Fast estimation of the difference between two PAM/JTT evolutionary distances in triplets of homologous sequences

BACKGROUND: The estimation of the difference between two evolutionary distances within a triplet of homologs is a common operation that is used for example to determine which of two sequences is closer to a third one. The most accurate method is currently maximum likelihood over the entire triplet. However, this approach is relatively time consuming. RESULTS: We show that an alternative estimator, based on pairwise estimates and therefore much faster to compute, has almost the same statistical power as the maximum likelihood estimator. We also provide a numerical approximation for its variance, which could otherwise only be estimated through an expensive re-sampling approach such as bootstrapping. An extensive simulation demonstrates that the approximation delivers precise confidence intervals. To illustrate the possible applications of these results, we show how they improve the detection of asymmetric evolution, and the identification of the closest relative to a given sequence in a group of homologs. CONCLUSION: The results presented in this paper constitute a basis for large-scale protein cross-comparisons of pairwise evolutionary distances

Thermal inactivation and conformational lock studies on glucose oxidase

In this study, the dissociative thermal inactivation and conformational lock theories are applied for the homodimeric enzyme glucose oxidase (GOD) in order to analyze its structure. For this purpose, the rate of activity reduction of glucose oxidase is studied at various temperatures using b-D-glucose as the substrate by incubation of enzyme at various temperatures in the wide range between 40 and 70 �C using UV–Vis spectrophotometry. It was observed that in the two ranges of temperatures, the enzyme has two different forms. In relatively low temperatures, the enzyme is in its dimeric state and has normal activity. In high temperatures, the activity almost disappears and it aggregates. The above achievements are confirmed by dynamic light scattering. The experimental parameter ‘‘n’’ as the obvious number of conformational locks at the dimer interface of glucose oxidase is obtained by kinetic data, and the value is near to two. To confirm the above results, the X-ray crystallography structure of the enzyme, GOD (pdb, 1gal), was also studied. The secondary and tertiary structures of the enzyme to track the thermal inactivation were studied by circular dichroism and fluorescence spectroscopy, respectively. We proposed a mechanism model for thermal inactivation of GOD based on the absence of the monomeric form of the enzyme by circular dichroism and fluorescence spectroscopy

Effects of metal-contaminated soils on the accumulation of heavy metals in gotu kola (Centella asiatica) and the potential health risks: a study in Peninsular Malaysia

Centella asiatica is a commonly used medicinal plant in Malaysia. As heavy metal accumulation in medicinal plants which are highly consumed by human is a serious issue, thus the assessment of heavy metals in C. asiatica is important for the safety of consumers. In this study, the heavy metal accumulation in C. asiatica and the potential health risks were investigated. Samples of C. asiatica and surface soils were collected from nine different sites around Peninsular Malaysia. The concentration of six heavy metals namely Cd, Cu, Ni, Fe, Pb and Zn were determined by air-acetylene flame atomic absorption spectrophotometer (AAS). The degree of anthropogenic influence was assessed by calculating the enrichment factor (EF) and index of geoaccumulation (Igeo). The heavy metal uptake into the plant was estimated through the calculation of translocation factor (TF), bioconcentration factor (BCF) and correlation study. Estimated daily intakes (EDI) and target hazard quotients (THQ) were used to determine the potential health risk of consuming C. asiatica. The results showed that the overall surface soil was polluted by Cd, Cu and Pb, while the uptake of Zn and Ni by the plants was high. The value of EDI and THQ showed that the potential of Pb toxicity in C. asiatica was high as well. As heavy metal accumulation was confirmed in C. asiatica, daily consumption of the plant derived from polluted sites in Malaysia was not recommended

Optimizing substitution matrix choice and gap parameters for sequence alignment

<p>Abstract</p> <p>Background</p> <p>While substitution matrices can readily be computed from reference alignments, it is challenging to compute optimal or approximately optimal gap penalties. It is also not well understood which substitution matrices are the most effective when alignment accuracy is the goal rather than homolog recognition. Here a new parameter optimization procedure, POP, is described and applied to the problems of optimizing gap penalties and selecting substitution matrices for pair-wise global protein alignments.</p> <p>Results</p> <p>POP is compared to a recent method due to Kim and Kececioglu and found to achieve from 0.2% to 1.3% higher accuracies on pair-wise benchmarks extracted from BALIBASE. The VTML matrix series is shown to be the most accurate on several global pair-wise alignment benchmarks, with VTML200 giving best or close to the best performance in all tests. BLOSUM matrices are found to be slightly inferior, even with the marginal improvements in the bug-fixed RBLOSUM series. The PAM series is significantly worse, giving accuracies typically 2% less than VTML. Integer rounding is found to cause slight degradations in accuracy. No evidence is found that selecting a matrix based on sequence divergence improves accuracy, suggesting that the use of this heuristic in CLUSTALW may be ineffective. Using VTML200 is found to improve the accuracy of CLUSTALW by 8% on BALIBASE and 5% on PREFAB.</p> <p>Conclusion</p> <p>The hypothesis that more accurate alignments of distantly related sequences may be achieved using low-identity matrices is shown to be false for commonly used matrix types. Source code and test data is freely available from the author's web site at <url>http://www.drive5.com/pop</url>.</p

Rapid interhemispheric climate links via the Australasian monsoon during the last deglaciation

Recent studies have proposed that millennial-scale reorganization of the ocean-atmosphere circulation drives increased upwelling in the Southern Ocean, leading to rising atmospheric carbon dioxide levels and ice age terminations. Southward migration of the global monsoon is thought to link the hemispheres during deglaciation, but vital evidence from the southern sector of the vast Australasian monsoon system is yet to emerge. Here we present a 230thorium-dated stalagmite oxygen isotope record of millennial-scale changes in Australian–Indonesian monsoon rainfall over the last 31,000 years. The record shows that abrupt southward shifts of the Australian–Indonesian monsoon were synchronous with North Atlantic cold intervals 17,600–11,500 years ago. The most prominent southward shift occurred in lock-step with Heinrich Stadial 1 (17,600–14,600 years ago), and rising atmospheric carbon dioxide. Our findings show that millennial-scale climate change was transmitted rapidly across Australasia and lend support to the idea that the 3,000-year-long Heinrich 1 interval could have been critical in driving the last deglaciation

Recent Results from the VERITAS Collaboration

A decade after the discovery of TeV gamma-rays from the blazar Mrk 421 (Punch et al. 1992), the list of TeV blazars has increased to five BL Lac objects: Mrk 421 (Punch et al. 1992; Petry et al. 1996; Piron et al. 2001), Mrk 501 (Quinn et al. 1996; Aharonian et al. 1999; Djannati-Atai et al. 1999), 1ES2344+514 (Catanese et al. 1998), H1426+428 (Horan et al. 2000, 2002; Aharonian et al. 2002; Djannati-Atai et al. 2002) and 1ES1959+650 (Nishiyama et al. 1999; Konopelko et al. 2002; Holder et al. 2002). In this paper we report results from recent observations of Mrk 421, H1426+428 and 1ES1959+650 using the Whipple Observatory 10 m telescope