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https://www.readbyqxmd.com/read/29352482/influence-of-pharmacogenetic-polymorphisms-and-demographic-variables-on-metformin-pharmacokinetics-in-an-admixed-brazilian-cohort
#1
Ana Beatriz Santoro, Mariana Rodrigues Botton, Claudio José Struchiner, Guilherme Suarez-Kurtz
AIM: To identify pharmacogenetic and demographic variables that influence the systemic exposure to metformin in an admixed Brazilian cohort. METHODS: The extreme discordant phenotype was used to select 106 data sets from nine metformin bioequivalence trials, comprising 256 healthy adults. Eleven single-nucleotide polymorphisms in SLC22A1, SLC22A2, SLC47A1 SLC47A2 and in transcription factor SP1 were genotyped and a validated panel of ancestry informative markers was used to estimate the individual proportions of biogeographical ancestry...
January 20, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29352405/virus-particle-detection-by-convolutional-neural-network-in-transmission-electron-microscopy-images
#2
Eisuke Ito, Takaaki Sato, Daisuke Sano, Etsuko Utagawa, Tsuyoshi Kato
A new computational method for the detection of virus particles in transmission electron microscopy (TEM) images is presented. Our approach is to use a convolutional neural network that transforms a TEM image to a probabilistic map that indicates where virus particles exist in the image. Our proposed approach automatically and simultaneously learns both discriminative features and classifier for virus particle detection by machine learning, in contrast to existing methods that are based on handcrafted features that yield many false positives and require several postprocessing steps...
January 19, 2018: Food and Environmental Virology
https://www.readbyqxmd.com/read/29352398/efficient-biosynthesis-of-l-phenylglycine-by-an-engineered-escherichia-coli-with-a-tunable-multi-enzyme-coordinate-expression-system
#3
Qiaoli Liu, Junping Zhou, Taowei Yang, Xian Zhang, Meijuan Xu, Zhiming Rao
Whole-cell catalysis with co-expression of two or more enzymes in a single host as a simple low-cost biosynthesis method has been widely studied and applied but hardly with regulation of multi-enzyme expression. Here we developed an efficient whole-cell catalyst for biosynthesis of L-phenylglycine (L-Phg) from benzoylformic acid through co-expression of leucine dehydrogenase from Bacillus cereus (BcLeuDH) and NAD+-dependent mutant formate dehydrogenase from Candida boidinii (CbFDHA10C) in Escherichia coli with tunable multi-enzyme-coordinate expression system...
January 19, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29352392/impact-of-dexamethasone-concentration-on-cartilage-tissue-formation-from-human-synovial-derived-stem-cells-in-vitro
#4
Ryota Chijimatsu, Masato Kobayashi, Kosuke Ebina, Toru Iwahashi, Yosuke Okuno, Makoto Hirao, Atsunori Fukuhara, Norimasa Nakamura, Hideki Yoshikawa
Human synovial mesenchymal stem cells (hSMSCs) are a promising cell source for cartilage regeneration because of their superior chondrogenic potential in vitro. This study aimed to further optimize the conditions for inducing chondrogenesis of hSMSCs, focusing on the dose of dexamethasone in combination with transforming growth factor-β3 (TGFβ3) and/or bone morphogenetic protein-2 (BMP2). When hSMSCs-derived aggregates were cultured with TGFβ3, dexamethasone up to 10 nM promoted chondrogenesis, but attenuated it with heterogeneous tissue formation when used at concentrations over than 100 nM...
January 19, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29352243/nucleolin-and-erbb2-inhibition-reduces-tumorigenicity-of-erbb2-positive-breast-cancer
#5
Eya Wolfson, Shira Solomon, Eran Schmukler, Yona Goldshmit, Ronit Pinkas-Kramarski
ErbB2, a member of the ErbB family of receptor tyrosine kinases, is an essential player in the cell's growth and proliferation signaling pathways. Amplification or overexpression of ErbB2 is observed in ∼30% of breast cancer patients, and often drives cellular transformation and cancer development. Recently, we have shown that ErbB2 interacts with the nuclear-cytoplasmic shuttling protein nucleolin, an interaction which enhances cell transformation in vitro, and increases mortality risk and disease progression rate in human breast cancer patients...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352178/compositional-bias-in-na%C3%A3-ve-and-chemically-modified-phage-displayed-libraries-uncovered-by-paired-end-deep-sequencing
#6
Bifang He, Katrina F Tjhung, Nicholas J Bennett, Ying Chou, Andrea Rau, Jian Huang, Ratmir Derda
Understanding the composition of a genetically-encoded (GE) library is instrumental to the success of ligand discovery. In this manuscript, we investigate the bias in GE-libraries of linear, macrocyclic and chemically post-translationally modified (cPTM) tetrapeptides displayed on the M13KE platform, which are produced via trinucleotide cassette synthesis (19 codons) and NNK-randomized codon. Differential enrichment of synthetic DNA {S}, ligated vector {L} (extension and ligation of synthetic DNA into the vector), naïve libraries {N} (transformation of the ligated vector into the bacteria followed by expression of the library for 4...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352141/pressure-effect-on-impurity-local-vibrational-mode-and-phase-transitions-in-n-type-iron-doped-indium-phosphide
#7
Chih-Ming Lin, I-Jui Hsu, Sin-Cheng Lin, Yu-Chun Chuang, Wei-Ting Chen, Yen-Fa Liao, Jenh-Yih Juang
The evolution of iron local vibrational mode (Fe LVM) and phase transitions in n-type iron-doped indium phosphide (InP:Fe) were investigated at ambient temperature. In-situ angle-dispersive X-ray diffraction measurements revealed that InP:Fe starts to transform from zinc-blende (ZB) to rock-salt (RS) structure around 8.2(2) GPa and completes around 16.0(2) GPa. The Raman shift of both transverse and longitudinal optical modes increases monotonically with increasing pressure, while their intensities become indiscernible at 11...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352139/mitochondrial-glutamine-metabolism-via-got2-supports-pancreatic-cancer-growth-through-senescence-inhibition
#8
Seungyeon Yang, Sunsook Hwang, Minjoong Kim, Sung Bin Seo, Jeong-Hwa Lee, Seung Min Jeong
Cellular senescence, which leads to a cell cycle arrest of damaged or dysfunctional cells, is an important mechanism to restrain the malignant progression of cancer cells. Because metabolic changes underlie many cell-fate decisions, it has been suggested that cell metabolism might play key roles in senescence pathways. Here, we show that mitochondrial glutamine metabolism regulates senescence in human pancreatic ductal adenocarcinoma (PDAC) cells. Glutamine deprivation or inhibition of mitochondrial aspartate transaminase (GOT2) results in a profound induction of senescence and a suppression of PDAC growth...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352019/opposing-roles-of-tgf%C3%AE-and-bmp-signaling-in-prostate-cancer-development
#9
Xin Lu, Eun-Jung Jin, Xi Cheng, Shan Feng, Xiaoying Shang, Pingna Deng, Shan Jiang, Qing Chang, Sharif Rahmy, Seema Chaudhary, Xuemin Lu, Ren Zhao, Y Alan Wang, Ronald A DePinho
SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGFβ receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate cancer model. These studies demonstrated that the molecular actions of TGFBR2 result in both SMAD4-dependent constraint of proliferation and SMAD4-independent activation of apoptosis. In contrast, BMPR2 deletion extended survival relative to Pten deletion alone, establishing its promoting role in BMP6-driven prostate cancer progression...
December 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29351992/involvement-of-aryl-hydrocarbon-receptor-in-myelination-and-in-human-nerve-sheath-tumorigenesis
#10
Ghjuvan'Ghjacumu Shackleford, Nirmal Kumar Sampathkumar, Mehdi Hichor, Laure Weill, Delphine Meffre, Ludmila Juricek, Ingrid Laurendeau, Aline Chevallier, Nicolas Ortonne, Frédérique Larousserie, Marc Herbin, Ivan Bièche, Xavier Coumoul, Mathieu Beraneck, Etienne-Emile Baulieu, Frédéric Charbonnier, Eric Pasmant, Charbel Massaad
Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in xenobiotic metabolism. Plexiform neurofibromas (PNFs) can transform into malignant peripheral nerve sheath tumors (MPNSTs) that are resistant to existing therapies. These tumors are primarily composed of Schwann cells. In addition to neurofibromatosis type 1 (NF1) gene inactivation, further genetic lesions are required for malignant transformation. We have quantified the mRNA expression levels of AHR and its associated genes in 38 human samples...
January 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29351904/er%C3%AE-mediated-nuclear-sequestration-of-rsk2-is-required-for-er-breast-cancer-tumorigenesis
#11
Katarzyna A Ludwik, Oliver Gene McDonald, David R Brenin, Deborah A Lannigan
Although ribosomal protein S6 kinase A3 (RSK) activation status positively correlates with patient responses to anti-estrogen hormonal therapies, the mechanistic basis for these observations is unknown. Using multiple in vitro and in vivo models of ER+ breast cancer, we report that ERα sequesters active RSK2 into the nucleus to promote neoplastic transformation and facilitate metastatic tumor growth. RSK2 physically interacted with ERα through its N-terminus to activate a pro-neoplastic transcriptional network critical to the ER+ lineage in the mammary gland, thereby providing a gene signature that effectively stratified patient tumors according to ERα status...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29351873/biochar-amendment-for-batch-composting-of-nitrogen-rich-organic-waste-effect-on-degradation-kinetics-composting-physics-and-nutritional-properties
#12
Mayur Shirish Jain, Rohit Jambhulkar, Ajay S Kalamdhad
Composting is an efficient technology to reduce pathogenic bodies and stabilize the organic matter in organic wastes. This research work investigates an effect of biochar as amendment to improve the composting efficiency and its effect on degradation kinetics, physical and nutritional properties. Biochar (2.5, 5 and 10% (w/w)) were added into a mixture of Hydrilla verticillata, cow dung and sawdust having ratio of 8:1:1 (control), respectively. Biochar addition resulted in advanced thermophilic temperatures (59 °C) and could improve the physical properties of composting process...
January 9, 2018: Bioresource Technology
https://www.readbyqxmd.com/read/29351859/structural-and-immunological-characterization-of-hydroxyl-radical-modified-human-igg-clinical-correlation-in-rheumatoid-arthritis
#13
Sidra Islam, Abdul Rouf Mir, Mir Yasir Arfat, Farzana Khan, Masihuz Zaman, Asif Ali, Moinuddin
Structural alterations in proteins under oxidative stress have been widely implicated in the immuno-pathology of various disorders. This study has evaluated the extent of damage in the conformational characteristics of IgG by hydroxyl radical (OH) and studied its implications in the immuno-pathology of rheumatoid arthritis (RA). Using various biophysical and biochemical techniques, changes in aromatic microenvironment of the IgG and the protein aggregation became evident after treatment with OH. The SDS-PAGE study confirmed the protein aggregation while far ultraviolet circular dichroism spectroscopy (Far-UV CD) and fourier transform infrared spectroscopy (FTIR) inferred towards the alterations in secondary structure of IgG under OH stress...
January 10, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29351858/determination-of-semicarbazide-in-fish-by-molecularly-imprinted-stir-bar-sorptive-extraction-coupled-with-high-performance-liquid-chromatography
#14
Tang Tang, Fangdi Wei, Xu Wang, Yujie Ma, Yueyue Song, Yunsu Ma, Quan Song, Guanhong Xu, Yao Cen, Qin Hu
A novel molecularly imprinted stir bar (MI-SB) for sorptive extraction of semicarbazide (SEM) was prepared in present paper. The coating of the stir bar was characterized by scanning electron microscopy, Fourier-transform infrared spectroscopy, dynamic adsorption and static adsorption tests. The saturated adsorption of MI-SB was about 4 times over that of non-imprinted stir bar (NI-SB). The selectivity of MI-SB for SEM was much better than NI-SB. A method to determine SEM was established by coupling MI-SB sorptive extraction with HPLC-UV...
January 4, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29351552/in-situ-recording-of-ionic-currents-in-projection-neurons-and-kenyon-cells-in-the-olfactory-pathway-of-the-honeybee
#15
Jan Kropf, Wolfgang Rössler
The honeybee olfactory pathway comprises an intriguing pattern of convergence and divergence: ~60.000 olfactory sensory neurons (OSN) convey olfactory information on ~900 projection neurons (PN) in the antennal lobe (AL). To transmit this information reliably, PNs employ relatively high spiking frequencies with complex patterns. PNs project via a dual olfactory pathway to the mushroom bodies (MB). This pathway comprises the medial (m-ALT) and the lateral antennal lobe tract (l-ALT). PNs from both tracts transmit information from a wide range of similar odors, but with distinct differences in coding properties...
2018: PloS One
https://www.readbyqxmd.com/read/29351444/activated-human-t-lymphocytes-inhibit-tgf%C3%AE-induced-fibroblast-to-myofibroblast-differentiation-via-prostaglandins-d2-and-e2
#16
Shannon H Lacy, Amali P Epa, Stephen J Pollock, Collynn F Woeller, Thomas H Thatcher, Richard P Phipps, Patricia J Sime
In pulmonary fibrosis (PF), fibroblasts and myofibroblasts proliferate and deposit excessive extracellular matrix in the interstitium, impairing normal lung function. As most forms of PF have a poor prognosis and limited treatment options, PF represents an urgent unmet need for novel, effective therapeutics. While the role of immune cells in lung fibrosis is unclear, recent studies suggest that T lymphocyte (T cell) activation may be impaired in PF patients. Further, we have previously shown that activated T cells can produce prostaglandins with anti-scarring potential...
December 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351434/cub-domain-containing-protein-1-cdcp1-negatively-regulates-tgf%C3%AE-signaling-and-myofibroblast-differentiation
#17
Nina Noskovičová, Katharina Heinzelmann, Gerald Burgstaller, Jürgen Behr, Oliver Eickelberg
Fibroblasts are thought to be the prime cell type for producing and secreting extracellular matrix (ECM) proteins in the connective tissue. The profibrotic cytokine, transforming growth factor-beta 1 (TGFβ1) activates and transdifferentiates fibroblasts into αSMA-expressing myofibroblasts, which exhibit increased ECM secretion, in particular collagens. Little information, however, exists about cell-surface molecules on fibroblasts that mediate this transdifferentiation process. We recently identified, using unbiased cell-surface proteome analysis, Cub domain containing protein 1 (CDCP1) to be strongly downregulated by TGFβ1...
January 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351393/liver-tissue-metabolically-transformed-by-alcohol-induces-immune-recognition-of-liver-self-proteins-but-not-in-vivo-inflammation
#18
Michael J Duryee, Benjamin M Wiese, Jordan R Bowman, Jared D Vanlandingham, Lynell W Klassen, Geoffrey E Thiele, Carlos D Hunter, Daniel R Anderson, Ted R Mikuls, Geoffrey M Thiele
Precision cut liver slices (PCLSs) provide a novel model for studies in alcoholic liver disease (ALD). This is relevant, as in vivo ethanol exposure does not appear to generate significant liver damage in ethanol fed mice, except in the NIAAA binge model of ALD. Previous studies have shown that the two metabolites of ethanol consumption, malondialdhyde (MDA) and acetaldehyde (AA), combine to form (MAA), which has been correlated with the development and progression of ALD. In this study murine PCLSs were incubated with ethanol and examined for the production of MAA...
December 28, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29351344/the-morphing-of-geographical-features-by-fourier-transformation
#19
Jingzhong Li, Pengcheng Liu, Wenhao Yu, Xiaoqiang Cheng
This paper presents a morphing model of vector geographical data based on Fourier transformation. This model involves three main steps. They are conversion from vector data to Fourier series, generation of intermediate function by combination of the two Fourier series concerning a large scale and a small scale, and reverse conversion from combination function to vector data. By mirror processing, the model can also be used for morphing of linear features. Experimental results show that this method is sensitive to scale variations and it can be used for vector map features' continuous scale transformation...
2018: PloS One
https://www.readbyqxmd.com/read/29351335/the-effects-of-an-acute-exercise-bout-on-gh-and-igf-1-in-prediabetic-and-healthy-african-americans-a-pilot-study-investigating-gene-expression
#20
Nathaniel T Berry, Monica Hubal, Laurie Wideman
The incidence of pre-diabetes (PD) and Type-2 Diabetes Mellitus (T2D) is a worldwide epidemic. African American (AA) individuals are disproportionately more likely to become diabetic than other ethnic groups. Over the long-term, metabolic complications related to diabetes result in significant alterations in growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Considering the limited exercise-related studies in the area of gene expression changes with disease progression, the objective of this study was to examine differences in exercise-induced gene expression related to the GH and IGF-1 pathways in peripheral blood mononuclear cells (PBMCs) of healthy (CON) and PD AA individuals...
2018: PloS One
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