A grammar-based distance metric enables fast and accurate clustering of large sets of 16S sequences

Background: We propose a sequence clustering algorithm and compare the partition quality and execution time of the proposed algorithm with those of a popular existing algorithm. The proposed clustering algorithm uses a grammar-based distance metric to determine partitioning for a set of biological sequences. The algorithm performs clustering in which new sequences are compared with cluster-representative sequences to determine membership. If comparison fails to identify a suitable cluster, a new cluster is created. Results: The performance of the proposed algorithm is validated via comparison to the popular DNA/RNA sequence clustering approach, CD-HIT-EST, and to the recently developed algorithm, UCLUST, using two different sets of 16S rDNA sequences from 2,255 genera. The proposed algorithm maintains a comparable CPU execution time with that of CD-HIT-EST which is much slower than UCLUST, and has successfully generated clusters with higher statistical accuracy than both CD-HIT-EST and UCLUST. The validation results are especially striking for large datasets. Conclusions: We introduce a fast and accurate clustering algorithm that relies on a grammar-based sequence distance. Its statistical clustering quality is validated by clustering large datasets containing 16S rDNA sequences

Metformin:historical overview

Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes. Its history is linked to Galega officinalis (also known as goat's rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose. Guanidine derivatives, including metformin, were synthesised and some (not metformin) were used to treat diabetes in the 1920s and 1930s but were discontinued due to toxicity and the increased availability of insulin. Metformin was rediscovered in the search for antimalarial agents in the 1940s and, during clinical tests, proved useful to treat influenza when it sometimes lowered blood glucose. This property was pursued by the French physician Jean Sterne, who first reported the use of metformin to treat diabetes in 1957. However, metformin received limited attention as it was less potent than other glucose-lowering biguanides (phenformin and buformin), which were generally discontinued in the late 1970s due to high risk of lactic acidosis. Metformin's future was precarious, its reputation tarnished by association with other biguanides despite evident differences. The ability of metformin to counter insulin resistance and address adult-onset hyperglycaemia without weight gain or increased risk of hypoglycaemia gradually gathered credence in Europe, and after intensive scrutiny metformin was introduced into the USA in 1995. Long-term cardiovascular benefits of metformin were identified by the UK Prospective Diabetes Study (UKPDS) in 1998, providing a new rationale to adopt metformin as initial therapy to manage hyperglycaemia in type 2 diabetes. Sixty years after its introduction in diabetes treatment, metformin has become the most prescribed glucose-lowering medicine worldwide with the potential for further therapeutic applications

Metformin and the gastrointestinal tract

Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, recent evidence also implicates the gut as an important site of action. Metformin has a number of actions within the gut. It increases intestinal glucose uptake and lactate production, increases GLP-1 concentrations and the bile acid pool within the intestine, and alters the microbiome. A novel delayed-release preparation of metformin has recently been shown to improve glycaemic control to a similar extent to immediate-release metformin, but with less systemic exposure. We believe that metformin response and tolerance is intrinsically linked with the gut. This review examines the passage of metformin through the gut, and how this can affect the efficacy of metformin treatment in the individual, and contribute to the side effects associated with metformin intolerance

Reaction of families and lines of melon to powdery mildew Reação de famílias e linhagens de melão ao oídio

Powdery mildew, caused by Podosphaera xanthii, is an important disease of melon in the Brazilian Northeast. The objective of this work was to evaluate the reaction of families, lines and cultivars of melon to P. xanthii. Two experiments in simple lattice were carried out under field conditions in the municipalities of Mossoró and Baraúna to evaluate 144 families. In a greenhouse, an experiment was carried out in a completely randomized design to evaluate 19 lines and the cultivars Yellow Queen, Chilton and Hy Mark. Disease was assessed by a severity scale. There was genetic variability among families. The families 4, 5, 11, 14, 18, 23, 33, 42, 101, 112 and 140 were identified in both sites as resistant. The lines LOF-027, LOF-105, LPS-124, MEL-008 and cultivar Chilton showed resistance to race 1 of the fungus.<br>O oídio, causado por Podosphaera xanthii, é uma importante doença do melão no Nordeste brasileiro. O objetivo do presente trabalho foi avaliar a reação de famílias, linhagens e cultivares de melão a P. xanthii. Foram conduzidos, em condições de campo, nos municípios de Mossoró e Baraúna, experimentos em látice simples para avaliar 144 famílias. Em casa de vegetação, foi conduzido um experimento em delineamento inteiramente casualizado para avaliar 19 linhagens e as cultivares Yellow Queen, Chilton e Hy Mark. A severidade da doença foi avaliada mediante uma escala de notas. Houve variabilidade genética entre as famílias. Foram identificadas como resistentes, em ambos os locais, as famílias 4, 5, 11, 14, 18, 23, 33, 42, 101, 112 e 140. As linhagens LOF-027, LOF-105, LPS-124, MEL-008 e a cultivar Chilton mostraram resistência à raça 1 do fungo