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https://www.readbyqxmd.com/read/30340896/discovery-of-5-2-chloro-4-1h-imidazol-1-yl-1-1-biphenyl-4-yl-1h-tetrazole-as-potent-and-orally-efficacious-s-nitrosoglutathione-reductase-gsnor-inhibitors-for-the-potential-treatment-of-copd
#1
Nagarajan Muthukaman, Sanjay Deshmukh, Shital Tondlekar, Macchindra Tambe, Dnyandeo Pisal, Neelam Sarode, Siddharth Mhatre, Samitabh Chakraborti, Daisy Shah, Vikram M Bhosale, Abhay Kulkarni, Mahamad Yunnus A Mahat, Satyawan B Jadhav, Girish S Gudi, Neelima Khairatkar-Joshi, Laxmikant A Gharat
Endogenous nitrosothiols (SNOs) including S-nitrosoglutathione (GSNO) serve as reservoir for bioavailable nitric oxide (NO) and mediate NO-based signaling, inflammatory status and smooth muscle function in the lung. GSNOR inhibition increases pulmonary GSNO and induces bronchodilation while reducing inflammation in lung diseases. In this letter, design, synthesis and structure-activity relationships (SAR) of novel imidazole-biaryl-tetrazole based GSNOR inhibitors are described. Many potent inhibitors (30, 39, 41, 42, 44, 45 and 58) were identified with low nanomolar activity (IC50 s: <15 nM) along with adequate metabolic stability...
October 10, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/30333842/deciphering-the-genetic-architecture-of-cooked-rice-texture
#2
Gopal Misra, Saurabh Badoni, Cyril John Domingo, Rosa Paula O Cuevas, Cindy Llorente, Edwige Gaby Nkouaya Mbanjo, Nese Sreenivasulu
The textural attributes of cooked rice determine palatability and consumer acceptance. Henceforth, understanding the underlying genetic basis is pivotal for the genetic improvement of preferred textural attributes in breeding programs. We characterized diverse set of 236 Indica accessions from 37 countries for textural attributes, which includes adhesiveness (ADH), hardness (HRD), springiness (SPR), and cohesiveness (COH) as well as amylose content (AC). A set of 147,692 high quality SNPs resulting from genotyping data of 700K high Density Rice Array (HDRA) derived from the Indica diversity panels of 218 lines were retained for marker-trait associations of textural attributes using single-locus (SL) genome wide association studies (GWAS) which resulted in identifying hotspot on chromosome 6 for AC and ADH attributes...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/30328850/studying-nad-p-h-cofactor-binding-to-alcohol-dehydrogenases-through-global-analysis-of-circular-dichroism-spectra
#3
Marija Marolt, Steffen Lüdeke
The initial step in reactions catalyzed by NAD(P)H-dependent alcohol dehydrogenases (ADHs) is the binding of the cofactor to the active site. To study this process, we measured NAD(P)H concentration-dependent circular dichroism (CD) in the presence of purified enzymes (ADH from horse liver, HLADH; ADH-A from Rhodococcus ruber; YGL157w from Saccharomyces cerevisiae) or enzyme-containing whole cell extract (ADH from Lactobacillus brevis, LbADH). We determined the proportions of binding and non-binding NAD(P)H and the associated dissociation constants (Kd) from matrix least-squares global fitting of law of mass action-derived model...
October 17, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/30328568/san-ao-decoction-regulates-urine-volume-on-bronchial-asthma-model-mice
#4
Min Wang, Yan Sun, Shu-Jing Zhang, Yu-Shan Gao, Ya-Nan Wei, Peng-Na Zhao, Miao Liu, Jia-Min Yang, Feng-Jie Zheng, Hong Xu, Yu-Hang Li
OBJECTIVE: To observe the effect of San-Ao Decoction (, SAD) on water metabolism of bronchial asthra model mice. METHODS: Forty-five female BALB/c mice were randomly divided into control, model and SAD groups by a random number table, 15 mice in each group. A composite method with ovalbumin (OVA) sensitization and challenge was developed to establish bronchial asthma model. Mice in the control group were intraperitoneally injected with distilled water without aerosol inhalation challenge...
October 17, 2018: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/30320893/alcohol-dehydrogenases-aldehyde-dehydrogenases-and-alcohol-use-disorders-a-critical-review
#5
Howard J Edenberg, Jeanette N McClintick
Alcohol use disorders (AUD) are complex traits, meaning that variations in many genes contribute to the risk, as does the environment. Although the total genetic contribution to risk is substantial, most individual variations make only very small contributions. By far the strongest contributors are functional variations in two genes involved in alcohol (ethanol) metabolism. A functional variant in alcohol dehydrogenase 1B (ADH1B) is protective in people of European and Asian descent, and a different functional variant in the same gene is protective in those of African descent...
October 15, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/30319745/biocatalyst-artificial-metalloenzyme-cascade-based-on-alcohol-dehydrogenase
#6
Simone Morra, Anca Pordea
Chemo-enzymatic cascades of enzymes with transition metal catalysts can offer efficient synthetic strategies, but their development is challenging due to the incompatibility between proteins and transition metal complexes. Rhodium catalysts can be combined with alcohol dehydrogenases to regenerate nicotinamide cofactors using formate as the hydride donor. However, their use is limited, due to binding of the metals to residues on the enzyme surface, leading to mutual enzyme and catalyst inactivation. In this work, we replaced the zinc from Thermoanaerobacter brockii alcohol dehydrogenase (TbADH) with Rh(iii) catalysts possessing nitrogen donor ligands, by covalent conjugation to the active site cysteine, to create artificial metalloenzymes for NADP+ reduction...
October 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/30318287/radiologic-and-pathologic-features-associated-with-upgrade-of-atypical-ductal-hyperplasia-at-surgical-excision
#7
Kristin E Williams, Amanda Amin, Jacqueline Hill, Carissa Walter, Marc Inciardi, Jason Gatewood, Mark Redick, Jo Wick, Suzanne Hunt, Onalisa Winblad
RATIONALE AND OBJECTIVES: To evaluate radiologic and pathologic features associated with upgrade of atypical ductal hyperplasia (ADH) to ductal carcinoma in situ or invasive breast cancer at surgical excision, in order to identify patients who may consider alternatives to excision. MATERIALS AND METHODS: This retrospective analysis examined patients who underwent surgical excision of biopsy-proven ADH at our institution. Imaging and pathology from biopsy were reviewed to determine radiologic (lesion size, radiologic abnormality, biopsy type, needle gauge, number of cores, percent of lesion removed) and pathologic features (histologic calcifications, presence of necrosis, micropapillary features, extent of ADH) associated with ADH upgrade...
October 12, 2018: Academic Radiology
https://www.readbyqxmd.com/read/30318023/the-alcohol-dehydrogenase-with-a-broad-range-of-substrate-specificity-regulates-vitality-and-reproduction-of-the-plant-parasitic-nematode-bursaphelenchus-xylophilus
#8
Linsong Wang, Tingting Zhang, Zhengsong Pan, Lulu Lin, Guoqing Dong, Min Wang, Ronggui Li
Pine wilt disease, which is caused by the pine wood nematode (PWN), Bursaphelenchus xylophilus, has caused huge damage to pine forests around the world. In this study, we analysed the PWN transcriptome to investigate the expression of genes related to the associated bacterial species Pseudomonas fluorescens and found that the gene adh-1 encoding alcohol dehydrogenase (ADH) was upregulated. The open reading frame of adh-1, which encoded a protein of 352 amino acid residues, was cloned from B. xylophilus. Recombinant ADH with a relative molecular weight of 39 kDa, was present mainly in inclusion bodies and was overexpressed in Escherichia coli BL21 (DE3) and purified after refolding...
October 15, 2018: Parasitology
https://www.readbyqxmd.com/read/30316512/discovering-a-new-catabolic-pathway-of-d-ribonate-in-mycobacterium-smegmatis
#9
Shengkai Luo, Hua Huang
In vivo growth study indicates that Mycobacterium smegmatis could utilize D-ribonate as sole carbon source under an unknown pathway. To clarify this pathway, we start with the statistical analysis of genome neighborhood networks(GNNs) of erythrulose kinase which has been approved to participate in several sugars' degradation. In M. smegmatis, two novel dehydrogenases (3HCDH & ADH_short) and one unknown isomerase (AP_endonuc) are targeted and characterized, for the catabolism of D-ribonate in this organism, this acid sugar is firstly oxidized into 2-keto-D-ribonate by a dehydrogenase, and then sequentially isomerized to 3-keto D-ribonate by an AP_endonuc isomerase; afterward, through decarboxylation, this 3-keto sugar acid is degraded into D-erythrulose which enters a known pathway through erythrulose kinase...
October 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30303493/an-update-on-tolvaptan-for-autosomal-dominant-polycystic-kidney-disease
#10
E Poch, L Rodas, M Blasco, A Molina, L Quintana
Tolvaptan is an orally active antagonist of vasopressin (antidiuretic hormone [ADH]) V2 receptors. By blocking water reabsorption in kidney collecting ducts, it prompts renal free-water excretion and has been used for the treatment of hyponatremia, both euvolemic due to the syndrome of inappropriate ADH secretion, and hypervolemic due to liver cirrhosis and congestive heart failure. In the past few years, it has been shown that vasopressin and its second messenger cyclic adenosine monophosphate (cAMP) play an important role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD)...
September 2018: Drugs of Today
https://www.readbyqxmd.com/read/30293936/autosomal-dominant-hypercholesterolemia-in-catalonia-correspondence-between-clinical-biochemical-and-genetic-diagnostics-in-967-patients-studied-in-a-multicenter-clinical-setting
#11
Jesús M Martín-Campos, Núria Plana, Rosaura Figueras, Daiana Ibarretxe, Assumpta Caixàs, Eduardo Esteve, Antonio Pérez, Marta Bueno, Marta Mauri, Rosa Roig, Susana Martínez, Xavier Pintó, Luís Masana, Josep Julve, Francisco Blanco-Vaca
BACKGROUND: Autosomal dominant hypercholesterolemia (ADH) is associated with mutations in the low-density lipoprotein (LDL) receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) genes, and it is estimated to be greatly underdiagnosed. The most cost-effective strategy for increasing ADH diagnosis is a cascade screening from mutation-positive probands. OBJECTIVE: The objective of this study was to evaluate the results from 2008 to 2016 of ADH genetic analysis performed in our clinical laboratory, serving most lipid units of Catalonia, a Spanish region with approximately 7...
September 7, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/30291951/introduction-of-bifunctional-alcohol-acetaldehyde-dehydrogenase-gene-adhe-in-fructobacillus-fructosus-settled-its-fructophilic-characteristics
#12
Shintaro Maeno, Akinobu Kajikawa, Leon Dicks, Akihito Endo
Fructophilic lactic acid bacteria (FLAB) are unique in the sense that they prefer D-fructose over D-glucose as main carbon source. If D-glucose is metabolised, electron acceptors are required and significant levels of acetate are produced. These bacteria are found in environments rich in D-fructose, such as flowers, fruits and the gastrointestinal tract of insects feeding on fructose-rich diets. Fructobacillus spp. are representatives of this unique group, and their fructophilic characteristics are well conserved...
October 3, 2018: Research in Microbiology
https://www.readbyqxmd.com/read/30282032/endogenous-rrna-sequence-variation-can-regulate-stress-response-gene-expression-and-phenotype
#13
Chad M Kurylo, Matthew M Parks, Manuel F Juette, Boris Zinshteyn, Roger B Altman, Jordana K Thibado, C Theresa Vincent, Scott C Blanchard
Prevailing dogma holds that ribosomes are uniform in composition and function. Here, we show that nutrient limitation-induced stress in E. coli changes the relative expression of rDNA operons to alter the rRNA composition within the actively translating ribosome pool. The most upregulated operon encodes the unique 16S rRNA, rrsH, distinguished by conserved sequence variation within the small ribosomal subunit. rrsH-bearing ribosomes affect the expression of functionally coherent gene sets and alter the levels of the RpoS sigma factor, the master regulator of the general stress response...
October 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/30281370/atypical-ductal-lesions-of-the-breast-criteria-significance-and-laboratory-updates
#14
Ellen G East, Cody S Carter, Celina G Kleer
CONTEXT.—: Atypical ductal hyperplasia (ADH) is a challenging diagnosis defined by cytologic and architectural features that carries an increased risk of subsequent carcinoma when diagnosed in isolation. In addition, ADH may secondarily involve benign breast lesions, wherein it carries variable clinical significance. OBJECTIVES.—: To review the diagnostic criteria and clinical significance of ADH in isolation and as it involves benign breast lesions, and to review the evolving literature on its molecular signature...
October 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/30280450/case-series-and-systematic-review-of-acquired-diaphragmatic-hernia-after-liver-transplantation
#15
Juliet A Emamaullee, Victor Nekrasov, Susan Gilmour, Norman Kneteman, George Yanni, Rohit Kohli, Daniel Thomas, Yuri Genyk
BACKGROUND: ADH is a rare and potentially fatal complication following LT. In this study, a systematic review was completed to identify risk factors which may contribute to ADH. METHODS: Transplant databases at three LT programs were reviewed. Four pediatric and zero adult cases were identified. Next, a systematic review was completed. Fourteen studies describing 41 patients with ADH were identified. Patient demographics, transplant characteristics, and features of ADH diagnosis were examined...
October 2, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/30276556/improved-bioethanol-production-using-crispr-cas9-to-disrupt-the-adh2-gene-in-saccharomyces-cerevisiae
#16
Ting Xue, Kui Liu, Duo Chen, Xue Yuan, Jingping Fang, Hansong Yan, Luqiang Huang, Youqiang Chen, Wenjin He
Bioethanol, as a form of renewable and clean energy, has become increasingly important to the energy supply. One major obstacle in ethanol production is developing a high-capacity system. Existing approaches for regulating the ethanol production pathway are relatively insufficient, with nonspecific genetic manipulation. Here, we used CRISPR/Cas9 technology to disrupt the alcohol dehydrogenase (ADH) 2 gene via complete deletion of the gene and introduction of a frameshift mutation in the ADH2 locus. Sequencing demonstrated the accurate knockout of the target gene with 91...
October 1, 2018: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/30275907/enhancement-of-photosynthetic-isobutanol-production-in-engineered-cells-of-synechocystis-pcc-6803
#17
Rui Miao, Hao Xie, Peter Lindblad
Background: Cyanobacteria, oxygenic photoautotrophic prokaryotes, can be engineered to produce various valuable chemicals from solar energy and CO2 in direct processes. The concept of photosynthetic production of isobutanol, a promising chemical and drop-in biofuel, has so far been demonstrated for Synechocystis PCC 6803 and Synechococcus elongatus PCC 7942. In Synechocystis PCC 6803, a heterologous expression of α-ketoisovalerate decarboxylase (Kivd) from Lactococcus lactis resulted in an isobutanol and 3-methyl-1-butanol producing strain...
2018: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/30268890/mechanisms-involved-in-the-death-of-steatotic-wif-b9-hepatocytes-co-exposed-to-benzo-a-pyrene-and-ethanol-a-possible-key-role-for-xenobiotic-metabolism-and-nitric-oxide
#18
Arnaud Tête, Isabelle Gallais, Muhammad Imran, Martine Chevanne, Marie Liamin, Lydie Sparfel, Simon Bucher, Agnès Burel, Normand Podechard, Brice M R Appenzeller, Bernard Fromenty, Nathalie Grova, Odile Sergent, Dominique Lagadic-Gossmann
We previously demonstrated that co-exposing pre-steatotic hepatocytes to benzo[a]pyrene (B[a]P), a carcinogenic environmental pollutant, and ethanol, favored cell death. Here, the intracellular mechanisms underlying this toxicity were studied. Steatotic WIF-B9 hepatocytes, obtained by a 48h-supplementation with fatty acids, were then exposed to B[a]P/ethanol (10 nM/5 mM, respectively) for 5 days. Nitric oxide (NO) was demonstrated to be a pivotal player in the cell death caused by the co-exposure in steatotic hepatocytes...
September 27, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/30261143/construction-of-injectable-self-healing-macroporous-hydrogels-via-a-template-free-method-for-tissue-engineering-and-drug-delivery
#19
Lei Wang, Fen Deng, Wenwen Wang, Afeng Li, Conglie Lu, Hao Chen, Gang Wu, Kaihui Nan, Lingli Li
Because of their ease of handling and excellent biocompatibility, injectable macroporous hydrogels have received a considerable interest in the fields of tissue engineering and drug delivery systems because of their unique application in minimally invasive surgical procedures. In this study, in situ forming, injectable, macroporous, self-healing gelatin (GE)/oxidized alginate (OSA)/adipic acid dihydrazide (ADH) hydrogels were prepared using a high-speed shearing treatment and were stabilized by Schiff base reaction and acylhydrazone bonds...
October 18, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/30257818/efficiency-of-single-dose-of-tolvaptan-treatment-during-the-triphasic-episode-after-surgery-for-craniopharyngioma
#20
Fatih Gürbüz, Mehmet Taştan, İhsan Turan, Bilgin Yüksel
Inappropriate ADH syndrome (SIADH) may develop after intracranial surgery. SIADH in pediatric age is mostly seen in intracranial mass and not only after surgery. The management of these clinical conditions in patients is important for the clinical course of the patient. Fluid restriction is standard therapy in SIADH. Resistant hyponatremic pattern may be encountered in some cases. Vaptans have recently started to be used in hyponatremia due to SIADH. A patient with SIADH of triphasic episode presented to our clinical practice after surgery of craniopharyngioma...
September 27, 2018: Journal of Clinical Research in Pediatric Endocrinology
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