Sequence analysis of the cupin gene family in Synechocystis PCC6803

The recently described cupin superfamily of proteins includes the germin and germinlike proteins, of which the cereal oxalate oxidase is the best characterized. This superfamily also includes seed storage proteins, in addition to several microbial enzymes and proteins with unknown function. All these proteins are characterized by the conservation of two central motifs, usually containing two or three histidine residues presumed to be involved with metal binding in the catalytic active site. The present study on the coding regions of Synechocystis PCC6803 identifies a previously unknown group of 12 related cupins, each containing the characteristic two-motif signature. This group comprises 11 single-domain proteins, ranging in length from 104 to 289 residues, and includes two phosphomannose isomerases and two epimerases involved in cell wall synthesis, a member of the pirin group of nuclear proteins, a possible transcriptional regulator, and a close relative-of a cytochrome c551 from Rhodococcus. Additionally, there is a duplicated, two-domain protein that has close similarity to an oxalate decarboxylase from the fungus Collybia velutipes and that is a putative progenitor of the storage proteins of land plants

A sequence, structure and electrostatic analysis of the disulphide oxidoreductases

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Microbial relatives of seed storage proteins: conservation of motifs in a functionally diverse superfamily of enzymes

Plant storage proteins comprise a major part of the human diet. Sequence analysis has revealed that these proteins probably share a common ancestor with a fungal oxalate decarboxylase and/or related bacterial genes. Additionally, all these proteins share a central core sequence with several other functionally diverse enzymes and binding proteins, many of which are associated with synthesis of the extracellular matrix during sporulation/encystment. A possible prokaryotic relative of this sequence is a bacterial protein (SASP) known to bind to DNA and thereby protect spores from extreme environmental conditions. This ability to maintain cell viability during periods of dehydration in spores and seeds may relate to absolute conservation of residues involved in structure determination

Microstructure and precipitation effects in Inconel Alloy 600

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Cardiovascular mortality following liver transplantation: predictors and temporal trends over 30 years

Aims There has been significant evolution in operative and post-transplant therapies following liver transplantation (LT). We sought to study their impact on cardiovascular (CV) mortality, particularly in the longer term. Methods and results A retrospective cohort study was conducted of all adult LTs in Australia and New Zealand across three 11-year eras from 1985 to assess prevalence, modes, and predictors of early (≤30 days) and late (>30 days) CV mortality. A total of 4265 patients were followed-up for 37 409 person-years. Overall, 1328 patients died, and CV mortality accounted for 228 (17.2%) deaths. Both early and late CV mortality fell significantly across the eras (P < 0.001). However, CV aetiologies were consistently the leading cause of early mortality and accounted for ∼40% of early deaths in the contemporary era. Cardiovascular deaths occurred significantly later than non-cardiac aetiologies (8.8 vs. 5.2 years, P < 0.001). On multivariable Cox regression, coronary artery disease [hazard ratio (HR) 4.6, 95% confidence interval (CI) 1.2-21.6; P = 0.04] and era of transplantation (HR 0.44; 95% CI 0.28-0.70; P = 0.01) were predictors of early CV mortality, while advancing age (HR 1.05, 95% CI 1.02-1.10; P = 0.005) was an independent predictors of late CV mortality. Most common modes of CV death were cardiac arrest, cerebrovascular events, and myocardial infarction. Conclusion Despite reductions in CV mortality post-LT over 30 years, they still account for a substantial proportion of early and late deaths. The late occurrence of CV deaths highlights the importance of longitudinal follow-up to study the efficacy of targeted risk-reduction strategies in this unique patient population.Anoop N Koshy, Paul J Gow, Hui-Chen Han, Andrew W Teh, Robert Jones, Adam Testro ... et al

New direct-acting antivirals in the development for hepatitis C virus infection

A large number of new therapies are in development for chronic hepatitis C including direct-acting antiviral drugs (DAA), which target specific hepatitis C virus enzymes. Two of these compounds have already advanced into phase 3 development in the USA and EU, and many more are in phase 2 trials and likely to advance. In this review, the results of recent studies on ribavirin analogues, nonstructural (NS) 3/4 serine protease inhibitors, NS5B polymerase inhibitors, cyclophilin inhibitors, silimarin components, and thiazolides have been updated. Each compound includes a brief summary of its proposed mechanism of action, results of early clinical trials, and more advanced trial data where available. These compounds are likely to be the first approved in the USA and EU and will initially be used in combination with the current standard of care. It is possible that future treatment paradigms with these agents will offer the potential of interferon-free regimens. It is most likely that patients for these new therapies will be selected carefully by identifying and treating first those who have excellent sustained virologic response rates with 24 weeks of pegylated interferon and ribavirin, the current standard of care. It is also likely that there will be a need to identify those patients who are not likely to have a sustained virologic response with the addition of a protease inhibitor to the current standard of care and delaying their therapy until combination viral suppression therapy becomes an option. The cost and side effects of the DAA will be important considerations for treating physicians. This review is current through 2009; however, data are rapidly changing