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https://www.readbyqxmd.com/read/28645153/defective-mitochondrial-rna-processing-due-to-pnpt1-variants-causes-leigh-syndrome
#1
Sanna Matilainen, Christopher J Carroll, Uwe Richter, Liliya Euro, Max Pohjanpelto, Anders Paetau, Pirjo Isohanni, Anu Suomalainen
Leigh syndrome is a severe infantile encephalopathy with an exceptionally variable genetic background. We studied the exome of a child manifesting with Leigh syndrome at one month of age and progressing to death by the age of 2.4 years, and identified novel compound heterozygous variants in PNPT1, encoding the polynucleotide phosphorylase (PNPase). Expression of the wild type PNPT1 in the subject's myoblasts functionally complemented the defects, and the pathogenicity was further supported by structural predictions and protein and RNA analyses...
June 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28645027/validity-of-the-growth-model-of-the-computerized-visual-perception-assessment-tool-for-chinese-characters-structures
#2
Huey-Min Wu, Cheng-Hsaun Li, Bor-Chen Kuo, Yu-Mao Yang, Chin-Kai Lin, Wei-Hsiang Wan
Morphological awareness is the foundation for the important developmental skills involved with vocabulary, as well as understanding the meaning of words, orthographic knowledge, reading, and writing. Visual perception of space and radicals in two-dimensional positions of Chinese characters' morphology is very important in identifying Chinese characters. The important predictive variables of special and visual perception in Chinese characters identification were investigated in the growth model in this research...
June 20, 2017: Research in Developmental Disabilities
https://www.readbyqxmd.com/read/28645005/application-of-stem-cell-derived-neuronal-cells-to-evaluate-neurotoxic-chemotherapy
#3
Claudia Wing, Masaaki Komatsu, Shannon M Delaney, Matthew Krause, Heather E Wheeler, M Eileen Dolan
The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin), taxanes (paclitaxel, docetaxel and nab-paclitaxel), a targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy...
June 15, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28644987/thiophene-thiazole-benzene-replacement-on-guanidine-derivatives-targeting-%C3%AE-2-adrenoceptors
#4
Aoife Flood, Cristina Trujillo, Goar Sanchez-Sanz, Brendan Kelly, Carolina Muguruza, Luis F Callado, Isabel Rozas
Searching for improved antagonists of α2-adrenoceptors, a thorough theoretical study comparing the aromaticity of phenyl-, pyridinyl-, thiophenyl- and thiazolylguanidinium derivatives has been carried out [at M06-2X/6-311++G(p,d) computational level] confirming that thiophene and thiazole will be good 'ring equivalents' to benzene in these guanidinium systems. Based on these results, a small but chemically diverse library of guanidine derivatives (15 thiophenes and 2 thiazoles) were synthesised to explore the effect that the bioisosteric change has on affinity and activity at α2-adrenoceptors in comparison with our previously studied phenyl derivatives...
June 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28644986/designing-novel-inhibitors-against-histone-acetyltransferase-hat-%C3%A2-gcn5-of-plasmodium-falciparum
#5
Amarjeet Kumar, Krishanu Bhowmick, Kunwar Somesh Vikramdeo, Neelima Mondal, Naidu Subbarao, Suman Kumar Dhar
During active proliferation phase of intra-erythrocytic cycle, the genome of P. falciparum is regulated epigenetically and evolutionary conserved parasite-specific histone proteins are extensively acetylated. The reversible process of lysine acetylation, causing transcriptional activation and its deacetylation, causing transcriptional repression is regulated by balanced activities of HATs and HDACs. They are also known to regulate antigenic variations and gametocytic conversion in P. falciparum. These histone modifying enzymes have been identified as potential targets for development of anitmalarials in literature...
June 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28644981/chemical-profiling-and-antioxidant-evaluation-of-yangxinshi-tablet-by-hplc-esi-q-tof-ms-ms-combined-with-dpph-assay
#6
Junfeng Zhu, Xiaojiao Yi, Jinghui Zhang, Shuqing Chen, Yongjiang Wu
Yangxinshi Tablet (YXST) is a Chinese patent medicine commonly used to treat cardiovascular diseases. However, its detailed chemical basis and mechanisms of action have not been clarified. In this study, high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-Q-TOF-MS) was applied for comprehensive analysis of the chemical constituents in YXST. A total of 127 compounds, including 19 phenolic acids, 12 alkaloids, 51 flavanoids, 32 triterpenoids, 2 lignans, 2 phenylethanoid glycosides, 2 anthraquinones, 1 coumarin, and 6 other compounds, were identified or tentatively deduced by comparing their retention times and MS spectra with those of authentic standards or literature data...
June 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28644959/generation-and-characterization-of-aptamers-targeting-factor-xia
#7
R S Woodruff, I Ivanov, I M Verhamme, M-F Sun, D Gailani, B A Sullenger
BACKGROUND: The plasma protease factor XIa (FXIa) has become a target of interest for therapeutics designed to prevent or treat thrombotic disorders. METHODS: We used a solution-based, directed evolution approach called systematic evolution of ligands by exponential enrichment (SELEX) to isolate RNA aptamers that target the FXIa catalytic domain. RESULTS: Two aptamers, designated 11.16 and 12.7, were identified that bound to previously identified anion binding and serpin bindings sites on the FXIa catalytic domain...
June 9, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28644955/turning-on-proteasomes
#8
Jan Henrik Krahn, Farnusch Kaschani, Markus Kaiser
While proteasome inhibitors are now well-established research tools and chemotherapeutics, proteasome activators are much less explored. In this issue of Cell Chemical Biology, in a study from the groups of Berkers and Ovaa (Leestemaker et al., 2017), a chemical screen was used to identify a p38 MAPK inhibitor as a proteasome activator. This compound furthermore enhanced clearance of protein aggregates, thereby implicating alternative chemotherapeutic options for treating neurodegenerative diseases.
June 22, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28644930/trends-in-open-and-endoscopic-cubital-tunnel-release-in-the-medicare-patient-population
#9
Tsun Yee Law, Zachary S Hubbard, Lee Onn Chieng, Harvey W Chim
BACKGROUND: Cubital tunnel syndrome (CUT) is the second most common peripheral neuropathy with an annual incidence of 24.7 per 100 000, affecting nearly twice as many men as women. With increasing focus on cost-effectiveness and cost-containment in medicine, a critical understanding of utilization of health care resources for open and endoscopic approaches for cubital tunnel release is of value. The purpose of this study was to evaluate the costs and utilization trends of open and endoscopic cubital tunnel release...
July 2017: Hand: Official Journal of the American Association for Hand Surgery
https://www.readbyqxmd.com/read/28644912/biofilm-formation-and-disinfectant-resistance-of-salmonella-spp-in-mono-and-dual-species-with-pseudomonas-aeruginosa
#10
Xinyi Pang, Yishan Yang, Hyun-Gyun Yuk
AIMS: This study aimed to evaluate the biofilm formation and disinfectant resistance of Salmonella cells in mono- and dual-species biofilms with Pseudomonas aeruginosa, and to investigate the role of extracellular polymeric substances (EPS) in protection of biofilms against disinfection treatment. METHODS AND RESULTS: The populations of Salmonella in mono- or dual-species biofilms with P. aeruginosa on stainless steel (SS) coupons were determined before and after exposure to commercial disinfectant, 50 μg ml(-1) chlorine or 200 μg ml(-1) Ecolab(®) Whisper(™) V (a blend of four effective quaternary ammonium compounds)...
June 23, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28644885/organic-anion-transporting-polypeptide-1b3-can-form-homo-and-hetero-oligomers
#11
Yuchen Zhang, Kelli H Boxberger, Bruno Hagenbuch
OATP1B3 is a 12 transmembrane domain protein expressed at the basolateral membrane of human hepatocytes where it mediates the uptake of numerous drugs and endogenous compounds. Previous western blot results suggest the formation of OATP1B3 multimers. In order to better understand the function of OATP1B3 under normal physiological conditions, we investigated its oligomerization status. We transiently transfected OATP1B3 with a C-terminal His-, FLAG- or HA-tag in HEK293 cells and used co-immunoprecipitation and a Proximity Ligation Assay to detect interactions between the different constructs...
2017: PloS One
https://www.readbyqxmd.com/read/28644879/identification-of-a-novel-fungus-trichoderma-asperellum-gdfs1009-and-comprehensive-evaluation-of-its-biocontrol-efficacy
#12
Qiong Wu, Ruiyan Sun, Mi Ni, Jia Yu, Yaqian Li, Chuanjin Yu, Kai Dou, Jianhong Ren, Jie Chen
Due to its efficient broad-spectrum antimicrobial activity, Trichoderma has been established as an internationally recognized biocontrol fungus. In this study, we found and identified a novel strain of Trichoderma asperellum, named GDFS1009. The mycelium of T. asperellum GDFS1009 exhibits a high growth rate, high sporulation capacity, and strong inhibitory effects against pathogens that cause cucumber fusarium wilt and corn stalk rot. T. asperellum GDFS1009 secretes chitinase, glucanase, and protease, which can degrade the cell walls of fungi and contribute to mycoparasitism...
2017: PloS One
https://www.readbyqxmd.com/read/28644803/cardiac-strain-imaging-with-coherent-compounding-of-diverging-waves
#13
Julien Grondin, Vincent Sayseng, Elisa E Konofagou
Current methods of cardiac strain imaging at high frame rate suffer from motion matching artifacts or poor lateral resolution. Coherent compounding has been shown to improve echocardiographic image quality while maintaining high frame rate but has never been used to image cardiac strain. However, myocardial velocity can have an impact on coherent compounding due to displacements between frames. The objective of this study was to investigate the feasibility and performance of coherent compounding for cardiac strain imaging at a low and a high myocardial velocity...
June 20, 2017: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
https://www.readbyqxmd.com/read/28644734/high-throughput-phenotypic-screening-of-kinase-inhibitors-to-identify-drug-targets-for-polycystic-kidney-disease
#14
Tijmen H Booij, Hester Bange, Wouter N Leonhard, Kuan Yan, Michiel Fokkelman, Steven J Kunnen, Johannes G Dauwerse, Yu Qin, Bob van de Water, Gerard J P van Westen, Dorien J M Peters, Leo S Price
Polycystic kidney disease (PKD) is a prevalent disorder characterized by renal cysts that lead to kidney failure. Various signaling pathways have been targeted to stop disease progression, but most interventions still focus on alleviating PKD-associated symptoms. The mechanistic complexity of the disease, as well as the lack of functional in vitro assays for compound testing, has made drug discovery for PKD challenging. To identify modulators of PKD, Pkd1(-/-) kidney tubule epithelial cells were applied to a scalable and automated 3D cyst culture model for compound screening, followed by phenotypic profiling to determine compound efficacy...
June 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28644732/lipophilicity-and-biomimetic-properties-to-support-drug-discovery
#15
Fotios Tsopelas, Constantinos Giaginis, Anna Tsantili-Kakoulidou
Lipophilicity, expressed as the octanol-water partition coefficient, constitutes the most important property in drug action, influencing both pharmacokinetic and pharmacodynamics processes as well as drug toxicity. On the other hand, biomimetic properties defined as the retention outcome on HPLC columns containing a biological relevant agent, provide a considerable advance for rapid experimental -based estimation of ADME properties in early drug discovery stages. Areas covered: This review highlights the paramount importance of lipophilicity in almost all aspects of drug action and safety...
June 23, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28644726/cytotoxic-and-genotoxic-actions-of-casiopeina-iii-ea-cas-iii-ea-in-somatic-and-germ-cells-of-drosophila-melanogaster
#16
L M Vidal, E Pimentel, M P Cruces, S Hernández, L Ruiz-Azuara
Casiopeinas® are a group of newly synthesized drugs designed to treat cancer. These copper (Cu) complexes exhibit cytostatic, cytotoxic, genotoxic, and antineoplastic activities through different mechanisms of action. To evaluate the influence of these compounds, some in vivo studies were performed using predominantly somatic cells. The aim of the present study was to examine the cytotoxic and genotoxic actions of Casiopeina III-Ea (Cas III-Ea) in somatic as well as germ cells of Drosophila melanogaster. For cytotoxicity, the productivity and some morphometric parameters were measured and genotoxicity was assessed by means of the somatic mutation and recombination test assay in the wing...
June 23, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28644710/study-of-artemisinin-and-sugars-accumulation-in-artemisia-vulgaris-and-artemisia-dracunculus-hairy-root-cultures
#17
Kateryna O Drobot, Nadiia A Matvieieva, Andriy M Ostapchuk, Maxim A Kharkhota
We studied the effect of genetic transformation on biologically active compounds (artemisinin and its co-products (ART) as well as sugars) accumulation in Artemisia vulgaris and A.dracunculus "hairy" root cultures. Glucose, fructose, sucrose and mannitol were accumulated in A. vulgaris and A. dracunculus "hairy" root lines. Genetic transformation has led in some cases to the sugars content increasing or appearing of non-relevant for the control plants carbohydrates. Sucrose content was 1.6 times higher in A...
June 23, 2017: Preparative Biochemistry & Biotechnology
https://www.readbyqxmd.com/read/28644689/two-new-prenylflavonoids-from-morus-alba
#18
Li Gao, Yuan-Dong Li, Bao-Kun Zhu, Zhi-Yu Li, Li-Bin Huang, Xian-Yi Li, Fei Wang, Fu-Cai Ren, Tou-Gen Liao
Two new prenylflavonoids, morusalbols A and B (1 and 2), were isolated from the branches and leaves of Morus alba, together with three known compounds, kuwanon C (3), morusin (4), morusinol (5). The structures of these two prenylflavonoids were elucidated by extensive analyzes of the spectroscopic data.
June 23, 2017: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/28644650/nature-of-the-spin-liquid-ground-state-in-a-breathing-kagome-compound-studied-by-nmr-and-series-expansion
#19
J-C Orain, B Bernu, P Mendels, L Clark, F H Aidoudi, P Lightfoot, R E Morris, F Bert
In the vanadium oxyfluoride compound (NH_{4})_{2}[C_{7}H_{14}N][V_{7}O_{6}F_{18}] (DQVOF), the V^{4+} (3d^{1}, S=1/2) ions realize a unique, highly frustrated breathing kagome lattice composed of alternately sized, corner-sharing equilateral triangles. Here we present an ^{17}O NMR study of DQVOF, which isolates the local susceptibility of the breathing kagome network. By a fit to series expansion, we extract the ratio of the interactions within the breathing kagome plane, J_{∇}/J_{Δ}=0.55(4), and the mean antiferromagnetic interaction J[over ¯]=60(7)  K...
June 9, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28644630/expanding-the-therapeutic-potential-of-the-iron-chelator-deferasirox-in-the-development-of-aqueous-stable-ti-iv-anticancer-complexes
#20
Sergio A Loza-Rosas, Alexandra M Vázquez-Salgado, Kennett I Rivero, Lenny J Negrón, Yamixa Delgado, Josué A Benjamín-Rivera, Angel L Vázquez-Maldonado, Timothy B Parks, Charlene Munet-Colón, Arthur D Tinoco
The recent X-ray structure of titanium(IV)-bound human serum transferrin (STf) exhibiting citrate as a synergistic anion reveals a difference in Ti(IV) coordination versus iron(III), the metal endogenously delivered by the protein to cells. This finding enriches our bioinspired drug design strategy for Ti(IV)-based anticancer therapeutics, which applies a family of Fe(III) chelators termed chemical transferrin mimetic (cTfm) ligands to inhibit Fe bioavailability in cancer cells. Deferasirox, a drug used for iron overload disease, is a cTfm ligand that models STf coordination to Fe(III), favoring Fe(III) binding versus Ti(IV)...
June 23, 2017: Inorganic Chemistry
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