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https://www.readbyqxmd.com/read/28935901/a-brain-targeting-lipidated-peptide-for-neutralizing-rna-mediated-toxicity-in-polyglutamine-diseases
#1
Qian Zhang, Mengbi Yang, Kasper K Sørensen, Charlotte S Madsen, Josephine T Boesen, Ying An, Shao Hong Peng, Yuming Wei, Qianwen Wang, Knud J Jensen, Zhong Zuo, Ho Yin Edwin Chan, Jacky Chi Ki Ngo
Polyglutamine (PolyQ) diseases are progressive neurodegenerative disorders caused by both protein- and RNA-mediated toxicities. We previously showed that a peptidyl inhibitor, P3, which binds directly to expanded CAG RNA can inhibit RNA-induced nucleolar stress and suppress RNA-induced neurotoxicity. Here we report a N-acetylated and C-amidated derivative of P3, P3V8, that showed a more than 20-fold increase in its affinity for expanded CAG RNA. The P3V8 peptide also more potently alleviated expanded RNA-induced cytotoxicity in vitro, and suppressed polyQ neurodegeneration in Drosophila with no observed toxic effects...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28932213/petri-net-based-model-of-helicobacter-pylori-mediated-disruption-of-tight-junction-proteins-in-stomach-lining-during-gastric-carcinoma
#2
Anam Naz, Ayesha Obaid, Faryal M Awan, Aqsa Ikram, Jamil Ahmad, Amjad Ali
Tight junctions help prevent the passage of digestive enzymes and microorganisms through the space between adjacent epithelial cells lining. However, Helicobacter pylori encoded virulence factors negatively regulate these tight junctions and contribute to dysfunction of gastric mucosa. Here, we have predicted the regulation of important tight junction proteins, such as Zonula occludens-1, Claudin-2 and Connexin32 in the presence of pathogenic proteins. Molecular events such as post translational modifications and crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation are explored which may compromise the integrity of these tight junction proteins...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28927011/assessing-autophagy-in-sciatic-nerves-of-a-rat-model-that-develops-inflammatory-autoimmune-peripheral-neuropathies
#3
REVIEW
Susana Brun, Nicolas Schall, Hélène Jeltsch-David, Jérôme de Sèze, Sylviane Muller
The rat sciatic nerve has attracted widespread attention as an excellent model system for studying autophagy alterations in peripheral neuropathies. In our laboratory, we have developed an original rat model, which we used currently in routine novel drug screening and to evaluate treatment strategies for chronic inflammatory demyelinating polyneuropathy (CIDP) and other closely related diseases. Lewis rats injected with the S-palmitoylated P0(180-199) peptide develop a chronic, sometimes relapsing-remitting type of disease...
September 18, 2017: Cells
https://www.readbyqxmd.com/read/28926699/effects-of-high-pressure-on-phospholipid-bilayers
#4
Wei Ding, Michail Palaiokostas, Ganesh Shahane, Wen Wang, Mario Orsi
The response of lipid membranes to changes in external pressure is important for many biological processes, and it can also be exploited for technological applications. In this work, we employ all-atom molecular dynamics simulations to characterize the changes in the physical properties of phospholipid bilayers brought about by high pressure (1000 bar). In particular, we study how the response differs, in relation to different chain unsaturation levels, by comparing mono-unsaturated 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and bi-unsaturated dioleoyl-phosphatidylcholine (DOPC) bilayers...
September 19, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28924009/site-specific-regulation-of-p2x7-receptor-function-in-microglia-gates-morphine-analgesic-tolerance
#5
Heather Leduc-Pessah, Nicholas L Weilinger, Churmy Y Fan, Nicole E Burma, Roger J Thompson, Tuan Trang
Tolerance to the analgesic effects of opioids is a major problem in chronic pain management. Microglia are implicated in opioid tolerance, but the core mechanisms regulating their response to opioids remain obscure. By selectively ablating microglia in the spinal cord using a saporin-conjugated antibody to Mac1, we demonstrate a causal role for microglia in the development, but not maintenance, of morphine tolerance in male rats. Increased P2X7 receptor (P2X7R) activity is a cardinal feature of microglial activation, and in this study we found that morphine potentiates P2X7R-mediated Ca(2+) responses in resident spinal microglia acutely isolated from morphine tolerant rats...
September 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28923322/cycloartane-type-triterpene-glycosides-anopanins-a-c-with-monoacyldigalactosylglycerols-from-anodendron-paniculatum
#6
Viet Duc Ho, Thi Nhu Hanh Hoang, Quoc Hung Vo, Van Kiem Phan, Tuan Anh Le, Viet Ty Pham, Minh Hien Nguyen, Takeshi Kodama, Takuya Ito, Hiroyuki Morita, Ain Raal, Thi Hoai Nguyen
Three cycloartane-type triterpene glycosides (anopanins A-C), together with three known monoacyldigalactosylglycerols gingerglycolipids A-C and (2S)-1-O-palmitoyl-3-O-[α-d-galactopyranosyl-(1→6)-β-d-galactopyranosyl]-sn-glycerol, were isolated from the aerial parts of Anodendron paniculatum collected in Viet Nam. The chemical structures of the present compounds were elucidated by means of 1D and 2D NMR and HRESIMS spectroscopy, and by comparing to the reported data in the literature. These compounds did not show significant growth inhibitory activities (IC50 > 100 μg/mL) against the tested cancer cell lines LU-1 (lung adenocarcinoma), KB (epidermoid carcinoma), Hep-G2 (hepatoma cancer), MKN-7 (stomach cancer), and SW-480 (colon adenocarcinoma)...
September 15, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28920575/the-p2x7-receptor-forms-a-dye-permeable-pore-independent-of-its-intracellular-domain-but-dependent-on-membrane-lipid-composition
#7
Akira Karasawa, Kevin Michalski, Polina Mikhelzon, Toshimitsu Kawate
The P2X7 receptor mediates extracellular-ATP signaling implicated in the development of devastating diseases such as chronic pain and cancer. Activation of the P2X7 receptor leads to opening of the characteristic dye-permeable membrane pore for molecules up to ~900 Da. However, it remains controversial what constitutes this peculiar pore and how it opens. Here we show that the panda P2X7 receptor, when purified and reconstituted into liposomes, forms an intrinsic dye-permeable pore in the absence of other cellular components...
September 18, 2017: ELife
https://www.readbyqxmd.com/read/28919642/membrane-binding-of-parkinson-s-protein-%C3%AE-synuclein-effect-of-phosphorylation-at-positions-87-and-129-by-the-s-to-d-mutation-approach
#8
Pravin Kumar, Nathalie Schilderink, Vinod Subramaniam, Martina Huber
Human α-synuclein, a protein relevant in the brain with so-far unknown function, plays an important role in Parkinson's disease. The phosphorylation state of αS was related to the disease, prompting interest in this process. The presumed physiological function and the disease action of αS involves membrane interaction. Here, we study the effect of phosphorylation at positions 87 and 129, mimicked by the mutations S87A, S129A (nonphosphorylated) and S87D, S129D (phosphorylated) on membrane binding. Local binding is detected by spin-label continuous-wave electron paramagnetic resonance...
July 2017: Israel Journal of Chemistry
https://www.readbyqxmd.com/read/28917050/preparation-of-selenocysteine-containing-forms-of-human-selenok-and-selenos
#9
Zhengqi Zhang, Jun Liu, Sharon Rozovsky
Selenoprotein K (SELENOK) and Selenoprotein S (SELENOS) are the members of the endoplasmic-reticulum-associated degradation (ERAD) complex, which is responsible for translocating misfolded proteins from the endoplasmic reticulum (ER) to the cytosol for degradation. Besides its involvement in the ERAD, SELENOK was shown to bind and stabilize the palmitoyl transferase DHHC6, and thus contributes to palmitoylation. SELENOK and SELENOS reside in the ER membrane by the way of a single transmembrane helix. Both contain an intrinsically disordered region with a selenocysteine (Sec) located one or two residues away from the C-terminus...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28916587/melanoma-risk-variants-prevent-mc1r-palmitoylation-and-activation
#10
(no author information available yet)
Palmitoylation-deficient MC1R variants accelerate BRAF(V60E)-driven melanomagenesis.
September 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28912102/cholesterol-affects-the-interaction-between-an-ionic-liquid-and-phospholipid-vesicles-a-study-by-differential-scanning-calorimetry-and-nanoplasmonic-sensing
#11
Giacomo Russo, Joanna Witos, Antti H Rantamäki, Susanne K Wiedmer
The present work aims at studying the interactions between cholesterol-rich phosphatidylcholine-based lipid vesicles and trioctylmethylphosphonium acetate ([P8881][OAc]), a biomass dissolving ionic liquid (IL). The effect of cholesterol was assayed by using differential scanning calorimetry (DSC) and nanoplasmonic sensing (NPS) measurement techniques. Cholesterol-enriched dipalmitoyl-phosphatidylcholine vesicles were exposed to different concentrations of the IL, and the derived membrane perturbation was monitored by DSC...
September 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28905694/sphingomonas-carri-sp-nov-isolated-from-a-car-air-conditioning-system
#12
Hyosun Lee, Dong-Uk Kim, Suyeon Lee, Jungpyo Yun, Sooyeon Park, Jung-Hoon Yoon, So Yoon Park, Jong-Ok Ka
A Gram-stain-negative, yellow-pigmented bacterial strain, designated PR0302T, was isolated from a car evaporator core collected in Korea. The cells were strictly aerobic, non-spore-forming and rod-shaped. The strain grew at 15-37 °C (optimum, 25 °C), at pH 6.0-8.0 (optimum, 7.0) and in the presence of 0-1 % (w/v) NaCl. Phylogenetically, the strain was closely related to members of the genus Sphingomonas(97.04-91.22 % 16S rRNA gene sequence similarities) and showed the highest sequence similarity of 97...
September 14, 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/28899863/a-unified-approach-to-targeting-the-lysosome-s-degradative-and-growth-signaling-roles
#13
Vito W Rebecca, Michael C Nicastri, Noel McLaughlin, Colin Fennelly, Quentin McAfee, Amruta Ronghe, Michel Nofal, Chun-Yan Lim, Eric Witze, Cynthia I Chude, Gao Zhang, Gretchen M Alicea, Shengfu Piao, Sengottuvelan Murugan, Rani Ojha, Samuel M Levi, Zhi Wei, Julie S Barber-Rotenberg, Maureen E Murphy, Gordon B Mills, Yiling Lu, Joshua Rabinowitz, Ronen Marmorstein, Qin Liu, Shujing Liu, Xiaowei Xu, Meenhard Herlyn, Roberto Zoncu, Donita C Brady, David W Speicher, Jeffrey D Winkler, Ravi K Amaravadi
Lysosomes serve dual roles in cancer metabolism, executing catabolic programs (i.e. autophagy and macropinocytosis), while promoting mTORC1-dependent anabolism. Antimalarial compounds such as chloroquine or quinacrine have been used as lysosomal inhibitors, but fail to inhibit mTOR signaling. Further, the molecular target of these agents has not been identified. We report a screen of novel dimeric antimalarials that identifies dimeric quinacrines (DQs) as potent anticancer compounds, which concurrently inhibit mTOR and autophagy...
September 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28899783/induced-sensitivity-to-egfr-inhibitors-is-mediated-by-palmitoylated-cysteine-1025-of-egfr-and-requires-oncogenic-kras
#14
Akriti Kharbanda, Kristin Runkle, Wei Wang, Eric S Witze
Currently, there are no effective therapeutic strategies targeting Kras driven cancers, and therefore, identifying new targeted therapies and overcoming drug resistance have become paramount for effective long-term cancer therapy. We have found that reducing expression of the palmitoyl transferase DHHC20 increases cell death induced by the EGFR inhibitor gefitinib in Kras and EGFR mutant cell lines, but not MCF7 cells harboring wildtype Kras. We show that the increased gefitinib sensitivity in cancer cells induced by DHHC20 inhibition is mediated directly through loss of palmitoylation on a previously identified cysteine residue in the C-terminal tail of EGFR...
September 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28894292/partitioning-of-adipose-lipid-metabolism-by-altered-expression-and-function-of-ppar-isoforms-after-bariatric-surgery
#15
C Jahansouz, H Xu, A V Hertzel, S Kizy, K A Steen, R Foncea, F J Serrot, N Kvalheim, G Luthra, K Ewing, D B Leslie, S Ikramuddin, D A Bernlohr
BACKGROUND: Bariatric surgery remains the most effective treatment for reducing adiposity and eliminating type 2 diabetes; however, the mechanism(s) responsible have remained elusive. Peroxisome proliferator-activated receptors (PPAR) encompass a family of nuclear hormone receptors that upon activation exert control of lipid metabolism, glucose regulation and inflammation. Their role in adipose tissue following bariatric surgery remains undefined. MATERIALS AND METHODS: Subcutaneous adipose tissue biopsies and serum were obtained and evaluated from time of surgery and on postoperative day 7 in patients randomized to Roux-en-Y gastric bypass (n=13) or matched caloric restriction (n=14), as well as patients undergoing vertical sleeve gastrectomy (n=33)...
August 14, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28891931/beneficial-effects-of-common-bean-on-adiposity-and-lipid-metabolism
#16
Henry J Thompson, John N McGinley, Elizabeth S Neil, Mark A Brick
In developed countries which are at the epicenter of the obesity pandemic, pulse crop consumption is well below recommended levels. In a recent systematic review and meta-analysis of 21 randomized controlled clinical trials, pulse consumption was associated with improved weight control and reduced adiposity, although the underlying mechanisms were a matter of speculation. Common bean (Phaseolus vulgaris L.) is the most widely consumed pulse crop and was the focus of this investigation. Using outbred genetic models of dietary induced obesity resistance and of dietary induced obesity sensitivity in the rat, the impact of bean consumption was investigated on the efficiency with which consumed food was converted to body mass (food efficiency ratio), body fat accumulation, adipocyte morphometrics, and patterns of protein expression associated with lipid metabolism...
September 9, 2017: Nutrients
https://www.readbyqxmd.com/read/28891286/conformation-preservation-of-alpha-helical-peptides-within-supramolecular-filamentous-assemblies
#17
Yi Li, Yuzhu Wang, Shih-Hao Ou, Lye Lin Lock, Xuankuo Xu, Sanchayita Ghose, Zheng Jian Li, Honggang Cui
Hydrogen-bonded β-sheets are the most commonly explored building motifs for creating peptide-based filamentous nanostructures, however, most bioactive epitopes must assume an α-helix conformation to exert their functions. Incorporating α-helical sequences into β-sheet-forming peptides often involves the use of a flexible spacer to alleviate the steric impact of the intermolecular hydrogen bonding on the α-helical conformation. In this context, we report our findings on the alkylation-regulated conformation preservation of α-helical peptides within their filamentous assemblies...
September 11, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28878621/the-networks-of-genes-encoding-palmitoylated-proteins-in-axonal-and-synaptic-compartments-are-affected-in-ppt1-overexpressing-neuronal-like-cells
#18
Francesco Pezzini, Marzia Bianchi, Salvatore Benfatto, Francesca Griggio, Stefano Doccini, Rosalba Carrozzo, Arvydas Dapkunas, Massimo Delledonne, Filippo M Santorelli, Maciej M Lalowski, Alessandro Simonati
CLN1 disease (OMIM #256730) is an early childhood ceroid-lipofuscinosis associated with mutated CLN1, whose product Palmitoyl-Protein Thioesterase 1 (PPT1) is a lysosomal enzyme involved in the removal of palmitate residues from S-acylated proteins. In neurons, PPT1 expression is also linked to synaptic compartments. The aim of this study was to unravel molecular signatures connected to CLN1. We utilized SH-SY5Y neuroblastoma cells overexpressing wild type CLN1 (SH-p.wtCLN1) and five selected CLN1 patients' mutations...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28878070/effect-of-the-phosphorylation-of-the-cm2-protein-on-influenza-c-virus-replication
#19
Takanari Goto, Yoshitaka Shimotai, Yoko Matsuzaki, Yasushi Muraki, Ri Sho, Kanetsu Sugawara, Seiji Hongo
CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication. Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined. In this study, phosphorylation site(s) at residues 78 and/or 103 of CM2 were substituted with alanine residue(s) and the effects of the loss of phosphorylation on influenza C virus replication were analyzed...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28870825/prolonged-but-non-permanent-expression-of-a-transgene-in-ependymal-cells-of-adult-rats-using-an-adenovirus-mediated-transposon-gene-transfer-system
#20
Jun-Ichi Suzuki, Mari Dezawa, Masaaki Kitada
Ependymal cells have been considered one of prime targets for gene therapy in the central nervous system as they can secrete proteins directly into the cerebrospinal fluid. In this study, we have explored the probability of permanent exogenous gene expression using a combined adenovirus/transposon system. To this end, we created three adenoviruses; adenovirus #1 containing a CAG promoter-driven enhanced green fluorescent protein tagged with a palmitoylation site (palEGFP), whose DNA sequence was flanked by two different Tol2 ends, #2 containing a human FoxJ1 promoter-driven T2TP transposase, and #3 containing an EF-1 alpha promoter-driven T2TP transposase...
September 1, 2017: Brain Research
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