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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/29342436/iris-melanoma-outcomes-based-on-the-american-joint-committee-on-cancer-classification-eighth-edition-in-432-patients
#3
Carol L Shields, Maura Di Nicola, Vladislav P Bekerman, Swathi Kaliki, Carolina Alarcon, Enzo Fulco, Jerry A Shields
PURPOSE: The American Joint Committee on Cancer (AJCC) classification was updated to the eighth edition in January 2017, providing staging for iris melanoma. This study evaluated outcomes of iris melanoma per the AJCC classification, eighth edition. DESIGN: Retrospective case series. PARTICIPANTS: Four hundred thirty-two patients with iris melanoma. METHODS: Management including tumor resection, plaque radiotherapy, or enucleation...
January 13, 2018: Ophthalmology
https://www.readbyqxmd.com/read/29342415/lysosomes-targeting-imaging-and-anticancer-properties-of-novel-bis-naphthalimide-derivatives
#4
Rui-Xue Rong, Shan-Shan Wang, Xuan Liu, Ren-Feng Li, Ke-Rang Wang, Zhi-Ran Cao, Xiao-Liu Li
A series of novel N,N-bis(3-aminopropyl)methylamine bridged bis-naphthalimide derivatives NI1-NI8 containing saturated nitrogenous heterocycles were designed and synthesized, their cytotoxic activities against Hela, MCF-7, A549 and MGC-803 cells were investigated, Compounds NI1-NI4 modified with piperidine and piperazine exhibited good and selective cytotoxic activity, for instance, compounds NI1 and NI4 showed potent cytotoxic activity against Hela cells and MGC-803 cells with the IC50 values of 2.89, 060, 2...
January 9, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29342361/high-speed-spectroscopic-transient-absorption-imaging-of-defects-in-graphene
#5
Kai-Chih Huang, Jeremy McCall, Pu Wang, Chien-Sheng Liao, Gregory Eakins, Ji-Xin Cheng, Chen Yang
Graphene grain boundaries (GBs) and other nano-defects can deteriorate electronic properties. Here, using transient absorption (TA) microscopy, we directly visualized GBs by TA intensity increase due to change in density of state. We also observed a faster decay due to defect-accelerated carrier relaxation in the GB area. By line-illumination and parallel detection, we increased the TA intensity imaging speed to 1,000 frames per second, which is 6 orders of magnitude faster than Raman microscopy. Combined with a resonant optical delay tuner which scans a 5...
January 17, 2018: Nano Letters
https://www.readbyqxmd.com/read/29342329/when-the-gold-standard-is-not-always-golden-the-value-of-invasive-hemodynamic-assessment-to-overcome-the-pitfalls-of-echocardiography-in-challenging-cases-of-mitral-stenosis
#6
Yenal Harper, Salem A Salem, Shadwan Alsafwah, Santhosh Koshy, Nadish Garg
Mitral stenosis is a uncommon valvular lesion in the developed countries. Noninvasive evaluation is the first-line modality for assessment of mitral stenosis, however the noninvasive methods may have limitations in certain cases. Invasive hemodynamics can be used as adjunct tool for assessment of mitral stenosis in such difficult cases. Mitral valve using three-dimensional planimetry is a promising technique for assessment of mitral stenosis.
January 2018: Echocardiography
https://www.readbyqxmd.com/read/29342281/phenotypic-analysis-of-hiv-1-e157q-integrase-polymorphism-and-impact-on-virological-outcome-in-patients-initiating-an-integrase-inhibitor-based-regimen
#7
Charlotte Charpentier, Isabelle Malet, Elisabeth Andre-Garnier, Alexandre Storto, Laurence Bocket, Corinne Amiel, Laurence Morand-Joubert, Camille Tumiotto, Thuy Nguyen, Anne Maillard, Audrey Rodallec, Marie Leoz, Brigitte Montes, Véronique Schneider, Jean-Christophe Plantier, Julia Dina, Coralie Pallier, Audrey Mirand, Catherine Roussel, Anne Signori-Schmuck, Stéphanie Raymond, Vincent Calvez, Constance Delaugerre, Anne-Geneviève Marcelin, Diane Descamps
Objectives: To assess the phenotypic susceptibility of the E157Q polymorphism in HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q-mutated virus initiating an IN inhibitor (INI)-based regimen. Methods: This was a multicentre study assessing IN sequences from INI-naive patients among 17 French HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG contexts were assessed in a recombinant phenotypic assay. Results: Prevalence of the E157Q polymorphism was 2...
January 12, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29342275/hot-spot-kif5a-mutations-cause-familial-als
#8
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/29342254/distinctive-desmoplastic-3d-morphology-associated-with-brafv600e-in-papillary-thyroid-cancers
#9
M Tarabichi, A Antoniou, S Le Pennec, D Gacquer, N de Saint Aubain, L Craciun, T Cielen, I Laios, D Larsimont, G Andry, J E Dumont, C Maenhaut, V Detours
Context: Although 60% of papillary thyroid carcinomas are BRAFV600E mutant (PTCV600E), the higher aggressiveness of these cancers is still debated. Objective: In PTCV600E we aimed to further characterize the extent of the stroma and its activation, the 3D tumor-stroma interface, and the proliferation rates of tumor and stromal fibroblasts. Design: We analyzed exomes, trancriptomes and images of 364 PTC from The Cancer Genome Atlas (TCGA), including 211 PTCV600E; stained 22 independent PTC for BRAFV600E and Ki67; sequenced the exomes and stained BRAFV600E in 5 primary tumor blocks and 4 nodal metastases from one PTCV600E patient; and reconstructed the 3D volumes of one tumor and one metastatic blocks at histological resolution...
January 12, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29342241/ipat-intelligent-prediction-and-association-tool-for-genomic-research
#10
Chunpeng James Chen, Zhiwu Zhang
Summary: The ultimate goal of genomic research is to effectively predict phenotypes from genotypes so that medical management can improve human health and molecular breeding can increase agricultural production. Genomic prediction or selection (GS) plays a complementary role to genome-wide association studies (GWAS), which is the primary method to identify genes underlying phenotypes. Unfortunately, most computing tools cannot perform data analyses for both GWAS and GS. Furthermore, the majority of these tools are executed through a command-line interface (CLI), which requires programming skills...
January 11, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29342230/metformin-as-an-anti-cancer-agent-actions-and-mechanisms-targeting-cancer-stem-cells
#11
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/29342221/genotype-by-environment-interactions-affecting-heterosis-in-maize
#12
Zhi Li, Lisa Coffey, Jacob Garfin, Nathan D Miller, Michael R White, Edgar P Spalding, Natalia de Leon, Shawn M Kaeppler, Patrick S Schnable, Nathan M Springer, Candice N Hirsch
The environment can influence heterosis, the phenomena in which the offspring of two inbred parents exhibits phenotypic performance beyond the inbred parents for specific traits. In this study we measured 25 traits in a set of 47 maize hybrids and their inbred parents grown in 16 different environments with varying levels of average productivity. By quantifying 25 vegetative and reproductive traits across the life cycle we were able to analyze interactions between the environment and multiple distinct instances of heterosis...
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
#13
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/29342198/three-dimensional-printing-model-improves-morphological-understanding-in-acetabular-fracture-learning-a-multicenter-randomized-controlled-study
#14
Zhenfei Huang, Wenhao Song, Yaoshen Zhang, Qiang Zhang, Dongsheng Zhou, Xi Zhou, Yu He
Conventional education results in unsatisfactory morphological understanding of acetabular fractures due to lack of three-dimensional (3D) details and tactile feedback of real fractures. Virtual reality (VR) and 3D printing (3DP) techniques are widely applied in teaching. The purpose of this study was to identify the effect of physical model (PM), VR and 3DP models in education of morphological understanding of acetabular fractures. 141 students were invited to participate in this study. Participants were equally and randomly assigned to the PM, VR and 3DP learning groups...
2018: PloS One
https://www.readbyqxmd.com/read/29342193/analysis-of-copy-number-loss-of-the-erbb4-receptor-tyrosine-kinase-in-glioblastoma
#15
DeAnalisa C Jones, Adriana Scanteianu, Matthew DiStefano, Mehdi Bouhaddou, Marc R Birtwistle
Current treatments for glioblastoma multiforme (GBM)-an aggressive form of brain cancer-are minimally effective and yield a median survival of 14.6 months and a two-year survival rate of 30%. Given the severity of GBM and the limitations of its treatment, there is a need for the discovery of novel drug targets for GBM and more personalized treatment approaches based on the characteristics of an individual's tumor. Most receptor tyrosine kinases-such as EGFR-act as oncogenes, but publicly available data from the Cancer Cell Line Encyclopedia (CCLE) indicates copy number loss in the ERBB4 RTK gene across dozens of GBM cell lines, suggesting a potential tumor suppressor role...
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
#16
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/29342163/doxylamine-pyridoxine-for-nausea-and-vomiting-of-pregnancy-randomized-placebo-controlled-trial-prespecified-analyses-and-reanalysis
#17
Navindra Persaud, Christopher Meaney, Khaled El-Emam, Rahim Moineddin, Kevin Thorpe
BACKGROUND: Doxylamine-pyridoxine is recommended as a first line treatment for nausea and vomiting during pregnancy and it is commonly prescribed. We re-analysed the findings of a previously reported superiority trial of doxylamine-pyridoxine for the treatment of nausea and vomiting during pregnancy using the clinical study report obtained from Health Canada. METHODS AND FINDINGS: We re-analysed individual level data for a parallel arm randomized controlled trial that was conducted in six outpatient obstetrical practices in the United States...
2018: PloS One
https://www.readbyqxmd.com/read/29342139/structure-and-mutagenesis-reveal-essential-capsid-protein-interactions-for-kshv-replication
#18
Xinghong Dai, Danyang Gong, Hanyoung Lim, Jonathan Jih, Ting-Ting Wu, Ren Sun, Z Hong Zhou
Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, a cancer that commonly affects patients with AIDS and which is endemic in sub-Saharan Africa. The KSHV capsid is highly pressurized by its double-stranded DNA genome, as are the capsids of the eight other human herpesviruses. Capsid assembly and genome packaging of herpesviruses are prone to interruption and can therefore be targeted for the structure-guided development of antiviral agents. However, herpesvirus capsids-comprising nearly 3,000 proteins and over 1,300 Å in diameter-present a formidable challenge to atomic structure determination and functional mapping of molecular interactions...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342125/induction-of-pro-apoptotic-endoplasmic-reticulum-stress-in-multiple-myeloma-cells-by-neo214-perillyl-alcohol-conjugated-to-rolipram
#19
Thomas C Chen, Nymph Chan, Shirin Labib, Jiali Yu, Hee-Yeon Cho, Florence M Hofman, Axel H Schönthal
Despite the introduction of new therapies for multiple myeloma (MM), many patients are still dying from this disease and novel treatments are urgently needed. We have designed a novel hybrid molecule, called NEO214, that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were investigated in a panel of MM cell lines. We found that NEO214 effectively killed MM cells in vitro with a potency that was over an order of magnitude stronger than that of its individual components, either alone or in combination...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29342111/cytotoxicity-evaluation-of-turmeric-extract-incorporated-oil-in-water-nanoemulsion
#20
Hee Jeong Yoon, Xiaowei Zhang, Min Gyeong Kang, Gyeong Jin Kim, Sun Young Shin, Sang Hong Baek, Bom Nae Lee, Su Jung Hong, Jun Tae Kim, Kwonho Hong, Hojae Bae
To overcome the drawbacks of conventional drug delivery system, nanoemulsion have been developed as an advanced form for improving the delivery of active ingredients. However, safety evaluation is crucial during the development stage before the commercialization. Therefore, the aim of this study was to evaluate the cytotoxicity of two types of newly developed nanoemulsions. Turmeric extract-loaded nanoemulsion powder-10.6 (TE-NEP-10.6, high content of artificial surfactant Tween 80), which forms the optimal nanoemulsion, and the TE-NEP-8...
January 17, 2018: International Journal of Molecular Sciences
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