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https://www.readbyqxmd.com/read/28432265/artemida-trial-a-randomized-trial-of-efficacy-12-months-international-double-blind-actovegin-a-randomized-controlled-trial-to-assess-the-efficacy-of-actovegin-in-poststroke-cognitive-impairment
#1
Alla Guekht, Ingmar Skoog, Sally Edmundson, Vladimir Zakharov, Amos D Korczyn
BACKGROUND AND PURPOSE: Poststroke cognitive impairment is a debilitating consequence of stroke. The aim of this study was to assess whether Actovegin confers cognitive benefit in patients who have had an ischemic stroke. METHODS: This was a 12-month, parallel-group, randomized, multicenter, double-blind, placebo-controlled study. Eligible patients were ≥60 years of age with a Montreal Cognitive Assessment test score of ≤25 points. Patients were randomized into 2 groups within 1 week of acute supratentorial ischemic stroke in a 1:1 ratio: Actovegin (a deproteinized hemoderivative of calf blood, 2000 mg/d for ≤20 intravenous infusions followed by 1200 mg/d orally) or placebo for 6 months...
April 21, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28431013/dna-double-strand-break-repair-in-penaeus-monodon-is-predominantly-dependent-on-homologous-recombination
#2
Shikha Srivastava, Sumedha Dahal, Sharanya J Naidu, Deepika Anand, Vidya Gopalakrishnan, Rajendran Kooloth Valappil, Sathees C Raghavan
DNA double-strand breaks (DSBs) are mostly repaired by nonhomologous end joining (NHEJ) and homologous recombination (HR) in higher eukaryotes. In contrast, HR-mediated DSB repair is the major double-strand break repair pathway in lower order organisms such as bacteria and yeast. Penaeus monodon, commonly known as black tiger shrimp, is one of the economically important crustaceans facing large-scale mortality due to exposure to infectious diseases. The animals can also get exposed to chemical mutagens under the culture conditions as well as in wild...
April 1, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28423730/the-sclttaxbcr-abl-transgenic-mouse-model-closely-reflects-the-differential-effects-of-dasatinib-on-normal-and-malignant-hematopoiesis-in-chronic-phase-cml-patients
#3
Claudia Schubert, Nicolas Chatain, Till Braunschweig, Mirle Schemionek, Kristina Feldberg, Melanie Hoffmann, Olli Dufva, Satu Mustjoki, Tim H Brümmendorf, Steffen Koschmieder
The second generation tyrosine kinase inhibitor (TKI) dasatinib is a clinically approved drug for chronic myeloid leukemia (CML) as well as Ph+ acute lymphoblastic leukemia. In addition to its antileukemic effects, dasatinib was shown to impact on normal hematopoiesis and cells of the immune system.Due to the fact that the murine in vivo studies so far have not been performed in a chronic-phase CML model under steady-state conditions, our aim was to study the hematopoietic effects of dasatinib (20 mg/kg p.o...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423717/non-homologous-end-joining-induced-alterations-in-dna-methylation-a-source-of-permanent-epigenetic-change
#4
Brittany Allen, Antonio Pezone, Antonio Porcellini, Mark T Muller, Michal M Masternak
In addition to genetic mutations, epigenetic revision plays a major role in the development and progression of cancer; specifically, inappropriate DNA methylation or demethylation of CpG residues may alter the expression of genes that promote tumorigenesis. We hypothesize that DNA repair, specifically the repair of DNA double strand breaks (DSB) by Non-Homologous End Joining (NHEJ) may play a role in this process. Using a GFP reporter system inserted into the genome of HeLa cells, we are able to induce targeted DNA damage that enables the cells, after successfully undergoing NHEJ repair, to express WT GFP...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423708/targeting-the-centriolar-replication-factor-stil-synergizes-with-dna-damaging-agents-for-treatment-of-ovarian-cancer
#5
Noa Rabinowicz, Lingegowda S Mangala, Kevin R Brown, Cintia Checa-Rodriguez, Asher Castiel, Oren Moskovich, Giulia Zarfati, Luba Trakhtenbrot, Adva Levy-Barda, Dahai Jiang, Cristian Rodriguez-Aguayo, Sunila Pradeep, Yael van Praag, Gabriel Lopez-Berestein, Ahuvit David, Ilya Novikov, Pablo Huertas, Robert Rottapel, Anil K Sood, Shai Izraeli
Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422714/toll-like-receptor-3-as-an-immunotherapeutic-target-for-kras-mutated-colorectal-cancer
#6
Radhashree Maitra, Titto Augustine, Yitzchak Dayan, Carol Chandy, Matthew Coffey, Sanjay Goel
New therapeutic interventions are essential for improved management of patients with metastatic colorectal cancer (mCRC). This is especially critical for those patients whose tumors harbor a mutation in the KRAS oncogene (40-45% of all patients). This patient cohort is excluded from receiving anti-EGFR monoclonal antibodies that have added a significant therapeutic benefit for KRAS wild type CRC patients. Reovirus, a double stranded (ds) RNA virus is in clinical development for patients with chemotherapy refractory KRAS mutated tumors...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418654/a-robust-and-accurate-tight-binding-quantum-chemical-method-for-structures-vibrational-frequencies-and-non-covalent-interactions-of-large-molecular-systems-parameterized-for-all-spd-block-elements-z-1-86
#7
Stefan Grimme, Christoph Bannwarth, Philip Shushkov
We propose a novel, special purpose semi-empirical tight binding (TB) method for the calculation of structures, vibrational frequencies, and non-covalent interactions of large molecular systems with 1000 or more atoms. The functional form of the method is related to the self-consistent density functional TB scheme and mostly avoids element-pair specific parameters. The parameterization covers all spd-block elements and the lanthanides up to Z=86 using reference data at the hybrid density functional theory level...
April 18, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28418082/non-digestible-carbohydrates-supplementation-increases-mir-32-expression-in-the-healthy-human-colorectal-epithelium-a-randomized-controlled-trial
#8
Fiona C Malcomson, Naomi D Willis, Iain McCallum, Long Xie, Bart Lagerwaard, Seamus Kelly, Michael Bradburn, Nigel J Belshaw, Ian T Johnson, John C Mathers
Colorectal cancer (CRC) risk is modulated by diet and there is convincing evidence of reduced risk with higher non-digestible carbohydrates (NDCs) consumption. Resistant starch (RS), a NDC, positively modulates the expression of oncogenic microRNAs, suggesting that this could be a mechanism through which NDCs protect against CRC. The present study aimed to investigate the effects of supplementation with two NDCs, RS and polydextrose (PD), on microRNA expression in the macroscopically-normal human rectal epithelium using samples from the DISC Study, a randomised, double-blind, placebo-controlled dietary intervention...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28416668/ambiguity-in-the-causes-for-decadal-trends-in-atmospheric-methane-and-hydroxyl
#9
Alexander J Turner, Christian Frankenberg, Paul O Wennberg, Daniel J Jacob
Methane is the second strongest anthropogenic greenhouse gas and its atmospheric burden has more than doubled since 1850. Methane concentrations stabilized in the early 2000s and began increasing again in 2007. Neither the stabilization nor the recent growth are well understood, as evidenced by multiple competing hypotheses in recent literature. Here we use a multispecies two-box model inversion to jointly constrain 36 y of methane sources and sinks, using ground-based measurements of methane, methyl chloroform, and the C(13)/C(12) ratio in atmospheric methane (δ(13)CH4) from 1983 through 2015...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28414320/inhibition-of-dna2-nuclease-as-a-therapeutic-strategy-targeting-replication-stress-in-cancer-cells
#10
S Kumar, X Peng, J Daley, L Yang, J Shen, N Nguyen, G Bae, H Niu, Y Peng, H-J Hsieh, L Wang, C Rao, C C Stephan, P Sung, G Ira, G Peng
Replication stress is a characteristic feature of cancer cells, which is resulted from sustained proliferative signaling induced by activation of oncogenes or loss of tumor suppressors. In cancer cells, oncogene-induced replication stress manifests as replication-associated lesions, predominantly double-strand DNA breaks (DSBs). An essential mechanism utilized by cells to repair replication-associated DSBs is homologous recombination (HR). In order to overcome replication stress and survive, cancer cells often require enhanced HR repair capacity...
April 17, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28410749/efficacy-and-safety-of-k-877-a-novel-selective-peroxisome-proliferator-activated-receptor-%C3%AE-modulator-spparm%C3%AE-in-combination-with-statin-treatment-two-randomised-double-blind-placebo-controlled-clinical-trials-in-patients-with-dyslipidaemia
#11
Hidenori Arai, Shizuya Yamashita, Koutaro Yokote, Eiichi Araki, Hideki Suganami, Shun Ishibashi
BACKGROUND AND AIMS: Substantial residual cardiovascular risks remain despite intensive statin treatment. Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins. K-877 (pemafibrate) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy. The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment...
March 24, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28401753/self-assembly-of-complex-multi-metal-nanostructures-from-perforated-lamellar-block-copolymer-thin-films
#12
Seung Keun Cha, Gil Yong Lee, Jeong Ho Mun, Hyeong Min Jin, Chang Yun Moon, Jun Soo Kim, Kwang Ho Kim, Seong-Jun Jeong, Sang Ouk Kim
We introduce a facile and effective fabrication of complex multi-metallic nanostructures by means of block copolymer self-assembly. Two- and three-dimensional complex nanostructures, such as 'nanomesh', and 'double layered nanomeshes', and 'surface parallel cylinders on nanomesh', can be achieved by employing the self-assembly of perforated lamellar morphology in block copolymer thin films. Simultaneous integration of various metallic elements, including Pt, Au, and Co, into the self-assembled morphologies generates multi-metal complex nanostructures with highly interconnected morphology and large surface...
April 12, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28397787/correlated-mutation-in-the-evolution-of-catalysis-in-uracil-dna-glycosylase-superfamily
#13
Bo Xia, Yinling Liu, Jose Guevara, Jing Li, Celeste Jilich, Ye Yang, Liangjiang Wang, Brian N Dominy, Weiguo Cao
Enzymes in Uracil DNA glycosylase (UDG) superfamily are essential for the removal of uracil. Family 4 UDGa is a robust uracil DNA glycosylase that only acts on double-stranded and single-stranded uracil-containing DNA. Based on mutational, kinetic and modeling analyses, a catalytic mechanism involving leaving group stabilization by H155 in motif 2 and water coordination by N89 in motif 3 is proposed. Mutual Information analysis identifies a complexed correlated mutation network including a strong correlation in the EG doublet in motif 1 of family 4 UDGa and in the QD doublet in motif 1 of family 1 UNG...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28397068/amniotic-mesenchymal-stem-cells-decrease-a%C3%AE-deposition-and-improve-memory-in-app-ps1-transgenic-mice
#14
Xiao-Yu Zheng, Qian-Quan Wan, Chuan-Yi Zheng, Hong-Long Zhou, Xing-Yu Dong, Qing-Shan Deng, Hui Yao, Qiang Fu, Mou Gao, Zhong-Jie Yan, Shan-Shan Wang, Yu You, Jun Lv, Xiang-Yu Wang, Ke-En Chen, Mao-Ying Zhang, Ru-Xiang Xu
Transplantation of human amniotic mesenchymal stem cells (hAM-MSCs) seems to be a promising strategy for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, the clinical therapeutic effects of hAM-MSCs and their mechanisms of action in AD remain to be determined. Here, we used amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice to evaluate the effects of hAM-MSC transplantation on AD-related neuropathology and cognitive dysfunction. We found that hAM-MSC transplantation into the hippocampus dramatically reduced amyloid-β peptide (Aβ) deposition and rescued spatial learning and memory deficits in APP/PS1 mice...
April 10, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28394905/use-of-a-machine-learning-framework-to-predict-substance-use-disorder-treatment-success
#15
Laura Acion, Diana Kelmansky, Mark van der Laan, Ethan Sahker, DeShauna Jones, Stephan Arndt
There are several methods for building prediction models. The wealth of currently available modeling techniques usually forces the researcher to judge, a priori, what will likely be the best method. Super learning (SL) is a methodology that facilitates this decision by combining all identified prediction algorithms pertinent for a particular prediction problem. SL generates a final model that is at least as good as any of the other models considered for predicting the outcome. The overarching aim of this work is to introduce SL to analysts and practitioners...
2017: PloS One
https://www.readbyqxmd.com/read/28393891/progressive-slowdown-prevention-of-cellular-senescence-by-cd9-targeted-delivery-of-rapamycin-using-lactose-wrapped-calcium-carbonate-nanoparticles
#16
Raj Kumar Thapa, Hanh Thuy Nguyen, Jee-Heon Jeong, Jae Ryong Kim, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Cellular senescence, a state of irreversible growth arrest and altered cell function, causes aging-related diseases. Hence, treatment modalities that could target aging cells would provide a robust therapeutic avenue. Herein, for the first time, we utilized CD9 receptors (overexpressed in senescent cells) for nanoparticle targeting in addition to the inherent β-galactosidase activity. In our study, CD9 monoclonal antibody-conjugated lactose-wrapped calcium carbonate nanoparticles loaded with rapamycin (CD9-Lac/CaCO3/Rapa) were prepared for targeted rapamycin delivery to senescent cells...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28391912/effects-of-atorvastatin-on-biomarkers-of-immune-activation-inflammation-and-lipids-in-virologically-suppressed-human-immunodeficiency-virus-1-infected-individuals-with-low-density-lipoprotein-cholesterol-130%C3%A2-mg-dl-aids-clinical-trials-group-study-a5275
#17
Daniel E Nixon, Ronald J Bosch, Ellen S Chan, Nicholas T Funderburg, Sally Hodder, Jordan E Lake, Michael M Lederman, Karin L Klingman, Judith A Aberg
BACKGROUND: Persistent immune activation and inflammation in virologically suppressed human immunodeficiency virus (HIV) infection are linked to excess cardiovascular risk. OBJECTIVE: To evaluate atorvastatin as a strategy to reduce cardiovascular risk. METHODS: A5275 was a multicenter, prospective, randomized, double-blind, placebo-controlled, cross-over pilot study of atorvastatin (10 mg/day for 4 weeks then 20 mg/day for 16 weeks) with a planned enrollment of 97 HIV-infected participants ≥18 years old, receiving boosted protease inhibitor-based antiretroviral therapy for ≥6 months, with plasma HIV-1 RNAs below limits of quantification ≥180 days, and fasting low-density lipoprotein (LDL) cholesterol ≥70 and <130 mg/dL...
January 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28391763/detection-by-real-time-pcr-and-pyrosequencing-of-the-cry1ab-and-cry1ac-genes-introduced-in-gm-constructs
#18
Frederic Debode, Erik Janssen, Claude Bragard, Gilbert Berben
The presence of GMOs in food and feed is mainly detected by the use of targets focusing on promoters and terminators. As some genes are frequently used in GM construction, they also constitute excellent screening elements and their use is increasing. In this work, we propose a new target for the detection of cry1Ab and cry1Ac genes by real-time PCR and pyrosequencing. The specificity, sensitivity and robustness of the real-time PCR method were tested following the recommendations of international guidelines and the method met the expected performance criteria...
April 10, 2017: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
https://www.readbyqxmd.com/read/28388136/analysis-of-large-anisotropy-spin-recoupling-pulses-for-distance-measurement-under-magic-angle-spinning-nmr-shows-the-superiority-and-robustness-of-a-phase-modulated-saturation-pulse
#19
E Nimerovsky, M Makrinich, A Goldbourt
The distance between a spin one-half and an attached spin possessing a large anisotropy can be obtained using different dipolar recoupling sequences that are based on the rotational-echo double resonance technique under magic-angle spinning solid-state NMR. The general difference between these sequences with respect to the coupled spin is the set of pulses applied in order to drive this spin out of equilibrium, thereby recoupling the dipolar interaction. Since complete inversion is practically not possible due to the coupled-spin anisotropy, using one or another pulse depends on the experimental and spin conditions: the spinning speed, the strength of the radio frequency field, the size of the anisotropic interaction (quadrupolar or chemical shiftanisotropy couplings), the offset, and the accuracy of setting the magic angle...
March 28, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28383247/implementation-of-activated-ion-electron-transfer-dissociation-on-a-quadrupole-orbitrap-linear-ion-trap-hybrid-mass-spectrometer
#20
Nicholas M Riley, Michael S Westphall, Alexander S Hebert, Joshua J Coon
Using concurrent IR photoactivation during electron transfer dissociation (ETD) reactions, i.e., activated ion ETD (AI-ETD), significantly increases dissociation efficiency resulting in improved overall performance. Here we describe the first implementation of AI-ETD on a quadrupole-Orbitrap-quadrupole linear ion trap (QLT) hybrid MS system (Orbitrap Fusion Lumos) and demonstrate the substantial benefits it offers for peptide characterization. First, we show that AI-ETD can be implemented in a straightforward manner by fastening the laser and guiding optics to the instrument chassis itself, making alignment with the trapping volume of the QLT simple and robust...
April 17, 2017: Analytical Chemistry
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