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https://www.readbyqxmd.com/read/29346770/integrative-analyses-of-de-novo-mutations-provide-deeper-biological-insights-into-autism-spectrum-disorder
#1
Atsushi Takata, Noriko Miyake, Yoshinori Tsurusaki, Ryoko Fukai, Satoko Miyatake, Eriko Koshimizu, Itaru Kushima, Takashi Okada, Mako Morikawa, Yota Uno, Kanako Ishizuka, Kazuhiko Nakamura, Masatsugu Tsujii, Takeo Yoshikawa, Tomoko Toyota, Nobuhiko Okamoto, Yoko Hiraki, Ryota Hashimoto, Yuka Yasuda, Shinji Saitoh, Kei Ohashi, Yasunari Sakai, Shouichi Ohga, Toshiro Hara, Mitsuhiro Kato, Kazuyuki Nakamura, Aiko Ito, Chizuru Seiwa, Emi Shirahata, Hitoshi Osaka, Ayumi Matsumoto, Saoko Takeshita, Jun Tohyama, Tomoko Saikusa, Toyojiro Matsuishi, Takumi Nakamura, Takashi Tsuboi, Tadafumi Kato, Toshifumi Suzuki, Hirotomo Saitsu, Mitsuko Nakashima, Takeshi Mizuguchi, Fumiaki Tanaka, Norio Mori, Norio Ozaki, Naomichi Matsumoto
Recent studies have established important roles of de novo mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the "de novo paradigm" of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244) and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346611/combined-roles-of-atp-and-small-hairpin-rna-in-the-activation-of-rig-i-revealed-by-solution-based-analysis
#2
Neelam Shah, Simone A Beckham, Jacqueline A Wilce, Matthew C J Wilce
RIG-I (retinoic acid inducible gene-I) is a cytosolic innate immune protein that senses viral dsRNA with a 5'-triphosphate overhang. Upon interaction with dsRNA a de-repression of the RIG-I CARD domains takes place that ultimately leads to the production of type I interferons and pro-inflammatory cytokines. Here we investigate the RIG-I conformational rearrangement upon interaction with an activating 5'-triphosphate-10-base pair dsRNA hairpin loop (10bp) compared with a less active 5'-triphosphate-8-base pair dsRNA hairpin loop (8bp)...
January 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29346575/abacavir-induces-arterial-thrombosis-in-a-murine-model
#3
Victor Collado-Diaz, Isabel Andujar, Ainhoa Sanchez-Lopez, Samuel Orden, María Amparo Blanch-Ruiz, María Angeles Martinez-Cuesta, Ana Blas-García, Juan V Esplugues, Ángeles Álvarez
Objective and methods: The effects of abacavir were evaluated in a validated model of arterial thrombosis. The role of ATP-P2X7-receptors and the actions of two vascular-damaging agents (diclofenac or rofecoxib) and other NRTIs were also analysed. Results: Abacavir dose-dependently promoted thrombus formation. This effect was reversed by a P2X7-receptor antagonist and was non-existent in P2X7 KO mice. The effects of abacavir were similar to those of diclofenac and rofecoxib...
January 16, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29346547/how-to-do-or-not-to-do-%C3%A2-a-health-financing-incidence-analysis
#4
John E Ataguba, Augustine D Asante, Supon Limwattananon, Virginia Wiseman
Financing incidence analysis (FIA) assesses how the burden of health financing is distributed in relation to household ability to pay (ATP). In a progressive financing system, poorer households contribute a smaller proportion of their ATP to finance health services compared to richer households. A system is regressive when the poor contribute proportionately more. Equitable health financing is often associated with progressivity. To conduct a comprehensive FIA, detailed household survey data containing reliable information on both a cardinal measure of household ATP and variables for extracting contributions to health services via taxes, health insurance and out-of-pocket (OOP) payments are required...
January 15, 2018: Health Policy and Planning
https://www.readbyqxmd.com/read/29345850/effects-of-glutaraldehyde-didecyldimethylammonium-bromide-combined-disinfectant-on-the-cell-surface-of-staphylococcus-aureus
#5
Wenshu Lin, Jialin Yi, Yuelin Zhang, Zhirui Deng, Qin Chen, Bing Niu
AIMS: The effects of a new glutaraldehyde-didecyldimethylammonium bromide combination disinfectant (GD) on the cell surface of Staphylococcus aureus, a representative Gram-positive bacterium, were investigated in this study. METHODS AND RESULTS: Results of bacterial surface structural analysis showed that GD significantly changed the bacterial morphology. The membrane fluidity decreased and outer membrane permeabilization increased after contact with GD. Furthermore, the integrity of the cytoplasmic membrane was destroyed by over 99% after exposure to GD for a short time...
January 18, 2018: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/29345310/a-potential-role-of-knockout-serum-replacement-as-a-porcine-follicular-fluid-substitute-for-in-vitro-maturation-lipid-metabolism-approach
#6
Jun-Xue Jin, Sanghoon Lee, Erif Maha Nugraha Setyawan, Anukul Taweechaipaisankul, Geon A Kim, Ho Jae Han, Curie Ahn, Byeong Chun Lee
The use of supplements, such as porcine follicular fluid (pFF), fetal bovine serum and human serum albumin are widely used during in vitro maturation (IVM) in different species but these supplements contain undefined components that cause technical difficulties in standardization and influence the efficiency of IVM. Knockout serum replacement (KSR) is a synthetic protein source, without any undefined growth factors or differentiation-promoting factors. Therefore, it is feasible to use KSR as a defined component for avoiding effects of unknown molecules in an IVM system...
January 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29345215/relationship-of-weekend-warrior-and-regular-physical-activity-patterns-with-metabolic-syndrome-and-its-associated-diseases-among-chinese-rural-adults
#7
Jing Xiao, Minjie Chu, Huan Shen, Wenlong Ren, Zhou Li, Tianqi Hua, Hong Xu, Yuanyuan Liang, Yuexia Gao, Xun Zhuang
Little is known about the "weekend warrior" pattern of physical activity (PA) where people perform all their PA in 1 or 2 sessions per week. We investigated the relationship of weekend warrior and other PA patterns with metabolic syndrome (MS) and its associated diseases. Data on sociodemographic and lifestyle characteristics were collected from the Nantong Metabolic Syndrome Study that included 13,505 women and 6,997 men between 2007 and 2008. Compared with inactive participants, weekend warriors were at lower risk of MS, diabetes, and hypertension; respective odds ratios (95% confidence intervals) for men and women were 0...
January 18, 2018: Journal of Sports Sciences
https://www.readbyqxmd.com/read/29344634/underlying-mechanism-of-the-photodynamic-activity-of-hematoporphyrin%C3%A2-induced-apoptosis-in-u87-glioma-cells
#8
Shi-Xiang Yuan, Jun-Liang Li, Xin-Ke Xu, Wei Chen, Cheng Chen, Kun-Qi Kuang, Fang-Yu Wang, Kai Wang, Fang-Cheng Li
Photodynamic therapy (PDT) is a relatively novel type of tumor therapy method with low toxicity and limited side‑effects. The aim of the present study was to investigate the underlying mechanism and potential microRNAs (miRNAs) involved in the treatment of glioma by PDT with hematoporphyrin, a clinical photosensitizer. The photodynamic activity of hematoporphyrin on the cell viability and apoptosis of gliomas was investigated by MTT, and flow cytometry and fluorescence microscopy, respectively. Alterations in singlet oxygen and mitochondrial membrane potential were detected...
January 18, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29344142/isolation-and-identification-of-tumor-initiating-cell-properties-in-human-gallbladder-cancer-cell-lines-using-the-marker-cluster-of-differentiation-133
#9
Jiwei Yu, Zhaohui Tang, Wei Gong, Mingdi Zhang, Zhiwei Quan
The present study aimed to isolate and identify the properties of the cluster of differentiation (CD)133+ subset in human gallbladder cancer cells. The CD133+ and CD133- subpopulations of the GBC-SD cell line were separated using immunomagnetic separation, and the biological features of the two subpopulations were analyzed in vitro and in vivo. In particular, the present study aimed to determine whether the two subpopulations were resistant to anti-tumor reagents and to identify the underlying molecular mechanisms involved...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343829/targeted-inhibitors-of-p-glycoprotein-increase-chemotherapeutic-induced-mortality-of-multidrug-resistant-tumor-cells
#10
Amila K Nanayakkara, Courtney A Follit, Gang Chen, Noelle S Williams, Pia D Vogel, John G Wise
Overexpression of ATP-binding cassette (ABC) transporters is often linked to multidrug resistance (MDR) in cancer chemotherapies. P-glycoprotein (P-gp) is one of the best studied drug transporters associated with MDR. There are currently no approved drugs available for clinical use in cancer chemotherapies to reverse MDR by inhibiting P-glycoprotein. Using computational studies, we previously identified several compounds that inhibit P-gp by targeting its nucleotide binding domain and avoiding its drug binding domains...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343827/targeted-nudt5-inhibitors-block-hormone-signaling-in-breast-cancer-cells
#11
Brent D G Page, Nicholas C K Valerie, Roni H G Wright, Olov Wallner, Rebecka Isaksson, Megan Carter, Sean G Rudd, Olga Loseva, Ann-Sofie Jemth, Ingrid Almlöf, Jofre Font-Mateu, Sabin Llona-Minguez, Pawel Baranczewski, Fredrik Jeppsson, Evert Homan, Helena Almqvist, Hanna Axelsson, Shruti Regmi, Anna-Lena Gustavsson, Thomas Lundbäck, Martin Scobie, Kia Strömberg, Pål Stenmark, Miguel Beato, Thomas Helleday
With a diverse network of substrates, NUDIX hydrolases have emerged as a key family of nucleotide-metabolizing enzymes. NUDT5 (also called NUDIX5) has been implicated in ADP-ribose and 8-oxo-guanine metabolism and was recently identified as a rheostat of hormone-dependent gene regulation and proliferation in breast cancer cells. Here, we further elucidate the physiological relevance of known NUDT5 substrates and underscore the biological requirement for NUDT5 in gene regulation and proliferation of breast cancer cells...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29343707/sensory-neuronal-p2rx4-receptors-controls-bdnf-signaling-in-inflammatory-pain
#12
Sarah Lalisse, Jennifer Hua, Manon Lenoir, Nathalie Linck, François Rassendren, Lauriane Ulmann
Chronic inflammatory and neuropathic pains are major public health concerns. Potential therapeutic targets include the ATP-gated purinergic receptors (P2RX) that contribute to these pathological types of pain in several different cell types. The purinergic receptors P2RX2 and P2RX3 are expressed by a specific subset of dorsal root ganglion neurons and directly shape pain processing by primary afferents. In contrast the P2RX4 and P2RX7 are mostly expressed in myeloid cells, where activation of these receptors triggers the release of various pro-inflammatory molecules...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343702/analysis-of-mitochondrial-function-in-human-induced-pluripotent-stem-cells-from-patients-with-mitochondrial-diabetes-due-to-the-a3243g-mutation
#13
Masaki Matsubara, Hajime Kanda, Hiromi Imamura, Mayumi Inoue, Michio Noguchi, Kiminori Hosoda, Akira Kakizuka, Kazuwa Nakao
We previously established human induced pluripotent stem (iPS) cells in two diabetic patients from different families with the mitochondrial A3243G mutation and isolated isogenic iPS cell clones with either undetectable or high levels of the mutation in both patients. In the present study, we analyzed the mitochondrial functions of two mutation-undetectable and two mutation-high clones in each patient through four methods to assess complex I activity, mitochondrial membrane potential, mitochondrial respiration, and mitochondrial ATP production...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343701/alanine-mutation-of-the-catalytic-sites-of-pantothenate-synthetase-causes-distinct-conformational-changes-in-the-atp-binding-region
#14
Bharati Pandey, Sonam Grover, Sukriti Goyal, Anchala Kumari, Aditi Singh, Salma Jamal, Jagdeep Kaur, Abhinav Grover
The enzyme Pantothenate synthetase (PS) represents a potential drug target in Mycobacterium tuberculosis. Its X-ray crystallographic structure has demonstrated the significance and importance of conserved active site residues including His44, His47, Asn69, Gln72, Lys160 and Gln164 in substrate binding and formation of pantoyl adenylate intermediate. In the current study, molecular mechanism of decreased affinity of the enzyme for ATP caused by alanine mutations was investigated using molecular dynamics (MD) simulations and free energy calculations...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343628/keeping-the-home-fires-burning-amp-activated-protein-kinase
#15
REVIEW
D Grahame Hardie
Living cells obtain energy either by oxidizing reduced compounds of organic or mineral origin or by absorbing light. Whichever energy source is used, some of the energy released is conserved by converting adenosine diphosphate (ADP) to adenosine triphosphate (ATP), which are analogous to the chemicals in a rechargeable battery. The energy released by the conversion of ATP back to ADP is used to drive most energy-requiring processes, including cell growth, cell division, communication and movement. It is clearly essential to life that the production and consumption of ATP are always maintained in balance, and the AMP-activated protein kinase (AMPK) is one of the key cellular regulatory systems that ensures this...
January 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29343524/antitumor-properties-of-raf709-a-highly-selective-and-potent-inhibitor-of-raf-kinase-dimers-in-tumors-driven-by-mutant-ras-or-braf
#16
Wenlin Shao, Yuji Mishina, Yun Feng, Giordano Caponigro, Vesselina G Cooke, Stacy Rivera, Yingyun Wang, Fang Shen, Joshua M Korn, Lesley Mathews Griner, Gisele Nishiguchi, Alice Rico, John Tellew, Jacob Haling, Robert Aversa, Valery R Polyakov, Richard Zang, Mohammad Hekmat-Nejad, Payman Amiri, Mallika Singh, Nicholas Keen, Michael P Dillon, Emma Lees, Savithri Ramurthy, William R Sellers, Darrin D Stuart
Resistance to the RAF inhibitor vemurafenib arises commonly in melanomas driven by the activated BRAF oncogene. Here we report antitumor properties of RAF709, a novel ATP-competitive kinase inhibitor with high potency and selectivity against RAF kinases. RAF709 exhibited a mode of RAF inhibition distinct from RAF monomer inhibitors such as vemurafenib, showing equal activity against both RAF monomers and dimers. As a result, RAF709 inhibited MAPK signaling activity in tumor models harboring either BRAFV600 alterations or mutant N- and KRAS-driven signaling, with minimal paradoxical activation of wild-type RAF...
January 17, 2018: Cancer Research
https://www.readbyqxmd.com/read/29343514/trpm2-channel-mediated-regulation-of-autophagy-maintains-mitochondrial-function-and-promotes-gastric-cancer-cell-survival-via-the-jnk-signaling-pathway
#17
Shekoufeh Almasi, Barry E Kennedy, Mariam El Aghil, Andra M Sterea, Shashi Gujar, Santiago Partida-Sánchez, Yassine El Hiani
A lack of effective treatment is one of the main factors contributing to gastric cancer-related death. Discovering effective targets and understanding their underlying anticancer mechanism is key to achieving the best response to treatment and to limiting side effects. Although recent studies have shown that the cation channel transient receptor potential melastatin-2 (TRPM2) is crucial for cancer cell survival, the exact mechanism remains unclear, limiting its therapeutic potential. Here, using molecular and functional assays, we investigated the role of TRPM2 in survival of gastric cancer cells...
January 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29343229/the-colombo-twin-and-singleton-follow-up-study-a-population-based-twin-study-of-psychiatric-disorders-and-metabolic-syndrome-in-sri-lanka
#18
Kaushalya Jayaweera, Lisa Aschan, Gayani Pannala, Anushka Adikari, Nicholas Glozier, Khalida Ismail, Carmine M Pariante, Fruhling Rijsdijk, Sisira Siribaddana, Helena M S Zavos, Patricia A Zunszain, Athula Sumathipala, Matthew Hotopf
BACKGROUND: The disease burden related to mental disorders and metabolic syndrome is growing in low-and middle-income countries (LMIC). The Colombo Twin and Singleton Study (COTASS) is a population-based sample of twins and singletons in Colombo, Sri Lanka. Here we present prevalence estimates for metabolic syndrome (metS) and mental disorders from a follow-up (COTASS-2) of the original study (COTASS-1), which was a mental health survey. METHODS: In COTASS-2, participants completed structured interviews, anthropometric measures and provided fasting blood and urine samples...
January 17, 2018: BMC Public Health
https://www.readbyqxmd.com/read/29342419/investigation-of-the-transport-of-xanthine-dehydrogenase-inhibitors-by-the-urate-transporter-abcg2
#19
Makiko Nakamura, Kyoko Fujita, Yu Toyoda, Tappei Takada, Hiroshi Hasegawa, Kimiyoshi Ichida
Hyperuricemia induces gout and kidney stones and accelerates the progression of renal and cardiovascular diseases. Adenosine 5'-triphosphate-binding cassette subfamily G member 2 (ABCG2) is a urate transporter, and common dysfunctional variants of ABCG2, non-functional Q126X (rs72552713) and semi-functional Q141K (rs2231142), are risk factors for hyperuricemia and gout. A recent genome wide association study suggested that allopurinol, a serum uric acid-lowering drug that inhibits xanthine dehydrogenase, is a potent substrate of ABCG2...
November 22, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29342317/osteoblast-like-mc3t3-e1-cells-prefer-glycolysis-for-atp-production-but-adipocyte-like-3t3-l1-cells-prefer-oxidative-phosphorylation
#20
Anyonya R Guntur, Akos A Gerencser, Phuong T Le, Victoria E DeMambro, Sheila A Bornstein, Shona A Mookerjee, David E Maridas, David E Clemmons, Martin D Brand, Clifford J Rosen
Mesenchymal stromal cells (MSCs) are early progenitors that can differentiate into osteoblasts, chondrocytes and adipocytes. We hypothesized that osteoblasts and adipocytes utilize distinct bioenergetic pathways during MSC differentiation. To test this hypothesis, we compared the bioenergetic profiles of pre-osteoblast MC3T3-E1 cells and calvarial osteoblasts with pre-adipocyte 3T3L1 cells, before and after differentiation. Differentiated MC3T3-E1 osteoblasts met ATP demand mainly by glycolysis with minimal reserve glycolytic capacity, whereas non-differentiated cells generated ATP through oxidative phosphorylation...
January 17, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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