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Causey TB Shanmugam KT Yomano LP Ingram LO 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(8):2235-2240
Escherichia coli TC44, a derivative of W3110, was engineered for the production of pyruvate from glucose by combining mutations to minimize ATP yield, cell growth, and CO2 production (DeltaatpFH DeltaadhE DeltasucA) with mutations that eliminate acetate production [poxB::FRT (FLP recognition target) DeltaackA] and fermentation products (DeltafocA-pflB DeltafrdBC DeltaldhA DeltaadhE). In mineral salts medium containing glucose as the sole carbon source, strain TC44(DeltafocA-pflB DeltafrdBC DeltaldhA DeltaatpFH DeltaadhE DeltasucA poxB::FRT DeltaackA) converted glucose to pyruvate with a yield of 0.75 g of pyruvate per g of glucose (77.9% of theoretical yield; 1.2 g of pyruvate liters(-1).h(-1)). A maximum of 749 mM pyruvate was produced with excess glucose. Glycolytic flux was >50% faster for TC44 producing pyruvate than for the wild-type W3110 during fully aerobic metabolism. The tolerance of E. coli to such drastic changes in metabolic flow and energy production implies considerable elasticity in permitted pool sizes for key metabolic intermediates such as pyruvate and acetyl-CoA. In strain TC44, pyruvate yield, pyruvate titer, and the rate of pyruvate production in mineral salts medium were equivalent or better than previously reported for other biocatalysts (yeast and bacteria) requiring complex vitamin feeding strategies and complex nutrients. TC44 offers the potential to improve the economics of pyruvate production by reducing the costs of materials, product purification, and waste disposal. 相似文献
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Victoria K. Shanmugam Sean McNish Nawar Shara Katherine J. Hubley Bhaskar Kallakury David M. Dunning Christopher E. Attinger John S. Steinberg 《The Journal of foot and ankle surgery》2013,52(6):781-785
We present the case of a 63-year-old white male with bilateral chronic leg ulcers due to polycythemia vera and hydroxyurea therapy who demonstrated dramatic healing of his wounds in response to ruxolitinib (Jakafi®, Novartis), a novel Janus kinase-1 and -2 inhibitor. This patient's wound had previously been refractory to multiple surgical interventions and immunosuppression. After the initiation of ruxolitinib, the patient underwent successful split-thickness skin grafting, with resultant healing of his wounds. He was stable without prednisone and other immunosuppressant therapy and had healed at 6 months. Ruxolitinib therapy could represent a novel option for patients who develop persistent inflammatory wounds in the setting of polycythemia vera and hydroxyurea therapy. 相似文献
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Mohamed Safwan Priya Ramachandran Mettu Srinivas Reddy Naresh Shanmugam Mohamed Rela 《Pediatric transplantation》2016,20(8):1045-1050
LT has played a significant role in improving the outcome of children with BA. We review our five‐yr experience of LDLT for children with BA. Records of all children who underwent LDLT in our institution over a five‐yr period (August 2010–June 2015) were reviewed and those with a primary diagnosis of BA were selected for our study. Data were extracted from a prospectively maintained database. Additional data were collected by review of case notes and imaging studies. Analysis was carried out using standard statistical means. One hundred and thirty‐two children underwent LDLT at our center over the study period, of which 58 children (31 females) had a primary diagnosis of BA. Thirty‐three (56.9%) children had undergone a prior KPE and 25 (43.1%) had a primary LT. Thirty‐four children had at least one post‐op complication, of which 13 had minor complications (Clavien grades I and II) and 21 had major complications (Clavien grade >II). Thirty‐day survival was 96.6% and one‐yr survival was 91.4%. Univariate analysis of variables comparing children who did and did not have a KPE prior to LT showed that age at LT, weight at LT, PELD, and GRWR were significantly different. LDLT provides excellent outcomes in children with BA. Primary LDLT and LT after KPE provide equivalent results, although the former is technically more challenging as the child is younger. 相似文献
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Dhanushka Gunawardena Kirubakaran Shanmugam Mitchell Low Louise Bennett Suresh Govindaraghavan Richard Head Lezanne Ooi Gerald Münch 《European journal of nutrition》2014,53(1):335-343