Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1

Thioredoxins (TRX) are traditionally considered as enzymes catalyzing redox reactions. However, redox-independent functions of thioredoxins have been described in different organisms, although the underlying molecular mechanisms are yet unknown. We report here the characterization of the first generated endogenous redox-inactive thioredoxin in an animal model, the TRX-1 in the nematode Caenorhabditis elegans. We find that TRX-1 dually regulates the formation of an endurance larval stage (dauer) by interacting with the insulin pathway in a redox-independent manner and the cGMP pathway in a redox-dependent manner. Moreover, the requirement of TRX-1 for the extended longevity of worms with compromised insulin signalling or under calorie restriction relies on TRX-1 redox activity. In contrast, the nuclear translocation of the SKN-1 transcription factor and increased LIPS-6 protein levels in the intestine upon trx-1 deficiency are strictly redox-independent. Finally, we identify a novel function of C. elegans TRX-1 in male food-leaving behaviour that is redox-dependent. Taken together, our results position C. elegans as an ideal model to gain mechanistic insight into the redox-independent functions of metazoan thioredoxins, overcoming the limitations imposed by the embryonic lethal phenotypes of thioredoxin mutants in higher organisms

Calculation of the relative metastabilities of proteins in subcellular compartments of Saccharomyces cerevisiae

[abridged] Background: The distribution of chemical species in an open system at metastable equilibrium can be expressed as a function of environmental variables which can include temperature, oxidation-reduction potential and others. Calculations of metastable equilibrium for various model systems were used to characterize chemical transformations among proteins and groups of proteins found in different compartments of yeast cells. Results: With increasing oxygen fugacity, the relative metastability fields of model proteins for major subcellular compartments go as mitochondrion, endoplasmic reticulum, cytoplasm, nucleus. In a metastable equilibrium setting at relatively high oxygen fugacity, proteins making up actin are predominant, but those constituting the microtubule occur with a low chemical activity. A reaction sequence involving the microtubule and spindle pole proteins was predicted by combining the known intercompartmental interactions with a hypothetical program of oxygen fugacity changes in the local environment. In further calculations, the most-abundant proteins within compartments generally occur in relative abundances that only weakly correspond to a metastable equilibrium distribution. However, physiological populations of proteins that form complexes often show an overall positive or negative correlation with the relative abundances of proteins in metastable assemblages. Conclusions: This study explored the outlines of a thermodynamic description of chemical transformations among interacting proteins in yeast cells. The results suggest that these methods can be used to measure the degree of departure of a natural biochemical process or population from a local minimum in Gibbs energy.Comment: 32 pages, 7 figures; supporting information is available at http://www.chnosz.net/yeas

Prototype generation on structural data using dissimilarity space representation

Data reduction techniques play a key role in instance-based classification to lower the amount of data to be processed. Among the different existing approaches, prototype selection (PS) and prototype generation (PG) are the most representative ones. These two families differ in the way the reduced set is obtained from the initial one: While the former aims at selecting the most representative elements from the set, the latter creates new data out of it. Although PG is considered to delimit more efficiently decision boundaries, the operations required are not so well defined in scenarios involving structural data such as strings, trees, or graphs. This work studies the possibility of using dissimilarity space (DS) methods as an intermediate process for mapping the initial structural representation to a statistical one, thereby allowing the use of PG methods. A comparative experiment over string data is carried out in which our proposal is faced to PS methods on the original space. Results show that the proposed strategy is able to achieve significantly similar results to PS in the initial space, thus standing as a clear alternative to the classic approach, with some additional advantages derived from the DS representation.This work was partially supported by the Spanish Ministerio de Educación, Cultura y Deporte through a FPU fellowship (AP2012–0939), Vicerrectorado de Investigación, Desarrollo e Innovación de la Universidad de Alicante through FPU program (UAFPU2014–5883), and the Spanish Ministerio de Economía y Competitividad through Project TIMuL (No. TIN2013-48152-C2-1-R supported by EU FEDER funds)

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Instance reduction for one-class classification

Instance reduction techniques are data preprocessing methods originally developed to enhance the nearest neighbor rule for standard classification. They reduce the training data by selecting or generating representative examples of a given problem. These algorithms have been designed and widely analyzed in multi-class problems providing very competitive results. However, this issue was rarely addressed in the context of one-class classification. In this specific domain a reduction of the training set may not only decrease the classification time and classifier’s complexity, but also allows us to handle internal noisy data and simplify the data description boundary. We propose two methods for achieving this goal. The first one is a flexible framework that adjusts any instance reduction method to one-class scenario by introduction of meaningful artificial outliers. The second one is a novel modification of evolutionary instance reduction technique that is based on differential evolution and uses consistency measure for model evaluation in filter or wrapper modes. It is a powerful native one-class solution that does not require an access to counterexamples. Both of the proposed algorithms can be applied to any type of one-class classifier. On the basis of extensive computational experiments, we show that the proposed methods are highly efficient techniques to reduce the complexity and improve the classification performance in one-class scenarios

Seasonal changes and coliform load of Jalaur river, province of Iloilo, Panay island, Philippines

Determination of the presence/absence of coliforms as the pollution indicator bacteria, total coliform count (TCC) and fecal coliform counts specifically Echerichia coli were carried out on specific sampling points in Jalaur River namely: Banban Pequeño (upstream), Calinog, Moroboro, Dingle, Passi near Sugar Central Mill and National Power Corporation (NPC) (midstream), and Nabitasan, Leganes (downstream) during the wet and dry months. Samples were analyzed using a defined technology, the Colilert® method, and its accuracy was verified with the conventional method (APHA Standard Methods). Results showed that coliforms were present in all sampling sites. In Calinog, total coliform count (TCC) was high (900 x101 MPN/100 ml) in July. Increased coliform abundance was associated with high rainfall due to animal wastes that were carried by runoffs. In September, Passi, near NPC, TCC and E. coli counts were 640 x101 and 630 x 101 MPN/100 ml, respectively. Reduction in counts in January, February and March was observed. Sediments in Passi near Sugar Central Mill during milling time in February showed a high TCC of 116 x 104 MPN/100 ml which was attributed to reduced current and disturbance, and silty loam sediments texture that favored bacterial adsorption to sediments. Dingle site exhibited a domination of other coliforms over E. coli in January and March. In Leganes, highest TCC of 551 x 101 MPN/100 ml was obtained in September. Coliform loads varied by season which was influenced by the availability of the nutrients and tolerance range to physical and chemical factors in the environment. Variability of the resultant interaction can also be attributed to climate changes such as extreme weather events—El niño phenomenon and increased nutrient loadings during heavy rains hence, increased coliform concentration in the river. The presence of coliforms in Jalaur River is indicative of contamination that can be aggravated by climate changes and implies that a potential health risk associated with pathogens causing water-borne diseases is present.This research was supported by the Silliman University-Commission on Higher Education (CHED) Zonal Center Region VI, St. Paul University Iloilo, Southeast Asian Fisheries Development Center (SEAFDEC), Aquaculture Department