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https://www.readbyqxmd.com/read/28346693/using-a-novel-nqo1-bioactivatable-drug-beta-lapachone-arq761-to-enhance-chemotherapeutic-effects-by-metabolic-modulation-in-pancreatic-cancer
#1
Muhammad Shaalan Beg, Xiumei Huang, Molly A Silvers, David E Gerber, Joyce Bolluyt, Venetia Sarode, Farjana Fattah, Ralph J Deberardinis, Matthew E Merritt, Xian-Jin Xie, Richard Leff, Daniel Laheru, David A Boothman
Novel, tumor-selective therapies are needed to increase the survival rate of pancreatic cancer patients. K-Ras-mutant-driven NAD(P)H:quinone oxidoreductase 1 (NQO1) is over-expressed in pancreatic tumor versus associated normal tissue, while catalase expression is lowered compared to levels in associated normal pancreas tissue. ARQ761 undergoes a robust, futile redox cycle in NQO1+ cancer cells, producing massive hydrogen peroxide (H2 O2 ) levels; normal tissues are spared by low NQO1 and high catalase expression...
March 27, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28346493/aberrant-neuronal-activity-induced-signaling-and-gene-expression-in-a-mouse-model-of-rasopathy
#2
Franziska Altmüller, Santosh Pothula, Anil Annamneedi, Saeideh Nakhei-Rad, Carolina Montenegro-Venegas, Eneko Pina-Fernández, Claudia Marini, Monica Santos, Denny Schanze, Dirk Montag, Mohammad R Ahmadian, Oliver Stork, Martin Zenker, Anna Fejtova
Noonan syndrome (NS) is characterized by reduced growth, craniofacial abnormalities, congenital heart defects, and variable cognitive deficits. NS belongs to the RASopathies, genetic conditions linked to mutations in components and regulators of the Ras signaling pathway. Approximately 50% of NS cases are caused by mutations in PTPN11. However, the molecular mechanisms underlying cognitive impairments in NS patients are still poorly understood. Here, we report the generation and characterization of a new conditional mouse strain that expresses the overactive Ptpn11D61Y allele only in the forebrain...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346441/altering-the-threshold-of-an-excitable-signal-transduction-network-changes-cell-migratory-modes
#3
Yuchuan Miao, Sayak Bhattacharya, Marc Edwards, Huaqing Cai, Takanari Inoue, Pablo A Iglesias, Peter N Devreotes
The diverse migratory modes displayed by different cell types are generally believed to be idiosyncratic. Here we show that the migratory behaviour of Dictyostelium was switched from amoeboid to keratocyte-like and oscillatory modes by synthetically decreasing phosphatidylinositol-4,5-bisphosphate levels or increasing Ras/Rap-related activities. The perturbations at these key nodes of an excitable signal transduction network initiated a causal chain of events: the threshold for network activation was lowered, the speed and range of propagating waves of signal transduction activity increased, actin-driven cellular protrusions expanded and, consequently, the cell migratory mode transitions ensued...
March 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28346426/mrl-proteins-cooperate-with-activated-ras-in-glia-to-drive-distinct-oncogenic-outcomes
#4
E Taylor, N Alqadri, L Dodgson, D Mason, E Lyulcheva, G Messina, D Bennett
The Mig10/RIAM/Lpd (MRL) adapter protein Lpd regulates actin dynamics through interactions with Scar/WAVE and Ena/VASP proteins to promote the formation of cellular protrusions and to stimulate invasive migration. However, the ability of MRL proteins to interact with multiple actin regulators and to promote serum response factor (SRF) signalling has raised the question of whether MRL proteins employ alternative downstream mechanisms to drive oncogenic processes in a context-dependent manner. Here, using a Drosophila model, we show that overexpression of either human Lpd or its Drosophila orthologue Pico can promote growth and invasion of Ras(V12)-induced cell tumours in the brain...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28345583/synergistic-effects-of-micro-electrolysis-photocatalysis-on-water-treatment-and-fish-performance-in-saline-recirculating-aquaculture-system
#5
Zhangying Ye, Shuo Wang, Weishan Gao, Haijun Li, Luowei Pei, Mingwei Shen, Songming Zhu
A new physico-chemical process for TAN (total ammonia nitrogen) removal and disinfection is introduced in saline recirculating aquaculture system (RAS), in which the biofilter is replaced with an integrated electrolysis cell and an activated carbon filter. The electrolysis cell which is based on micro current electrolysis combined with UV-light was self-designed. After the fundamental research, a small pilot scale RAS was operated for 30 days to verify the technical feasibility. The system was stocked by 42 GIFT tilapia (Oreochromis niloticus) fish with the rearing density of 13 kg/m(3)...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345122/effect-of-laser-on-pain-relief-and-wound-healing-of-recurrent-aphthous-stomatitis-a-systematic-review
#6
REVIEW
Valerie G A Suter, Sophia Sjölund, Michael M Bornstein
The aim of this systematic review was to assess a potential benefit of laser use in the treatment of recurrent aphthous stomatitis (RAS). The primary outcome variables were pain relief, duration of wound healing and reduction in episode frequency. A PICO approach was used as a search strategy in Medline, Embase and Cochrane databases. After scanning and excluding titles, abstracts and full texts, 11 studies (ten RCTs and one non-randomised controlled trial) were included. Study selection and data extraction was done by two observers...
March 27, 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/28343981/global-epidemiology-of-hcv-subtypes-and-resistance-associated-substitutions-evaluated-by-sequencing-based-subtype-analyses
#7
Tania Welzel, Neeru Bhardwaj, Charlotte Hedskog, Krishna Chodavarapu, Gregory Camus, John McNally, Diana Brainard, Michael D Miller, Hongmei Mo, Evguenia Svarovskaia, Ira Jacobson, Stefan Zeuzem, Kosh Agarwal
BACKGROUND & AIMS: Hepatitis C virus (HCV) is highly variable with 7 genotypes and 67 subtypes characterized to date. HCV genotype (GT) and subtype, and presence of resistance associated substitutions (RASs) represent the key viral determinants for the selection of direct-acting antiviral (DAA) treatment regimens. However, currently available HCV genotyping assays have limitations in differentiating between HCV subtypes and RAS prevalence in different subtypes is largely undefined. METHODS: In this study, we compared HCV GT and subtypes with INNO-LiPA 2...
March 23, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28343148/de-novo-mutations-in-cbl-causing-early-onset-paediatric-moyamoya-angiopathy
#8
Stéphanie Guey, Lou Grangeon, Francis Brunelle, Françoise Bergametti, Jeanne Amiel, Stanislas Lyonnet, Audrey Delaforge, Minh Arnould, Béatrice Desnous, Céline Bellesme, Dominique Hervé, Jan C Schwitalla, Markus Kraemer, Elisabeth Tournier-Lasserve, Manoelle Kossorotoff
BACKGROUND: Moyamoya angiopathy (MMA) is characterised by a progressive stenosis of the terminal part of the internal carotid arteries and the development of abnormal collateral deep vessels. Its pathophysiology is unknown. MMA can be the sole manifestation of the disease (moyamoya disease) or be associated with various conditions (moyamoya syndrome) including some Mendelian diseases. We aimed to investigate the genetic basis of moyamoya using a whole exome sequencing (WES) approach conducted in sporadic cases without any overt symptom suggestive of a known Mendelian moyamoya syndrome...
March 25, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28341836/fam46c-is-critical-for-the-anti-proliferation-and-pro-apoptotic-effects-of-norcantharidin-in-hepatocellular-carcinoma-cells
#9
Qiao-Yan Zhang, Xiao-Qiang Yue, Yi-Ping Jiang, Ting Han, Hai-Liang Xin
Norcantharidin (NCTD), a demethylated analog of cantharidin derived from Chinese traditional medicine blister beetle, has been currently used as an anticancer drug for various cancers including hepatocellular carcinoma (HCC). In this study, for a more comprehensive understanding of the targets of NCTD in HCC, next-generation RNA-Seq was utilized. We revealed that the expression of FAM46C, which has been reported as a tumor suppressor for multiple myeloma, was enhanced after NCTD treatment. Re-analysis of TCGA (The Cancer Genome Atlas) LIHC (liver hepatocellular carcinoma) dataset demonstrated that FAM46C expression was significantly lower in HCC tissues than in normal liver tissues...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28341711/a-cardiac-enriched-microrna-mir-378-blocks-cardiac-hypertrophy-by-targeting-ras-signaling
#10
Raghu S Nagalingam, Nagalingam R Sundaresan, Mahesh P Gupta, David L Geenen, R John Solaro, Madhu Gupta
No abstract text is available yet for this article.
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28341660/the-noncoding-rna-linc-adamts5-cooperates-with-rreb1-to-protect-from-intervertebral-disc-degeneration-through-inhibiting-adamts5-expression
#11
Kun Wang, Yu Song, Wei Liu, Xinghuo Wu, Yukun Zhang, Shuai Li, Liang Kang, Ji Tu, Kangcheng Zhao, Wenbin Hua, Cao Yang
Previous studies have indicated the important roles of ADAMTS5 in intervertebral disc degeneration. However, the mechanisms that regulate ADAMTS5 expression in nuclear pulposus (NP) cells remain largely unknown. Evidence suggests that intergenic transcription may be associated with genes that encode transcriptional regulators. Here, we identified a long intergenic noncoding RNA, linc-ADAMTS5, that was transcribed in the opposite direction of ADAMTS5. In this study, through mining computational algorithm programs, and public available data sets, we identified Ras responsive element binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells...
March 24, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28339090/inhibition-of-farnesyl-pyrophosphate-synthase-attenuates-high-glucose%C3%A2-induced-vascular-smooth-muscle-cells-proliferation
#12
Guo-Ping Chen, Xiao-Qin Zhang, Tao Wu, Jie Han, Dan Ye
The proliferation of vascular smooth muscle cells (VSMCs) is one of the main features of atherosclerosis accelerated by hyperglycemia. Our previous studies found that farnesyl pyrophosphate synthase (FPPS, EC 2.5.1.10), an essential enzyme in the mevalonate pathway, was upregulated in aorta media from diabetic mice along with the process of atherosclerosis. However, the exact role of FPPS in high glucose‑induced proliferation of VSMCs is largely unclear. In our study, we found that alendronate (an FPPS inhibitor) attenuated diabetic accelerated atherosclerosis in vivo and suppressed high glucose‑induced VSMCs proliferation in vitro...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28339035/duration-of-simulated-microgravity-affects-the-differentiation-of-mesenchymal-stem-cells
#13
Li Xue, Yaohui Li, Jun Chen
Previous evidence has suggested that physical microenvironments and mechanical stresses, independent of soluble factors, influence mesenchymal stem cell (MSC) fate. In the present study, simulated microgravity (SMG) was demonstrated to regulate the differentiation of mesenchymal stem cells. This may be a novel strategy for tissue engineering and regenerative medicine. Rat MSCs were cultured for 72 h or 10 days in either normal gravity or a clinostat to model microgravity, followed with culture in diverse differential media...
March 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338001/renin-angiotensin-system-acting-on-reactive-oxygen-species-in-paraventricular-nucleus-induces-sympathetic-activation-via-at1r-pkc%C3%AE-rac1-pathway-in-salt-induced-hypertension
#14
Qing Su, Chan-Juan Huo, Hong-Bao Li, Kai-Li Liu, Xiang Li, Qing Yang, Xin-Ai Song, Wen-Sheng Chen, Wei Cui, Guo-Qing Zhu, Xiao-Lian Shi, Jin-Jun Liu, Yu-Ming Kang
Brain renin-angiotensin system (RAS) could regulate oxidative stress in the paraventricular nucleus (PVN) in the development of hypertension. This study was designed to explore the precise mechanisms of RAS acting on reactive oxygen species (ROS) in salt-induced hypertension. Male Wistar rats were administered with a high-salt diet (HS, 8.0% NaCl) for 8 weeks to induced hypertension. Those rats were received PVN infusion of AT1R antagonist losartan (LOS, 10 μg/h) or microinjection of small interfering RNAs for protein kinase C γ (PKCγ siRNA) once a day for 2 weeks...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337834/retinal-dystrophy-in-two-boys-with-costello-syndrome-due-to-the-hras-p-gly13cys-mutation
#15
Mary Ella Pierpont, Mary Richards, W Keith Engel, Nancy J Mendelsohn, C Gail Summers
Features of Costello Syndrome, a systemic disorder caused by germline mutations in the proto-oncogene HRAS from the RAS/MAPK pathway, include failure-to-thrive, short stature, coarse facial features, cardiac defects including hypertrophic cardiomyopathy, intellectual disability, and predisposition to neoplasia. Two unrelated boys with Costello syndrome and an HRAS mutation (p.Gly13Cys) are presented with their ophthalmologic findings. Both had early symptoms of nystagmus, photophobia, and vision abnormalities...
March 23, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28335584/atrap-expression-in-brown-adipose-tissue-does-not-influence-the-development-of-diet-induced-metabolic-disorders-in-mice
#16
Kohji Ohki, Hiromichi Wakui, Kengo Azushima, Kazushi Uneda, Sona Haku, Ryu Kobayashi, Kotaro Haruhara, Sho Kinguchi, Miyuki Matsuda, Masato Ohsawa, Akinobu Maeda, Shintaro Minegishi, Tomoaki Ishigami, Yoshiyuki Toya, Akio Yamashita, Satoshi Umemura, Kouichi Tamura
Activation of tissue renin-angiotensin system (RAS), mainly mediated by an angiotensin II (Ang II) type 1 receptor (AT1R), plays an important role in the development of obesity-related metabolic disorders. We have shown that AT1R-associated protein (ATRAP), a specific binding protein of AT1R, functions as an endogenous inhibitor to prevent excessive activation of tissue RAS. In the present study, we newly generated ATRAP/Agtrap-floxed (ATRAP(fl/fl)) mice and adipose tissue-specific ATRAP downregulated (ATRAP(adipoq)) mice by the Cre/loxP system using Adipoq-Cre...
March 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28335476/inhibition-of-neoplastic-transformation-and-chemically-induced-skin-hyperplasia-in-mice-by-traditional-chinese-medicinal-formula-si-wu-tang
#17
Mandy M Liu, Kevin M Huang, Steven Yeung, Andy Chang, Suhui Zhang, Nan Mei, Cyrus Parsa, Robert Orlando, Ying Huang
Exploring traditional medicines may lead to the development of low-cost and non-toxic cancer preventive agents. Si-Wu-Tang (SWT), comprising the combination of four herbs, Rehmanniae, Angelica, Chuanxiong, and Paeoniae, is one of the most popular traditional Chinese medicines for women's diseases. In our previous studies, the antioxidant Nrf2 pathways were strongly induced by SWT in vitro and in vivo. Since Nrf2 activation has been associated with anticarcinogenic effects, the purpose of this study is to evaluate SWT's activity of cancer prevention...
March 18, 2017: Nutrients
https://www.readbyqxmd.com/read/28334144/the-effects-of-plant-nutritional-strategy-on-soil-microbial-denitrification-activity-through-rhizosphere-primary-metabolites
#18
Julien P Guyonnet, Florian Vautrin, Guillaume Meiffren, Clément Labois, Amélie A M Cantarel, Serge Michalet, Gilles Comte, Feth El Zahar Haichar
The aim of this study was to determine (i) whether plant nutritional strategy affects the composition of primary metabolites exuded into the rhizosphere and (ii) their impact on denitrification activity in soil. We answer this question by analysing primary metabolite contents extracted from the root-adhering soil (RAS) and the roots of three grasses representing different nutrient management strategies: conservative (Festuca paniculata), intermediate (Bromus erectus) and exploitative (Dactylis glomerata). We also investigated the impact of primary metabolites on soil microbial denitrification enzyme activity (DEA) without carbon addition, comparing for each plant RAS and bulk soils...
February 18, 2017: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/28333924/csl-encodes-a-leucine-rich-repeat-protein-implicated-in-red-violet-light-signaling-to-the-circadian-clock-in-chlamydomonas
#19
Ayumi Kinoshita, Yoshimi Niwa, Kiyoshi Onai, Takashi Yamano, Hideya Fukuzawa, Masahiro Ishiura, Takuya Matsuo
The green alga Chlamydomonas reinhardtii shows various light responses in behavior and physiology. One such photoresponse is the circadian clock, which can be reset by external light signals to entrain its oscillation to daily environmental cycles. In a previous report, we suggested that a light-induced degradation of the clock protein ROC15 is a trigger to reset the circadian clock in Chlamydomonas. However, light signaling pathways of this process remained unclear. Here, we screened for mutants that show abnormal ROC15 diurnal rhythms, including the light-induced protein degradation at dawn, using a luciferase fusion reporter...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28333644/random-forest-classifier-for-zero-shot-learning-based-on-relative-attribute
#20
Yuhu Cheng, Xue Qiao, Xuesong Wang, Qiang Yu
For the zero-shot image classification with relative attributes (RAs), the traditional method requires that not only all seen and unseen images obey Gaussian distribution, but also the classifications on testing samples are made by maximum likelihood estimation. We therefore propose a novel zero-shot image classifier called random forest based on relative attribute. First, based on the ordered and unordered pairs of images from the seen classes, the idea of ranking support vector machine is used to learn ranking functions for attributes...
March 21, 2017: IEEE Transactions on Neural Networks and Learning Systems
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