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https://www.readbyqxmd.com/read/28098860/chondroitin-sulfate-proteoglycan-protein-is-stimulated-by-interleukin%C3%A2-11-and-promotes-endometrial-epithelial-cancer-cell-proliferation-and-migration
#1
Amy Winship, Michelle Van Sinderen, Ariella Heffernan-Marks, Eva Dimitriadis
Endometrial cancer is the most common gynecological cancer. We identified interleukin 11 (IL11) as a critical mediator of endometrial tumourigenesis and demonstrated that IL11 regulates chondroitin sulfate proteoglycan (CSPG4) in human placental trophoblasts. CSPG4 is a cell membrane protein overexpressed in numerous human cancers, although its role in endometrial cancer has not been investigated. We examined CSPG4 expression and localization in primary human type I endometrioid grade (G) 1-3 tumours by qPCR and immunohistochemistry and determined whether IL11 stimulated CSPG4...
January 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28098806/antibacterial-activities-and-possible-modes-of-action-of-acacia-nilotica-l-del-against-multidrug-resistant-escherichia-coli-and-salmonella
#2
Muhammad Bilal Sadiq, Joel Tarning, Tay Zar Aye Cho, Anil Kumar Anal
Medicinal plants are frequently used for the treatment of various infectious diseases. The objective of this study was to evaluate the antibacterial activity and mode of action of Acacia nilotica and the antibiogram patterns of foodborne and clinical strains of Escherichia coli and Salmonella. The mechanism of action of acacia extracts against E. coli and Salmonella was elucidated by observing morphological damages including cell integrity and cell membrane permeability, as well as changes in cell structures and growth patterns in kill-time experiments...
January 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28098781/distinct-neurotoxicity-profile-of-listeriolysin-o-from-listeria-monocytogenes
#3
Jana Maurer, Sabrina Hupp, Carolin Bischoff, Christina Foertsch, Timothy J Mitchell, Trinad Chakraborty, Asparouh I Iliev
Cholesterol-dependent cytolysins (CDCs) are protein toxins that originate from Gram-positive bacteria and contribute substantially to their pathogenicity. CDCs bind membrane cholesterol and build prepores and lytic pores. Some effects of the toxins are observed in non-lytic concentrations. Two pathogens, Streptococcus pneumoniae and Listeria monocytogenes, cause fatal bacterial meningitis, and both produce toxins of the CDC family-pneumolysin and listeriolysin O, respectively. It has been demonstrated that pneumolysin produces dendritic varicosities (dendrite swellings) and dendritic spine collapse in the mouse neocortex, followed by synaptic loss and astrocyte cell shape remodeling without elevated cell death...
January 13, 2017: Toxins
https://www.readbyqxmd.com/read/28098764/iqgap1-in-podosomes-invadosomes-is-involved-in-the-progression-of-glioblastoma-multiforme-depending-on-the-tumor-status
#4
Deborah Rotoli, Natalia Dolores Pérez-Rodríguez, Manuel Morales, María Del Carmen Maeso, Julio Ávila, Ali Mobasheri, Pablo Martín-Vasallo
Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signaling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumors, suggesting a role for this protein in cell proliferation, transformation and invasion...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28098449/targeting-type-2-diabetes-with-c-glucosyl-dihydrochalcones-as-selective-sodium-glucose-co-transporter-2-sglt2-inhibitors-synthesis-and-biological-evaluation
#5
Ana R Jesus, Diogo Vila-Viçosa, Miguel Machuqueiro, Ana P Marques, Timothy M Dore, Amélia P Rauter
Inhibiting glucose reabsorption by sodium glucose co-transporter proteins (SGLTs) in the kidneys is a relatively new strategy for treating type 2 diabetes. Selective inhibition of SGLT2 over SGLT1 is critical for minimizing adverse side effects associated with SGLT1 inhibition. A library of C-glucosyl dihydrochalcones and their dihydrochalcone and chalcone precursors was synthesized and tested as SGLT1/SGLT2 inhibitors using a cell-based fluorescence assay of glucose uptake. The most potent inhibitors of SGLT2 (IC50 = 9-23 nM) were considerably weaker inhibitors of SGLT1 (IC50 = 10-19 μM)...
January 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28098447/the-stories-tryptophans-tell-exploring-protein-dynamics-of-heptosyltransferase-i-from-escherichia-coli
#6
Joy M Cote, Carlos Andres Ramirez-Mondragon, Zarek S Siegel, Daniel Joseph Czyzyk, Jiali Gao, Yuk Yin Sham, Ishita Mukerji, Erika A Taylor
Heptosyltransferase I (HepI) catalyzes the addition of a single L-glycero-β-D-manno-heptose sugar (heptose) onto the membrane incorporated Kdo2-Lipid A as part of the biosynthesis of the core region of lipopolysaccharide (LPS). Gram-negative bacteria with gene knockouts of HepI have reduced virulence with enhanced susceptibility to hydrophobic antibiotics, making design of inhibitors against HepI of interest. Previous studies have shown that HepI protein dynamics are partially rate limiting, and therefore disruption of protein dynamics might provide a new strategy for inhibiting HepI...
January 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28098291/investigation-into-the-bioavailability-of-milk-protein-derived-peptides-with-dipeptidyl-peptidase-iv-inhibitory-activity-using-caco-2-cell-monolayers
#7
Isabelle M E Lacroix, Xiu-Min Chen, David D Kitts, Eunice C Y Li-Chan
In recent years, peptides derived from a variety of dietary proteins have been reported to exhibit inhibitory activity against the dipeptidyl-peptidase IV (DPP-IV) enzyme, a target in the management of type 2 diabetes. While much attention has been given to the production and identification of peptides with DPP-IV inhibitory activity from food proteins, particularly dairy proteins, little is known on the bioavailability of these molecules. In this study, the stability and transport of five previously identified milk-derived peptides (LKPTPEGDL, LPYPY, IPIQY, IPI and WR) and a whey protein isolate (WPI) digest with DPP-IV-inhibitory activity were investigated using Caco-2 cell monolayers as a model system for human intestinal absorption...
January 18, 2017: Food & Function
https://www.readbyqxmd.com/read/28098232/crystal-structure-of-sec10-a-subunit-of-the-exocyst-complex
#8
Jianxing Chen, Atsushi Yamagata, Keiko Kubota, Yusuke Sato, Sakurako Goto-Ito, Shuya Fukai
The exocyst complex is a heterooctameric protein complex composed of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84. This complex plays an essential role in trafficking secretory vesicles to the plasma membrane through its interaction with phosphatidylinositol 4,5-bisphosphate and small GTPases. To date, the near-full-length structural information of each subunit has been limited to Exo70, although the C-terminal half structures of Sec6, Sec15 and Exo84 and the structures of the small GTPase-binding domains of Sec3, Sec5 and Exo84 have been reported...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098200/cullin-7-mediates-proteasomal-and-lysosomal-degradations-of-rat-eag1-potassium-channels
#9
Po-Hao Hsu, Yu-Ting Ma, Ya-Ching Fang, Jing-Jia Huang, Yu-Ling Gan, Pei-Tzu Chang, Guey-Mei Jow, Chih-Yung Tang, Chung-Jiuan Jeng
Mammalian Eag1 (Kv10.1) potassium (K(+)) channels are widely expressed in the brain. Several mutations in the gene encoding human Eag1 K(+) channel have been associated with congenital neurodevelopmental anomalies. Currently very little is known about the molecules mediating protein synthesis and degradation of Eag1 channels. Herein we aim to ascertain the protein degradation mechanism of rat Eag1 (rEag1). We identified cullin 7 (Cul7), a member of the cullin-based E3 ubiquitin ligase family, as a novel rEag1 binding partner...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098199/optogenetic-modulation-of-urinary-bladder-contraction-for-lower-urinary-tract-dysfunction
#10
Jae Hong Park, Jin Ki Hong, Ja Yun Jang, Jieun An, Kyu-Sung Lee, Tong Mook Kang, Hyun Joon Shin, Jun-Kyo Francis Suh
As current clinical approaches for lower urinary tract (LUT) dysfunction such as pharmacological and electrical stimulation treatments lack target specificity, thus resulting in suboptimal outcomes with various side effects, a better treatment modality with spatial and temporal target-specificity is necessary. In this study, we delivered optogenetic membrane proteins, such as channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to bladder smooth muscle cells (SMCs) of mice using either the Cre-loxp transgenic system or a viral transfection method...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098136/exome-and-genome-sequencing-of-nasopharynx-cancer-identifies-nf-%C3%AE%C2%BAb-pathway-activating-mutations
#11
Yvonne Y Li, Grace T Y Chung, Vivian W Y Lui, Ka-Fai To, Brigette B Y Ma, Chit Chow, John K S Woo, Kevin Y Yip, Jeongsun Seo, Edwin P Hui, Michael K F Mak, Maria Rusan, Nicole G Chau, Yvonne Y Y Or, Marcus H N Law, Peggy P Y Law, Zoey W Y Liu, Hoi-Lam Ngan, Pok-Man Hau, Krista R Verhoeft, Peony H Y Poon, Seong-Keun Yoo, Jong-Yeon Shin, Sau-Dan Lee, Samantha W M Lun, Lin Jia, Anthony W H Chan, Jason Y K Chan, Paul B S Lai, Choi-Yi Fung, Suet-Ting Hung, Lin Wang, Ann Margaret V Chang, Simion I Chiosea, Matthew L Hedberg, Sai-Wah Tsao, Andrew C van Hasselt, Anthony T C Chan, Jennifer R Grandis, Peter S Hammerman, Kwok-Wai Lo
Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-κB pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28097795/impaired-n-linked-glycosylation-of-uptake-and-efflux-transporters-in-human-nonalcoholic-fatty-liver-disease
#12
John D Clarke, Petr Novak, April D Lake, Rhiannon N Hardwick, Nathan J Cherrington
BACKGROUND & AIMS: N-linked glycosylation of proteins is critical for proper protein folding and trafficking to the plasma membrane. Drug transporters are one class of proteins that have reduced function when glycosylation is impaired. N-linked glycosylation of plasma proteins has also been investigated as a biomarker for several liver diseases, including non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to assess the transcriptomic expression of genes involved in protein processing and glycosylation, and to determine the glycosylation status of key drug transporters during human NAFLD progression...
January 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28097745/immature-core-protein-of-hepatitis-c-virus-induces-an-unfolded-protein-response-through-inhibition-of-erad-l-in-a-yeast-model-system
#13
Shota Takahashi, Naoko Sato, Junichi Kikuchi, Hideaki Kakinuma, Jun Okawa, Yukiko Masuyama, Singo Iwasa, Hayato Irokawa, Gi-Wook Hwang, Akira Naganuma, Michinori Kohara, Shusuke Kuge
The structural protein Core of hepatitis C virus (HCV), a cytosolic protein, induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in hepatocytes, and is responsible for the pathogenesis of persistent HCV infection. Using yeast as a model system, we evaluated mechanisms underlying Core-induced interference of ER homeostasis and UPR, and found that UPR is induced by the immature Core (aa 1-191, Core191) but not by the mature Core (aa 1-177, Core177). Interestingly, Core191 inhibits both ERAD-L, a degradation system responsible for misfolded/unfolded proteins in the ER lumen, and ERAD-M, a degradation system responsible for proteins carrying a misfolded/unfolded region in the ER membrane...
January 18, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28097727/energetics-kinetics-and-pathway-of-snare-folding-and-assembly-revealed-by-optical-tweezers
#14
REVIEW
Yongli Zhang
Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are universal molecular engines that drive membrane fusion. Particularly, synaptic SNAREs mediate fast calcium-triggered fusion of neurotransmitter-containing vesicles with plasma membranes for synaptic transmission, the basis of all thought and action. During membrane fusion, complementary SNAREs located on two apposed membranes (often called t- and v-SNAREs) join together to assemble into a parallel four-helix bundle, releasing the energy to overcome the energy barrier for fusion...
January 18, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28097390/a-role-of-plc-pkc-dependent-pathway-in-glp-1-stimulated-insulin-secretion
#15
REVIEW
Makoto Shigeto, Chae Young Cha, Patrik Rorsman, Kohei Kaku
Glucagon-like peptide-1 (GLP-1) is an endogenous glucose-lowering hormone and GLP-1 receptor agonists are currently being used as antidiabetic drugs clinically. The canonical signalling pathway (including cAMP, Epac2, protein kinase A (PKA) and KATP channels) is almost universally accepted as the main mechanism of GLP-1-stimulated insulin secretion. This belief is based on in vitro studies that used nanomolar (1-100 nM) concentrations of GLP-1. Recently, it was found that the physiological concentrations (1-10 pM) of GLP-1 also stimulate insulin secretion from isolated islets, induce membrane depolarization and increase of intracellular [Ca(2+)] in isolated β cells/pancreatic islets...
January 17, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28097376/elemental-labelling-and-mass-spectrometry-for-the-specific-detection-of-sulfenic-acid-groups-in-model-peptides-a-proof-of-concept
#16
Mona Sharar, Essa M Saied, Mario C Rodriguez, Christoph Arenz, Maria Montes-Bayón, Michael W Linscheid
Oxidative transformation of cysteine thiol groups into different functional groups is considered a significant posttranslational modification of great importance in pathological and physiological processes. A cysteine sulfenic acid (SA) residue is the transient state for thiol group oxidation and it can react with free thiols to form disulfide bonds or can be further oxidized with reactive oxygen/reactive nitrogen species (ROS/RNS) to form sulfinic and sulfonic acids. The increase in ROS/RNS concentrations is correlated to age-related diseases such as cancer and Alzheimer's disease...
January 17, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28097063/interferon-%C3%AE-responses-to-plasmodium-falciparum-vaccine-candidate-antigens-decrease-in-the-absence-of-malaria-transmission
#17
Cyrus Ayieko, Bilha S Ogola, Lyticia Ochola, Gideon A M Ngwena, George Ayodo, James S Hodges, Gregory S Noland, Chandy C John
BACKGROUND: Malaria elimination campaigns are planned or active in many countries. The effects of malaria elimination on immune responses such as antigen-specific IFN- γ responses are not well characterized. METHODS: IFN- γ responses to the P. falciparum antigens circumsporozoite protein, liver stage antigen-1, thrombospondin-related adhesive protein, apical membrane antigen-1, MB2, and merozoite surface protein-1 were tested by ELISA in 243 individuals in highland Kenya in April 2008, October 2008, and April 2009, after a one-year period of interrupted malaria transmission from April 2007 to March 2008...
2017: PeerJ
https://www.readbyqxmd.com/read/28096658/anticancer-and-anti-inflammatory-activities-of-girinimbine-isolated-from-murraya-koenigii
#18
Venoos Iman, Syam Mohan, Siddig Ibrahim Abdelwahab, Hamed Karimian, Noraziah Nordin, Mehran Fadaeinasab, Mohamad Ibrahim Noordin, Suzita Mohd Noor
Therapy that directly targets apoptosis and/or inflammation could be highly effective for the treatment of cancer. Murraya koenigii is an edible herb that has been traditionally used for cancer treatment as well as inflammation. Here, we describe that girinimbine, a carbazole alkaloid isolated from M. koenigii, induced apoptosis and inhibited inflammation in vitro as well as in vivo. Induction of apoptosis in human colon cancer cells (HT-29) by girinimbine revealed decreased cell viability in HT-29, whereas there was no cytotoxic effect on normal colon cells...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28096469/super-resolution-visualization-of-caveolae-deformation-in-response-to-osmotic-stress
#19
Lu Yang, Suzanne Scarlata
Caveolae are protein dense plasma membrane domains structurally composed of caveolin -1 or -3 along with other proteins. Our previous studies have shown that caveolae enhance calcium signals generated through the Gαq/phospholipase Cβ signaling pathway, and that subjecting cells to hypo-osmotic stress reverses this enhancement. In this study, we have used super-resolution fluorescence microscopy supplemented by fluorescence correlation studies to determine the structural factors that underlie this behavior...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096465/sequences-within-the-c-terminus-of-the-metabotropic-glutamate-receptor-mglur5-are-responsible-for-inner-nuclear-membrane-localization
#20
Ismail Sergin, Yuh-Jiin I Jong, Steven K Harmon, Vikas Kumar, Karen L O'Malley
Traditionally G-protein coupled receptors (GPCR) are thought to be located on the cell surface where they transmit extracellular signals to the cytoplasm. However recent studies indicate that some GPCRs are also localized to various subcellular compartments such as the nucleus where they appear required for various biological functions. For example, the metabotropic glutamate receptor 5, mGluR5, is concentrated at the inner nuclear membrane (INM) where it mediates Ca2+ changes in the nucleoplasm by coupling with Gq/11...
January 17, 2017: Journal of Biological Chemistry
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