Optimized ancestral state reconstruction using Sankoff parsimony

<p>Abstract</p> <p>Background</p> <p>Parsimony methods are widely used in molecular evolution to estimate the most plausible phylogeny for a set of characters. Sankoff parsimony determines the minimum number of changes required in a given phylogeny when a cost is associated to transitions between character states. Although optimizations exist to reduce the computations in the number of taxa, the original algorithm takes time <it>O</it>(<it>n</it>²) in the number of states, making it impractical for large values of <it>n</it>.</p> <p>Results</p> <p>In this study we introduce an optimization of Sankoff parsimony for the reconstruction of ancestral states when ultrametric or additive cost matrices are used. We analyzed its performance for randomly generated matrices, Jukes-Cantor and Kimura's two-parameter models of DNA evolution, and in the reconstruction of elongation factor-1<it>α </it>and ancestral metabolic states of a group of eukaryotes, showing that in all cases the execution time is significantly less than with the original implementation.</p> <p>Conclusion</p> <p>The algorithms here presented provide a fast computation of Sankoff parsimony for a given phylogeny. Problems where the number of states is large, such as reconstruction of ancestral metabolism, are particularly adequate for this optimization. Since we are reducing the computations required to calculate the parsimony cost of a single tree, our method can be combined with optimizations in the number of taxa that aim at finding the most parsimonious tree.</p

Transforaminal endoscopic surgery for symptomatic lumbar disc herniations: a systematic review of the literature

The study design includes a systematic literature review. The objective of the study was to evaluate the effectiveness of transforaminal endoscopic surgery and to compare this with open microdiscectomy in patients with symptomatic lumbar disc herniations. Transforaminal endoscopic techniques for patients with symptomatic lumbar disc herniations have become increasingly popular. The literature has not yet been systematically reviewed. A comprehensive systematic literature search of the MEDLINE and EMBASE databases was performed up to May 2008. Two reviewers independently checked all retrieved titles and abstracts and relevant full text articles for inclusion criteria. Included articles were assessed for quality and outcomes were extracted by the two reviewers independently. One randomized controlled trial, 7 non-randomized controlled trials and 31 observational studies were identified. Studies were heterogeneous regarding patient selection, indications, operation techniques, follow-up period and outcome measures and the methodological quality of these studies was poor. The eight trials did not find any statistically significant differences in leg pain reduction between the transforaminal endoscopic surgery group (89%) and the open microdiscectomy group (87%); overall improvement (84 vs. 78%), re-operation rate (6.8 vs. 4.7%) and complication rate (1.5 vs. 1%), respectively. In conclusion, current evidence on the effectiveness of transforaminal endoscopic surgery is poor and does not provide valid information to either support or refute using this type of surgery in patients with symptomatic lumbar disc herniations. High-quality randomized controlled trials with sufficiently large sample sizes are direly needed to evaluate if transforaminal endoscopic surgery is more effective than open microdiscectomy

Early Treatment with Basal Insulin Glargine in People with Type 2 Diabetes: Lessons from ORIGIN and Other Cardiovascular Trials

Dysglycemia results from a deficit in first-phase insulin secretion compounded by increased insulin insensitivity, exposing beta cells to chronic hyperglycemia and excessive glycemic variability. Initiation of intensive insulin therapy at diagnosis of type 2 diabetes mellitus (T2DM) to achieve normoglycemia has been shown to reverse glucotoxicity, resulting in recovery of residual beta-cell function. The United Kingdom Prospective Diabetes Study (UKPDS) 10-year post-trial follow-up reported reductions in cardiovascular outcomes and all-cause mortality in persons with T2DM who initially received intensive glucose control compared with standard therapy. In the cardiovascular outcome trial, outcome reduction with an initial glargine intervention (ORIGIN), a neutral effect on cardiovascular disease was observed in the population comprising prediabetes and T2DM. Worsening of glycemic control was prevented over the 6.7 year treatment period, with few serious hypoglycemic episodes and only moderate weight gain, with a lesser need for dual or triple oral treatment versus standard care. Several other studies have also highlighted the benefits of early insulin initiation as first-line or add-on therapy to metformin. The decision to introduce basal insulin to metformin must, however be individualized based on a risk-benefit analysis. The landmark ORIGIN trial provides many lessons relating to the concept and application of early insulin therapy for the prevention and safe and effective induction and maintenance of glycemic control in type 2 diabetes

Joining S100 proteins and migration:for better or for worse, in sickness and in health

The vast diversity of S100 proteins has demonstrated a multitude of biological correlations with cell growth, cell differentiation and cell survival in numerous physiological and pathological conditions in all cells of the body. This review summarises some of the reported regulatory functions of S100 proteins (namely S100A1, S100A2, S100A4, S100A6, S100A7, S100A8/S100A9, S100A10, S100A11, S100A12, S100B and S100P) on cellular migration and invasion, established in both culture and animal model systems and the possible mechanisms that have been proposed to be responsible. These mechanisms involve intracellular events and components of the cytoskeletal organisation (actin/myosin filaments, intermediate filaments and microtubules) as well as extracellular signalling at different cell surface receptors (RAGE and integrins). Finally, we shall attempt to demonstrate how aberrant expression of the S100 proteins may lead to pathological events and human disorders and furthermore provide a rationale to possibly explain why the expression of some of the S100 proteins (mainly S100A4 and S100P) has led to conflicting results on motility, depending on the cells used. © 2013 Springer Basel