Read by QxMD icon Read

protein model

Mohammad T Mazhab-Jafari, Alexis Rohou, Carla Schmidt, Stephanie A Bueler, Samir Benlekbir, Carol V Robinson, John L Rubinstein
Vacuolar-type ATPases (V-ATPases) are ATP-powered proton pumps involved in processes such as endocytosis, lysosomal degradation, secondary transport, TOR signalling, and osteoclast and kidney function. ATP hydrolysis in the soluble catalytic V1 region drives proton translocation through the membrane-embedded VO region via rotation of a rotor subcomplex. Variability in the structure of the intact enzyme has prevented construction of an atomic model for the membrane-embedded motor of any rotary ATPase. We induced dissociation and auto-inhibition of the V1 and VO regions of the V-ATPase by starving the yeast Saccharomyces cerevisiae, allowing us to obtain a ~3...
October 24, 2016: Nature
Mijung Kwon, Jae-Hoon Kim, Yevangelina Rybak, Alex Luna, Chel Hun Choi, Joon-Yong Chung, Stephen M Hewitt, Asha Adem, Elizabeth Tubridy, Juan Lin, Steven K Libutti
Filamin A interacting protein 1-like (FILIP1L) is an inhibitor of the canonical WNT pathway. WNT/β-catenin signaling and its downstream pathway, epithelial-to-mesenchymal transition (EMT), play a key role in ovarian cancer metastasis and chemoresistance. To study the clinical implications of FILIP1L in regulating the WNT/β-catenin pathway, the expression of FILIP1L, β-catenin, SNAIL and SLUG was analyzed by immunohistochemistry on tissue microarrays of 369 ovarian samples ranging from normal to metastatic...
October 20, 2016: Oncotarget
Alexandre Chlenski, Marija Dobratic, Helen R Salwen, Mark Applebaum, Lisa J Guerrero, Ryan Miller, Gillian DeWane, Elena Solomaha, Jeremy D Marks, Susan L Cohn
SPARC is a matrix protein that mediates interactions between cells and the microenvironment. In cancer, SPARC may either promote or inhibit tumor growth depending upon the tumor type. In neuroblastoma, SPARC is expressed in the stromal Schwannian cells and functions as a tumor suppressor. Here, we developed a novel in vivo model of stroma-rich neuroblastoma using non-tumorigenic SHEP cells with modulated levels of SPARC, mixed with tumorigenic KCNR cells. Tumors with stroma-derived SPARC displayed suppressed growth, inhibited angiogenesis and increased lipid accumulation...
October 20, 2016: Oncotarget
Juke S Lolkema, Dirk Jan Slotboom
The recently determined crystal structure of the bacterial Na(+)-citrate symporter CitS provides unexpected structural and mechanistic insights. The protein has a fold that has not been seen in other proteins, but the oligomeric state, domain organization and proposed transport mechanism strongly resemble those of the sodium-dicarboxylate symporter vcINDY, and the putative exporters YdaH and MtrF, thus hinting at convergence in structure and function. CitS and the related proteins are predicted to translocate their substrates by an elevator-like mechanism, in which a compact transport domain slides up and down through the membrane while the dimerization domain is stably anchored...
October 21, 2016: Current Opinion in Structural Biology
Nelly Rahkonen, Aki Stubb, Maia Malonzo, Sanna Edelman, Maheswara Reddy Emani, Elisa Närvä, Harri Lähdesmäki, Hannele Ruohola-Baker, Riitta Lahesmaa, Riikka Lund
MicroRNAs (miRNA) are central regulators of diverse biological processes and are important in the regulation of stem cell self-renewal. One of the widely studied miRNA-protein regulators is the Lin28-Let-7 pair. In this study, we demonstrate that contrary to the well-established models of mouse ES cells (mESC) and transformed human cancer cells, the pluripotent state of human ES cells (hESC) involves expression of mature Let-7 family miRNAs with concurrent expression of all LIN28 proteins. We show that mature Let-7 miRNAs are regulated during hESC differentiation and have opposite expression profile with LIN28B...
September 24, 2016: Stem Cell Research
Hoon-Seong Choi, Dae-Hyun Roh, Seo-Yeon Yoon, Soon-Gu Kwon, Sheu-Ran Choi, Suk-Yun Kang, Ji-Young Moon, Ho-Jae Han, Hyun-Woo Kim, Alvin J Beitz, Jang-Hern Lee
Although we have recently demonstrated that carrageenan-induced inflammation upregulates the expression of spinal interleukin (IL)-1β, which inhibits spinal astrocyte activation and results in the delayed development of Mirror-Image Pain (MIP), little is known regarding the mechanisms that underlie how spinal IL-1β inhibits the astrocyte activation. In this study, we examined the effect of spinal IL-1β on astrocyte gap junctions (GJ) and the development of MIP. Following unilateral carrageenan (CA) injection, mechanical allodynia (MA) was evaluated at various time points...
October 20, 2016: Experimental Neurology
Thomas Schmidt, Alan J Situ, Tobias S Ulmer
The solvation of membrane proteins by both lipids and water makes their membrane immersion difficult to predict and the choice of a membrane mimic challenging. To characterize protein-lipid contacts and bicelle membrane mimics, we examined protein-lipid cross-relaxation of integrin αIIb and β3(A711P) transmembrane helices in isotropic phospholipid bicelles (q=0.5 and 0.7). Long-chain bicelle lipids dominated contacts with central helix segments, whereas both short- and long-chain lipids contacted the terminal turns of each helix in corroboration of the mixed bicelle model...
October 24, 2016: Journal of Physical Chemistry Letters
Ying Tang, Aiqin Chen, Yu Chen, Lixia Guo, Hengfen Dai, Yang Huang, Qianqian Chen, Chun Lin
BACKGROUND: The pathogenesis of multiple chronic visceral pain syndromes, such as irritable bowel syndrome (IBS), is not well known, and as a result current therapies are ineffective. The objective of this study was to investigate the effect of spinal protein kinase M zeta (PKMζ) on visceral pain sensitivity in rats with IBS to better understand the pathogenesis and investigate the effect of zeta inhibitory peptide (ZIP) as a therapy for chronic visceral pain. METHODS: Visceral hypersensitivity rats were produced by neonatal maternal separation (NMS)...
2016: PloS One
Hideki Ushiku, Keishi Yamashita, Hiroshi Kawamata, Mina Waraya, Hiroshi Katoh, Keigo Yokoi, Toshimichi Tanaka, Satoru Ishii, Nobuyuki Nishizawa, Mariko Kikuchi, Naoko Minatani, Ken Kojo, Hiroshi Tajima, Ryo Nishiyama, Takashi Kaizu, Yusuke Kumamoto, Masahiko Watanabe
OBJECTIVES: We have identified homeobox-only protein (HOPX) as a tumor suppressor gene in various human cancer, and its expression was reduced by promoter DNA hypermethylation. Homeobox-only protein is strongly expressed on pancreatic islet cells; however, clinical relevance of HOPX expression has remained elusive in pancreatic neuroendocrine tumor (pNET). METHODS: We investigated 36 patients with pNET who undertook surgical resection between 1988 and 2012 for HOPX expression and DNA methylation to reveal its clinical significance...
October 2016: Pancreas
Andreas Gollner, Dorothea Rudolph, Heribert Arnhof, Markus Bauer, Sophia Maria Blake, Guido Boehmelt, Xiao-Ling Cockcroft, Georg Dahmann, Peter Ettmayer, Thomas Gerstberger, Jale Karolyi-Oezguer, Dirk Kessler, Christiane Kofink, Juergen Ramharter, Jörg Rinnenthal, Alexander Savchenko, Renate Schnitzer, Harald Weinstabl, Ulrike Weyer-Czernilofsky, Tobias Wunberg, Darryl B McConnell
Scaffold modification based on Wang´s pioneering MDM2-p53 inhibitors led to novel, chemically stable spiro-oxindole compounds bearing a spiro[3H-indole-3,2´-pyrrolidin]-2(1H)-one scaffold that are not prone to epimerization as observed for the initial spiro[3H-indole-3,3´-pyrrolidin]-2(1H)-one scaffold. Further structure based optimization inspired by natural product architectures led to a complex fused ring system ideally suited to bind to the MDM2 protein and to interrupt its protein-protein interaction (PPI) with TP53...
October 24, 2016: Journal of Medicinal Chemistry
Karen Druart, Julien Bigot, Edouard Audit, Thomas Simonson
Multistate protein design explores sidechain mutations with the backbone allowed to sample a small, predetermined library of conformations. To achieve Boltzmann sampling of sequences and conformations, we use a hybrid Monte Carlo (MC) scheme: a trial hop between backbone models is followed by a short MC segment where sidechain rotamers adjust to the new backbone, before applying a Metropolis-like acceptance test. The theoretical form and a practical approximation for the acceptance test are derived. We then compute backbone conformational free energies for two SH2 and SH3 proteins using different routes and protocols, and verify that for simple test problems, the free energy behaves like a state function, a hallmark of Boltzmann sampling...
October 24, 2016: Journal of Chemical Theory and Computation
Michael S Samuel, Nicola Rath, Siti F Masre, Sarah T Boyle, David A Greenhalgh, Marina Kochetkova, Sheila Bryson, David Stevenson, Michael F Olson
The serine/threonine kinases ROCK1 and ROCK2 are central mediators of actomyosin contractile force generation that act downstream of the RhoA small GTP-binding protein. As a result, they have key roles in regulating cell morphology and proliferation, and have been implicated in numerous pathological conditions and diseases including hypertension and cancer. Here we describe the generation of a gene-targeted mouse line that enables CRE-inducible expression of a conditionally-active fusion between the ROCK2 kinase domain and the hormone-binding domain of a mutated estrogen receptor (ROCK2:ER)...
October 24, 2016: Genesis: the Journal of Genetics and Development
José Alcaraz-Quiles, Esther Titos, Mireia Casulleras, Marco Pavesi, Cristina López-Vicario, Bibiana Rius, Aritz Lopategi, Andrea de Gottardi, Ivo Graziadei, Henning Gronbaek, Pere Ginès, Mauro Bernardi, Vicente Arroyo, Joan Clària
: Acute-on-chronic liver failure (ACLF) in cirrhosis is an increasingly recognized syndrome characterized by acute decompensation, organ failure(s) and high short-term mortality. Recent findings suggest that an over-exuberant systemic inflammation plays a primary role in ACLF progression. In this study, we examined whether genetic factors shape systemic immune responses in patients with decompensated cirrhosis. Six single nucleotide polymorphisms (SNPs) in inflammation-related genes (IL-1β: rs1143623, IL-1ra: rs4251961, IL-10: rs1800871, SOCS3: rs4969170, NOD2: rs3135500 and CMKLR1: rs1878022) were genotyped in 279 cirrhotic patients with (n=178) and without (n=101) ACLF from the CANONIC study of the CLIF consortium...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Y-F Wang, S Zhang, X-Q Li, Y Wang
OBJECTIVE: To investigate Long non-coding RNA HULC (HULC) expression in cervical cancer and to evaluate its clinical significance. PATIENTS AND METHODS: HULC expression in 244 pairs of human cervical cancer and adjacent normal tissues was detected by real-time quantitative RT-PCR assay. The correlation between HULC and clinicopathological factors was also evaluated. The clinical and prognostic significance of HULC expression was analyzed statistically by Kaplan-Meier estimate and Cox regression model...
October 2016: European Review for Medical and Pharmacological Sciences
Kathryn M Kingsmore, Daniel K Logsdon, Desiree H Floyd, Shayn M Peirce, Benjamin W Purow, Jennifer M Munson
Glioblastoma (GBM) prognosis remains dismal due in part to the invasiveness of GBM cells. Interstitial fluid flow (IFF) has been shown to increase invasion of glioma cells in vitro through the CXCR4 receptor interacting with autologous, pericellular gradients of CXCL12 (autologous chemotaxis) or through the CD44 receptor interactions with the extracellular matrix (hyaluronan-mediated mechanotransduction). These mechanisms have not been examined together and thus we hypothesized that both mechanisms contribute to invasion in populations of cancer cells...
October 24, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Kelly D Moynihan, Cary F Opel, Gregory L Szeto, Alice Tzeng, Eric F Zhu, Jesse M Engreitz, Robert T Williams, Kavya Rakhra, Michael H Zhang, Adrienne M Rothschilds, Sudha Kumari, Ryan L Kelly, Byron H Kwan, Wuhbet Abraham, Kevin Hu, Naveen K Mehta, Monique J Kauke, Heikyung Suh, Jennifer R Cochran, Douglas A Lauffenburger, K Dane Wittrup, Darrell J Irvine
Checkpoint blockade with antibodies specific for cytotoxic T lymphocyte-associated protein (CTLA)-4 or programmed cell death 1 (PDCD1; also known as PD-1) elicits durable tumor regression in metastatic cancer, but these dramatic responses are confined to a minority of patients. This suboptimal outcome is probably due in part to the complex network of immunosuppressive pathways present in advanced tumors, which are unlikely to be overcome by intervention at a single signaling checkpoint. Here we describe a combination immunotherapy that recruits a variety of innate and adaptive immune cells to eliminate large tumor burdens in syngeneic tumor models and a genetically engineered mouse model of melanoma; to our knowledge tumors of this size have not previously been curable by treatments relying on endogenous immunity...
October 24, 2016: Nature Medicine
J N Sheets, M Iwanicki, J F Liu, B E Howitt, M S Hirsch, J A A Gubbels, R Drapkin, K A Egland
The cause of death among the majority of epithelial ovarian cancer (EOC) patients involves passive dissemination of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into adjacent organs. Thus, it is important to identify the factors that mediate EOC metastasis and implantation, including clearance of the mesothelium. Sushi domain containing 2 (SUSD2) encodes a type I transmembrane protein containing several functional domains inherent to adhesion molecules. Immunohistochemical analysis determined the presence of SUSD2 in several subtypes of EOC, with the strongest staining observed in high-grade serous ovarian carcinomas (HGSOCs)...
October 24, 2016: Oncogenesis
Giorgina B Piccoli, Federica Ventrella, Irene Capizzi, Federica N Vigotti, Elena Mongilardi, Giorgio Grassi, Valentina Loi, Gianfranca Cabiddu, Paolo Avagnina, Elisabetta Versino
Low-protein diets (LPDs) are often considered as contraindicated in diabetic patients, and are seldom studied. The aim of this observational study was to provide new data on this issue. It involved 149 diabetic and 300 non-diabetic patients who followed a LPD, with a personalized approach aimed at moderate protein restriction (0.6 g/day). Survival analysis was performed according to Kaplan-Meier, and multivariate analysis with Cox model. Diabetic versus non-diabetic patients were of similar age (median 70 years) and creatinine levels at the start of the diet (2...
October 21, 2016: Nutrients
Marcus von Nordheim, Michel Boinay, Remo Leisi, Christoph Kempf, Carlos Ros
Cutthroat trout virus (CTV) is a non-pathogenic fish virus belonging to the Hepeviridae family, and it is distantly related to hepatitis E virus (HEV). Here, we report the development of an efficient cell culture system where CTV can consistently replicate to titers never observed before with a hepevirus. By using the rainbow trout gill (RTGill-W1) cell line, CTV reaches 10(10) geq/mL intracellularly and 10⁸ geq/mL extracellularly within 5-6 days in culture. We additionally established a qPCR system to investigate CTV infectivity, and developed a specific antibody directed against the viral capsid protein encoded by ORF2...
October 20, 2016: Viruses
Yichen Du, Ramak Esfandi, William G Willmore, Apollinaire Tsopmo
The purpose of this study was to determine, for the first time, antioxidant activities of seven peptides (P1-P7) derived from hydrolysis of oat proteins in a cellular model. In the oxygen radical absorbance capacity (ORAC) assay, it was found that P2 had the highest radical scavenging activity (0.67 ± 0.02 µM Trolox equivalent (TE)/µM peptide) followed by P5, P3, P6, P4, P1, and P7 whose activities were between 0.14-0.61 µM TE/µM). In the hepatic HepG2 cells, none of the peptides was cytotoxic at 20-300 µM...
October 20, 2016: Antioxidants (Basel, Switzerland)
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"