Search

Your search keyword '"Nicotinamide adenine dinucleotide (phosphate) transhydrogenase"' showing total 3 results
Start Over Descriptor "Nicotinamide adenine dinucleotide (phosphate) transhydrogenase"
3 results on '"Nicotinamide adenine dinucleotide (phosphate) transhydrogenase"'

1. Thermodynamic analysis of computed pathways integrated into the metabolic networks of E. coli and Synechocystis reveals contrasting expansion potential

Author

Asplund-Samuelsson, Johannes, Janasch, Markus, Hudson, Elton P., Asplund-Samuelsson, Johannes, Janasch, Markus, and Hudson, Elton P.

Abstract

Introducing biosynthetic pathways into an organism is both reliant on and challenged by endogenous biochemistry. Here we compared the expansion potential of the metabolic network in the photoautotroph Synechocystis with that of the heterotroph E. coli using the novel workflow POPPY (Prospecting Optimal Pathways with PYthon). First, E. coli and Synechocystis metabolomic and fluxomic data were combined with metabolic models to identify thermodynamic constraints on metabolite concentrations (NET analysis). Then, thousands of automatically constructed pathways were placed within each network and subjected to a network-embedded variant of the max-min driving force analysis (NEM). We found that the networks had different capabilities for imparting thermodynamic driving forces toward certain compounds. Key metabolites were constrained differently in Synechocystis due to opposing flux directions in glycolysis and carbon fixation, the forked tri-carboxylic acid cycle, and photorespiration. Furthermore, the lysine biosynthesis pathway in Synechocystis was identified as thermodynamically constrained, impacting both endogenous and heterologous reactions through low 2-oxoglutarate levels. Our study also identified important yet poorly covered areas in existing metabolomics data and provides a reference for future thermodynamics-based engineering in Synechocystis and beyond. The POPPY methodology represents a step in making optimal pathway-host matches, which is likely to become important as the practical range of host organisms is diversified., Export Date: 13 February 2018; Article; CODEN: MEENF; Correspondence Address: Hudson, E.P.; Science for Life Laboratory, School of Biotechnology, KTH Royal Institute of Technology, P-Box 1031, Sweden; email: paul.hudson@scilifelab.se; Funding details: 2016-06160, VR, Vetenskapsrådet; Funding details: RBP14-0013, SSF, Stiftelsen för Strategisk Forskning. QC 20180228

Published
2018
Full Text
View/download PDF

2. Rare causes of primary adrenal insufficiency: Genetic and clinical characterization of a large nationwide cohort

Author

Güran, Tülay, Buonocore, Federica, Saka, Nurçin, Özbek, Mehmet Nuri, Aycan, Zehra, Bereket, Abdullah, Baş, Firdevs, Darcan, Sükran, Bideci, Aysun, Güven, Ayla, Demir, Korcan, Akıncı, Ayşehan, Büyükinan, Muammer, Aydın, Banu Küçükemre, Turan, Serap, Ağladıoğlu, Sebahat Yılmaz, Atay, Zeynep, Abalı, Zehra Yavaş, Çatlı, Gönül, Yüksel, Bilgin, Akçay, Teoman, Yıldız, Metin, Özen, Samim, Doger, Esra, Demirbilek, Hüseyin, Uçar, Ahmet, Işık, Emregül, Özhan, Bayaram, Bolu, Semih, Özgen, İlker Tolga, Suntharalingham, Jenifer P., Achermann, John C., Uludağ Üniversitesi/Tıp Fakültesi/Pediatrik Endokrinoloji ve Diyabet Anabilim Dalı., and Tarım, Ömer

Subjects
Male, Genetic procedures, ABCD1 gene, Turkey, Epidemiology, CYP11A1 gene, Gene, Infant, newborn, Structured questionnaire, Chain cleavage enzyme, High throughput sequencing, MC2R gene, Missense mutation, Child, Endocrinology & metabolism, Priority journal, Achalasia Addisonianism Alacrimia Syndrome, Melanocortin 2 Receptor, Alacrima, Nonsense mutation, Follow-up, Genetic analysis, MRAP gene, Cyp11A1, NR0B1 gene, AAAS gene, NR5A1 gene, Acth receptor, Cohort studies, Female, Molecular diagnosis, Nicotinamide adenine dinucleotide (phosphate) transhydrogenase, Cohort analysis, Primary adrenal insufficiency, Human, Sequence capture, Adolescent, Child, preschool, Age of onset, Major clinical study, Killer-cell deficiency, Hypoplasia congenita, Article, Next generation sequencing, Frameshift mutation, NNT gene, Genetics, Humans, Steroidogenic factor-I, Clinical evaluation, Genetic variation, Gene deletion, Infant, DNA, Mutational analysis, Newborn, Cholesterol monooxygenase (side chain cleaving), Dax-1 nrob1, Onset age, Clinical feature, Preschool child, Missense mutations, Mutation, Corticotropin, Genetic variability, Gene expression, Familial glucocorticoid deficiency, Adrenal insufficiency
Abstract

Context: Primary adrenal insufficiency (PAI) is a life-threatening condition that is often due to monogenic causes in children. Although congenital adrenal hyperplasia occurs commonly, several other important molecular causes have been reported, often with overlapping clinical and biochemical features. The relative prevalence of these conditions is not known, but making a specific diagnosis can have important implications for management. Objective: The objective of the study was to investigate the clinical and molecular genetic characteristics of a nationwide cohort of children with PAI of unknown etiology. Design: A structured questionnaire was used to evaluate clinical, biochemical, and imaging data. Genetic analysis was performed using Haloplex capture and next-generation sequencing. Patients with congenital adrenal hyperplasia, adrenoleukodystrophy, autoimmune adrenal insufficiency, or obvious syndromic PAI were excluded. Setting: The study was conducted in 19 tertiary pediatric endocrinology clinics. Patients: Ninety-five children (48 females, aged 0-18 y, eight familial) with PAI of unknown etiology participated in the study. Results: A genetic diagnosis was obtained in 77 patients (81%). The range of etiologies was as follows: MC2R (n = 25), NR0B1 (n = 12), STAR (n = 11), CYP11A1 (n = 9), MRAP (n = 9), NNT (n = 7), ABCD1 (n = 2), NR5A1 (n = 1), and AAAS (n = 1). Recurrent mutations occurred in several genes, such as c.560delT in MC2R, p.R451W in CYP11A1, and c. IVS3ds + 1delG in MRAP. Several important clinical and molecular insights emerged. Conclusion: This is the largest nationwide study of the molecular genetics of childhood PAI undertaken. Achieving a molecular diagnosis in more than 80% of children has important translational impact for counseling families, presymptomatic diagnosis, personalized treatment (eg, mineralocorticoid replacement), predicting comorbidities (eg, neurological, puberty/fertility), and targeting clinical genetic testing in the future. Türk Pediatrik Endokrinoloji Araştırma Bursu- UPE-2014-2 Wellcome Trust/European Commission - 098513/Z/12/Z National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London European Commission - PIEF-GA-2012-328959

Published
2016

3. Rare causes of primary adrenal insufficiency: Genetic and clinical characterization of a large nationwide cohort

Author

Guran T., Buonocore F., Saka N., Ozbek M.N., Aycan Z., Bereket A., Bas F., Darcan S., Bideci A., Guven A., Demir K., Akinci A., Buyukinan M., Aydin B.K., Turan S., Agladioglu S.Y., Atay Z., Abali Z.Y., Tarim O., Catli G., Yuksel B., Akcay T., Yildiz M., Ozen S., Doger E., Demirbilek H., Ucar A., Isik E., Ozhan B., Bolu S., Ozgen I.T., Suntharalingham J.P., Achermann J.C., ÖZGEN, İLKER TOLGA, Ege Üniversitesi, Achermann, John -- 0000-0001-8787-6272, GUVEN, AYLA -- 0000-0002-2026-1326, Turan, Serap -- 0000-0002-5172-5402, Ucar, Ahmet -- 0000-0001-8144-8437, yuksel, bilgin -- 0000-0003-4378-3255, and [Guran, Tulay -- Aycan, Zehra -- Bereket, Abdullah -- Turan, Serap] Marmara Univ, Dept Pediat Endocrinol & Diabet, Fevzi Cakmak Mh Mimar Sinan Cd 41, TR-34899 Istanbul, Turkey -- [Guran, Tulay] Univ Birmingham, Inst Metab & Syst Res, Birmingham B15 2TT, W Midlands, England -- [Buonocore, Federica -- Suntharalingham, Jenifer P. -- Achermann, John C.] UCL, Inst Child Hlth, Dept Genet & Genom Med, London WC1N 1EH, England -- [Saka, Nurcin -- Bas, Firdevs -- Aydin, Banu Kucukemre -- Abali, Zehra Yavas] Istanbul Univ, Istanbul Fac Med, Dept Pediat Endocrinol & Diabet, TR-34452 Istanbul, Turkey -- [Ozbek, Mehmet Nuri -- Demirbilek, Huseyin] Diyarbakir Childrens Hosp, Clin Pediat Endocrinol, TR-21100 Diyarbakir, Turkey -- [Aycan, Zehra -- Agladioglu, Sebahat Yilmaz] Childrens Hlth & Dis Training & Res Hosp, Dr Sami Ulus Obstet & Gynecol, Clin Pediat Endocrinol, TR-06100 Ankara, Turkey -- [Darcan, Sukran -- Ozen, Samim] Ege Univ, Dept Pediat Endocrinol & Diabet, TR-35040 Izmir, Turkey -- [Bideci, Aysun -- Doger, Esra] Gazi Univ, Dept Pediat Endocrinol & Diabet, TR-06550 Ankara, Turkey -- [Guven, Ayla -- Yildiz, Metin] Goztepe Educ & Res Hosp, Pediat Endocrinol Clin, TR-34810 Istanbul, Turkey -- [Guven, Ayla] Amasya Univ, Fac Med, Dept Pediat, TR-05189 Amasya, Turkey -- [Demir, Korcan] Dr Behcet Uz Childrens Hosp, Pediat Endocrinol Clin, Izmir, Turkey -- [Akinci, Aysehan] Inonu Univ, Dept Pediat Endocrinol & Diabetes, Malatya, Turkey -- [Buyukinan, Muammer] Konya Training & Res Hosp, Clin Pediat Endocrinol, TR-42100 Konya, Turkey -- [Tarim, Omer] Uludag Univ, Dept Pediat Endocrinol & Diabet, TR-16059 Bursa, Turkey -- [Catli, Gonul] Eylul Univ, Dept Pediat Endocrinol & Diabet, TR-35210 Izmir, Turkey -- [Yuksel, Bilgin] Cukurova Univ, Dept Pediat Endocrinol & Diabet, TR-01330 Adana, Turkey -- [Akcay, Teoman] Kanuni Sultan Suleyman Educ & Res Hosp, Clin Pediat Endocrinol, TR-34303 Istanbul, Turkey -- [Ucar, Ahmet] Sanliurfa Childrens Hosp, Pediat Endocrinol Clin, TR-63300 Sanliurfa, Turkey -- [Isik, Emregul] Gaziantep Childrens Hosp, Pediat Endocrinol Clin, TR-27010 Gaziantep, Turkey -- [Ozhan, Bayram] Pamukkale Univ, Fac Med, Dept Pediat Endocrinol & Diabet, TR-20160 Denizli, Turkey -- [Bolu, Semih] Duzce Univ, Fac Med, Dept Pediat Endocrinol & Diabet, TR-81620 Duzce, Turkey -- [Ozgen, Ilker Tolga] Bezm I Alem Vakif Univ, Dept Pediat Endocrinol & Diabet, TR-34093 Istanbul, Turkey

Subjects
Male, ABCD1 gene, frameshift mutation, Turkey, clinical evaluation, nonsense mutation, Gene Expression, CYP11A1 gene, genetic analysis, preschool child, Cohort Studies, newborn, genetic variability, MC2R gene, genetics, Age of Onset, Child, next generation sequencing, food and beverages, cohort analysis, MRAP gene, NR0B1 gene, AAAS gene, ComputingMilieux_MANAGEMENTOFCOMPUTINGANDINFORMATIONSYSTEMS, female, priority journal, Child, Preschool, NR5A1 gene, Female, epidemiology, InformationSystems_MISCELLANEOUS, adrenal insufficiency, sequence capture, mutational analysis, structured questionnaire, onset age, Adolescent, Article, high throughput sequencing, molecular diagnosis, primary adrenal insufficiency, NNT gene, Humans, human, gene, gene deletion, missense mutation, ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, Infant, Newborn, Genetic Variation, Infant, nicotinamide adenine dinucleotide (phosphate) transhydrogenase, Original Articles, DNA, cholesterol monooxygenase (side chain cleaving), major clinical study, clinical feature, ComputingMethodologies_PATTERNRECOGNITION, Mutation, corticotropin, genetic procedures, Adrenal Insufficiency
Abstract

WOS: 000377212700036, PubMed ID: 26523528, Context: Primary adrenal insufficiency (PAI) is a life-threatening condition that is often due to monogenic causes in children. Although congenital adrenal hyperplasia occurs commonly, several other important molecular causes have been reported, often with overlapping clinical and biochemical features. The relative prevalence of these conditions is not known, but making a specific diagnosis can have important implications for management. Objective: The objective of the study was to investigate the clinical and molecular genetic characteristics of a nationwide cohort of children with PAI of unknown etiology. Design: A structured questionnaire was used to evaluate clinical, biochemical, and imaging data. Genetic analysis was performed using Haloplex capture and next-generation sequencing. Patients with congenital adrenal hyperplasia, adrenoleukodystrophy, autoimmune adrenal insufficiency, or obvious syndromic PAI were excluded. Setting: The study was conducted in 19 tertiary pediatric endocrinology clinics. Patients: Ninety-five children (48 females, aged 0-18 y, eight familial) with PAI of unknown etiology participated in the study. Results: A genetic diagnosis was obtained in 77 patients (81%). The range of etiologies was as follows: MC2R (n = 25), NR0B1 (n = 12), STAR (n = 11), CYP11A1 (n = 9), MRAP (n = 9), NNT (n = 7), ABCD1 (n = 2), NR5A1 (n = 1), and AAAS (n = 1). Recurrent mutations occurred in several genes, such as c.560delT in MC2R, p.R451W in CYP11A1, and c. IVS3ds + 1delG in MRAP. Several important clinical and molecular insights emerged. Conclusion: This is the largest nationwide study of the molecular genetics of childhood PAI undertaken. Achieving a molecular diagnosis in more than 80% of children has important translational impact for counseling families, presymptomatic diagnosis, personalized treatment (eg, mineralocorticoid replacement), predicting comorbidities (eg, neurological, puberty/fertility), and targeting clinical genetic testing in the future., Turkish Pediatric Endocrinology Research Grant [UPE-2014-2]; Wellcome TrustWellcome Trust [098513/Z/12/Z]; National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London; European CommunityEuropean Community (EC) [PIEF-GA-2012-328959], This work was supported by Turkish Pediatric Endocrinology Research Grant UPE-2014-2. J.C.A. is a Wellcome Trust Senior Research Fellow in Clinical Science (Grant 098513/Z/12/Z), with support from the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. T.G. is a European Community, Marie-Curie research fellow (Grant PIEF-GA-2012-328959).

Published
2016

Catalog

Books, media, physical & digital resources
See catalog results