WD-40 repeat region regulates Apaf-1 self-association and procaspase-9 activation

The casp9 protein plays a critical role in apoptosis induced by a variety of death stimuli. A regulator of apoptosis, Apaf-1, binds to and activates pro-casp9 in the presence of cytochrome c and dATP, a requirement that is bypassed by deletion of the WD-40 repeats located in the C-terminal half of Apaf-1. In this report, we used constitutively active Apaf-1 mutant lacking the WD-40 repeat region to study the mechanism and regulation of pro-casp9 activation. Mutational analysis revealed that only a small portion of the CED-4 homologous region (residues 456-559) could be deleted without destroying the ability of Apaf-1-(1-559) to activate pro-casp9. Apaf-1 can self-associate to form oligomers. Disruption of Apaf-1 self-association by deletion (Delta109-559) or mutation of the P-loop region (K149R) abrogated Apaf-1-mediated pro-casp9 activation. Forced oligomerization of the caspase recruitment domain of Apaf-1 was sufficient for pro-casp9 activation. Dimerization of chimeric Fpk-pro-casp9 protein with the dimerizer drug FK1012 induced pro-casp9 processing and apoptosis in cells. Significantly, the C-terminal region containing WD-40 repeats interacted with its N-terminal CED-4 homologous region, as determined by immunoprecipitation experiments. Importantly, expression of the WD-40 repeat region inhibited Apaf-1 self-association and proteolytic activation of pro-casp9. These studies provide a mechanism by which Apaf-1 promotes autoactivation of pro-casp9 through Apaf-1 self-association, a process that is negatively regulated by the WD-40 repeats.     

Hyperinsulinaemia, dyslipaemia and cardiovascular risk in girls with a history of premature pubarche

Girls with a history of premature pubarche, i.e. appearance of pubic hair before 8 years of age, show hyperinsulinism in response to an oral glucose tolerance test. As hyperinsulinaemia has a major role in dyslipaemia, and is considered an independent risk factor for cardiovascular disease, we assessed the patterns of plasma insulin concentration after a standard oral glucose tolerance test as well as fasting serum lipid, lipoprotein, and sex hormone-binding globulin concentrations in girls (n = 81) with premature pubarche compared with girls (n = 55) matched with them for stage and bone age to ascertain their metabolic states to identify those potentially at risk for the development of premature cardiovascular disease. Mean serum insulin concentrations were higher in patients at all pubertal stages, and associated with elevated serum triglyceride, very low density cholesterol and very low density triglyceride concentrations (p value range 0.04 to < 0.0001) but reduced sex hormone-binding globulin. Premature pubarche patients also displayed higher low density to high density lipoprotein cholesterol ratios compared with control subjects (p = 0.004 to 0.008). In conclusion, hyperinsulinaemia, decreased sex hormone-binding globulin concentrations and an unfavourable lipid pattern are common features in premature pubarche girls supporting the contention that atherogenic abnormalities composing the metabolic syndrome could start in childhood. To determine the clinical sequelae of such clustering of metabolic deviations, girls who were identified need to be followed up for the potential development of premature cardiovascular disease.     

Trypanosoma cruzi genotypes associated with domestic Triatoma sordida in Bolivia

Triatoma sordida is the second species of Triatominae considered of epidemiological significance in Bolivia. Associated with Triatoma infestans in various regions, it is as yet the only triatomine species established in human dwellings in localities of Velasco province, Department of Santa Cruz. This domestication is considered as primary. Flagellate parasites were detected in 16.2% of domiciliary T. sordida and the kDNA-PCR confirmed the presence of Trypanosoma cruzi. Frequencies of T. cruzi clonets 20 and 39, common clonets in Bolivian domestic cycle (T. infestans), were established by their direct detection in feces using PCR and hybridization. These clonets present low frequencies in T. sordida and synanthropic mammals. Forty-six stocks were isolated and analysed by multilocus enzyme electrophoresis (MLEE). The MLEE showed a higher clonal diversity than in T. infestans domestic cycle and the genotypes were clustered in the two principal lineages of T. cruzi. Within each lineage, a broad variability was observed. Mixture of genotypes was mostly observed in mammals. The large diversity of T. cruzi in this cycle should be related to its sylvatic origin. Moreover, the current limited sample of stocks suggests a lineage association with specific hosts.     

A Tale of Two Dams: The Impact of Reservoir Management on Rural Depopulation in Central Spain

In rural areas, depopulation is mainly due to a lack of economic and employment opportunities. In this context, the reservoirs already built can be a source of socioeconomic development based on tourism and outdoor leisure activities. The condition for this development to materialize is that reservoir management considers these activities. In Central Spain, a process of rural depopulation has been generated in the municipalities around the reservoirs at the Upper Tagus River, as water management allows water transfers from the Tagus to the Segura River without taking into account regulations that prioritize and protect donor basin users. Through the comparison of reservoir water management and demographic data of two rural areas close to the reservoirs, this article reveals the direct relationship between reservoir management that enables recreational uses with its consequent socioeconomic development and the maintenance of the population in the territory. Consequently, reservoir water management based on the socioeconomic development of reservoir banks is necessary and a priority over transfers to another basin.

     

Parallel source separation system for heart and lung sounds

The Journal of Supercomputing - In this paper, we propose a parallel source separation system designed to extract heart and lung sounds from single-channel mixtures. The proposed system is based on...     

A comparison study of wavelet transforms for the visualization of differentially methylated regions in DNA samples

The Journal of Supercomputing - DNA methylation analysis has become an important topic in the study of human health. DNA methylation analysis requires not only a specific treatment of DNA samples...     

Missing data imputation for fuzzy rule-based classification systems

Fuzzy rule-based classification systems (FRBCSs) are known due to their ability to treat with low quality data and obtain good results in these scenarios. However, their application in problems with missing data are uncommon while in real-life data, information is frequently incomplete in data mining, caused by the presence of missing values in attributes. Several schemes have been studied to overcome the drawbacks produced by missing values in data mining tasks; one of the most well known is based on preprocessing, formerly known as imputation. In this work, we focus on FRBCSs considering 14 different approaches to missing attribute values treatment that are presented and analyzed. The analysis involves three different methods, in which we distinguish between Mamdani and TSK models. From the obtained results, the convenience of using imputation methods for FRBCSs with missing values is stated. The analysis suggests that each type behaves differently while the use of determined missing values imputation methods could improve the accuracy obtained for these methods. Thus, the use of particular imputation methods conditioned to the type of FRBCSs is required.     

SIMCAN: A flexible, scalable and expandable simulation platform for modelling and simulating distributed architectures and applications

In this paper we propose a new simulation platform called SIMCAN, for analyzing parallel and distributed systems. This platform is aimed to test parallel and distributed architectures and applications. The main characteristics of SIMCAN are flexibility, accuracy, performance, and scalability. Thence, the proposed platform has a modular design that eases the integration of different basic systems on a single architecture. Its design follows a hierarchical schema that includes simple modules, basic systems (computing, memory managing, I/O, and networking), physical components (nodes, switches, …), and aggregations of components. New modules may also be incorporated as well to include new strategies and components. Also, a graphical configuration tool has been developed to help untrained users with the task of modelling new architectures. Finally, a validation process and some evaluation tests have been performed to evaluate the SIMCAN platform.     

An XPS and reduction study of PrCoO3

The perovskite-type oxide PrCoO₃ has been studied by means of X-ray photoelectron spectroscopy (XPS), reduction in H₂ and X-ray diffraction. Two types of oxygen were detected: lattice oxygen (binding energy = 528.4 eV) and adsorbed oxygen (binding energy = 530.9 eV). The increase in relative intensity of the peak corresponding to the latter species after reduction of PrCo0₃ to 3e^– per molecule is assigned to the formation of hydroxyl groups. Temperature-programmed reduction (TPR) results showed two reduction steps: to 1 e^– per molecule (Co^3.1 Co²⁺) at 475 to 635 K, and to 3e^– per molecule (Co²¹ Co⁰) at 725 to 815 K. Reduction in the first and second steps occurs according to the contracting sphere model and the nucleation mechanism, respectively. Reduction of Co³⁺ to Co²⁺ causes minimal structural changes in the perovskite. Reduction to 3e^– per molecule yielded Pr₂O₃ and metallic cobalt. After this reduction and reoxidation at 973 K, the perovskite structure was regained. By XPS and TPR it was shown that PrCo0₃ is more easily reducible than LaCo0₃. It is concluded that the cation in the A position of the structure plays a significant role in the bulk and surface properties of LnCo0₃ (Ln, lanthanide elements) oxides.     

Influence of preparation conditions on characteristics of the YBa2Cu3O7−δ compound

Synthesis of ceramic YBa₂Cu₃O_7– by solid-state reaction was performed under different conditions. Different values of cooling rate and oxygen flow were used, and no significant influence on superconducting characteristics of the samples was observed. A major influence on their mechanical properties was found.