Predicting the accuracy of multiple sequence alignment algorithms by using computational intelligent techniques

Multiple sequence alignments (MSAs) have become one of the most studied approaches in bioinformatics to perform other outstanding tasks such as structure prediction, biological function analysis or next-generation sequencing. However, current MSA algorithms do not always provide consistent solutions, since alignments become increasingly difficult when dealing with low similarity sequences. As widely known, these algorithms directly depend on specific features of the sequences, causing relevant influence on the alignment accuracy. Many MSA tools have been recently designed but it is not possible to know in advance which one is the most suitable for a particular set of sequences. In this work, we analyze some of the most used algorithms presented in the bibliography and their dependences on several features. A novel intelligent algorithm based on least square support vector machine is then developed to predict how accurate each alignment could be, depending on its analyzed features. This algorithm is performed with a dataset of 2180 MSAs. The proposed system first estimates the accuracy of possible alignments. The most promising methodologies are then selected in order to align each set of sequences. Since only one selected algorithm is run, the computational time is not excessively increased.     

Inhibition of DNA damage repair by artificial activation of PARP with siDNA

One of the major early steps of repair is the recruitment of repair proteins at the damage site, and this is coordinated by a cascade of modifications controlled by phosphatidylinositol 3-kinase-related kinases and/or poly (ADP-ribose) polymerase (PARP). We used short interfering DNA molecules mimicking double-strand breaks (called Dbait) or single-strand breaks (called Pbait) to promote DNA-dependent protein kinase (DNA-PK) and PARP activation. Dbait bound and induced both PARP and DNA-PK activities, whereas Pbait acts only on PARP. Therefore, comparative study of the two molecules allows analysis of the respective roles of the two signaling pathways: both recruit proteins involved in single-strand break repair (PARP, XRCC1 and PCNA) and prevent their recruitment at chromosomal damage. Dbait, but not Pbait, also inhibits recruitment of proteins involved in double-strand break repair (53BP1, NBS1, RAD51 and DNA-PK). By these ways, Pbait and Dbait disorganize DNA repair, thereby sensitizing cells to various treatments. Single-strand breaks repair inhibition depends on direct trapping of the main proteins on both molecules. Double-strand breaks repair inhibition may be indirect, resulting from the phosphorylation of double-strand breaks repair proteins and chromatin targets by activated DNA-PK. The DNA repair inhibition by both molecules is confirmed by their synthetic lethality with BRCA mutations.     

Crystal structures of Escherichia coli exonuclease I in complex with single-stranded DNA provide insights into the mechanism of processive digestion

Escherichia coli Exonuclease I (ExoI) digests single-stranded DNA (ssDNA) in the 3′-5′ direction in a highly processive manner. The crystal structure of ExoI, determined previously in the absence of DNA, revealed a C-shaped molecule with three domains that form a central positively charged groove. The active site is at the bottom of the groove, while an extended loop, proposed to encircle the DNA, crosses over the groove. Here, we present crystal structures of ExoI in complex with four different ssDNA substrates. The structures all have the ssDNA bound in essentially the predicted manner, with the 3′-end in the active site and the downstream end under the crossover loop. The central nucleotides of the DNA form a prominent bulge that contacts the SH3-like domain, while the nucleotides at the downstream end of the DNA form extensive interactions with an ‘anchor’ site. Seven of the complexes are similar to one another, but one has the ssDNA bound in a distinct conformation. The highest-resolution structure, determined at 1.95 Å, reveals an Mg²⁺ ion bound to the scissile phosphate in a position corresponding to Mg^B in related two-metal nucleases. The structures provide new insights into the mechanism of processive digestion that will be discussed.     

Distribution and abundance of the hedgehog (Erinaceus europaeus) L. in New Zealand, 1869–1973

An account is given of early liberations and the spread of hedgehogs throughout New Zealand between 1869 and 1973. Evidence, gathered largely from questionnaires and personal observations, is summarised in tables and maps to show the present range and abundance of the species. Hedgehogs dispersed from many points of liberation; their numbers increased dramatically in the South Island between 1910 and 1940, and in the North Island between 1920 and the 1950s. By the 1940s they had colonised most of the lowland areas, and their range had extended to the foot of the bushed mountainous regions; a few were found at altitudes of 2000 m. Since 1948 they have extended their range a little to include parts of the central volcanic plateau of the North Island, areas of inland Nelson, and northern Westland. Their numbers appear to have stabilised over the past 25 years. Today, hedgehogs are most abundant in intensively farmed lowland districts, towns, and suburbs. They become less numerous with increasing altitude, and few are encountered above 800 m or in wet, bushed areas. They are absent from areas where rainfall exceeds 250 cm/year or where more than 250 frosts occur annually. Factors limiting the abundance of hedgehogs in New Zealand are discussed.     

A flagellate protozoan from Mythimna separata (Lepidoptera: Noctuidae)

Abstract

A trypanosomatid flagellate, Herpetomonas sp., is recorded from an adult Mythimna separata (Walker) (Lepidoptera: Noctuidae). Promastigote, paramastigote, and opisthomastigote stages measured 3.4–12 × 1.3–4.3 μm, Giemsastained, with flagella measuring 13.8–18.7 μm. A few amastigotes (3.9–8.3 × 3.7–6.7 μm) were also observed. Fourteen larvae fed with a suspension of flagellates were found later to be infected with the protozoan. No flagellate infections were found in the hymenopteran parasitoid, Apanteles ruficus (Haliday), or the hyperparasitoid, Trichomalopsis sp.     

The potential effect of sustained hypoxia on nitrogen cycling in sediment from the southern North Sea: a mesocosm experiment

The potential effect of sustained hypoxia (up to 70 days) on the production of N₂ gas through denitrification and anammox, as well as sediment–water exchange of nitrite, nitrate and ammonia, oxygen consumption and penetration, were measured in mesocosms using sediment collected from the southern North Sea (north of Dogger Bank). As expected, both the penetration of oxygen into, and consumption of oxygen by, the sediment decreased by 42 and 46 %, respectively, once hypoxia was established. Importantly, the oxygen regime did not change significantly (P > 0.05) during the experiment, suggesting that organic carbon was not depleted. During the first 10 days, the exchange of NO₃ ^?, NO₂ ^? and NH₄ ⁺ between the sediment and water was erratic but once a steady state was established the sediment acted as either a sink for fixed nitrogen under hypoxia or as a source in the controls. Over the course of the mesocosm experiment the rate of both anammox and denitrification increased, with anammox increasing disproportionately under hypoxia relative to the controls, whereas the rate of increase in denitrification was the same for both. Under sustained hypoxia the production of N₂ gas increased by 72 % relative to the controls, with this increase in N₂ production remaining constant regardless of the duration of hypoxia. Longer periods of stratification and oxygen depletion are predicted to occur more regularly in the bottom waters of shallow coastal seas as one manifestation of climate change. Under sustained hypoxia the potential for nitrogen removal by the production of N₂ gas in this region of the southern North Sea was estimated to increase from 2.1 kt N 150 days^?1 to 3.6 kt 150 days^?1, while the efflux of dissolved inorganic nitrogen ceased altogether; both of which could down regulate the productivity of this region as a whole.