An ensemble evolutionary constraint-based approach to understand the emergence of metabolic phenotypes

Constraint-based modeling is largely used in computational studies of metabolism. We propose here a novel approach that aims to identify ensembles of flux distributions that comply with one or more target phenotype(s). The methodology has been tested on a small-scale model of yeast energy metabolism. The target phenotypes describe the differential pattern of ethanol production and O₂ consumption observed in “Crabtree-positive” and “Crabtree-negative” yeasts in changing environment (i.e., when the upper limit of glucose uptake is varied). The ensembles were obtained either by selection among sampled flux distributions or by means of a search heuristic (genetic algorithm). The former approach provided indication about the probability to observe a given phenotype, but the resulting ensembles could not be unambiguously partitioned into “Crabtree-positive” and “Crabtree-negative” clusters. On the contrary well-separated clusters were obtained with the latter method. The cluster analysis further allowed identification of distinct groups within each target phenotype. The method may thus prove useful in characterizing the design principles underlying metabolic plasticity arising from evolving physio-pathological or developmental constraints.     

A data collection protocol for real-time sensor applications

The nature of many sensor applications as well as continuously changing sensor data often imposes real-time requirements on wireless sensor network protocols. Due to numerous design constraints, such as limited bandwidth, memory and energy of sensor platforms, and packet collisions that can potentially lead to an unbounded number of retransmissions, timeliness techniques designed for real-time systems and real-time databases cannot be applied directly to wireless sensor networks. Our objective is to design a protocol for sensor applications that require periodic collection of raw data reports from the entire network in a timely manner. We formulate the problem as a graph coloring problem. We then present TIGRA (Timely Sensor Data Collection using Distributed Graph Coloring) — a distributed heuristic for graph coloring that takes into account application semantics and special characteristics of sensor networks. TIGRA ensures that no interference occurs and spatial channel reuse is maximized by assigning a specific time slot for each node. Although the end-to-end delay incurred by sensor data collection largely depends on a specific topology, platform, and application, TIGRA provides a transmission schedule that guarantees a deterministic delay on sensor data collection.     

An analysis of the transition proportion for binarization in handwritten historical documents

In this paper, we will present a mathematical analysis of the transition proportion for the normal threshold (NorT) based on the transition method. The transition proportion is a parameter of NorT which plays an important role in the theoretical development of NorT. We will study the mathematical forms of the quadratic equation from which NorT is computed. Through this analysis, we will describe how the transition proportion affects NorT. Then, we will prove that NorT is robust to inaccurate estimations of the transition proportion. Furthermore, our analysis extends to thresholding methods that rely on Bayes rule, and it also gives the mathematical bases for potential applications of the transition proportion as a feature to estimate stroke width and detect regions of interest. In the majority of our experiments, we used a database composed of small images that were extracted from DIBCO 2009 and H-DIBCO 2010 benchmarks. However, we also report evaluations using the original (H-)DIBCO?s benchmarks.     

Candida albicans homologue of GGP1/GAS1 gene is functional in Saccharomyces cerevisiae and contains the determinants for glycosylphosphatidylinositol attachment

The GGP1/GAS1/CWH52 gene of Saccharomyces cerevisiae encodes a major exocellular 115 kDa glycoprotein (gp115) anchored to the plasma membrane through a glycosylphosphatidylinositol (GPI). The function of gp115 is still unknown but the analysis of null mutants suggests a possible role in the control of morphogenesis. PHR1 gene isolated from Candida alibicans is homologous to the GGP1 gene. In this report we have analysed the ability of PHR1 to complement a ggp1Δ mutation in S. cerevisiae. The expression of PHR1 controlled by its natural promoter or by the GGP1 promoter has been studied. In both cases we have observed a complete complementation of the mutant phenotype. Moreover, immunological analysis has revealed that PHR1 in budding yeast gives rise to a 75–80 kDa protein anchored to the membrane through a GPI, indicating that the signal for GPI attachment present in the C. albicans gene product is functional in S. cerevisiae.     

Synthesis,Computational Studies and Assessment of in Vitro Activity of Squalene Derivatives as Carbonic Anhydrase Inhibitors

We report novel molecules incorporating the nontoxic squalene scaffold and different carbonic anhydrase inhibitors (CAIs). Potent inhibitory action, in the low-nanomolar range, was detected against isoforms hCA II for sulfonamide derivatives, which proved to be selective against this isoform over the tumor-associate hCA IX and XII isoforms. On the other hand, coumarin derivatives showed weak potency but high selectivity against the tumor-associated isoform CA IX. These compounds are interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. In addition, an in silico study of inhibitor-bound hCA II revealed extensive interactions with the hydrophobic pocket of the active site and provided molecular insights into the binding properties of these new inhibitors.     

Processing of tomato: impact on in vitro bioaccessibility of lycopene and textural properties

BACKGROUND: Human studies have demonstrated that processing of tomato can greatly increase lycopene bioavailability. However, the difference between processing methods is not widely investigated. In the current study different thermal treatments of tomato were evaluated with regard to their impact on in vitro bioaccessibility and retention of lycopene and β‐carotene as well as textural properties. Thermal treatments used were low (60 °C) and high (90 °C) temperature blanching followed by boiling. RESULTS: Lycopene was relatively stable during thermal treatment, whereas β‐carotene was significantly (P < 0.05) reduced by all heat treatments except for low temperature blanching. In vitro bioaccessibility of lycopene was significantly increased from 5.1 ± 0.2 to 9.2 ± 1.8 and 9.7 ± 0.6 mg kg^?1 for low and high temperature blanching, respectively. An additional boiling step after blanching did not further improve lycopene bioaccessibility for any treatment, but significantly reduced the consistency of low temperature treated samples. CONCLUSION: Choice and order of processing treatments can have a large impact on both lycopene bioavailability and texture of tomato products. Further investigations are needed, but this study provides one of the first steps towards tomato products tailored to optimise nutritional benefits. Copyright © 2010 Society of Chemical Industry     

Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury

Acute kidney injury (AKI) is a public health problem worldwide. Sirtuins are a family of seven NAD+-dependent deacylases, Overexpression of Sirtuin 1, 3, and 5 protect against AKI. However, the role of Sirtuin 7 (Sirt7) in AKI is not known. Here, we analyzed how Sirt7 deficient mice (KO-Sirt7) were affected by AKI. As expected, wild-type and Sirt7 heterozygotes mice that underwent renal ischemia/reperfusion (IR) exhibited the characteristic hallmarks of AKI: renal dysfunction, tubular damage, albuminuria, increased oxidative stress, and renal inflammation. In contrast, the KO-Sirt7+IR mice were protected from AKI, exhibiting lesser albuminuria and reduction in urinary biomarkers of tubular damage, despite similar renal dysfunction. The renoprotection in the Sirt7-KO+IR group was associated with reduced kidney weight, minor expression of inflammatory cytokines and less renal infiltration of inflammatory cells. This anti-inflammatory effect was related to diminished p65 expression and in its active phosphorylation, as well as by a reduction in p65 nuclear translocation. Sirt7 deficient mice are protected from AKI, suggesting that this histone deacetylase promotes tubular damage and renal inflammation. Therefore, our findings indicate that Sirt7 inhibitors may be an attractive therapeutic target to reduce NFκB signaling.     

Bromine, Chlorine, and Iodine Determination in Soybean and its Products by ICP-MS After Digestion Using Microwave-Induced Combustion

A method for bromine, chlorine, and iodine determination in soybean and related products was developed by inductively coupled plasma mass spectrometry (ICP-MS) after digestion by microwave-induced combustion (MIC). Samples were pressed as pellets and combusted using pressurized oxygen (20 bar) and ammonium nitrate solution (50 μL of 6 mol L^?1) as the igniter. Analytes were absorbed in alkaline solution (100 mmol L^?1 NH₄OH), and a reflux step of 5 min, microwave power of 1,400 W, was applied after combustion in order to improve analyte recoveries. For Cl determination by ICP-MS, a dynamic reaction cell was used with ammonia as the reaction gas. The accuracy was evaluated using certified reference materials (CRMs) and spiked samples. Using MIC, the agreement with CRM values and spike recoveries was higher than 95 % for all analytes for certified reference materials of a similar composition (National Institute of Standards and Technology (NIST), corn bran and NIST, whole milk). Limits of detection were 0.03, 1.2, and 0.002 μg g^?1 for Br, Cl, and I, respectively. The residual carbon content in the digests obtained after MIC procedure was lower than 0.5 %. Blanks were always negligible and no memory effects were observed. Digestion by MIC allowed processing up to eight samples by each run in 25 min with high efficiency of digestion providing a suitable medium for further bromine, chlorine, and iodine determination by ICP-MS.