Protein Networks Reveal Detection Bias and Species Consistency When Analysed by Information-Theoretic Methods

We apply our recently developed information-theoretic measures for the characterisation and comparison of protein–protein interaction networks. These measures are used to quantify topological network features via macroscopic statistical properties. Network differences are assessed based on these macroscopic properties as opposed to microscopic overlap, homology information or motif occurrences. We present the results of a large–scale analysis of protein–protein interaction networks. Precise null models are used in our analyses, allowing for reliable interpretation of the results. By quantifying the methodological biases of the experimental data, we can define an information threshold above which networks may be deemed to comprise consistent macroscopic topological properties, despite their small microscopic overlaps. Based on this rationale, data from yeast–two–hybrid methods are sufficiently consistent to allow for intra–species comparisons (between different experiments) and inter–species comparisons, while data from affinity–purification mass–spectrometry methods show large differences even within intra–species comparisons.     

Optimization of androstenedione production in an organic–aqueous two-liquid phase system

A systematic evaluation of the effect of key operational parameters on the selective cleavage of sitosterol to 4-androstene-3,17-dione (AD) with Mycobacterium sp. NRRL B-3805 in a dioctyl phthalate: aqueous buffer two-liquid phase system was performed. Of the parameters assessed, buffer composition, biomedium pH, temperature, and biomass and substrate concentration were those that mostly affected overall bioconversion rate. The optimum pH was 7.5 with Tris buffer. The highest bioconversion rate was observed at 35 °C, although at 40 °C bioconversion activity was virtually lost. Michaelis–Menten type kinetics adequately described the bioconversion system. Increasing biomass concentration from 10 to 70 g_{wet cell weight} l⁻¹ favored AD final yield, although the specific AD yield slightly decreased.     

Structure of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase complexed with chalepin,a natural product inhibitor,at 1.95 A resolution

The structure of the glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi complexed with chalepin, a natural product from Pilocarpus spicatus, has been determined by X-ray crystallography to 1.95 Å resolution. The structure is in the apo form without cofactors in the subunits of the tetrameric gGAPDH in the asymmetric unit. Unequivocal density corresponding to the inhibitor was clearly identified in one monomer. The final refined model of the complex shows extensive conformational changes when compared with the native structure. The mode of binding of chalepin to gGAPDH and its implications for inhibitor design are discussed.     

Increased resistance to hydrogen peroxide‐induced cardiac contracture is associated with decreased myocardial oxidative stress in hypothyroid rats

The purpose of this study was to determine whether decreased oxidative stress would increase the resistance to cardiac contracture induced by H₂O₂ in hypothyroid rats. Male Wistar rats were divided into two groups: control and hypothyroid. Hypothyroidism was induced via thyroidectomy. Four weeks post surgery, blood samples were collected to perform thyroid hormone assessments, and excised hearts were perfused at a constant flow with or without H₂O₂ (1 mmol/L), being divided into two sub‐groups: control, hypothyroid, control + H₂O₂, hypothyroid + H₂O₂. Lipid peroxidation (LPO) was evaluated by chemiluminescence (CL) and thiobarbituric acid reactive substances (TBARS) methods, and protein oxidation by carbonyls assay in heart homogenates. Cardiac tissue was also screened for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, and for total radical‐trapping antioxidant potential (TRAP). Analyses of SOD and glutathione‐S‐transferase (GST) protein expression were also performed in heart homogenates. Hypothyroid hearts were found to be more resistant to H₂O₂‐induced contracture (60% elevation in LVEDP) as compared to control. CL, TBARS, carbonyl, as well as SOD, CAT, GPx activities and TRAP levels were reduced (35, 30, 40, 30, 16, 25, and 33%, respectively) in the cardiac homogenates of the hypothyroid group as compared to controls. A decrease in SOD and GST protein levels by 20 and 16%, respectively, was also observed in the hypothyroid group. These results suggest that a hypometabolic state caused by thyroid hormone deficiency can lead to an improved response to H₂O₂ challenge and is associated with decreased oxidative myocardial damage. Copyright © 2009 John Wiley & Sons, Ltd.     

Favorable 2′-substitution in the loop region of a thrombin-binding DNA aptamer

Simple 2′-OMe-chemical modification in the loop region of the 15mer G-rich DNA sequence GGTTGGTGTGGTTGG is reported. The G-quadruplex structure of this thrombin-binding aptamer (TBA), is stabilized by single modifications (T?→?2′-OMe-U), depending on the position of the modification. The structural stability also renders significantly increased inhibition of thrombin-induced fibrin polymerization, a process closely associated with blood-clotting.     

Biological control on gastrointestinal nematodes in cattle with association of nematophagous fungi

This study aimed to evaluate the efficacy of the association of the nematophagous fungi (Duddingtonia flagrans-AC001); (Pochonia chlamydosporia-VC4) and (Arthrobotrys robusta-I31) in a pelletised formulation of a sodium alginate matrix. The viability and activity of pellet germination and fungal activity (after encapsulation) were evaluated using in vitro and in vivo tests. Next, 12 heads of cattle, Dutch mestizo x zebu, with an average age of 12 months were dewormed with an anthelmintic. Next, 20 days after treatment with the anthelmintic, the animals were randomly divided into two groups of six animals each, and placed in two paddocks with 7.0?ha each of Brachiaria decumbens with historical grazing by animals naturally infected by gastrointestinal nematode parasites. At first, each animal was treated with 2?g of pellets per 10?kg of animal, containing the associated fungi (AC001?+?VC4?+?I31) administered twice a week in conjunction with commercial feed. Each animal in the control group received 2?g of pellets without mycelia added to the feed. The percentage reduction of infective larvae in the in vitro test was 94% (p?in vivo test, the treated animals with fungal association had lower egg counts per gram of faeces (p?相似文献   

Genetic Stratigraphy of Key Demographic Events in Arabia

At the crossroads between Africa and Eurasia, Arabia is necessarily a melting pot, its peoples enriched by successive gene flow over the generations. Estimating the timing and impact of these multiple migrations are important steps in reconstructing the key demographic events in the human history. However, current methods based on genome-wide information identify admixture events inefficiently, tending to estimate only the more recent ages, as here in the case of admixture events across the Red Sea (∼8–37 generations for African input into Arabia, and 30–90 generations for “back-to-Africa” migrations). An mtDNA-based founder analysis, corroborated by detailed analysis of the whole-mtDNA genome, affords an alternative means by which to identify, date and quantify multiple migration events at greater time depths, across the full range of modern human history, albeit for the maternal line of descent only. In Arabia, this approach enables us to infer several major pulses of dispersal between the Near East and Arabia, most likely via the Gulf corridor. Although some relict lineages survive in Arabia from the time of the out-of-Africa dispersal, 60 ka, the major episodes in the peopling of the Peninsula took place from north to south in the Late Glacial and, to a lesser extent, the immediate post-glacial/Neolithic. Exchanges across the Red Sea were mainly due to the Arab slave trade and maritime dominance (from ∼2.5 ka to very recent times), but had already begun by the early Holocene, fuelled by the establishment of maritime networks since ∼8 ka. The main “back-to-Africa” migrations, again undetected by genome-wide dating analyses, occurred in the Late Glacial period for introductions into eastern Africa, whilst the Neolithic was more significant for migrations towards North Africa.