-interference-spectroscopy-and-quartz-crystal-microbalance-detect-differential-adsorption-of-lipid-vesicles-with-different-phase-transition-temperatures-on-sio2-tio2-and-au-surfaces
#8
Taisuke Kojima
Quantitative analysis of biomolecular adsorption on a substrate is crucial for understanding biomolecular interactions. A quartz crystal microbalance (QCM) is a highly sensitive device to detect such interactions based on mass. However, the physicochemical analysis by the QCM alone often leads to overestimation of the actual adsorbed mass. Here a combined reflectometric interference spectroscopy (RIfS) and QCM is developed to simultaneously analyze adsorption of biomolecules. The RIfS detects the adsorbed mass based on the reflectance and predicts the adsorbed condition by modeling the reflection spectra using the transfer matrix method...
November 22, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29164502/superovulation-alters-dna-methyltransferase-protein-expression-in-mouse-oocytes-and-early-embryos
#9
Fatma Uysal, Saffet Ozturk, Gokhan Akkoyunlu
PURPOSE: DNA methylation is an epigenetic mechanism that plays critical roles during mammalian oocyte and preimplantation embryo development. It is achieved by adding a methyl group to the fifth carbon atom of cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites using DNA methyltransferase (DNMT) enzymes for de novo and maintenance methylation processes. DNMT1, DNMT3A, and DNMT3B play important roles in establishing methylation of developmentally related genes in oocytes and early embryos...
November 22, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29164426/the-impact-of-vascular-disease-treatment-on-platelet-derived-microvesicles
#10
Justyna Rosińska, Maria Łukasik, Wojciech Kozubski
Platelet-derived microvesicles (pMVs) are small, heterogeneous vesicles released from platelet membranes as a result of activation. These microvesicles possess a wide range of properties, including prothrombotic, proatherogenic, proinflammatory, immunomodulatory, and even anticoagulant activity. The elevated release of these microvesicles has been observed in various metabolic, inflammatory, thrombotic, and vascular diseases, including ischemic heart disease, stroke, hypertension, diabetes, and connective tissue disease...
November 22, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29164135/a-protocol-for-improved-precision-and-increased-confidence-in-nanoparticle-tracking-analysis-concentration-measurements-between-50-and-120%C3%A2-nm-in-biological-fluids
#11
Martin E M Parsons, Damien McParland, Paulina B Szklanna, Matthew Ho Zhi Guang, Karen O'Connell, Hugh D O'Connor, Christopher McGuigan, Fionnuala Ní Áinle, Amanda McCann, Patricia B Maguire
Nanoparticle tracking analysis (NTA) can be used to quantitate extracellular vesicles (EVs) in biological samples and is widely considered a useful diagnostic tool to detect disease. However, accurately profiling EVs can be challenging due to their small size and heterogeneity. Here, we aimed to provide a protocol to facilitate high-precision particle quantitation by NTA in plasma, the supernatant of activated purified platelets [the platelet releasate (PR)] and in serum, to increase confidence in NTA particle enumeration...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29164114/interorganelle-communication-between-mitochondria-and-the-endolysosomal-system
#12
REVIEW
Gonzalo Soto-Heredero, Francesc Baixauli, María Mittelbrunn
The function of mitochondria and lysosomes has classically been studied separately. However, evidence has now emerged of intense crosstalk between these two organelles, such that the activity or stress status of one organelle may affect the other. Direct physical contacts between mitochondria and the endolysosomal compartment have been reported as a rapid means of interorganelle communication, mediating lipid or other metabolite exchange. Moreover, mitochondrial derived vesicles can traffic obsolete mitochondrial proteins into the endolysosomal system for their degradation or secretion to the extracellular milieu as exosomes, representing an additional mitochondrial quality control mechanism that connects mitochondria and lysosomes independently of autophagosome formation...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29164060/tissue-factor-expressing-tumor-derived-extracellular-vesicles-activate-quiescent-endothelial-cells-via-protease-activated-receptor-1
#13
Sara P Y Che, Jeannie Y Park, Tracy Stokol
Tissue factor (TF)-expressing tumor-derived extracellular vesicles (EVs) can promote metastasis and pre-metastatic niche formation, but the mechanisms by which this occurs remain largely unknown. We hypothesized that generation of activated factor X (FXa) by TF expressed on tumor-derived EV could activate protease-activated receptors (PARs) on non-activated endothelial cells to induce a pro-adhesive and pro-inflammatory phenotype. We obtained EV from TF-expressing breast (MDA-MB-231) and pancreatic (BxPC3 and Capan-1) tumor cell lines...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29164053/synergistic-protective-activity-of-tumor-specific-epitopes-engineered-in-bacterial-outer-membrane-vesicles
#14
Alberto Grandi, Michele Tomasi, Ilaria Zanella, Luisa Ganfini, Elena Caproni, Laura Fantappiè, Carmela Irene, Luca Frattini, Samine J Isaac, Enrico König, Francesca Zerbini, Simona Tavarini, Chiara Sammicheli, Fabiola Giusti, Ilaria Ferlenghi, Matteo Parri, Guido Grandi
Introduction: Bacterial outer membrane vesicles (OMVs) are naturally produced by all Gram-negative bacteria and, thanks to their plasticity and unique adjuvanticity, are emerging as an attractive vaccine platform. To test the applicability of OMVs in cancer immunotherapy, we decorated them with either one or two protective epitopes present in the B16F10EGFRvIII cell line and tested the protective activity of OMV immunization in C57BL/6 mice challenged with B16F10EGFRvIII. Materials and methods: The 14 amino acid B cell epitope of human epidermal growth factor receptor variant III (EGFRvIII) and the mutation-derived CD4+ T cell neo-epitope of kif18b gene (B16-M30) were used to decorate OMVs either alone or in combination...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29163826/hdac-inhibitors-enhance-neratinib-activity-and-when-combined-enhance-the-actions-of-an-anti-pd-1-immunomodulatory-antibody-in-vivo
#15
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Paul Dent
Patients whose NSCLC tumors become afatinib resistant presently have few effective therapeutic options to extend their survival. Afatinib resistant NSCLC cells were sensitive to clinically relevant concentrations of the irreversible pan-HER inhibitor neratinib, but not by the first generation ERBB1/2/4 inhibitor lapatinib. In multiple afatinib resistant NSCLC clones, HDAC inhibitors reduced the expression of ERBB1/3/4, but activated c-SRC, which resulted in higher total levels of ERBB1/3 phosphorylation. Neratinib also rapidly reduced the expression of ERBB1/2/3/4, c-MET and of mutant K-/N-RAS; K-RAS co-localized with phosphorylated ATG13 and with cathepsin B in vesicles...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163818/pediatric-brain-tumor-cells-release-exosomes-with-a-mirna-repertoire-that-differs-from-exosomes-secreted-by-normal-cells
#16
Ágota Tűzesi, Teresia Kling, Anna Wenger, Taral R Lunavat, Su Chul Jang, Bertil Rydenhag, Jan Lötvall, Steven M Pollard, Anna Danielsson, Helena Carén
High-grade gliomas (HGGs) are very aggressive brain tumors with a cancer stem cell component. Cells, including cancer stem cells, release vesicles called exosomes which contain small non-coding RNAs such as microRNAs (miRNAs). These are thought to play an important role in cell-cell communication. However, we have limited knowledge of the types of exosomal miRNAs released by pediatric HGG stem cells; a prerequisite for exploring their potential roles in HGG biology. Here we isolated exosomes released by pediatric glioma stem cells (GSCs) and compared their repertoire of miRNAs to genetically normal neural stem cells (NSCs) exosomes, as well as their respective cellular miRNA content...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163811/impaired-gabab-mediated-presynaptic-inhibition-increases-excitatory-strength-and-alters-short-term-plasticity-in-synapsin-knockout-mice
#17
Pierluigi Valente, Pasqualina Farisello, Flavia Valtorta, Pietro Baldelli, Fabio Benfenati
Synapsins are a family of synaptic vesicle phosphoproteins regulating synaptic transmission and plasticity. SYN1/2 genes are major epilepsy susceptibility genes in humans. Consistently, synapsin I/II/III triple knockout (TKO) mice are epileptic and exhibit severe impairments in phasic and tonic GABAergic inhibition that precede the appearance of the epileptic phenotype. These changes are associated with an increased strength of excitatory transmission that has never been mechanistically investigated. Here, we observed that an identical effect in excitatory transmission could be induced in wild-type (WT) Schaffer collateral-CA1 pyramidal cell synapses by blockade of GABAB receptors (GABABRs)...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163790/a-combination-of-circulating-mirnas-for-the-early-detection-of-ovarian-cancer
#18
Akira Yokoi, Yusuke Yoshioka, Akihiro Hirakawa, Yusuke Yamamoto, Mitsuya Ishikawa, Shun-Ichi Ikeda, Tomoyasu Kato, Kaoru Niimi, Hiroaki Kajiyama, Fumitaka Kikkawa, Takahiro Ochiya
Ovarian cancer is the leading cause of gynecologic cancer mortality, due to the difficulty of early detection. Current screening methods lack sufficient accuracy, and it is still challenging to propose a new early detection method that improves patient outcomes with less-invasiveness. Although many studies have suggested the utility of circulating microRNAs in cancer detection, their potential for early detection remains elusive. Here, we develop novel predictive models using a combination of 8 circulating serum miRNAs...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163768/inhibitor-of-growth-protein-4-interacts-with-beclin-1-and-represses-autophagy
#19
Valentina Sica, José Manuel Bravo-San Pedro, Guo Chen, Guillermo Mariño, Sylvie Lachkar, Valentina Izzo, Maria Chiara Maiuri, Mireia Niso-Santano, Guido Kroemer
Beclin 1 (BECN1) is a multifunctional protein that activates the pro-autophagic class III phosphatidylinositol 3-kinase (PIK3C3, best known as VPS34), yet also interacts with multiple negative regulators. Here we report that BECN1 interacts with inhibitor of growth family member 4 (ING4), a tumor suppressor protein that is best known for its capacity to interact with the tumor suppressor protein p53 (TP53) and the acetyltransferase E1A binding protein p300 (EP300). Removal of TP53 or EP300 did not affect the BECN1/ING4 interaction, which however was lost upon culture of cells in autophagy-inducing, nutrient free conditions...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163650/cumulus-cell-expansion-and-ultrastructural-changes-in-in-vitro-matured-bovine-oocytes-under-heat-stress
#20
J A Ahmed, N Nashiruddullah, D Dutta, R K Biswas, P Borah
Cumulus-oocyte complexes (COCs) from cows were matured under normal (38.5°C) and elevated temperatures (41°C) simulating heat stress and their maturation was assessed based on measurement of cumulus expansion in both groups. There was a significant reduction (P<0.01) in maturation rate in the heat stressed oocytes. The ultrastructural events associated with in vitro oocyte maturation and changes associated with elevated temperature were also studied by transmission electron microscopy (TEM). Normal maturation cellular events were marked by migration of Golgi and mitochondria from the cortical regions, and conversely by a migration of cortical granules from the inner regions to a sub-perivitelline zone...
2017: Iranian journal of veterinary research
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