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https://www.readbyqxmd.com/read/28637178/the-at04a-vaccine-against-proprotein-convertase-subtilisin-kexin-type-9-reduces-total-cholesterol-vascular-inflammation-and-atherosclerosis-in-apoe-3leiden-cetp-mice
#1
Christine Landlinger, Marianne G Pouwer, Claudia Juno, José W A van der Hoorn, Elsbet J Pieterman, J Wouter Jukema, Guenther Staffler, Hans M G Princen, Gergana Galabova
Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hypercholesterolaemia and atherosclerosis. PCSK9 binds to the low density lipoprotein receptor and enhances its degradation, which leads to the reduced clearance of low density lipoprotein cholesterol (LDLc) and a higher risk of atherosclerosis. In this study, the AT04A anti-PCSK9 vaccine was evaluated for its therapeutic potential in ameliorating or even preventing coronary heart disease in the atherogenic APOE*3Leiden...
June 19, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28636351/heats-of-formation-of-medium-size-organic-compounds-from-contemporary-electronic-structure-methods
#2
Yury Minenkov, Heng Wang, Zhandong Wang, S Mani Sarathy, Luigi Cavallo
Computational electronic structure calculations are routinely undertaken to predict thermodynamic properties of the various species. However, the application of highly accurate wave function theory methods, such as the "gold standard" coupled cluster approach including single, double and partly triple excitations in perturbative fashion, CCSD(T), to large molecules is limited due to high computational cost. In this work, the promising domain based local pair natural orbital coupled cluster approach, DLPNO-CCSD(T), has been tested to reproduce 113 accurate formation enthalpies of medium-size molecules (few dozens heavy atoms) important for bio- and combustion chemistry via the reaction based Feller-Peterson-Dixon approach...
June 21, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28635997/a-spin-column-free-approach-to-sodium-hydroxide-based-glycan-permethylation
#3
Yueming Hu, Chad R Borges
Glycan permethylation was introduced as a tool to facilitate the study of glycans in 1903. Since that time, permethylation procedures have been continually modified to improve permethylation efficiency and qualitative applicability. Typically, however, either laborious preparation steps or cumbersome and uneconomical spin columns have been needed to obtain decent permethylation yields on small glycan samples. Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS...
June 21, 2017: Analyst
https://www.readbyqxmd.com/read/28629733/an-optimized-protocol-for-the-generation-and-functional-analysis-of-human-mast-cells-from-cd34-enriched-cell-populations
#4
Yuzhi Yin, Yun Bai, Ana Olivera, Avanti Desai, Dean D Metcalfe
The culture of mast cells from human tissues such a cord blood, peripheral blood or bone marrow aspirates has advanced our understanding of human mast cells (huMC) degranulation, mediator production and response to pharmacologic agents. However, existing methods for huMC culture tend to be laborious and expensive. Combining technical approaches from several of these protocols, we designed a simplified and more cost effective approach to the culture of mast cells from human cell populations including peripheral blood and cryopreserved cells from lymphocytapheresis...
June 16, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28629522/erythropoietin-stem-cell-factor-and-cancer-cell-migration
#5
Maria J Vazquez-Mellado, Victor Monjaras-Embriz, Leticia Rocha-Zavaleta
Cell migration of normal cells is tightly regulated. However, tumor cells are exposed to a modified microenvironment that promotes cell migration. Invasive migration of tumor cells is stimulated by receptor tyrosine kinases (RTKs) and is regulated by growth factors. Erythropoietin (Epo) is a glycoprotein hormone that regulates erythropoiesis and is also known to be a potent chemotactic agent that induces cell migration by binding to its receptor (EpoR). Expression of EpoR has been documented in tumor cells, and the potential of Epo to induce cell migration has been explored...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28628742/acceleration-of-semiempirical-qm-mm-methods-through-mpi-hybrid-mpi-openmp-and-scf-accelerator-implementations
#6
Pedro Ojeda-May, Kwangho Nam
The present manuscript describes the strategy and implementation of scalable and efficient semiempirical (SE) QM/MM methods in CHARMM. The serial version of the code was first profiled to identify routines that require parallelization. Afterwards, the code was parallelized and accelerated with three approaches. The first approach was the parallelization of the entire QM/MM routines, including the Fock matrix diagonalization routines, using the CHARMM MPI machinery. In the second approach, two different self-consistent field (SCF) energy convergence accelerators were implemented using density and Fock matrices as targets for their extrapolations in the SCF procedure...
June 19, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28628628/transcriptional-mechanisms-associated-with-seed-dormancy-and-dormancy-loss-in-the-gibberellin-insensitive-sly1-2-mutant-of-arabidopsis-thaliana
#7
Sven K Nelson, Camille M Steber
While widespread transcriptome changes were previously observed with seed dormancy loss, this study specifically characterized transcriptional changes associated with the increased seed dormancy and dormancy loss of the gibberellin (GA) hormone-insensitive sleepy1-2 (sly1-2) mutant. The SLY1 gene encodes the F-box subunit of an SCF E3 ubiquitin ligase needed for GA-triggered proteolysis of DELLA repressors of seed germination. DELLA overaccumulation in sly1-2 seeds leads to increased dormancy that can be rescued without DELLA protein destruction either by overexpression of the GA receptor, GA-INSENSITIVE DWARF1b (GID1b-OE) (74% germination) or by extended dry after-ripening (11 months, 51% germination)...
2017: PloS One
https://www.readbyqxmd.com/read/28627603/role-of-stem-cell-factor-in-the-regulation-of-icc-proliferation-and-detrusor-contraction-in-rats-with-an-underactive-bladder
#8
Jianli Feng, Jin Gao, Shan Zhou, Yuanfeng Liu, Yu Zhong, Yong Shu, Ming Sen Meng, Jiaqiang Yan, Danning Sun, Qiang Fang, Daodong Sun
Stem cell factor (SCF) is critical in regulating the proliferation, differentiation and function of the interstitial cells of Cajal (ICCs), which are closely associated with smooth muscle dysfunction. The present study aimed to examine the effect of SCF on ICC proliferation and detrusor contraction in rats with an underactive bladder. Sprague‑Dawley rats were divided into four groups comprising control, control+SCF, detrusor underactivity (DU), and DU+SCF groups. The ICC count was determined using immunofluorescence; serum levels of SCF were determined using an enzyme‑linked immunosorbent assay; mRNA and protein levels of c‑kit and SCF in tissues were assessed using reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627566/theoretical-study-of-one-electron-oxidized-salen-complexes-of-group-7-mn-iii-tc-iii-and-re-iii-and-group-10-metals-ni-ii-pd-ii-and-pt-ii-with-the-3d-rism-gmc-qdpt-method-localized-vs-delocalized-ground-and-excited-states-in-solution
#9
Shinji Aono, Masayuki Nakagaki, Shigeyoshi Sakaki
One-electron oxidized salen complexes of Mn(iii) and Ni(ii) were recently reported to be unique mixed-valence compounds. Their electronic structures are sensitive to the salen ligand and solvation. We systematically investigated a series of one-electron oxidized salen complexes of group 7 metals (Mn(iii), Tc(iii), and Re(iii)) and their group 10 analogues (Ni(ii), Pd(ii), and Pt(ii)) using the general multi-configuration reference quasi-degenerate perturbation theory (GMC-QDPT) which was combined with the three-dimensional reference interaction site model self-consistent field theory (3D-RISM-SCF) to incorporate the solvation effect...
June 19, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28626366/current-developments-in-mobilization-of-hematopoietic-stem-and-progenitor-cells-and-their-interaction-with-niches-in-bone-marrow
#10
REVIEW
Rudolf Richter, Wolfgang Forssmann, Reinhard Henschler
The clinical application of hematopoietic stem and progenitor cells (HSPCs) has evolved from a highly experimental stage in the 1980s to a currently clinically established treatment for more than 20,000 patients annually who suffer from hematological malignancies and other severe diseases. Studies in numerous murine models have demonstrated that HSPCs reside in distinct niches within the bone marrow environment. Whereas transplanted HSPCs travel through the bloodstream and home to sites of hematopoiesis, HSPCs can be mobilized from these niches into the blood either physiologically or induced by pharmaceutical drugs...
June 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28619593/on-the-halt-of-spontaneous-capillary-flows-in-diverging-open-channels
#11
J Berthier, K A Brakke, D Gosselin, F Navarro, N Belgacem, D Chaussy, E Berthier
Due to their compactness and independence of exterior energy sources, capillary microsystems are increasingly used in many different scientific domains, from biotechnology to medicine and biology, chemistry, energy and space. Obtaining a capillary flow depends on channel geometry and contact angle. A general condition for the establishment of a spontaneous capillary flow in a uniform cross section channel has already been derived from Gibbs free energy. In this work, we consider spontaneous capillary flows (SCF) in diverging open rectangular channels and suspended channels, and we show that they do not flow indefinitely but stop at some location in the channel...
June 12, 2017: Medical Engineering & Physics
https://www.readbyqxmd.com/read/28618277/fate-and-adverse-effects-of-hexabromocyclododecane-diastereoisomers-hbcdds-in-a-soil-ryegrass-pot-system
#12
Hongkai Zhu, Hongwen Sun, Yiming Yao, Fei Wang, Yanwei Zhang, Xiaowei Liu
This study explored the fate and adverse effects of 3 main hexabromocyclododecane diastereoisomers (α-, β-, and γ-HBCDDs) in a soil pot system planted with ryegrass (Lolium perenne L.) using a short-term (8 weeks) experiment. At the end of the experiment, soil urease activity in planted spiked soil increased and catalase activity decreased; while there was no obvious change in sucrase and peroxidase activities. HBCDDs mainly accumulated in the root of ryegrass, with root concentration factors (RCF) in the range of 1...
May 31, 2017: Chemosphere
https://www.readbyqxmd.com/read/28614300/pten-counteracts-fbxl2-to-promote-ip3r3-and-ca-2-mediated-apoptosis-limiting-tumour-growth
#13
Shafi Kuchay, Carlotta Giorgi, Daniele Simoneschi, Julia Pagan, Sonia Missiroli, Anita Saraf, Laurence Florens, Michael P Washburn, Ana Collazo-Lorduy, Mireia Castillo-Martin, Carlos Cordon-Cardo, Said M Sebti, Paolo Pinton, Michele Pagano
In response to environmental cues that promote IP3 (inositol 1,4,5-trisphosphate) generation, IP3 receptors (IP3Rs) located on the endoplasmic reticulum allow the 'quasisynaptical' feeding of calcium to the mitochondria to promote oxidative phosphorylation. However, persistent Ca(2+) release results in mitochondrial Ca(2+) overload and consequent apoptosis. Among the three mammalian IP3Rs, IP3R3 appears to be the major player in Ca(2+)-dependent apoptosis. Here we show that the F-box protein FBXL2 (the receptor subunit of one of 69 human SCF (SKP1, CUL1, F-box protein) ubiquitin ligase complexes) binds IP3R3 and targets it for ubiquitin-, p97- and proteasome-mediated degradation to limit Ca(2+) influx into mitochondria...
June 14, 2017: Nature
https://www.readbyqxmd.com/read/28609481/the-ubiquitin-conjugating-enzyme-cdc34-is-essential-for-cytokinesis-in-contrast-to-putative-subunits-of-a-scf-complex-in-trypanosoma-brucei
#14
Federico Rojas, Joanna Koszela, Jacqueline Búa, Briardo Llorente, Richard Burchmore, Manfred Auer, Jeremy C Mottram, María Teresa Téllez-Iñón
The ubiquitin-proteasome system is a post-translational regulatory pathway for controlling protein stability and activity that underlies many fundamental cellular processes, including cell cycle progression. Target proteins are tagged with ubiquitin molecules through the action of an enzymatic cascade composed of E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, and E3 ubiquitin ligases. One of the E3 ligases known to be responsible for the ubiquitination of cell cycle regulators in eukaryotes is the SKP1-CUL1-F-box complex (SCFC)...
June 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28604067/resveratrol-improves-cell-cycle-arrest-in-chronic-prostatitis-rats-by-c-kit-scf-suppression
#15
Yi He, Huizhi Zeng, Yang Yu, Jiashu Zhang, Xiaona Zeng, Fengtao Gong, Qi Liu, Bo Yang
Chronic prostatitis (CP) with complex pathogenesis is difficult for treatment. c-kit has been associated with the control of cell proliferation of prostate cells. This study aims to evaluate the role of resveratrol, an activator of Sirt1, in regulating the expression of c-kit in CP and investigate the consequent effects on cell cycle. Rat model of CP was established through subcutaneous injections of diphtheria-pertussis-tetanus vaccine and subsequently treated with resveratrol. Hematoxylin and eosin staining was performed to identify the histopathological changes in prostates...
June 12, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28594334/self-consistent-hybrid-functionals-for-solids-a-fully-automated-implementation
#16
Alessandro Erba
A fully-automated algorithm for the determination of the system-specific optimal fraction of exact exchange in self-consistent hybrid functionals of the density-functional-theory is illustrated, as implemented into the public CRYSTAL program. The exchange fraction of this new class of functionals is self-consistently updated proportionally to the inverse of the dielectric response of the system within an iterative procedure [Phys. Rev. B 89, 195112 (2014)]. Each iteration of the present scheme, in turn, implies convergence of a self-consistent-field (SCF) and a coupled-perturbed-Hartree-Fock/Kohn-Sham (CPHF/KS) procedure...
June 8, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/28589936/variation-in-auxin-sensing-guides-aux-iaa-transcriptional-repressor-ubiquitylation-and-destruction
#17
Martin Winkler, Michael Niemeyer, Antje Hellmuth, Philipp Janitza, Gideon Christ, Sophia L Samodelov, Verona Wilde, Petra Majovsky, Marco Trujillo, Matias D Zurbriggen, Wolfgang Hoehenwarter, Marcel Quint, Luz Irina A Calderón Villalobos
Auxin is a small molecule morphogen that bridges SCF(TIR1/AFB)-AUX/IAA co-receptor interactions leading to ubiquitylation and proteasome-dependent degradation of AUX/IAA transcriptional repressors. Here, we systematically dissect auxin sensing by SCF(TIR1)-IAA6 and SCF(TIR1)-IAA19 co-receptor complexes, and assess IAA6/IAA19 ubiquitylation in vitro and IAA6/IAA19 degradation in vivo. We show that TIR1-IAA19 and TIR1-IAA6 have distinct auxin affinities that correlate with ubiquitylation and turnover dynamics of the AUX/IAA...
June 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28587355/morphological-and-functional-changes-in-bone-marrow-mesenchymal-stem-cells-in-rats-with-heart-failure
#18
Xiuli Wang, Chunmei Li, Haibin Gong
The changes in bone marrow-derived mesenchymal stem cells (BMSCs), in terms of cell morphology and protein expression in rats with heart failure, were studied. Pressure overload chronic heart failure rat model was induced with partial constriction of the abdominal aorta. BMSCs from the model and the sham operation groups were isolated and cultured (cell density, 10(8) cells/l), and supernatant was collected after 72 h. Enzyme-linked immunosorbent assay was used to measure HGF, IGF-1, PDGF, SCF, FGF and VEGF levels in the supernatant...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28583475/ubiquitin-c-terminal-hydrolase-l3-promotes-interferon-antiviral-activity-by-stabilizing-type-i-interferon-receptor
#19
Peng Zhao, Tingting Guo, Liping Qian, Xiaofang Wang, Yukang Yuan, Qiao Cheng, Yibo Zuo, Jin Liu, Ying Miao, Qian Feng, Liting Zhang, Shuhua Wu, Hui Zheng
Type-I interferons (IFN-I) are important antiviral drugs which are widely used in clinical therapy of diverse viral infections. However, understanding the detailed mechanisms for IFN-I antiviral signaling remains a major challenge, and may provide novel targets for IFN-based antiviral therapy. So far, the roles of deubiquitinases (DUBs) in regulating IFN-I antiviral activity are still largely unexplored. Here, we find that Ubiquitin C-terminal hydrolase-L3 (UCHL3) plays an important role in regulating type I-interferon (IFN-I) mediated antiviral response...
June 3, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28580775/persistent-distention-of-colon-damages-interstitial-cells-of-cajal-through-ca-2-erk-ap-1-mir-34c-scf-deregulation
#20
Shu Yang, Fang Dong, Dandan Li, Haimei Sun, Bo Wu, Tingyi Sun, Yaxi Wang, Ping Shen, Fengqing Ji, Deshan Zhou
Gastrointestinal motility disorders (GMDs) are attributed to loss of interstitial cells of Cajal (ICC), whose survival and function are deeply dependent on the activation of KIT/SCF signalling. Based on the facts that gastrointestinal distention is common in GMD patients and SCF produced by smooth muscle cells (SMCs) is usually decreased before ICC loss, we considered a possible contribution of persistent gastrointestinal distention/stretch to SCF deficiency. In this study, chronic colonic distention mouse model, diabetic gastrointestinal paresis mouse model, cultured mouse colonic SMCs and colon specimens from Hirschsprung's disease patients were used...
June 4, 2017: Journal of Cellular and Molecular Medicine
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