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https://www.readbyqxmd.com/read/28549591/single-allele-lmbrd1-knockout-results-in-cardiac-hypertrophy
#1
Linda Tzu-Ling Tseng, Chieh-Liang Lin, Kuei-Hsiang Pan, Kai-Yuan Tzen, Ming-Jai Su, Chia-Ti Tsai, Yi-Han Li, Pai-Chi Li, Fu-Tien Chiang, Shin C Chang, Ming-Fu Chang
BACKGROUND/PURPOSE: LMBD1 protein, a type IV-B plasma membrane protein possessing nine putative trans-membrane domains, was previously demonstrated at cellular level to play a critical part in the signaling cascade of insulin receptor through its involvement in regulating clathrin-mediated endocytosis. However, at physiological level, the significance of LMBD1 protein in cardiac development remains unclear. METHODS: To understand the role of Lmbrd1 gene involved in the cardiac function, heterozygous knockout mice were used as an animal model system...
May 23, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28545069/behavioral-alterations-are-associated-with-vitamin-b12-deficiency-in-the-transcobalamin-receptor-cd320-ko-mouse
#2
Kaveri Arora, Jeffrey M Sequeira, Alejandro I Hernández, Juan M Alarcon, Edward V Quadros
Vitamin B12 (cobalamin) deficiency is prevalent worldwide and causes megaloblastic anemia and neurologic deficits. While the anemia can be treated, the neurologic deficits can become refractive to treatment as the disease progresses. Therefore, timely intervention is critical for a favorable outcome. Moreover, the metabolic basis for the neuro-pathologic changes and the role of cobalamin deficiency in the pathology still remains unexplained. Using a transcobalamin receptor / CD320 knockout mouse that lacks the receptor for cellular uptake of transcobalamin bound cobalamin, we aimed to determine whether cobalamin deficiency in the central nervous system produced functional neurologic deficits in the mouse that would parallel those observed in humans...
2017: PloS One
https://www.readbyqxmd.com/read/28544088/antivitamin-b12-inhibition-of-the-human-b12-processing-enzyme-cblc-crystal-structure-of-an-inactive-ternary-complex-with-glutathione-as-the-cosubstrate
#3
Markus Ruetz, Aranganathan Shanmuganathan, Carmen Gherasim, Agnes Karasik, Robert Salchner, Christoph Kieninger, Klaus Wurst, Ruma Banerjee, Markos Koutmos, Bernhard Kräutler
B12 antivitamins are important and robust tools for investigating the biological roles of vitamin B12 . Here, the potential antivitamin B12 2,4-difluorophenylethynylcobalamin (F2PhEtyCbl) was prepared, and its 3D structure was studied in solution and in the crystal. Chemically inert F2PhEtyCbl resisted thermolysis of its Co-C bond at 100 °C, was stable in bright daylight, and also remained intact upon prolonged storage in aqueous solution at room temperature. It binds to the human B12 -processing enzyme CblC with high affinity (KD =130 nm) in the presence of the cosubstrate glutathione (GSH)...
May 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28539414/moderately-elevated-homocysteine-does-not-contribute-to-thoracic-aortic-aneurysm-in-mice
#4
Jasmin Roohi, Benjamin Kang, David Bernard, Djahida Bedja, Harry C Dietz, Lawrence C Brody
Background: Moderate hyperhomocysteinemia is an attractive target for intervention because it is present in 5-7% of the population and can be reversed by diet. This approach presupposes that hyperhomocysteinemia is directly involved in the disease process. Epidemiologic studies have indicated that moderately elevated homocysteine may contribute to thoracic aortic aneurysm (TAA) dilatation and dissection in humans. In vitro, elevated homocysteine disrupts the structure and function of extracellular matrix components, suggesting that moderate hyperhomocysteinemia may contribute to the development and/or progression of TAA...
May 24, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28538514/long-term-outcome-of-4-patients-with-transcobalamin-deficiency-caused-by-2-novel-tcn2-mutations
#5
Marwan Nashabat, Gustavo Maegawa, Peter H Nissen, Ebba Nexo, Hussain Al-Shamrani, Mohammed Al-Owain, Majid Alfadhel
Cobalamin (vitamin B12 [Cbl]) is an essential cofactor for many biochemical pathways. Transcobalamin (TC) is required to internalize Cbl into the cells through membrane receptor-mediated endocytosis. Cbl is then processed in the cytoplasm and mitochondria by complementation factors leading to its active metabolites; methylcobalamin and 5-deoxyadenosyl-cobalamin. Deficiency of TC results in an elevation in methylmalonic acid and homocysteine. Patients usually present with macrocytic anemia, pancytopenia, failure to thrive, gastrointestinal symptoms, and neurological dysfunction...
May 22, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28523235/effects-of-levodopa-carbidopa-intestinal-gel-versus-oral-levodopa-carbidopa-on-b-vitamin-levels-and-neuropathy
#6
Sebastian Loens, Elena Chorbadzhieva, Alexandra Kleimann, Dirk Dressler, Christoph Schrader
OBJECTIVES: To determine the possible interactions between levodopa therapy and plasma levels of B vitamins in patients with advanced idiopathic Parkinson's disease (IPD) in the context of either oral levodopa therapy or levodopa/carbidopa intestinal gel (LCIG). Secondly, to determine the prevalence of neuropathy and its relation to plasma levels of B vitamins and homocysteine. METHODS: Medication doses, neurographies, and serum levels of pyridoxine, cobalamin, folate, and homocysteine of eight LCIG and 13 orally treated advanced IPD patients matched for age, Hoehn & Yahr stage, and UPRDS III were collected...
May 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28505069/b-vitamin-intake-from-diet-and-supplements-and-breast-cancer-risk-in-middle-aged-women-results-from-the-prospective-nutrinet-sant%C3%A3-cohort
#7
Manon Egnell, Philippine Fassier, Lucie Lécuyer, Laurent Zelek, Marie-Paule Vasson, Serge Hercberg, Paule Latino-Martel, Pilar Galan, Mélanie Deschasaux, Mathilde Touvier
Experimental studies suggest a protective effect of B-vitamins on breast cancer risk, potentially modulated by alcohol intake. However, epidemiological studies are limited, especially regarding non-folate B-vitamins. Furthermore, few studies included quantitative assessment of supplemental intake. This prospective study aimed to investigate the associations between intakes of B-vitamins (dietary, supplemental, total) and breast cancer risk. 27,853 women aged ≥45 years from the NutriNet-Santé cohort (2009-2016) were included, with a median follow-up time of 4...
May 13, 2017: Nutrients
https://www.readbyqxmd.com/read/28496346/do-we-need-to-measure-vitamin-b12-and-magnesium-in-morbidly-obese-patients-with-type-2-diabetes-mellitus
#8
Anna Wåhlén, Arvo Haenni, Hans-Erik Johansson
OBJECTIVE: We aimed to investigate the prevalence of B12 deficiency in metformin-treated, morbidly obese, type 2 diabetes mellitus (T2DM) patients, compared to morbidly obese controls, as well as to evaluate the magnesium status. DESIGN: Retrospective cross-sectional analysis of plasma vitamin B12, plasma magnesium, glucometabolic status and clinical measurements in all consecutive morbidly obese patients was conducted during 1 year. SETTING: Outpatient Clinic of Obesity Care...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28492150/selective-screening-for-organic-acidurias-and-amino-acidopathies-in-pakistani-children
#9
Noreen Abbas Sherazi, Aysha Habib Khan, Lena Jafri, Azeema Jamil, Nasir Ali Khan, Bushra Afroze
OBJECTIVE: To determine the frequency of organic acidurais (OA) and amino acidopathies (AA) in selected high-risk patients screened in two years. STUDY DESIGN: Retrospective Observational study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital (AKUH), Karachi, from January 2013 to December 2014. METHODOLOGY: Patients with OA and AA were included in the study and patients with IMDs other than OA and AA were excluded...
April 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28483920/cobalamin-riboswitches-exhibit-a-broad-range-of-ability-to-discriminate-between-methylcobalamin-and-adenosylcobalamin
#10
Jacob T Polaski, Samantha M Webster, James E Johnson, Robert T Batey
Riboswitches are a widely distributed class of regulatory RNAs in bacteria that modulate gene expression via small molecule induced conforma- tional changes. Generally, these RNA elements are grouped into classes based upon conserved primary and secondary structure and their cognate effector molecule. While this approach has been very suc- cessful at identifying new riboswitch families and defining their distributions, small sequence differ- ences between structurally related RNAs can al- ter their ligand selectivity and regulatory behav- ior...
May 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28460586/supplementation-with-6s-5-methyltetrahydrofolate-or-folic-acid-equally-reduces-serum-homocysteine-concentrations-in-older-adults
#11
Ewa Sicińska, Anna Brzozowska, Wojciech Roszkowski, Paul M Finglas
Folic acid (FA) supplementation reduces the elevated serum homocysteine (Hcy) concentrations. [6 S]-5-methyltetrahydrofolate ([6 S]-5-MTHF) is an alternative to FA due to possible advantages, that is, no masking cobalamin deficiency. The study aim was to evaluate the effectiveness of [6 S]-5-MTHF in relations to FA supplementation in reducing the serum Hcy. Healthy volunteers, aged 50-65, had normal serum folate and did not use supplements with B-vitamins for 6 months. Forty subjects were divided into two groups: receiving 400 μg/d FA or the equimolar amount of [6 S]-5-MTHF...
May 2, 2017: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/28449119/mutations-in-thap11-cause-an-inborn-error-of-cobalamin-metabolism-and-developmental-abnormalities
#12
Anita M Quintana, Hung-Chun Yu, Alison Brebner, Mihaela Pupavac, Elizabeth A Geiger, Abigail Watson, Victoria L Castro, Warren Cheung, Shu-Huang Chen, David Watkins, Tomi Pastinen, Flemming Skovby, Bruce Appel, David S Rosenblatt, Tamim H Shaikh
CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. The HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription...
April 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28444757/hypocobalaminaemia-as-a-cause-of-bone-marrow-failure-and-pancytopenia-in-a-cat
#13
E L Stanley, A E Eatroff
CASE REPORT: A male Domestic Short-hair cat was presented for chronic weight loss, lethargy and hyporexia. Complete haematological examination revealed non-regenerative anaemia, neutropenia and thrombocytopenia, as well as Howell-Jolly bodies, anisocytosis, polychromasia and macrocytosis on blood smear evaluation. Histopathological evaluation of bone marrow biopsy disclosed hypocellularity consistent with bone marrow failure. Concurrent hypocobalaminaemia was identified and treated with parenteral cyanocobalamin supplementation...
May 2017: Australian Veterinary Journal
https://www.readbyqxmd.com/read/28442570/coordination-chemistry-controls-the-thiol-oxidase-activity-of-the-b12-trafficking-protein-cblc
#14
Zhu Li, Aranganathan Shanmuganathan, Markus Ruetz, Kazuhiro Yamada, Nicholas A Lesniak, Bernhard Kraeutler, Thomas C Brunold, Markos Koutmos, Ruma Banerjee
The cobalamin or B12 cofactor supports sulfur and one-carbon metabolism and the catabolism of odd-chain fatty acids, branched-chain amino acids and cholesterol. CblC is a B12 processing enzyme involved in an early cytoplasmic step in the cofactor trafficking pathway. It catalyzes the glutathione (GSH)-dependent dealkylation of alkylcobalamins and the reductive decyanation of cyanocobalamin. CblC from Caenorhabdiitis elegans (ceCblC) also exhibits a robust thiol oxidase activity converting reduced GSH to oxidized GSSG with concomitant scrubbing of ambient dissolved O2 The mechanism of thiol oxidation catalyzed by ceCblC is not known...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28439658/pan-genomic-approaches-in-lactobacillus-reuteri-as-a-porcine-probiotic-investigation-of-host-adaptation-and-antipathogenic-activity
#15
Jun-Yeong Lee, Geon Goo Han, Jaeyun Choi, Gwi-Deuk Jin, Sang-Kee Kang, Byung Jo Chae, Eun Bae Kim, Yun-Jaie Choi
After the introduction of a ban on the use of antibiotic growth promoters (AGPs) for livestock, reuterin-producing Lactobacillus reuteri is getting attention as an alternative to AGPs. In this study, we investigated genetic features of L. reuteri associated with host specificity and antipathogenic effect. We isolated 104 L. reuteri strains from porcine feces, and 16 strains, composed of eight strains exhibiting the higher antipathogenic effect (group HS) and eight strains exhibiting the lower effect (group LS), were selected for genomic comparison...
April 24, 2017: Microbial Ecology
https://www.readbyqxmd.com/read/28432454/cobalt-tetradehydrocorrins-coordinated-by-imidazolate-like-histidine-in-the-heme-pocket-of-horseradish-peroxidase
#16
Koji Oohora, Ning Tang, Yoshitsugu Morita, Takashi Hayashi
Horseradish peroxidase was reconstituted with cobalt tetradehydrocorrin, rHRP(Co(TDHC)), as a structural analog of cobalamin coordinated with an imidazolate-like His residue, which is generally seen in native enzymes. In contrast to the previously reported cobalt tetradehydrocorrin-reconstituted myoglobin, rMb(Co(TDHC)), the HRP matrix was expected to provide strong axial ligation by His170 which has imidazolate character. rHRP(Co(II)(TDHC)) was characterized by EPR and its reaction with reductants indicates a negative shift of its redox potential compared to rMb(Co(TDHC))...
April 21, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28424758/redox-related-epigenetic-mechanisms-in-glioblastoma-nuclear-factor-erythroid-derived-2-like-2-cobalamin-and-dopamine-receptor-subtype-4
#17
Matthew Scott Schrier, Malav Suchin Trivedi, Richard Carlton Deth
Glioblastoma is an exceptionally difficult cancer to treat. Cancer is universally marked by epigenetic changes, which play key roles in sustaining a malignant phenotype, in addition to disease progression and patient survival. Studies have shown strong links between the cellular redox state and epigenetics. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensitive transcription factor that upregulates endogenous antioxidant production, and is aberrantly expressed in many cancers, including glioblastoma...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28416508/hus-and-atypical-hus
#18
T Sakari Jokiranta
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by intravascular hemolysis, thrombocytopenia, and acute kidney failure. HUS is usually categorized as typical, caused by shiga-toxin producing E. coli (STEC) infection, atypical HUS (aHUS), usually caused by uncontrolled complement activation, or secondary HUS with a coexisting disease. In recent years, a general understanding of the pathogenetic mechanisms driving HUS has increased. Typical (i.e. STEC-HUS) follows a gastrointestinal infection with STEC, while aHUS is associated primarily with mutations or autoantibodies leading to dysregulated complement activation...
April 17, 2017: Blood
https://www.readbyqxmd.com/read/28406776/gastric-intestinal-metaplasia-an-intermediate-precancerous-lesion-in-the-cascade-of-gastric-carcinogenesis
#19
Tayyab Hamid Malik, Mujtaba Yousef Al Sayahan, Hussain Ali Al Ahmed, Xu Hong
Gastric intestinal metaplasia, an intermediate lesion in the development of intestinal-type gastric cancer, is observed in the milieu of long standing non-atrophic gastritis and atrophic gastritis. Most patients with intestinal metaplasia remain asymptomatic unless cobalamin deficiency occurs secondary to loss of glands (that produce intrinsic factor and acid). Genetic events that predispose to development of gastric intestinal metaplasia remains an enigma. Mechanisms leading to the progression of atrophy to metaplasia still needs to be comprehensively explored...
March 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28390190/systemic-scedosporium-prolificans-infection-in-an-11-month-old-border-collie-with-cobalamin-deficiency-secondary-to-selective-cobalamin-malabsorption-canine-imerslund-gr%C3%A3-sbeck-syndrome
#20
K Erles, A Mugford, D Barfield, T Leeb, P H Kook
An 11-month-old Border collie presented collapsed and continued to deteriorate rapidly despite supportive treatment. The dog had a history of failure to thrive and recurring respiratory infection. Laboratory abnormalities included neutrophilic leucocytosis, Heinz body anaemia, hyperammonaemia, hyperbilirubinaemia, proteinuria and hypocobalaminaemia. Post-mortem examination revealed multi-focal necrosis within the heart, kidneys, pancreas, liver, meninges and cerebral cortex. Fungal hyphae in lesions were identified as Scedosporium prolificans following culture...
April 8, 2017: Journal of Small Animal Practice
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