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1

Crouse, Matthew S., Joel Caton, and Alison K. Ward. "390 Micronutrients, One-Carbon Metabolism, and Epigenetics: Potential Developmental and Production Outcomes." Journal of Animal Science 98, Supplement_4 (November 3, 2020): 170. http://dx.doi.org/10.1093/jas/skaa278.312.

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Abstract One-carbon metabolism is the network of biochemical pathways in which methyl groups are transferred from one compound to another for methylation processes. Expansion of the core pathway connects one-carbon metabolism to polyamine synthesis, nucleotide synthesis, redox metabolism, and the citric acid cycle. One-carbon metabolites (OCM) are methyl donors and cofactors which play key roles in the one-carbon metabolism pathway and include B-vitamins (choline, vitamin B12, vitamin B6, riboflavin, and folate), minerals (cobalt and sulfur) and amino acids (methionine, serine, and glycine). One-carbon metabolites are fundamental methyl donors for epigenetic modifications. Immediately post-fertilization, the embryonic genome undergoes epigenetic remodeling, and is the time when cell division is greatest (cell divisions/total cell number). At this time OCM supplementation may have its greatest impact on programming of offspring development, growth and postnatal performance, due to established metabolic roles in epigenetics (methyl transfer), growth (polyamine and nucleotide synthesis), and energetics. Limited data are available, however, which directly investigates the developmental effects of OCM supplementation in ruminants. In dairy cows, OCM supplementation in late gestation increased calf birth weight, nutrient sensing pathway activation, and offspring performance through the pre-weaning period. Methyl deficient diets during the pre-conception period in ewes altered the offspring hepatic methylome at 90 days of gestation, as well as the body composition and insulin tolerance of ram lambs at 22-mo of age. Bovine embryonic fibroblasts cultured in vitro with increasing OCM had greater growth rates and mitochondrial respiration parameters. Additional research into the area of one-carbon metabolism and the roles that OCM supplementation may play on postnatal function will provide new knowledge that could lead to altered management practices and increased efficiency of beef cattle. USDA is an equal opportunity provider and employer.
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2

Cheng, Shouqiang, and Thomas A. Bobik. "Characterization of the PduS Cobalamin Reductase of Salmonellaenterica and Its Role in the Pdu Microcompartment." Journal of Bacteriology 192, no. 19 (July 23, 2010): 5071–80. http://dx.doi.org/10.1128/jb.00575-10.

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ABSTRACT Salmonella enterica degrades 1,2-propanediol (1,2-PD) in a coenzyme B12 (adenosylcobalamin, AdoCbl)-dependent fashion. Salmonella obtains AdoCbl by assimilation of complex precursors, such as vitamin B12 and hydroxocobalamin. Assimilation of these compounds requires reduction of their central cobalt atom from Co3+ to Co2+ to Co+, followed by adenosylation to AdoCbl. In this work, the His6-tagged PduS cobalamin reductase from S. enterica was produced at high levels in Escherichia coli, purified, and characterized. The anaerobically purified enzyme reduced cob(III)alamin to cob(II)alamin at a rate of 42.3 ± 3.2 μmol min−1 mg−1, and it reduced cob(II)alamin to cob(I)alamin at a rate of 54.5 ± 4.2 nmol min−1 mg−1 protein. The apparent K m values of PduS-His6 were 10.1 ± 0.7 μM for NADH and 67.5 ± 8.2 μM for hydroxocobalamin in cob(III)alamin reduction. The apparent K m values for cob(II)alamin reduction were 27.5 ± 2.4 μM with NADH as the substrate and 72.4 ± 9.5 μM with cob(II)alamin as the substrate. High-performance liquid chromatography (HPLC) and mass spectrometry (MS) indicated that each monomer of PduS contained one molecule of noncovalently bound flavin mononucleotide (FMN). Genetic studies showed that a pduS deletion decreased the growth rate of Salmonella on 1,2-PD, supporting a role in cobalamin reduction in vivo. Further studies demonstrated that the PduS protein is a component of the Pdu microcompartments (MCPs) used for 1,2-PD degradation and that it interacts with the PduO adenosyltransferase, which catalyzes the terminal step of AdoCbl synthesis. These studies further characterize PduS, an unusual MCP-associated cobalamin reductase, and, in conjunction with prior results, indicate that the Pdu MCP encapsulates a complete cobalamin assimilation system.
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3

Heldt, D., A. D. Lawrence, M. Lindenmeyer, E. Deery, P. Heathcote, S. E. Rigby, and M. J. Warren. "Aerobic synthesis of vitamin B12: ring contraction and cobalt chelation." Biochemical Society Transactions 33, no. 4 (August 1, 2005): 815–19. http://dx.doi.org/10.1042/bst0330815.

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The aerobic biosynthetic pathway for vitamin B12 (cobalamin) biosynthesis is reviewed. Particular attention is focused on the ring contraction process, whereby an integral carbon atom of the tetrapyrrole-derived macrocycle is removed. Previous work had established that this chemically demanding step is facilitated by the action of a mono-oxygenase called CobG, which generates a hydroxy lactone intermediate. This mono-oxygenase contains both a non-haem iron and an Fe-S centre, but little information is known about its mechanism. Recent work has established that in bacteria such as Rhodobacter capsulatus, CobG is substituted by an isofunctional protein called CobZ. This protein has been shown to contain flavin, haem and Fe-S centres. A mechanism is proposed to explain the function of CobZ. Another interesting aspect of the aerobic cobalamin biosynthetic pathway is cobalt insertion, which displays some similarity to the process of magnesium chelation in chlorophyll synthesis. The genetic requirements of cobalt chelation and the subsequent reduction of the metal ion are discussed.
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4

Mangiarotti, G., C. Canavese, M. Salomone, A. Thea, A. Pacitti, M. Gaido, V. Calitri, D. Pelizza, W. Canavero, and A. Vercellone. "Hypervitaminosis B12 in Maintenance Hemodialysis Patients Receiving Massive Supplementation of Vitamin B12." International Journal of Artificial Organs 9, no. 6 (November 1986): 417–20. http://dx.doi.org/10.1177/039139888600900611.

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We have administered routinely a multivitamin preparation containing a megadose of B12 to 106 hemodialysis patients after dialysis treatments. We found that these patients had very high levels of serum vitamin B12 which returned to original values only after a period of three years after stopping the vitamin. Discontinuing therapy had no effect on hemoglobin, mean erythrocyte corpuscular volume, or motor nerve conduction velocity. It is not known whether maintaining a prolonged high level of vitamin B12 is harmful. However, animal and epidemiologic studies have suggested that both cobalamin and cobalt may be potentially toxic. In view of the absence of demonstrable benefit and the possible risk of toxicity, we believe that the use of such megadose vitamin compounds in dialysis patients should be re-evaluated.
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5

Sailaja Devi, S., M. Radhakrishna Reddy, P. Sambasiva Reddy, K. Hussain Reddy, and K. Mohana Raju. "Synthesis and characterization of polymer supported vitamin B12 model compounds." Polymer International 49, no. 11 (2000): 1338–42. http://dx.doi.org/10.1002/1097-0126(200011)49:11<1338::aid-pi488>3.0.co;2-0.

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6

Frank, S., A. A. Brindley, E. Deery, P. Heathcote, A. D. Lawrence, H. K. Leech, R. W. Pickersgill, and M. J. Warren. "Anaerobic synthesis of vitamin B12: characterization of the early steps in the pathway." Biochemical Society Transactions 33, no. 4 (August 1, 2005): 811–14. http://dx.doi.org/10.1042/bst0330811.

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The anaerobic biosynthesis of vitamin B12 is slowly being unravelled. Recent work has shown that the first committed step along the anaerobic route involves the sirohydrochlorin (chelation of cobalt into factor II). The following enzyme in the pathway, CbiL, methylates cobalt-factor II to give cobalt-factor III. Recent progress on the molecular characterization of this enzyme has given a greater insight into its mode of action and specificity. Structural studies are being used to provide insights into how aspects of this highly complex biosynthetic pathway may have evolved. Between cobalt-factor III and cobyrinic acid, only one further intermediate has been identified. A combination of molecular genetics, recombinant DNA technology and bioorganic chemistry has led to some recent advances in assigning functions to the enzymes of the anaerobic pathway.
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7

Hossain, Md Jakir, Toshikazu Ono, Kosuke Wakiya, and Yoshio Hisaeda. "A vitamin B12 derivative catalyzed electrochemical trifluoromethylation and perfluoroalkylation of arenes and heteroarenes in organic media." Chemical Communications 53, no. 79 (2017): 10878–81. http://dx.doi.org/10.1039/c7cc06221d.

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8

Mitchell, L. M., G. McCallum, K. Mackie, M. Ewen, A. Ainslie, and T. G. McEvoy. "143 IN VITRO DEVELOPMENT OF OVINE OOCYTES FROM EWES OF CONTRASTING VITAMIN B12 STATUS." Reproduction, Fertility and Development 17, no. 2 (2005): 222. http://dx.doi.org/10.1071/rdv17n2ab143.

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Suboptimal circulating concentrations of vitamin B12 are commonly found in cattle and sheep grazing cobalt-deficient pastures. Vitamin B12 is a co-factor for enzymes involved in energy metabolism (methylmalonyl CoA mutase) and DNA synthesis/methylation (methionine synthase), and vitamin B12 status may therefore impact on cell division and gene expression in early embryos. The aim of this study was to determine the effect of vitamin B12 status on the in vitro development of ovine oocytes to the blastocyst stage. Mature Scottish Blackface ewes from cobalt-deficient farms were housed for ∼ four months and fed a cobalt-deficient diet (0.06 mg cobalt kg DM−1). At housing, 55 of the ewes were given an intra-ruminal slow-release cobalt bolus to compensate for the dietary deficit, and 52 remained untreated. The ovaries of all ewes were recovered at slaughter within the natural breeding season. Oocytes were aspirated and those with evenly granulated cytoplasm and >3 layers of cumulus cells were pooled according to ewe cobalt treatment, matured, fertilized, and cultured in vitro (∼20 oocytes per 50-μL drop under mineral oil). Oocytes were matured for 24 h in M199 + 10% fetal calf serum at 38.5°C in a humidified atmosphere of 5% CO2 in air prior to co-incubation for 18 h with frozen-thawed semen from a single ejaculate (1 × 106 live sperm mL−1). Presumptive zygotes were cultured for 7 Days in synthetic oviduct fluid + 0.4% fatty acid-free BSA (5% CO2, 5% O2, 90% N). Blastocysts formed at the end of the culture period were fixed and stained (Hoechst 33258) to count cell numbers. Data were analyzed by ANOVA and chi-square. For cobalt-supplemented and non-supplemented ewes, circulating concentrations of vitamin B12 at the time of slaughter were 1244 ± 52.5 and 372 ± 27.9 pmol L−1 (P < 0.001), respectively. Numbers of small (<5 mm) follicles per ewe were 17.6 ± 1.22 and 17.1 ± 1.31, and large (>5 mm) follicles per ewe were 1.8 ± 0.16 and 1.6 ± 0.18, respectively (NS). Cobalt-supplemented ewes yielded a lower proportion of matured oocytes that cleaved but an increased proportion of cleaved oocytes that formed blastocysts by Day 6 of the culture period (Table 1). The proportion of grade 1 and 2 blastocysts was also increased but cobalt treatment did not affect blastocyst cell numbers. In conclusion, results suggest that cleaved eggs derived from ewes of adequate, compared to suboptimal vitamin B12 status have improved developmental competence in vitro. Table 1. Effect of cobalt/vitamin B12 status on the in vitro development of ovine oocytes This work was funded by the Scottish Executive Environment and Rural Affairs Department.
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9

Brewer, K., G. A. Maylin, C. K. Fenger, and T. Tobin. "Cobalt use and regulation in horseracing: a review." Comparative Exercise Physiology 12, no. 1 (March 11, 2016): 1–10. http://dx.doi.org/10.3920/cep140008.

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Cobalt, atomic weight 58.9, is a metallic element and environmental substance found in the animal in microgram quantities, predominantly as vitamin B12, but is also a component of at least one mammalian enzyme unassociated with B12. Cobalt is a required trace mineral and has long been administered as a dietary supplement to humans and animals. Cobalt deficiency outside of its requirement in vitamin B12 has not been reported in humans. The administration of cobalt salts was once standard treatment for anaemia in humans, owing to its ability to stimulate red blood cell synthesis. Elemental cobalt acts by stabilising hypoxia inducible factor (HIF-1α), which activates the erythropoietin gene, which in turn increases haemoglobin/red blood cell synthesis, which had led to a presumption that cobalt may be performance enhancing in athletes. Administration of cobalt in amounts sufficient to significantly increase the haematocrit are associated with risk of toxicity in humans, and the only cobalt administration study in horses showed no effect on red blood cell parameters or toxicity. Because of the perception that cobalt administration may enhance athletic performance, racing regulators have recently begun to restrict cobalt use in horseracing which has led to the introduction of cobalt thresholds in several racing jurisdictions. The International Federation of Horseracing Authorities is considering an international regulatory threshold for cobalt of 100 ng/ml in urine, based on studies performed in five different countries. In the United States, the Racing Commissioners International has recently set a primary plasma threshold of 25 ng/ml and secondary threshold of 50 ng/ml. One New York and New Jersey racetrack owner has initiated testing for cobalt and has denied his facilities to trainers whose horses tested positive for excessive quantities of cobalt. This review seeks to summarise what is known about the use of cobalt in horse racing.
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10

Renz, Paul, Inka Pfitzner, Birgit Endres, and Oliver Hasselwander. "Synthesis of 4-Aza-5,6-dimethylbenzimidazole and Biosynthetic Preparation of 4-and 7-Aza-5,6-dimethylbenzimidazolylcobamide." Zeitschrift für Naturforschung C 52, no. 5-6 (June 1, 1997): 287–91. http://dx.doi.org/10.1515/znc-1997-5-601.

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Abstract We report on the preparation of 4-aza-5,6-dimethylbenzimidazolylcobamide and 5,6-dimethyl-7-azabenzimidazolylcobamide. These vitamin B12-analogs were required as reference compounds for comparison with a corrinoid previously isolated in small amounts from Eu­bacterium limosum grown in the presence of 4(5)-aminoimidazole. 4(7)-Aza-5,6-dimethylbenzimidazole was synthesized from N-1-benzyl-4-nitroimidazole which was reduced to N-1-benzyl-4-aminoimidazole and condensed with 1-dimethylamino-2-methylbutan-3-one to yield N-1-benzyl-4-aza-5,6-dimethylbenzimidazole. The benzyl group of this compound was split off by catalytic hydrogenation to form 4(7)-aza-5,6-dimethylbenz-imidazole. 4(7)-Aza-5,6-dimethylbenzimidazole was transformed by a growing culture of Propionibac­terium shermanii into 4-aza-5,6-dimethylbenzimidazolylcobamide and 5,6-dimethyl-7-azabenz-imidazolylcobamide. Both vitamin B 12-analogs were almost as active as Vitamin B12 in a growth test with the vitamin B12-dependent Escherichia coli-mutant DSM 4261.
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11

Evans, Harold J., and Mark Kliewer. "VITAMIN B12 COMPOUNDS IN RELATION TO THE REQUIREMENTS OF COBALT FOR HIGHER PLANTS AND NITROGEN-FIXING ORGANISMS*." Annals of the New York Academy of Sciences 112, no. 2 (December 16, 2006): 735–55. http://dx.doi.org/10.1111/j.1749-6632.1964.tb45052.x.

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12

Ferraccioli, Raffaella, Diana Borovika, Annette-Enrica Surkus, Carsten Kreyenschulte, Christoph Topf, and Matthias Beller. "Synthesis of cobalt nanoparticles by pyrolysis of vitamin B12: a non-noble-metal catalyst for efficient hydrogenation of nitriles." Catalysis Science & Technology 8, no. 2 (2018): 499–507. http://dx.doi.org/10.1039/c7cy01577a.

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13

Dobreva, Diana A., Albena V. Merdzhanova, Mona D. Stancheva, Doychin I. Terziyski, and Veselina Z. Panayotova. "Black Sea fish and shellfish as essential source of vitamin B12." International Journal of Scientific Reports 4, no. 8 (July 24, 2018): 199. http://dx.doi.org/10.18203/issn.2454-2156.intjscirep20183181.

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<p class="abstract"><strong>Background:</strong> Vitamins are very important for the human body because they are necessary for many biological absorption processes of other nutrients, for cells and tissues growth and repair. Because of this, there are many recommendations on daily vitamins intake, approved by the different country and world food organizations. Usually under the term "vitamin B<sub>12</sub>" is understood only cyanocobalamin, but actually this name is general and covers all potentially biologically active "cobalamins"- a group of cobalt-containing compounds. Animal foods, as different meat, milk, eggs, fish and shellfish are considered as the main dietary sources of this vitamin. They contain different forms (methylcobalamin and deoxyadenosylcobalamin) of vitamin B<sub>12</sub> in different amounts. There is limited information in the scientific literature about the vitamin B<sub>12</sub> content in black sea fish and shellfish. The aims of the present work were to determine and compare vitamin B<sub>12</sub> contents as well as relative daily intake of vitamins in different fish and shellfish species from Black Sea waters.</p><p class="abstract"><strong>Methods:</strong> Vitamin B<sub>12</sub> was analysed spectrophotometrically. The method for quantitative analysis includes extraction from the edible tissue and enzymatic hydrolysis to release the cobalt ions. </p><p class="abstract"><strong>Results:</strong> The quantities of vitamin B<sub>12</sub> found in the edible tissue of the analysed samples ranged from 0.63 μg.100 g<sup>-1</sup> ww to 21.5 μg.100 g<sup>-1</sup> ww.</p><p class="abstract"><strong>Conclusions:</strong> The observed results confirm that all fish and molluscs samples deliver significant quantities of the water-soluble vitamin B<sub>12</sub>.</p><p> </p>
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Bilgin, Ahmet, and Yaşar Gök. "SYNTHESIS AND CHARACTERIZATION OF A NEW DIOXIME AND ITS COBALT(III) COMPLEXES AS VITAMIN B12 MODELS." Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry 31, no. 9 (October 31, 2001): 1717–30. http://dx.doi.org/10.1081/sim-100107715.

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15

Yamaki, Regina Terumi, Luana Sena Nunes, Hygor Rodrigues De Oliveira, André S. Araújo, Marcos Almeida Bezerra, and Valfredo Azevedo Lemos. "Synthesis and Application of a New Thiazolylazo Reagent for Cloud Point Extraction and Determination of Cobalt in Pharmaceutical Preparations." Journal of AOAC INTERNATIONAL 94, no. 4 (July 1, 2011): 1304–9. http://dx.doi.org/10.1093/jaoac/94.4.1304.

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Abstract The synthesis and characterization of the reagent 2-(5-bromothiazolylazo)-4-chlorophenol and its application in the development of a preconcentration procedure for cobalt determination using flame atomic absorption spectrometry after cloud point extraction is presented. This procedure is based on cobalt complexing and entrapment of the metal chelates into micelles of a surfactant-rich phase of Triton X-114. The preconcentration procedure was optimized by using a response surface methodology through the application of the Box-Behnken matrix. Under optimum conditions, the procedure determined the presence of cobalt with an LOD of 2.8 μg/L and LOQ of 9.3 μg/L. The enrichment factor obtained was 25. The precision was evaluated as the RSD, which was 5.5% for 10 μg/L cobalt and 6.9% for 30 μg/L. The accuracy of the procedure was assessed by comparing the results with those found using inductively coupled plasma-optical emission spectrometry. After validation, the procedure was applied to the determination of cobalt in pharmaceutical preparation samples containing cobalamin (vitamin B12).
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Aliarabi, H., S. Bisheh Sari, M. M. Tabatabaei, A. Ahmadi, P. Zamani, D. Alipour, and Z. Zamani. "Effect of cobalt supplementation on performance of Mehraban lambs." Proceedings of the British Society of Animal Science 2009 (April 2009): 167. http://dx.doi.org/10.1017/s1752756200030064.

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A major physiological effect of cobalt deficiency is loss of appetite (Smith, 1997). Rumen micro-organisms require cobalt for the synthesis of Vitamin B12, which acts as a cofactor for protein and energy metabolism enzymes, namely methylmalonyl coenzyme A mutase and methionine synthase (Kennedy et, al. 1992). Cobalt deficiency, therefore, impairs the energy and protein metabolism and thus growth and development of the deficient animal, which can be defined as changes in the weight, shape and size of the body. Sheep tend to be extremely susceptible to Co deficiency and develop a normocytic and normochromic anaemia, anorexia, reduced weight gains and photosensitivity (Vellema et al., 1996). The present study was designed to evaluate the effects of dietary Co level on performance of Mehraban male lambs.
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Stangl, G. I., F. J. Schwarz, B. Jahn, and M. Kirchgessner. "Cobalt–deficiency–induced hyperhomocysteinaemia and oxidative status of cattle." British Journal of Nutrition 83, no. 1 (January 2000): 3–6. http://dx.doi.org/10.1017/s0007114500000027.

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In ruminants, Co is required for the synthesis of vitamin B12, which in turn is needed for the resynthesis of methionine by methylation of homocysteine and thus, cobalamin deficiency may induce hyperhomocysteinaemia which is brought into context with perturbations of the antioxidative–prooxidative balance. The present study was conducted to explore whether Co deficiency in cattle is also associated with homocysteine-induced disturbances of oxidative status. Co deficiency was induced in cattle by feeding two groups of animals on either a basal maize-silage-based diet that was moderately low in Co (83 μg Co/kg DM), or the same diet supplemented with Co to a total of 200 μg Co/kg DM, for 43 weeks. Co deficiency was apparent from a reduced vitamin B12 status in serum and liver and an accumulation of homocysteine in plasma which was in excess of 4·8 times higher in Co-deprived cattle than in controls. The much increased level of circulating homocysteine did not indicate severe disturbances in antioxidant–prooxidant balance as measured by individual markers of lipid peroxidation, protein oxidation, and the antioxidative defence system. There were no quantitative difference in plasma thiol groups, nor were there significant changes in concentrations of α-tocopherol, microsomal thiobarbituric acid-reactive substances and carbonyl groups in liver. However, there was a trend toward increased plasma carbonyl levels indicating a slight degradation of plasma proteins in the hyperhomocysteinaemic cattle. Analysis of the hepatic catalase (EC 1.11.1.6) activity revealed an 11 % reduction in Co-deficient cattle relative to the controls. These results indicate that long-term moderate Co deficiency may induce a severe accumulation of plasma homocysteine in cattle, but considerable abnormalities in oxidative status failed to appear.
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18

Spears, Jerry W. "139 Ruminal microbiota mineral requirements to optimize performance on different diets." Journal of Animal Science 98, Supplement_3 (November 2, 2020): 139–40. http://dx.doi.org/10.1093/jas/skaa054.243.

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Abstract This presentation will discuss mineral requirements of ruminal microorganisms, and the effect of trace mineral source on ruminal fermentation. Sulfur and phosphorus are required in relatively large amounts by ruminal microorganisms, and dietary deficiencies of these minerals have been related to impaired ruminal fermentation. A number of trace minerals are required in low concentrations by ruminal microorganisms. With the except of cobalt (Co) minimal trace mineral requirements of the host ruminant appear to be considerably greater than that needed for rumen microbial requirements. It is well known that certain bacteria can synthesize vitamin B12 from inorganic Co. Some bacteria require vitamin B12 as a growth factor, and adequate dietary Co is needed to allow sufficient ruminal B12 synthesis to meet their requirement. Vitamin B12 is needed as a cofactor for ruminal microorganisms to convert succinate to propionate. Dietary Co deficiency results in decreased ruminal propionate in ruminants fed high concentrate diets, and decreased fiber digestion in ruminants fed high fiber diets. Attempts have been made to use high concentrations of certain trace minerals to favorably manipulate ruminal fermentation. For example, attempts have been made to increase rumen protein bypass by feeding high dietary zinc (Zn). However, studies have indicated that high concentrations of copper (Cu), Zn, and iron reduce cellulose digestion in vitro. Recent studies have indicated lower fiber digestibility in cattle supplemented with sulfate sources of Cu, Zn, and manganese compared with those fed similar concentrations from hydroxy or certain organic sources. Additional research is needed to elucidate the mechanism(s) whereby trace mineral sources affect fiber digestibility differently.
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Iqbal, Sarosh, Hina Rasheed, Rabiya Javed Awan, Ramsha Javed Awan, Asma Mukhtar, and Mark G. Moloney. "Recent Advances in the Synthesis of Pyrroles." Current Organic Chemistry 24, no. 11 (September 11, 2020): 1196–229. http://dx.doi.org/10.2174/1385272824999200528125651.

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: Pyrroles are the most prevalent heterocyclic compounds, which are present as the basic cores in many natural products, such as vitamin B12, bile pigments like bilirubin and biliverdin, the porphyrins of heme, chlorophyll, chlorins, bacteriochlorins, and porphyrinogens. The biological activities of compounds having pyrrole analogs include antimicrobial (antibacterial, antifungal), anti-cancer (anti-cytotoxic, antimitotic), anti-tumor, anti-hyperlipidemic, anti-depressant, anti-inflammatory, antihyperglycemic, antiproliferative, anti-HIV and anti-viral activities. Accordingly, significant attention has been paid to develop competent methods for the synthesis of pyrroles with improved yields in short times. This review gives an overview of different methods for the synthesis of pyrrole using easily available precursors using the following routes. . Synthesis of monosubstituted pyrrole using 2,5-dimethoxyfuran . Synthesis of pyrrole using dialkylacetylene dicarboxylate . Synthesis of pyrroles using β-ketoester . Synthesis of pyrrole using 1,2-dicarbonyl compounds . Synthesis of pyrroles using 1,3-dicarbonyl compounds . Synthesis of pyrroles using 1,3-dicarbonyl, amine, nitro and aldehyde group . Synthesis of pyrroles using 1,4-dicarbonyl compound and amines . Synthesis of pyrrole using enones . Synthesis of pyrroles using moieties having acetylene group
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Rusling, James F. "Green synthesis via electrolysis in microemulsions." Pure and Applied Chemistry 73, no. 12 (January 1, 2001): 1895–905. http://dx.doi.org/10.1351/pac200173121895.

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Electrolysis in microemulsions is a promising approach for environmentally friendly chemical synthetic methods of the future. Employing microemulsions instead of organic solvents for electrosynthesis has the advantages of lower toxicity and cost, high dissolving power for reactants and mediators of unlike solubility, enhancement of reaction rates by controlling the reduction potentials of mediators, possible reaction pathway control, and recycling of microemulsion components. This paper reviews recent progress in using microemulsions for direct and mediated electrosynthesis, including formation of carbon­carbon bonds. Rates of mediated reactions can be controlled by manipulating microemulsion composition. Examples are presented, in which reaction pathways of direct and mediated electrolyses can be controlled with microemulsions to give desired products in high yields. Such control has been demonstrated with dissolved and surface-bound mediators. For a covalently linked scaffold of poly(l-lysine) and cobalt corrin vitamin B12 hexacarboxylate attached to graphite, catalytic turnover rate for reduction of 1,2-dibromocylcohexane was optimized by optimizing microemulsion composition.
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21

Kendall, N. R., A. M. Mackenzie, and S. B. Telfer. "The development of a soluble glass bolus to deliver selenium and cobalt to sheep." Proceedings of the British Society of Animal Science 1996 (March 1996): 245. http://dx.doi.org/10.1017/s0308229600032086.

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Trace element deficiencies have been reported throughout the UK and are known to decrease the productivity and welfare of animals. Selenium deficiency is characterised by muscular myopathy, white muscle disease or stiff lamb disease. Subclinical deficiencies can also cause reduced growth rate and impaired immune function. In ruminant animals, cobalt is required for the synthesis of vitamin B12 and deficiency leads to Pine, characterised by emaciation, anaemia and listlessness. Trace element deficiencies can be due to either a single element or multiple elements. Situations occur particularly in sheep where cobalt and/or selenium are deficient but where copper supplementation can be toxic. To correct these deficiencies, a single long-lasting and effective treatment in the form of a soluble glass bolus has been designed to release cobalt and selenium. This new bolus is similar to the commercial Cosecure® bolus, which is a Co/Se/Cu soluble glass, in which zinc replaces the copper.
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22

Ramanujam, V. V., and V. Alexander. "Vitamin B12 and coenzyme B12 models. 1. Synthesis and physical characterization of alkyl- and (non-alkyl)cobalt(III) complexes of 3,8-dimethyl-5,6-benzo-4,7-diazadeca-3,7-diene-2,9-dione dioxime." Inorganic Chemistry 26, no. 19 (September 1987): 3124–34. http://dx.doi.org/10.1021/ic00266a014.

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Bansal, Yogita, Manjinder Kaur, and Gulshan Bansal. "Antimicrobial Potential of Benzimidazole Derived Molecules." Mini-Reviews in Medicinal Chemistry 19, no. 8 (April 23, 2019): 624–46. http://dx.doi.org/10.2174/1389557517666171101104024.

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Structural resemblance of benzimidazole nucleus with purine nucleus in nucleotides makes benzimidazole derivatives attractive ligands to interact with biopolymers of a living system. The most prominent benzimidazole compound in nature is N-ribosyldimethylbenzimidazole, which serves as an axial ligand for cobalt in vitamin B12. This structural similarity prompted medicinal chemists across the globe to synthesize a variety of benzimidazole derivatives and to screen those for various biological activities, such as anticancer, hormone antagonist, antiviral, anti-HIV, anthelmintic, antiprotozoal, antimicrobial, antihypertensive, anti-inflammatory, analgesic, anxiolytic, antiallergic, coagulant, anticoagulant, antioxidant and antidiabetic activities. Hence, benzimidazole nucleus is considered as a privileged structure in drug discovery, and it is exploited by many research groups to develop numerous compounds that are purported to be antimicrobial. Despite a large volume of research in this area, no novel benzimidazole derived compound has emerged as clinically effective antimicrobial drug. In the present review, we have compiled various reports on benzimidazole derived antimicrobials, classified as monosubstituted, disubstituted, trisubstituted and tetrasubstituted benzimidazoles, bisbenzimidazoles, fused-benzimidazoles, and benzimidazole derivative-metal complexes. The purpose is to collate these research reports, and to generate a generalised outlay of benzimidazole derived molecules that can assist the medicinal chemists in selecting appropriate combination of substituents around the nucleus for designing potent antimicrobials.
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Banjari, Ines, Vlatka Matokovic, and Vedrana Skoro. "The question is whether intake of folic acid from diet alone during pregnancy is sufficient." Medical review 67, no. 9-10 (2014): 313–21. http://dx.doi.org/10.2298/mpns1410313b.

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Pregnancy and Folic Acid. Pregnancy is the most important period in life of every woman, partially for the number of physiological adaptations she is going through, partially for the expectance of new life. In addition, pregnancy is the ?critical window? for development later in childhood, as a period of foetal programming during which nutrition plays one of crucial roles. Despite the general belief that nutrition through pregnancy is adequate and characterized by better nutritional habits, a number of studies do not corroborate this belief. Role of Folic Acid. An adequate folate blood level is necessary for normal cell growth, synthesis of several compounds including deoxyribonucleic acid and ribonucleic acid, proper brain and neurologic functions; it is included in the regulation of homocysteine level, and closely related to the vitamin B12 metabolism. Folate deficiency in pregnancy is related to neural tube defects, other neurological disorders, preterm delivery and low birth weight. Food sources. A correlation between folate and the prevention of broad spectrum of chronic diseases has been confirmed. Emerging evidence from the epigenetic studies is now bringing even more light on the level of significance of folic acid. A wide range of plant and animal foods are the natural sources of folate; liver, yeast, mushrooms, and green leafy vegetables being the most significant. Different ways of food preparation influence the folate stability and its bioavailability varies from 25 to 50% from foods, 85% from enriched foods or 100% from supplements. Conclusion. A great amount of scientific results has led to official recommendations for folic acid supplementation in pregnant women as well as in a number of obligatory or voluntary fortification programmes in order to prevent the folate deficiency on the level of different population groups. Nevertheless, there must be a certain level of precaution for elderly because folate can mask the vitamin B12 deficiency with possible fatal outcomes.
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Pashchenko, A. G., I. I. Kovalchuk, and R. S. Fedoruk. "Mineral composition of the organism tissues and honeycombs of melliferous bees under the conditions of feeding them soybean flour and citrates of Cobalt and Nickel." Scientific Messenger of LNU of Veterinary Medicine and Biotechnology 21, no. 93 (April 2, 2019): 60–64. http://dx.doi.org/10.32718/nvlvet9311.

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The inadequacy of mineral nutrition leads to inhibition of physiological and metabolic reactions in the body of honeybees. It is known that Cobalt chloride is used to activate oviposition of the queen bee. It was established that Cobalt and Nickel citrate, obtained by the method of nanotechnology, corrects the mineral metabolism and affects the metabolism of bees. It is known that Cobalt plays an important role in the work of enzymes; synthesis of vitamin B12, promotes assimilation of vitamins A, E, C; increases protein metabolism, participates in hematopoiesis. Nickel also has a pronounced effect on hemopoiesis, namely on the morphological composition of blood. But its effect on the cell and subcellular level is not well understood. The results of studies of the effect of soybean flour with the addition of Cobalt and Nickel citrates on the content of mineral elements in the tissues of the body of bees and honeycombs are given. The research was carried out in the farms in the Lviv region, in April-May at the bees of the Carpathian breed. It was established that the content of Ferrum, Cuprum and Germanium in the tissues of bees increases with the addition of soybean flour with Сobalt citrate at a dose of 2 mg per 500 g of soy flour. When Nickel citrate was added to the feed at a dose of 1 mg per 500 g of soy flour, the content of Ferrum and Cuprum increased in honeycombs. The complex combination of Citrits Co and Ni, soy flour with sugar syrup was characterized by a decrease in the level of Zn in the tissues of the bees compared to its contents in the control group samples. In samples of biological material, the content of Сobalt, Nickel and the essential elements Cuprum, Zink, Ferrum, Selenium, Germanium was determined by atomic emission spectrometry with inductively coupled plasma. Citrates of the microelements were produced by the method of M. Kosinov and V. Kaplunenkо.
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26

Kajiwara, Yasuhiro, Patricio J. Santander, Charles A. Roessner, Lisa M. Pérez, and A. Ian Scott. "Genetically Engineered Synthesis and Structural Characterization of Cobalt−Precorrin 5A and −5B, Two New Intermediates on the Anaerobic Pathway to Vitamin B12: Definition of the Roles of the CbiF and CbiG Enzymes." Journal of the American Chemical Society 128, no. 30 (August 2006): 9971–78. http://dx.doi.org/10.1021/ja062940a.

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27

Singh, Namrata, Annamalai Pandurangan, Kavita Rana, Preeti Anand, Arsad Ahamad, and Amit Kumar Tiwari. "Benzimidazole: A short review of their antimicrobial activities." International Current Pharmaceutical Journal 1, no. 5 (April 7, 2012): 110–18. http://dx.doi.org/10.3329/icpj.v1i5.10284.

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Benzimidazole is the heterocyclic compound formed from benzene and imidazole ring containing nitrogen, oxygen sulphor and its derivatives are of wide interest because of their diverse biological activity and clinical applications, they are remarkably effective compounds both with respect to their inhibitory activity and their favourable selectivity ratio. Reported nucleus is a constituent of vitamin-B12. Benzimidazoles are regarded as a promising class of bioactive heterocyclic compounds that exhibit a range of biological activities like anti-microbial, anti-viral, anti-diabetic, anti-cancer activity, numerous anti-oxidant, anti-parasitic, anti-helmintics, anti-proliferative, anti-HIV, anti-convulsant, anti-inflammatory, anti-hypertensive, anti-neoplastic, proton pump inhibitor and anti-trichinellosis. Benzimidazoles exhibit significant activity as potential antitumor agents, smooth muscle cell proliferation inhibitors, a treatment for intestinal cystitis, and in diverse area of chemistry. Some of the important benzimidazole derivatives have been reported as thyroid receptor agonist gonadotropin releasing hormone receptor antagonists, non-nucleoside HIV-1 reverse transcriptase inhibitors and interestingly alkynylbenzimidazoles as modulators of metabotropic glutamate receptors. The imidazole core is a common moiety in a large number of natural products and pharmacologically active compounds. The synthesis of novel benzimidazole derivatives remains a main focus of medicinal research. This comprehensive overview summarizes the chemistry of different derivative of substituted benzimidazole along with their anti-microbial activity containing anti-malarial anti-fungal, anti-bacterial, anti-viral activities.DOI: http://dx.doi.org/10.3329/icpj.v1i5.10284International Current Pharmaceutical Journal 2012, 1(5): 119-127
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28

Schubert, Heidi L., Ruth S. Rose, Helen K. Leech, Amanda A. Brindley, Christopher P. Hill, Stephen E. J. Rigby, and Martin J. Warren. "Structure and function of SirC from Bacillus megaterium: a metal-binding precorrin-2 dehydrogenase." Biochemical Journal 415, no. 2 (September 25, 2008): 257–63. http://dx.doi.org/10.1042/bj20080785.

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In Bacillus megaterium, the synthesis of vitamin B12 (cobalamin) and sirohaem diverges at sirohydrochlorin along the branched modified tetrapyrrole biosynthetic pathway. This key intermediate is made by the action of SirC, a precorrin-2 dehydrogenase that requires NAD+ as a cofactor. The structure of SirC has now been solved by X-ray crystallography to 2.8 Å (1 Å = 0.1 nm) resolution. The protein is shown to consist of three domains and has a similar topology to the multifunctional sirohaem synthases Met8p and the N-terminal region of CysG, both of which catalyse not only the dehydrogenation of precorrin-2 but also the ferrochelation of sirohydrochlorin to give sirohaem. Guided by the structure, in the present study a number of active-site residues within SirC were investigated by site-directed mutagenesis. No active-site general base was identified, although surprisingly some of the resulting protein variants were found to have significantly enhanced catalytic activity. Unexpectedly, SirC was found to bind metal ions such as cobalt and copper, and to bind them in an identical fashion with that observed in Met8p. It is suggested that SirC may have evolved from a Met8p-like protein by loss of its chelatase activity. It is proposed that the ability of SirC to act as a single monofunctional enzyme, in conjunction with an independent chelatase, may provide greater control over the intermediate at this branchpoint in the synthesis of sirohaem and cobalamin.
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29

Weinberg, J. Brice, Youwei Chen, John C. Salerno, and Dipak K. Ghosh. "Inhibition of Nitric Oxide Synthase (NOS) 1, NOS2, and NOS3 Enzymatic Activities by Vitamin B12 and Related Corrins: Biochemical and Molecular Modeling Studies." Blood 110, no. 11 (November 16, 2007): 2663. http://dx.doi.org/10.1182/blood.v110.11.2663.2663.

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Abstract Cobalamins (Cbl) serve as important co-factors for methionine synthase and methylmalonyl-coA mutase. They also can block the activities of NO, as the cobalt in cobalamin binds NO and quenches its bioactivity. NO plays very important roles in normal physiology and in various pathologic processes. NO is synthesized by NO synthases (NOS), enzymes that convert L-arginine to L-citrulline and NO. We postulated that various corrin derivatives (e.g., cobalamins or cobinamides) would inhibit the enzymatic activity of NO synthase (NOS) by directly interacting with NOS. We used purified, recombinant neuronal NOS (NOS1), inducible NOS (NOS2), and endothelial NOS (NOS3) in in vitro assays measuring conversion of 14-C-L-arginine to 14-C-L-citrulline. Results showed that hydroxocobalamin (OH–Cbl), cobinamide (Cbi), and dicyanocobinamide (CN2–Cbi) were potent inhibitors of all three isoforms of NOS, while cyanocobalamin had much less activity (Table). In general, NOS1 was most inhibited, with affinities generally NOS1&gt;NOS3&gt;NOS2. Some corrins were extremely potent, with the ID50 of CN2-Cbi in the nM range. Methylcobalamin and adenosylcobalamin had very little ability to inhibit NOS activity, but light illumination of these two compounds (a process that liberates the methyl and adenosyl groups from cobalamin, generating OH–Cbl) “activated” them so that they had inhibitory activity comparable to native OH–Cbl. We examined the interactions of NOS2 with cobalamins and cobinamides by spectroscopy. Oxygen binding to the NOS heme iron in the ferrous state is an obligatory step in the NO synthase catalytic cycle. Carbon monoxide (CO, which serves as an oxygen mimic) causes a marked change in the NOS spectrum under reducing conditions. CN2–Cbi markedly diminished the CO-induced spectral changes in NOS2, indicating that CN2–Cbi likely blocks binding of CO to the NOS2 oxygenase domain under reduced conditions. This suggests that CN2–Cbi-mediated inhibition of NOS activity is due to blocking of oxygen binding to heme, a step required for the NOS catalytic cycle. Our molecular modeling investigations using manual computer-assisted docking indicate that the corrins can physically access the unusually large heme and substrate binding pocket of NOS. Binding appears to be best in the “base-off” conformation of the lower axial ligand dimethylbenzimidazole, with binding being facilitated by heme ring-corrin ring interactions and possibly by hydrogen bonding to arginine-binding groups in the active site pocket. The total “base-off” structure of CN2–Cbi and the great potential of OH–Cbl to hydrogen-bond in the pocket help explain their low ID50s for inhibition. The slightly larger active site pocket of NOS1 compared to NOS2 and NOS3 likely explains the lower ID50s for NOS1. While certain cobalamins and cobinamides have been previously noted to bind and quench/scavenge the actions of preformed NO, we show here for the first time that cobalamins and cobinamides can potently inhibit the enzymatic function of all NOS isoforms. These agents (or their derivatives) might serve as NOS inhibitors for treatment of various conditions. Also, native tissue corrins might act as important regulators of NOS activity in normal and pathological conditions in vivo. Dose (uM) for 50% inhibition of NOS activity (ID50) OH–Cbl Cbi CN2–Cbi CN–Cbl Me–Cbl Ado–Cbl NOS1 6 15 0.2 72 576 498 NOS2 21 50 2 1620 2310 2148 NOS3 9 43 0.3 519
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30

Greipp, Patricia T., Douglas A. Collins, Stephen J. Russell, Mary E. Harvey, Apollina Goel, and Philip R. Greipp. "In-111DAC Is a Novel Technique To Image Multiple Myeloma." Blood 108, no. 11 (November 16, 2006): 3488. http://dx.doi.org/10.1182/blood.v108.11.3488.3488.

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Abstract -Background: An increase in the Vitamin B12 (cobalamin) serum transport protein, transcobalamin II (TCII), has been noted in myeloma (MM) patients (Carmel, Blood. 1978.51(6):1057). Uptake of B12 bound to TCII is regulated by transcobalamin II receptors (TCII-R). Labeled thymidine studies have shown, in vitro, that TCII-R are up-regulated in proliferating malignant cells and correlate with increased incorporation of 3H-thymidine and DNA synthesis (Amagasaki, Blood, 76:1380; 1990). Via cobalt-57 labeled B12 studies, the up-regulation of TCII-R has been demonstrated in solid tumors, in vivo, by Flodh (Int J Cancer, 1968.4(5):694). Indium-111diethylenetriaminepentaacetate adenosylcobalamin (In-111DAC) is a novel radionuclide labeled B12 conjugate that has shown preferential uptake in malignant tissue compared to normal tissue via clinical gamma camera imaging of nude mice with sarcoma xenografts and human patients with various solid tumors (Collins, J Nuc Med, 1997.38(5):717 and Mayo Clin Proc, 2000.75(6):568). Nearly all the human tumors were visualized with In-111DAC and a correlation between increased In-111 uptake and higher invasiveness of the tumor at biopsy was observed. We questioned whether In-111DAC could be utilized to image MM, in vivo in murine models. Methods: In accordance with the Institutional Animal Care and Use Committee, we assessed In-111DAC as an imaging agent for MM in mice with subcutaneous (SQ) MM tumors and mice with systemic MM. 7 week old CB17/scid mice received total body irradiation 150cGy before 1x107 myeloma cells (KAS-6/1-gift of Dr. D.F. Jelinek) were injected SQ between the scapulae. Once tumors reached at least 5mm, both tumor bearing mice and saline control mice without tumor were injected intraperitoneally (IP) with 400 μCi In-111DAC. Mice with SQ tumors were injected with 400 μCi of free In-111 for comparison. Gamma camera images at 15h were followed by CT/SPECT (Single photon emission tomography) images at 18h after IP injection. To evaluate In-111DAC imaging in mice with systemic MM, 7 week old bg-nu-xid mice were injected via tail vein with 1x107 myeloma cells (5TGM1-gift of B.O. Oyajobi). Animals with late stage myeloma (day 23–28) and saline control animals were injected with In-111DAC 400 μCi, and were compared to control animals with late MM, injected with 400 μCi of free In-111. Animals underwent gamma camera and CT/SPECT imaging as in the time-frame above. All animals were sacrificed. Organs and tumors were harvested and weighed. Radioactivity was measured in a NaI scintillation well counter and recorded as cpm/mg. Results: Images and radioactivity measurements in the SQ MM model (KAS-6/1) demonstrated excellent uptake of In-111DAC within the tumor compared to normal tissue and controls. In the 5TGM1 systemic MM model, the spleen is a known sanctuary of MM and displayed especially strong uptake of In-111DAC compared to normal tissue. Conclusion: We report the first murine MM models to be imaged with In-111DAC. Our study affirms that In-111DAC is an excellent imaging agent for MM. In-111DAC imaging could be utilized clinically to complement standard staging studies to assess MM tumor burden in patients at time of diagnosis, relapse, or to assess treatment response; especially in patients with non-secretory disease. Moreover, our study strongly suggests the rationale to exploit TCII-R as a target for MM therapy.
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31

Heal, Katherine R., Wei Qin, Francois Ribalet, Anthony D. Bertagnolli, Willow Coyote-Maestas, Laura R. Hmelo, James W. Moffett, et al. "Two distinct pools of B12analogs reveal community interdependencies in the ocean." Proceedings of the National Academy of Sciences 114, no. 2 (December 27, 2016): 364–69. http://dx.doi.org/10.1073/pnas.1608462114.

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Organisms within all domains of life require the cofactor cobalamin (vitamin B12), which is produced only by a subset of bacteria and archaea. On the basis of genomic analyses, cobalamin biosynthesis in marine systems has been inferred in three main groups: select heterotrophic Proteobacteria, chemoautotrophic Thaumarchaeota, and photoautotrophic Cyanobacteria. Culture work demonstrates that many Cyanobacteria do not synthesize cobalamin but rather produce pseudocobalamin, challenging the connection between the occurrence of cobalamin biosynthesis genes and production of the compound in marine ecosystems. Here we show that cobalamin and pseudocobalamin coexist in the surface ocean, have distinct microbial sources, and support different enzymatic demands. Even in the presence of cobalamin, Cyanobacteria synthesize pseudocobalamin—likely reflecting their retention of an oxygen-independent pathway to produce pseudocobalamin, which is used as a cofactor in their specialized methionine synthase (MetH). This contrasts a model diatom,Thalassiosira pseudonana, which transported pseudocobalamin into the cell but was unable to use pseudocobalamin in its homolog of MetH. Our genomic and culture analyses showed that marine Thaumarchaeota and select heterotrophic bacteria produce cobalamin. This indicates that cobalamin in the surface ocean is a result of de novo synthesis by heterotrophic bacteria or via modification of closely related compounds like cyanobacterially produced pseudocobalamin. Deeper in the water column, our study implicates Thaumarchaeota as major producers of cobalamin based on genomic potential, cobalamin cell quotas, and abundance. Together, these findings establish the distinctive roles played by abundant prokaryotes in cobalamin-based microbial interdependencies that sustain community structure and function in the ocean.
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32

SCHEFFOLD, R. "ChemInform Abstract: Vitamin B12 and Related Compounds as Catalysts in Organic Synthesis." ChemInform 20, no. 10 (March 7, 1989). http://dx.doi.org/10.1002/chin.198910370.

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33

Joglar, Vanessa, Benjamin Pontiller, Sandra Martínez, Antonio Fuentes-Lema, María Pérez-Lorenzo, Daniel Lundin, Jarone Pinhassi, Emilio Fernández, and Eva Teira. "Microbial plankton community structure and function responses to vitamin B12 and B1 amendments in an upwelling system." Applied and Environmental Microbiology, September 8, 2021. http://dx.doi.org/10.1128/aem.01525-21.

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B vitamins are essential cofactors for practically all living organisms on Earth that are produced by a selection of microorganisms. An imbalance between high demand and limited production, in concert with abiotic processes, may explain the low availability of these vitamins in marine systems. Natural microbial communities from surface shelf water in the productive area off NW Spain were enclosed in mesocosms in winter, spring and summer 2016. In order to explore the impact of B-vitamin availability on microbial community composition (16S and 18S rRNA gene sequence analysis) and bacterial function (metatranscriptomics analysis) in different seasons, enrichment experiments were conducted with seawater from the mesocosms. Our findings revealed that significant increases in phytoplankton or prokaryote biomass associated with B12 and/or B1 amendments were not accompanied by significant changes in community composition, suggesting that most of the microbial taxa benefited from the external B-vitamin supply. Metatranscriptome analysis suggested that many bacteria were potential consumers of B12 and B1 vitamins, although the relative abundance of reads related to synthesis was ca. 3.6-fold higher than that related to uptake. Alteromonadales and Oceanospirillales accounted for important portions of B1 and B12 vitamin synthesis gene transcription, despite accounting for only minor portions of the bacterial community. Flavobacteriales appeared to be mostly involved in B12 and B1 vitamin uptake and Pelagibacterales expressed genes involved in B1 vitamin uptake. Interestingly, the relative expression of B12 and B1 vitamin synthesis genes among bacteria strongly increased upon inorganic nutrient amendments. Collectively, these findings suggest that upwelling events intermittently occurring during spring and summer in productive ecosystems may ensure an adequate production of these cofactors to sustain high levels of phytoplankton growth and biomass. Importance Section B-vitamins are essential growth factors for practically all living organisms on Earth that are produced by a selection of microorganisms. An imbalance between high-demand and limited-production may explain the low concentration of these compounds in marine systems. In order to explore the impact of B-vitamin availability on bacteria and algae in the coastal waters off NW Spain, six experiments were conducted with natural surface water enclosed in winter, spring and summer. Our findings revealed that increases in phytoplankton or bacteria growth associated with B12 and/or B1 amendments were not accompanied by significant changes in community composition, suggesting that most microorganisms benefited from the B-vitamin supply. Our analyses confirmed the role of many bacteria as consumers of B12 and B1 vitamins, although the relative abundance of genes related to synthesis was ca. 3.6-fold higher than that related to uptake.Interestingly, prokaryote expression of B12 and B1-synthesis genes strongly increased when inorganic nutrient were added. Collectively, these findings suggest that upwelling of cold and nutrient-rich waters occurring during spring and summer in this cooastal area may ensure an adequate production of B vitamins to sustain high levels of algae growth and biomass.
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RAMANUJAM, V. V., and V. ALEXANDER. "ChemInform Abstract: Vitamin B12 and Coenzyme B12 Models. Part 1. Synthesis and Physical Characterization of Alkyl- and (Non-alkyl)cobalt(III) Complexes of 3,8-Dimethyl-5,6-benzo-4,7-diazadeca-3,7-diene-2,9-dione Dioxime." ChemInform 19, no. 2 (January 12, 1988). http://dx.doi.org/10.1002/chin.198802306.

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35

"Effective Utilization of Pineapple Waste, Evaluation of Ferulic Acid, Micro Nutrients and Antioxidant Property." Proceedings International 2, no. 1 (July 15, 2020): 30. http://dx.doi.org/10.33263/proceedings21.030030.

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India is the second-largest producer of fruit and vegetable producers. Usually, after fruit intake, fruit peel is left as waste. The main bioactive components of pineapple are phenolic compounds, β-carotene, ascorbic acid, and flavonoids. Ferulic acid is a phenolic acid widely used in the nutritional and cosmetic fields. In this study, pineapple peel was dried, powdered, and vitamin content (A, B, B1, B2, B6, B12 & C), calcium, potassium, phosphorus, iron, manganese, zinc and food fiber were analyzed. Moreover, in the present study, traditional and non-conventional processes such as Soxhlet extraction, supreme fluid extraction, and normal solvent extraction was used for the extraction of ferulic acid, which is a precursor for vanillin synthesis. The quantification of ferulic acid was done by High performance fluid chromatographic (HPL C) method. After the above-mentioned extraction process overall phenolic and antioxidant activity were also evaluated and compared. The highest concentrations of ferulic acid (0.7696g/100 g), phenolic compound (2.365mg / GAE), antioxidant activity (45 percent), and yield (90.5 %) were obtained for Soxhlet extraction using methanol.
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36

Zhou, Joseph, and Utibe Effiong. "SAT-375 A 59 Year Old Female with Isolated Vitamin B6 Deficiency and Muscle Spasms." Journal of the Endocrine Society 4, Supplement_1 (April 2020). http://dx.doi.org/10.1210/jendso/bvaa046.746.

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Abstract Introduction Vitamins are essential micronutrients required by biological organisms in small quantities for maintaining basic cellular metabolism. Vitamin B6 is an important co-factor for many biochemical reactions in cellular metabolism related to the synthesis and catabolism of amino acids, fatty acids, neurotransmitters, and organelle-specific compounds, as well as in detoxifying reactive oxygen species within the cell. (1) Due to the role of Vitamin B6 in intracellular metabolism and synthesis of neurotransmitters, deficiency of the vitamin results in impaired transcellular signaling between neurons, and classically presents with muscular convulsions, hyperirritability, and peripheral neuropathy. (2) Case Presentation History We present a case of a 59-year old female with Type 2 diabetes who complained of muscle spasms. She experienced muscle spasms in her feet which have spread proximally to involve her legs. She also admitted to experiencing intermittent spasms in her left arm. The spasms occurred intermittently throughout the day and persist throughout the night, making it difficult for her to fall asleep. She had taken cyclobenzaprine twice daily and tried leg stretches, however her spasms persist. She had also tried baclofen in the past without significant alleviation of her symptoms. Evaluation An extensive investigation was conducted including tests for water-soluble vitamins. Her plasma pyridoxal 5-phosphate was 3 mcg/L (reference range 5-50 mcg/L), confirming vitamin B6 deficiency. She was also tested for Vitamins B1, B3, B12 and folate. None of the respective tests indicated deficiencies. Other test results were within normal limits. Treatment The patient received standard-dose intramuscular vitamin B6 injections for three weeks followed by oral supplements for 3 months. She was also given cyclobenzaprine (10 mg tablet) three times a day for muscle spasms in her legs. Although she had reported cyclobenzaprine did not significantly alleviate her spasms per se, it produces a sedative effect which improves her tolerance to the spasms and helps her to fall asleep at night. Conclusion This case illustrates the rare instance of isolated vitamin B6 deficiency with normal serum levels of other water-soluble vitamins, manifesting as myoclonic spasm involving the legs and arms in the absence of objective polyneuropathy. References i1 Parra, Marcelina, Seth Stahl, and Hanjo Hellmann. “Vitamin B6 and its role in cell metabolism and physiology.” Cells 7.7 (2018): 84. i2 Brown, Mary J., and Kevin Beier. “Vitamin B6 Deficiency (Pyridoxine).” StatPearls [Internet]. StatPearls Publishing, 2018.
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