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Cohesin proteins promote ribosomal RNA production and protein translation in yeast and human cells.

Cohesin is a protein complex known for its essential role in chromosome segregation. However, cohesin and associated factors have additional … and a reduction in the actively translating fraction of ribosomes, eiF2α-phosphorylation, and (35)S-methionine incorporation, all of which indicate a deficit in protein translation. Metabolic labeling shows that the eco1-W216G and smc1-Q843Δ mutants produce less ribosomal RNA, which is expected to constrain ribosome biogenesis. Further analysis shows that th …

The MMACHC proteome: hallmarks of functional cobalamin deficiency in humans.

Cobalamin (Cbl, B(12)) is an essential micronutrient required to fulfill the enzymatic reactions of cytosolic methylcobalamin-dependent methionine synthase and mitochondrial adenosylcobalamin-dependent methylmalonyl-CoA mutase. Mutations in the MMACHC gene (cblC complementation group) disrupt processing of the upper-axial ligand of newly internalized cobalamins, leading to functional deficiency of the vitamin. Patients with cblC disease present with both hyperhomocysteinemia and methylmalonic acidemia, cognitive dysfunction, and megaloblastic anemia. In the present study we show that cultured …

Effects of different levels of organic and inorganic chromium on growth performance and immunocompetence of broilers under heat stress.

This experiment was carried out to investigate the effects of different levels of organic and inorganic chromium on the performance, immune … rations of chromium (0, 600 and 1,200 μg kg(-1) chromium chloride or 600 and 1,200 μg/kg chromium L-methionine) from 1 to 49 days of age. Humoral immunity was assessed by intravenous injection of 7% sheep red blood cell (SRBC) followed by evaluation of serum for antibody titers in primary and secondary responses. Cell-mediated immunity was assessed by the cu …

Sheep and goat BSE propagate more efficiently than cattle BSE in human PrP transgenic mice.

A new variant of Creutzfeldt Jacob Disease (vCJD) was identified in humans and linked to the consumption of Bovine Spongiform Encephalopathy … ll ruminants-passaged BSE prions by inoculating two different transgenic mouse lines expressing the methionine (Met) allele of human PrP at codon 129 (tg650 and tg340) with several sheep and goat BSE isolates and compared their transmission characteristics with those of cattle BSE. While the molecular and neuropathological transmission features were undistin …

Chinese yellow wine and red wine inhibit matrix metalloproteinase-2 and improve atherosclerotic plaque in LDL receptor knockout mice.

Our previous study found that Chinese yellow wine could inhibit the production of homocysteine (HCY) induced extracellular matrix metalloproteinase-2 (MMP-2) in the cultured rat vascular smooth muscle cells. Little is known about the relationship between Chinese yellow wine and atherosclerosis or MMP-2 in vivo. Thirty-two LDL Receptor knockout mice on a high-fat and L-methionine diet developed plasma hyperhomocysteinemia and atherosclerosis. They were randomly divided into yellow wine group (n = 8), red wine group (n = 8), ethanol group (n = 8), and control group (n = 8), they were sacrificed …

Hereditary 1,25-dihydroxyvitamin D-resistant rickets with alopecia resulting from a novel missense mutation in the DNA-binding domain of the vitamin D receptor.

The rare genetic recessive disease, hereditary vitamin D resistant rickets (HVDRR), is caused by mutations in the vitamin D receptor (VDR) t … at the child was homozygous for a unique missense mutation in the VDR gene that converted valine to methionine at amino acid 26 (V26M) in the VDR DNA-binding domain (DBD). The mutant VDR was studied in the patient's cultured skin fibroblasts and found to exhibit normal [(3)H]1,25(OH)(2)D(3) binding and protein expression. However, the fibroblasts were unresp …

Флавивирусная политрансфераза РНК: структура, функция и ингибиция.

Многие флавивирусы являются значительными человеческими патогенами. Плюс-стренд геном РНК флавивируса содержит 5-футовую конструкцию верхнего предела 1 (m(7)GpppAmG). Флавивирус кодирует одну метилтрансферазу (MTase), расположенную на N-терминальной части NS5 в зависимости от RNA полимеразы (RdRp). В этой связи мы рассматриваем последние достижения в нашем понимании механизмов пальца и последствий для развития наркотиков. NS5 MTase катализирует как гунанин N7 и рибоза 2-OH метилации во время формирования вирусных колпаков. Репрезентативный флавирус MTases, от денге, желтой лихорадки и вируса З

Совпадение в аннотации оригинала
Many flaviviruses are significant human pathogens. The plus-strand RNA genome of a flavivirus contains a 5' terminal cap 1 structure (m(7)Gp … tivities, the crystal structures of flavivirus MTases showed a single binding site for S-adenosyl-L-methionine (SAM), the methyl donor. This finding indicates that the substrate GpppA-RNA must be repositioned to accept the N7 and 2'-O methyl groups from SAM during the sequential reactions. Further studies demonstrated that distinct RNA elements are required …

Heme oxygenase-1 protects against steatohepatitis in both cultured hepatocytes and mice.

BACKGROUND & AIMS: Heme oxygenase-1 (HO-1), an antioxidant defense enzyme, has been shown to protect against oxidant-induced tissue injury. We investigated the role of HO-1 in nutritional steatohepatitis in vitro and in vivo. METHODS: AML-12 hepatocytes were cultured in methionine- and choline-deficient (MCD) medium. Cells were transfected with an adenovirus vector that expressed HO-1 (Ad-HO-1) or incubated with the HO-1 inducer hemin or the HO-1 inhibitor stannic mesoporphyrin for 24 hours. C57BL6 mice and db/db mice were fed MCD or control diets, with or without hemin, for up to 4 weeks. R…

MTHFR C677T and postmenopausal breast cancer risk by intakes of one-carbon metabolism nutrients: a nested case-control study.

INTRODUCTION: The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene has been hypothesized to increase breast cancer risk. However, results have been inconsistent, and few studies have reported the association by menopausal status or by intakes of nutrients participating in one-carbon metabolism. Our aims were to investigate whether MTHFR C677T was associated with postmenopausal breast cancer risk and whether this relation was modified by intakes of folate, methionine, vitamins B(2), B(6), and B(12), and alcohol. METHODS: We studied 318 incident breast cancer cases and…

Tranilast, an antifibrogenic agent, ameliorates a dietary rat model of nonalcoholic steatohepatitis.

UNLABELLED: Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease and is one of the most common li … Tokushima Fatty (OLETF) rats and nondiabetic control Long-Evans Tokushima Otsuka (LETO) rats fed a methionine-deficient and choline-deficient diet. Treatment with 2% tranilast (420 mg/kg/day) for 8 weeks prevented the development of hepatic fibrosis and the activation of stellate cells, and down-regulated the expression of genes for TGF-beta and TGF-beta-ta …

Gas chromatography/time-of-flight mass spectrometry based metabonomic approach to differentiating hypertension- and age-related metabolic variation in spontaneously hypertensive rats.

Metabonomics is a systematic approach to the study of in vivo metabolic profiles and therefore allows deep insight into and a better underst … cid, citric acid, threonic acid, tyrosine, tryptophan, threonine, phenylalanine, serine, ornithine, methionine, 3-hydroxyproline, creatinine, erythrose, myo-inositol, D-methylglucopyranoside, tocopherol, sitosterol, and nonesterified cholesterol. Significantly elevated free fatty acids (FFA) were observed in SHR relative to those in WKY rats, and their level …

Paroxysmal extreme pain disorder M1627K mutation in human Nav1.7 renders DRG neurons hyperexcitable.

BACKGROUND: Paroxysmal extreme pain disorder (PEPD) is an autosomal dominant painful neuropathy with many, but not all, cases linked to gain … TS: Sequencing of SCN9A coding exons from an English patient, diagnosed with PEPD, has identified a methionine 1627 to lysine (M1627K) substitution in the linker joining segments S4 and S5 in domain IV. We confirm that M1627K depolarizes the voltage-dependence of fast-inactivation without substantially altering activation or slow-inactivation, and inactivate …

Demographic and nutritional factors associated with prolonged cholestatic jaundice in the premature infant.

OBJECTIVE: The primary aim of this study was to determine if an association exists between amino-acid levels and development of cholestasis. … andomization. On day 7 (parenteral phase of nutrition), blood urea nitrogen, citrulline, histidine, methionine and succinyl carnitine were higher, and serine, glutamate and thyroxine levels were lower in the neonates who developed cholestasis than in who did not. CONCLUSION: Cholestasis remains an important complication of parenteral nutrition, and several …

Structural and functional characterization of a P-III metalloproteinase, leucurolysin-B, from Bothrops leucurus venom.

Leucurolysin-B (leuc-B) is an hemorrhagic metalloproteinase found in the venom of Bothrops leucurus (white-tailed-jararaca) snake. By means … ein with trypsin. Leuc-B exhibits the characteristic motif of metalloproteinases, HEXXHXXGXXH and a methionine-containing turn of similar conformation ("Met-turn"), which forms a hydrophobic basis for the zinc ions and the three histidine residues involved as ligands. Leuc-B has been characterized as a P-III metalloproteinase and possesses a multidomain stru …

Inhibition of cystathionine-gamma-lyase leads to loss of glutathione and aggravation of mitochondrial dysfunction mediated by excitatory amino acid in the CNS.

Oxidative stress has been implicated in the pathogenesis and progression of neurodegenerative disorders and antioxidants potentially have a major role in neuroprotection. Optimum levels of glutathione (gamma-glutamylcysteinyl glycine), an endogenous thiol antioxidant are required for the maintenance of the redox status of cells. Cystathionine gamma-lyase is the rate-limiting enzyme for the synthesis of cysteine from methionine and availability of cysteine is a critical factor in glutathione synthesis. In the present study, we have examined the role of cystathionine gamma-lyase in maintaining t…

Limitations to the development of humanized antibody producing Chinese hamster ovary cells using glutamine synthetase-mediated gene amplification.

Recombinant Chinese hamster ovary (CHO) cells expressing a humanized antibody were obtained by transfection of an antibody expression vector (pKC-GS-HC-huS) into CHO-K1 cells and subsequent glutamine synthetase (GS)-mediated gene amplification in media containing different concentrations of methionine sulfoximine (MSX). Concentrations consisted of 25, 200, 500, and 1000 microM of MSX. The highest producer (HP) subclones were isolated from each MSX level by the limiting dilution method and were characterized with respect to antibody production. No positive relationship was observed between spec…

PET and PET-CT. State of the art and future prospects.

Fluoro-deoxyglucose positron emission tomography (FDG PET) enables the in vivo study of tissue metabolism, and thus is able to identify mali … e underlined that the use of PET-CT is almost mandatory for new tracers such as 11C-choline and 11C-methionine; these new tracers may be applied for studying tumours not assessable with FDG, such as prostate cancer. In conclusion PET-CT is at present the most advanced method for metabolic imaging, and is capable of precisely localizing and assessing tumours; …

Risk of non-Hodgkin lymphoma associated with polymorphisms in folate-metabolizing genes.

Genetic instability, including chromosomal imbalance, is important in the pathogenesis of lymphoproliferative disorders such as non-Hodgkin … . Polymorphisms studied include methylenetetrahydrofolate reductase (MTHFR) 677 C >T and 1298 A >C, methionine synthase (MTR) 2756 A>G, serine hydroxymethyltransferase (SHMT1) 1420 C >T, thymidylate synthase (TYMS) 1494del6 and 28-bp repeat, and reduced folate carrier (RFC) 80 G >A. Increased risks for NHL [odds ratio (OR), 1.48; 95% confidence intervals (CI …

Asymmetric dimethyl-L-arginine (ADMA): a possible link between homocyst(e)ine and endothelial dysfunction.

Hyperhomocyst(e)inemia is associated with an increased risk for atherosclerotic disease and venous thromboembolism. The impact of elevated p … ic hyperhomocyst(e)inemia, as well as after acute elevation of plasma homocyst(e)ine following oral methionine intake. The postulated mechanisms for ADMA accumulation are increased methylation of arginine residues within proteins, as well as reduced metabolism of ADMA by the enzyme DDAH, but they still need to be confirmed to be operative in vivo. Hyperhomoc …

Micronutrient antioxidant intake in patients with chronic pancreatitis.

Increased oxidative stress has been postulated to be an important mechanism in the pathophysiology of chronic pancreatitis (CP). Micronutrient deficiency may increase the oxidative stress as they assist in free radical clearance. The present study was undertaken to assess the intake of micronutrients, i.e. vitamins E and C, carotene, selenium, copper, zinc, manganese, magnesium, sulphur, riboflavin, methionine and choline in patients with CP. All consecutive patients with CP attending the Pancreas Clinic at the All India Institute of Medical Sciences were enrolled in the study. The usual dieta…