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https://www.readbyqxmd.com/read/29342448/generation-of-induced-pluripotent-stem-cell-line-cssi002-a-2851-from-a-patient-with-juvenile-huntington-disease
#1
Jessica Rosati, Eris Bidollari, Giovannina Rotundo, Daniela Ferrari, Barbara Torres, Laura Bernardini, Federica Consoli, Alessandro De Luca, Iolanda Santimone, Giuseppe Lamorte, Ferdinando Squitieri, Angelo Luigi Vescovi
Huntington Disease (HD) is an autosomal dominant disorder characterized by motor, cognitive and behavioral features caused by a CAG expansion in the HTT gene beyond 35 repeats. The juvenile form (JHD) may begin before the age of 20years and is associated with expanded alleles as long as 60 or more CAG repeats. In this study, induced pluripotent stem cells were generated from skin fibroblasts of a 8-year-old child carrying a large size mutation of 84 CAG repeats in the HTT gene. HD appeared at age 3 with mixed psychiatric (i...
January 9, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29342447/design-synthesis-and-anticancer-studies-of-novel-aminobenzazolyl-pyrimidines-as-tyrosine-kinase-inhibitors
#2
Rupesh Chikhale, Sonali Thorat, Rajan Kumar Choudhary, Nikhil Gadewal, Pramod Khedekar
Abnormal signalling from the Protein tyrosine kinases (PTKs) like receptor tyrosine kinases and intracellular tyrosine kinases can lead to diseases such as cancer especially non-small cell lung cancer, chronic myeloid leukaemia and gastrointestinal stromal tumours. Various Protein tyrosine kinase inhibitors are available but face poor bioavailability, severe toxicities and recent cases of drug-resistant cancers prompts for development of better drug molecules. In this study we report the design and development of a novel Protein Tyrosine Kinase (PTK) inhibitor on the basis of pharmacophore modelling...
January 4, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29342421/the-relation-between-plasma-%C3%AE-synuclein-level-and-clinical-symptoms-or-signs-of-parkinson-s-disease
#3
Michalina Malec-Litwinowicz, Andrzej Plewka, Danuta Plewka, Edyta Bogunia, Michał Morek, Andrzej Szczudlik, Michał Szubiga, Monika Rudzińska-Bar
INTRODUCTION: Parkinson disease (PD) is the common neurodegenerative disease. α-Synuclein (ASN), main aggregating protein in neural cells of CNS in PD, was found in peripheral fluids. Testing ASN in plasma is potential test for diagnose PD, but previous studies are controversial. The aim of this study was to investigate if plasma ASN level may be a valuable biomarker, is the level of plasma ASN concentration different in various motor subtypes of diseases, is there a relation between the level of plasma ASN and the severity of motor symptoms...
November 21, 2017: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29342418/functional-characterization-of-9-cyp2a13-allelic-variants-by-assessment-of-nicotine-c-oxidation-and-coumarin-7-hydroxylation
#4
Masaki Kumondai, Hiroki Hosono, Masamitsu Maekawa, Hiroaki Yamaguchi, Nariyasu Mano, Akifumi Oda, Noriyasu Hirasawa, Masahiro Hiratsuka
Cytochrome P450 2A13 (CYP2A13) is responsible for the metabolism of chemical compounds such as nicotine, coumarin, and tobacco-specific nitrosamine. Several of these compounds have been recognized as procarcinogens activated by CYP2A13. We recently showed that CYP2A13*2 contributes to inter-individual variations observed in bladder cancer susceptibility because CYP2A13*2 might cause a decrease in enzymatic activity. Other CYP2A13 allelic variants may also affect cancer susceptibility. In this study, we performed an in vitro analysis of the wild-type enzyme (CYP2A13...
November 22, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29342381/long-term-follow-up-of-monoclonal-gammopathy-of-undetermined-significance
#5
Robert A Kyle, Dirk R Larson, Terry M Therneau, Angela Dispenzieri, Shaji Kumar, James R Cerhan, S Vincent Rajkumar
Background Monoclonal gammopathy of undetermined significance (MGUS) occurs in approximately 3% of persons 50 years of age or older. Methods We studied 1384 patients who were residing in southeastern Minnesota and in whom MGUS was diagnosed at the Mayo Clinic in the period from 1960 through 1994; the median follow-up was 34.1 years (range, 0.0 to 43.6). The primary end point was progression to multiple myeloma or another plasma-cell or lymphoid disorder. Results During 14,130 person-years of follow-up, MGUS progressed in 147 patients (11%), a rate that was 6...
January 18, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29342370/fgf8-signaling-alters-the-osteogenic-cell-fate-in-the-hard-palate
#6
J Xu, Z Huang, W Wang, X Tan, H Li, Y Zhang, W Tian, T Hu, Y P Chen
Fibroblast growth factor (FGF) signaling has been implicated in the regulation of osteogenesis in both intramembranous and endochondral ossifications. In the developing palate, the anterior bony palate forms by direct differentiation of cranial neural crest (CNC)-derived mesenchymal cells, but the signals that regulate the osteogenic cell fate in the developing palate remain unclear. In the present study, we investigated the potential role of FGF signaling in osteogenic fate determination of the palatal mesenchymal cells...
January 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29342363/differential-effects-of-inhibitory-g-protein-isoforms-on-g-protein-gated-inwardly-rectifying-k-currents-in-adult-murine-atria
#7
Muriel Nobles, David Montaigne, Sonia Sebastian, Lutz Birnbaumer, Andrew Tinker
G-protein gated inwardly rectifying K+ (GIRK) channels are the major inwardly rectifying K+ currents in cardiac atrial myocytes and an important determinant of atrial electrophysiology. Inhibitory G-protein alpha subunits can both mediate activation via acetylcholine but can also supress basal currents in the absence of agonist. We studied this phenomenon using whole cell patch clamping in murine atria from mice with global genetic deletion of Gαi2, combined deletion of Gαi1/Gαi3 and littermate controls...
January 17, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29342359/semiconducting-photothermal-nanoagonist-for-remote-controlled-specific-cancer-therapy
#8
Xu Zhen, Chen Xie, Yuyan Jiang, Xiangzhao Ai, Bengang Xing, Kanyi Pu
Nanomedicines have shown success in cancer therapy, but the pharmacological actions of most nanomedicine are often nonspecific to cancer cells because of utilization of the therapeutic agents that induce cell apoptosis from inner organelles. We herein report the development of semiconducting photothermal nanoagonists that can remotely and specifically initiate the apoptosis of cancer cells from cell membrane. The organic nanoagonists comprise semiconducting polymer nanoparticles (SPNs) and capsaicin (Cap) as the photothermally-responsive nanocarrier and the agonist for activation of transient receptor potential cation channel subfamily V member 1 (TRPV1), respectively...
January 17, 2018: Nano Letters
https://www.readbyqxmd.com/read/29342309/prognostic-power-of-a-tumor-differentiation-gene-signature-for-bladder-urothelial-carcinomas
#9
Qianxing Mo, Fotis Nikolos, Fengju Chen, Zoe Tramel, Yu-Cheng Lee, Kazukuni Hayashi, Jing Xiao, Jianjun Shen, Keith Syson Chan
Background: Muscle-invasive bladder cancers (MIBCs) cause approximately 150 000 deaths per year worldwide. Survival for MIBC patients is heterogeneous, with no clinically validated molecular markers that predict clinical outcome. Non-MIBCs (NMIBCs) generally have favorable outcome; however, a portion progress to MIBC. Hence, development of a prognostic tool that can guide decision-making is crucial for improving clinical management of bladder urothelial carcinomas. Methods: Tumor grade is defined by pathologic evaluation of tumor cell differentiation, and it often associates with clinical outcome...
January 12, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29342297/an-exact-goodness-of-fit-test-based-on-the-occupancy-problems-to-study-zero-inflation-and-zero-deflation-in-biological-dosimetry-data
#10
Amanda Fernández-Fontelo, Pedro Puig, Elizabeth A Ainsbury, Manuel Higueras
The goal in biological dosimetry is to estimate the dose of radiation that a suspected irradiated individual has received. For that, the analysis of aberrations (most commonly dicentric chromosome aberrations) in scored cells is performed and dose response calibration curves are built. In whole body irradiation (WBI) with X- and gamma-rays, the number of aberrations in samples is properly described by the Poisson distribution, although in partial body irradiation (PBI) the excess of zeros provided by the non-irradiated cells leads, for instance, to the Zero-Inflated Poisson distribution...
January 12, 2018: Radiation Protection Dosimetry
https://www.readbyqxmd.com/read/29342275/hot-spot-kif5a-mutations-cause-familial-als
#11
David Brenner, Rüstem Yilmaz, Kathrin Müller, Torsten Grehl, Susanne Petri, Thomas Meyer, Julian Grosskreutz, Patrick Weydt, Wolfgang Ruf, Christoph Neuwirth, Markus Weber, Susana Pinto, Kristl G Claeys, Berthold Schrank, Berit Jordan, Antje Knehr, Kornelia Günther, Annemarie Hübers, Daniel Zeller, Christian Kubisch, Sibylle Jablonka, Michael Sendtner, Thomas Klopstock, Mamede de Carvalho, Anne Sperfeld, Guntram Borck, Alexander E Volk, Johannes Dorst, Joachim Weis, Markus Otto, Joachim Schuster, Kelly Del Tredici, Heiko Braak, Karin M Danzer, Axel Freischmidt, Thomas Meitinger, Tim M Strom, Albert C Ludolph, Peter M Andersen, Jochen H Weishaupt
Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations in KIF5A are also a cause of amyotrophic lateral sclerosis...
January 12, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29342230/metformin-as-an-anti-cancer-agent-actions-and-mechanisms-targeting-cancer-stem-cells
#12
Nipun Saini, Xiaohe Yang
Metformin, a first line medication for type II diabetes, initially entered the spotlight as a promising anti-cancer agent due to epidemiologic reports that found reduced cancer risk and improved clinical outcomes in diabetic patients taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Recently, the anti-cancer potential of metformin has gained increasing interest due to its inhibitory effects on cancer stem cells (CSCs), which are associated with tumor metastasis, drug resistance, and relapse...
October 7, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29342223/development-of-a-job-exposure-matrix-for-noise-in-the-swedish-soft-tissue-paper-industry
#13
Richard Lee Neitzel, Marianne Andersson, Helena Eriksson, Kjell Torén, Eva Andersson
Objectives: Noise exposure is a common occupational hazard, but has not been sufficiently characterized in paper mills. We developed a job-exposure matrix (JEM) for noise exposure for use in estimating exposures among Swedish soft tissue paper mill workers. Methods: We used a combination of area and personal dosimetry noise exposure measurements made at four soft tissue paper mills by industry and research staff between 1977 and 2013 to estimate noise exposures by department, location, and job title...
December 16, 2017: Annals of Work Exposures and Health
https://www.readbyqxmd.com/read/29342216/in-vitro-activity-of-novel-glycopolymer-against-clinical-isolates-of-multidrug-resistant-staphylococcus-aureus
#14
Vidya P Narayanaswamy, Scott A Giatpaiboon, John Uhrig, Paul Orwin, William Wiesmann, Shenda M Baker, Stacy M Townsend
The incidence of multidrug-resistant (MDR) organisms, including methicillin-resistant Staphylococcus aureus (MRSA), is a serious threat to public health. Progress in developing new therapeutics is being outpaced by antibiotic resistance development, and alternative agents that rapidly permeabilize bacteria hold tremendous potential for treating MDR infections. A new class of glycopolymers includes polycationic poly-N (acetyl, arginyl) glucosamine (PAAG) is under development as an alternative to traditional antibiotic strategies to treat MRSA infections...
2018: PloS One
https://www.readbyqxmd.com/read/29342203/biological-pathways-underlying-the-association-of-red-cell-distribution-width-and-adverse-clinical-outcome-results-of-a-prospective-cohort-study
#15
Giedre Zurauskaite, Marc Meier, Alaadin Voegeli, Daniel Koch, Sebastian Haubitz, Alexander Kutz, Luca Bernasconi, Andreas Huber, Mario Bargetzi, Beat Mueller, Philipp Schuetz
BACKGROUND: Red cell distribution width (RDW) predicts disease outcome in several patient populations, but its prognostic value in addition to other disease parameters in unselected medical inpatients remains unclear. Our aim was to investigate the association of admission RDW levels and mortality adjusted for several disease pathways in unselected medical patients from a previous multicenter study. METHODS: We included consecutive adult, medical patients at the time point of hospital admission through the emergency department into this observational, cohort study...
2018: PloS One
https://www.readbyqxmd.com/read/29342200/inhibiting-tgf-beta-signaling-preserves-the-function-of-highly-activated-in-vitro-expanded-natural-killer-cells-in-aml-and-colon-cancer-models
#16
Folashade Otegbeye, Evelyn Ojo, Stephen Moreton, Nathan Mackowski, Dean A Lee, Marcos de Lima, David N Wald
Natural killer cells harnessed from healthy individuals can be expanded ex vivo using various platforms to produce large doses for adoptive transfer into cancer patients. During such expansion, NK cells are increasingly activated and more efficient at killing cancer cells. Adoptive transfer however introduces these activated cells into a highly immunosuppressive tumor microenvironment mediated in part by excessive transforming growth factor beta (TGF-beta) from both cancer cells and their surrounding stroma...
2018: PloS One
https://www.readbyqxmd.com/read/29342186/doxorubicin-provoked-increase-of-mitotic-activity-and-concomitant-drain-of-g0-pool-in-therapy-resistant-be-2-c-neuroblastoma
#17
Isabell Hultman, Linnea Haeggblom, Ingvild Rognmo, Josefin Jansson Edqvist, Evelina Blomberg, Rouknuddin Ali, Lottie Phillips, Bengt Sandstedt, Per Kogner, Shahrzad Shirazi Fard, Lars Ährlund-Richter
In this study chemotherapy response in neuroblastoma (NB) was assessed for the first time in a transplantation model comprising non-malignant human embryonic microenvironment of pluripotent stem cell teratoma (PSCT) derived from diploid bona fide hESC. Two NB cell lines with known high-risk phenotypes; the multi-resistant BE(2)-C and the drug sensitive IMR-32, were transplanted to the PSCT model and the tumour growth was exposed to single or repeated treatments with doxorubicin, and thereafter evaluated for cell death, apoptosis, and proliferation...
2018: PloS One
https://www.readbyqxmd.com/read/29342181/optimization-of-mneongreen-for-homo-sapiens-increases-its-fluorescent-intensity-in-mammalian-cells
#18
Emiko Tanida-Miyake, Masato Koike, Yasuo Uchiyama, Isei Tanida
Green fluorescent protein (GFP) is tremendously useful for investigating many cellular and intracellular events. The monomeric GFP mNeonGreen is about 3- to 5-times brighter than GFP and monomeric enhanced GFP and shows high photostability. The maturation half-time of mNeonGreen is about 3-fold faster than that of monomeric enhanced GFP. However, the cDNA sequence encoding mNeonGreen contains some codons that are rarely used in Homo sapiens. For better expression of mNeonGreen in human cells, we synthesized a human-optimized cDNA encoding mNeonGreen and generated an expression plasmid for humanized mNeonGreen under the control of the cytomegalovirus promoter...
2018: PloS One
https://www.readbyqxmd.com/read/29342180/increased-prevalence-of-pregnancy-and-comparative-risk-of-program-attrition-among-individuals-starting-hiv-treatment-in-east-africa
#19
Charles B Holmes, Constantin T Yiannoutsos, Batya Elul, Elizabeth Bukusi, John Ssali, Andrew Kambugu, Beverly S Musick, Craig Cohen, Carolyn Williams, Lameck Diero, Nancy Padian, Kara K Wools-Kaloustian
BACKGROUND: The World Health Organization now recommends initiating all pregnant women on life-long antiretroviral therapy (ART), yet there is limited information about the characteristics and program outcomes of pregnant women already on ART in Africa. Our hypothesis was that pregnant women comprised an increasing proportion of those starting ART, and that sub-groups of these women were at higher risk for program attrition. METHODS AND FINDINGS: We used the International Epidemiology Databases to Evaluate AIDS- East Africa (IeDEA-EA) to conduct a retrospective cohort study including HIV care and treatment programs in Kenya, Uganda, and Tanzania...
2018: PloS One
https://www.readbyqxmd.com/read/29342177/a-new-fluorescent-dye-accumulation-assay-for-parallel-measurements-of-the-abcg2-abcb1-and-abcc1-multidrug-transporter-functions
#20
Edit Szabó, Dóra Türk, Ágnes Telbisz, Nóra Kucsma, Tamás Horváth, Gergely Szakács, László Homolya, Balázs Sarkadi, György Várady
ABC multidrug transporters are key players in cancer multidrug resistance and in general xenobiotic elimination, thus their functional assays provide important tools for research and diagnostic applications. In this study we have examined the potential interactions of three key human ABC multidrug transporters with PhenGreen diacetate (PGD), a cell permeable fluorescent metal ion indicator. The non-fluorescent, hydrophobic PGD rapidly enters the cells and, after cleavage by cellular esterases, in the absence of quenching metal ions, PhenGreen (PG) becomes highly fluorescent...
2018: PloS One
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