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https://www.readbyqxmd.com/read/29346777/prrt2-regulates-synaptic-fusion-by-directly-modulating-snare-complex-assembly
#1
Jeff Coleman, Ouardane Jouannot, Sathish K Ramakrishnan, Maria N Zanetti, Jing Wang, Vincenzo Salpietro, Henry Houlden, James E Rothman, Shyam S Krishnakumar
Mutations in proline-rich transmembrane protein 2 (PRRT2) are associated with a range of paroxysmal neurological disorders. PRRT2 predominantly localizes to the pre-synaptic terminals and is believed to regulate neurotransmitter release. However, the mechanism of action is unclear. Here, we use reconstituted single vesicle and bulk fusion assays, combined with live cell imaging of single exocytotic events in PC12 cells and biophysical analysis, to delineate the physiological role of PRRT2. We report that PRRT2 selectively blocks the trans SNARE complex assembly and thus negatively regulates synaptic vesicle priming...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346565/apigenin-induces-cell-shrinkage-in-candida-albicans-by-membrane-perturbation
#2
Heejeong Lee, Eun-Rhan Woo, Dong Gun Lee
Apigenin, a natural flavone, has been well characterized for its their anticarcinogenic property; however, its bioactivity against pathogenic fungi has not been investigated in detail. In the present study, we examined the antifungal activity and mode of action of apigenin. Apigenin inhibited the growth of fungal pathogens, which induced superficial infection and reduced biofilm mass. Three-dimensional flow cytometric analysis demonstrated that apigenin induced morphological changes, especially cell shrinkage, in Candida albicans...
January 16, 2018: FEMS Yeast Research
https://www.readbyqxmd.com/read/29346527/progesterone-effects-on-extracellular-vesicles-in-the-sheep-uterus
#3
Gregory W Burns, Kelsey E Brooks, Eleanore V O'Neil, Darren E Hagen, Susanta K Behura, Thomas E Spencer
Progesterone (P4) acts via the endometrium to promote conceptus growth and implantation for pregnancy establishment. Many cells release extracellular vesicles (EVs) that are membrane-bound vesicles of endosomal and plasma membrane origin. In sheep, endometrial-derived EVs were found to traffic to the conceptus trophectoderm. Thus, EVs are hypothesized to be an important mode of intercellular communication by transferring select RNAs, proteins, and lipids between the endometrium and conceptus. Electron microscopy analysis found that the endometrial luminal and glandular epithelia were the primary source of EVs in the uterus of cyclic sheep...
January 16, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29345989/assembly-of-copi-and-copii-vesicular-coat-proteins-on-membranes
#4
Julien Béthune, Felix T Wieland
In eukaryotes, distinct transport vesicles functionally connect various intracellular compartments. These carriers mediate transport of membranes for the biogenesis and maintenance of organelles, secretion of cargo proteins and peptides, and uptake of cargo into the cell. Transport vesicles have distinct protein coats that assemble on a donor membrane where they can select cargo and curve the membrane to form a bud. A multitude of structural elements of coat proteins have been solved by X-ray crystallography...
January 18, 2018: Annual Review of Biophysics
https://www.readbyqxmd.com/read/29345922/efficient-fusion-at-neutral-ph-by-human-immunodeficiency-virus-gp41-trimers-containing-the-fusion-peptide-and-transmembrane-domain
#5
Shuang Liang, Punsisi Ratnayake, Craig Keinath, Lihui Jia, Robert Wolfe, Ahinsa Ranaweera, David P Weliky
Human immunodeficiency virus (HIV) is membrane-enveloped and an initial infection step is joining/fusion of viral and cell membranes. This step is catalyzed by gp41 which is a single-pass integral viral membrane protein. The protein contains a ~170-residue ectodomain located outside the virus that is important for fusion, and includes the fusion peptide (FP), N-helix, loop, C-helix, and viral membrane-proximal external region (MPER). The virion initially has non-covalent complexes between three gp41 ectodomains and three gp120 proteins...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29345286/cyclooxygenase-2-expression-is-induced-by-celecoxib-treatment-in-lung-cancer-cells-and-is-transferred-to-neighbor-cells-via-exosomes
#6
Jayoung Kim, Seung-Woo Hong, Seonghan Kim, Daejin Kim, Dae Young Hur, Dong-Hoon Jin, Bomi Kim, Yeong Seok Kim
Lung cancer is one of most common types of cancer worldwide. Lung cancer results in a death higher rate each year compared to colon, breast and prostate cancer combined. Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX‑2), an enzyme of which the expression is induced by various stimuli, such as inflammation. In addition, celecoxib triggers COX-2 loading on exosomes. Exosomes are small vesicles composed of a lipid bilayer membrane and are found in most biological fluids, such as blood breast milk and urine...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345219/transcriptional-changes-when-myxococcus-xanthus-preys-on-escherichia-coli-suggest-myxobacterial-predators-are-constitutively-toxic-but-regulate-their-feeding
#7
Paul G Livingstone, Andrew D Millard, Martin T Swain, David E Whitworth
Predation is a fundamental ecological process, but within most microbial ecosystems the molecular mechanisms of predation remain poorly understood. We investigated transcriptome changes associated with the predation of Escherichia coli by the myxobacterium Myxococcus xanthus using mRNA sequencing. Exposure to pre-killed prey significantly altered expression of 1319 predator genes. However, the transcriptional response to living prey was minimal, with only 12 genes being significantly up-regulated. The genes most induced by prey presence (kdpA and kdpB, members of the kdp regulon) were confirmed by reverse transcriptase quantitative PCR to be regulated by osmotic shock in M...
January 18, 2018: Microbial Genomics
https://www.readbyqxmd.com/read/29344346/characterization-and-selective-incorporation-of-small-non-coding-rnas-in-non-small-cell-lung-cancer-extracellular-vesicles
#8
Chuang Li, Fang Qin, Fen Hu, Hui Xu, Guihong Sun, Guang Han, Tao Wang, Mingxiong Guo
Background: Extracellular vesicles (EVs) play important roles in intercellular communication through the delivery of their cargoes, which include proteins, lipids, and RNAs. Increasingly, multiple studies have reported the association between EV small non-coding RNAs and cancer, due to their regulatory functions in gene expression. Hence, analysis of the features of small non-coding RNA expression and their incorporation into EVs is important for cancer research. Results: We performed deep sequencing to investigate the expression of small RNAs in plasma EVs from lung adenocarcinoma (ADC) patients, lung squamous cell carcinoma (SQCC) patients, and healthy controls...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29344250/prevention-of-body-weight-loss-and-sarcopenia-by-a-novel-selective-androgen-receptor-modulator-in-cancer-cachexia-models
#9
Megumi Morimoto, Katsuji Aikawa, Takahito Hara, Masuo Yamaoka
Cancer cachexia is a syndrome that impairs the quality of life and overall survival of patients, and thus the effectiveness of anticancer agents. There are no effective therapies for cancer cachexia due to the complexity of the syndrome, and insufficient knowledge of its pathogenesis results in difficulty establishing appropriate animal models. Previously, promising results have been obtained in clinical trials using novel agents including the ghrelin receptor agonist anamorelin, and the selective androgen receptor modulator (SARM) enobosarm to treat cachexia in patients with cancer...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343745/malaria-infected-red-blood-cells-release-small-regulatory-rnas-through-extracellular-vesicles
#10
Kehinde Adebayo Babatunde, Smart Mbagwu, María Andrea Hernández-Castañeda, Swamy R Adapa, Michael Walch, Luis Filgueira, Laurent Falquet, Rays H Y Jiang, Ionita Ghiran, Pierre-Yves Mantel
The parasite Plasmodium falciparum causes the most severe form of malaria. Cell communication between parasites is an important mechanism to control population density and differentiation. The infected red blood cells (iRBCs) release small extracellular vesicles (EVs) that transfer cargoes between cells. The EVs synchronize the differentiation of the asexual parasites into gametocytes to initiate the transmission to the mosquito. Beside their role in parasite communication, EVs regulate vascular function. So far, the exact cargoes responsible for cellular communication remain unknown...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343679/ramsay-hunt-syndrome-with-multiple-cranial-neuropathy-in-an-human-immunodeficiency-virus-hiv-patient
#11
Divya Arya, Tushar Bajaj, Jose Gonzalez, Rene Elkin
BACKGROUND Ramsay Hunt syndrome is a rare otologic complication resulting from varicella zoster virus reactivation that can present with a myriad of clinical presentations. Most common being triad of ear pain, vesicles at auricle, and ear canal with same side facial palsy. CASE REPORT We report a case of a 29-year-old male with a human immunodeficiency virus (HIV) infection who presented with left facial palsy, vesicles, pain in the left ear, dysphagia, dizziness, and headache resulting from multiple cranial nerves involvement such as cranial nerve V, VII, VIII, IX, and X...
January 18, 2018: American Journal of Case Reports
https://www.readbyqxmd.com/read/29343551/two-subunits-of-the-exocyst-sec3p-and-exo70p-can-function-exclusively-on-the-plasma-membrane
#12
Dongmei Liu, Xia Li, David Shen, Peter Novick
The exocyst is an octameric complex that tethers secretory vesicles to the plasma membrane in preparation for fusion. We anchored each subunit with a transmembrane (TM) domain at its N- or C-terminus. Only N-terminally anchored TM-Sec3p and C-terminally anchored Exo70p-TM proved functional. These findings orient the complex with respect to the membrane and establish that Sec3p and Exo70p can function exclusively on the membrane. The functions of TM-Sec3p and Exo70p-TM were largely unaffected by blocks in endocytic recycling suggesting that they act on the plasma membrane, rather than on secretory vesicles...
January 17, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29343549/intracellular-vesicle-trafficking-plays-an-essential-role-in-mitochondrial-quality-control
#13
Mike Gerards, Giuseppe Cannino, Jose M González de Cózar, Howard T Jacobs
The Drosophila gene products Bet1, Slh and CG10144, predicted to function in intracellular vesicle trafficking, were previously found to be essential for mitochondrial nucleoid maintenance. Here we show that Slh and Bet1 co-operate to maintain mitochondrial functions. In their absence, mitochondrial content, membrane potential and respiration became abnormal, accompanied by mitochondrial proteotoxic stress, but without direct effects on mtDNA. Immunocytochemistry showed that both Slh and Bet1 are localized at the Golgi, together with a proportion of Rab5-positive vesicles...
January 17, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29343526/mutations-in-cyb561-causing-a-novel-orthostatic-hypotension-syndrome
#14
Maarten P van den Berg, Rowida Almomani, Italo Biaggioni, Martijn van Faassen, Pim van der Harst, Herman H Silljé, Irene Mateo Leach, Marc Hemmelder, Gerjan Navis, Gert-Jan Luijckx, Arjan P de Brouwer, Hanka Venselaar, Marcel M Verbeek, Paul A van der Zwaag, Jan D Jongbloed, J P van Tintelen, Ron A Wevers, Ido P Kema
Rationale: Orthostatic hypotension is a common clinical problem, but the underlying mechanisms have not been fully delineated. Objective: We describe two families, with four patients in total, suffering from severe life-threatening orthostatic hypotension due to a novel cause. Methods and Results: As in dopamine β-hydroxylase deficiency (DβH), concentrations of norepinephrine and epinephrine in the patients were very low. Plasma DβH activity, however, was normal and the DBH gene had no mutations. Molecular genetic analysis was performed to determine the underlying genetic cause...
January 17, 2018: Circulation Research
https://www.readbyqxmd.com/read/29342457/the-von-hippel-lindau-gene-is-required-to-maintain-renal-proximal-tubule-and-glomerulus-integrity-in-zebrafish-larvae
#15
Ellen van Rooijen, Glenn van de Hoek, Ive Logister, Henry Ajzenberg, Nine V A M Knoers, Freek van Eeden, Emile E Voest, Stefan Schulte-Merker, Rachel H Giles
BACKGROUND: von Hippel-Lindau (VHL) disease is characterized by the development of benign and malignant tumours in many organ systems, including renal cysts and clear cell renal cell carcinoma. It is not completely understood what underlies the development of renal pathology, and the use of murine Vhl models has been challenging due to limitations in disease conservation. We previously described a zebrafish model bearing inactivating mutations in the orthologue of the human VHL gene. METHODS: We used histopathological and functional assays to investigate the pronephric and glomerular developmental defects in vhl mutant zebrafish, supported by human cell culture assays...
January 17, 2018: Nephron
https://www.readbyqxmd.com/read/29342419/investigation-of-the-transport-of-xanthine-dehydrogenase-inhibitors-by-the-urate-transporter-abcg2
#16
Makiko Nakamura, Kyoko Fujita, Yu Toyoda, Tappei Takada, Hiroshi Hasegawa, Kimiyoshi Ichida
Hyperuricemia induces gout and kidney stones and accelerates the progression of renal and cardiovascular diseases. Adenosine 5'-triphosphate-binding cassette subfamily G member 2 (ABCG2) is a urate transporter, and common dysfunctional variants of ABCG2, non-functional Q126X (rs72552713) and semi-functional Q141K (rs2231142), are risk factors for hyperuricemia and gout. A recent genome wide association study suggested that allopurinol, a serum uric acid-lowering drug that inhibits xanthine dehydrogenase, is a potent substrate of ABCG2...
November 22, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29341927/book-lung-development-in-juveniles-and-adults-of-the-cobweb-spider-parasteatoda-tepidariorum-c-l-koch-1841-araneomorphae-theridiidae
#17
Roger D Farley
Light and transmission electron microscopy were used to study the development of new book lung lamellae in juvenile and adult spiders (Parasteatoda tepidariorum). As hypothesized earlier in a study of embryos, mesenchyme cells dispersed throughout the opisthosoma (EMT) are a likely source of precursor epithelial cells (MET) for the new lamellae. The precursor cells in juveniles and adults continue many of the complex activities observed in embryos, e.g., migration, alignment, lumen formation, thinning, elongation, and secretion of the cuticle of air channel walls and trabeculae...
January 13, 2018: Arthropod Structure & Development
https://www.readbyqxmd.com/read/29341915/influence-of-ligands-property-and-particle-size-of-gold-nanoparticles-on-the-protein-adsorption-and-corresponding-targeting-ability
#18
Wei Xiao, Jingyuan Xiong, Shuang Zhang, Yang Xiong, Huajin Zhang, Huile Gao
Nanoparticulated vesicles were widely used for carriers of drugs and imaging probes. To improve the targeting delivery efficiency of these vesicles, ligands were often functionalized onto their surfaces. However, the interaction between vesicles and plasma proteins may cover the ligands and hinder the targeting delivery. It is important to address the potential influence of ligands modification on plasma protein adsorption and the following targeting delivery. In this study, two common used ligands were chosen as the model: transferrin and RGD peptide...
January 13, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29341136/phylogeny-and-distribution-of-protein-kinase-c-variants-in-the-zebrafish
#19
Marion F Haug, Matthias Gesemann, Manuela Berger, Stephan C F Neuhauss
Conventional protein kinases - consisting of α, β, and γ family members - play key roles in numerous signal transduction events. Phylogenetic analysis demonstrated the existence of five prkcs (the genes representing PKCs) in zebrafish, two paralogous forms of prkca and -b and one prkcg variant. mRNA expression analysis showed distinct, mainly nervous system specific expression, for all five prkc genes. For prkca and prkcb paralogs prominent expression can be seen in the telencephalon, in diencephalic regions such as the habenula or the optic tectum, in hypothalamic areas and in distinct cerebellar structures...
January 17, 2018: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29340416/self-assembly-of-cationic-gemini-surfactants-alkanediyl-bis-dimethyldodecyl-ammonium-bromide-in-cyclohexane-effects-of-spacer-length-on-their-association-into-reverse-lyotropic-liquid-crystalline-or-reverse-vesicles
#20
Shenglu Deng, Jianxi Zhao
Herein, homogeneous solutions of cationic gemini surfactants, alkanediyl-α,ω-bis(dimethyldodecylammonium bromide), referred to as 12-s-12 where s = 2, 4, 6, 8, and 10, in cyclohexane have been prepared with the help of sodium hexanoate (SH) or sodium laurate (SL). These surfactants self-assembled in cyclohexane to form various aggregating structures, which were characterised by small-angle X-ray scattering (SAXS) together with polarised microscopy observations. The results showed that 12-2-12/SH, where the gemini had the shortest spacer among this series, formed an inverse micellar cubic liquid crystalline phase of the Fd3m structure...
January 17, 2018: Soft Matter
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