On the Evolution of Hexose Transporters in Kinetoplastid Potozoans

Glucose, an almost universally used energy and carbon source, is processed through several well-known metabolic pathways, primarily glycolysis. Glucose uptake is considered to be the first step in glycolysis. In kinetoplastids, a protozoan group that includes relevant human pathogens, the importance of glucose uptake in different phases of the life cycles is well established, and hexose transporters have been proposed as targets for therapeutic drugs. However, little is known about the evolutionary history of these hexose transporters. Hexose transporters contain an intracellular N- and C-termini, and 12 transmembrane spans connected by alternate intracellular and extracellular loops. In the present work we tested the hypothesis that the evolutionary rate of the transmembrane span is different from that of the whole sequence and that it is possible to define evolutionary units inside the sequence. The phylogeny of whole molecules was compared to that of their transmembrane spans and the loops connecting the transmembrane spans. We show that the evolutionary units in these proteins primarily consist of clustered rather than individual transmembrane spans. These analyses demonstrate that there are evolutionary constraints on the organization of these proteins; more specifically, the order of the transmembrane spans along the protein is highly conserved. Finally, we defined a signature sequence for the identification of kinetoplastid hexose transporters.

MRKAd5 HIV-1 Gag/Pol/Nef Vaccine-Induced T-Cell Responses Inadequately Predict Distance of Breakthrough HIV-1 Sequences to the Vaccine or Viral Load

Background: The sieve analysis for the Step trial found evidence that breakthrough HIV-1 sequences for MRKAd5/HIV-1 Gag/Pol/Nef vaccine recipients were more divergent from the vaccine insert than placebo sequences in regions with predicted epitopes. We linked the viral sequence data with immune response and acute viral load data to explore mechanisms for and consequences of the observed sieve effect. Methods: Ninety-one male participants (37 placebo and 54 vaccine recipients) were included; viral sequences were obtained at the time of HIV-1 diagnosis. T-cell responses were measured 4 weeks post-second vaccination and at the first or second week post-diagnosis. Acute viral load was obtained at RNA-positive and antibody-negative visits. Findings: Vaccine recipients had a greater magnitude of post-infection CD8+ T cell response than placebo recipients (median 1.68% vs 1.18%; p = 0.04) and greater breadth of post-infection response (median 4.5 vs 2; p = 0.06). Viral sequences for vaccine recipients were marginally more divergent from the insert than placebo sequences in regions of Nef targeted by pre-infection immune responses (p = 0.04; Pol p = 0.13; Gag p = 0.89). Magnitude and breadth of pre-infection responses did not correlate with distance of the viral sequence to the insert (p. 0.50). Acute log viral load trended lower in vaccine versus placebo recipients (estimated mean 4.7 vs 5.1) but the difference was not significant (p = 0.27). Neither was acute viral load associated with distance of the viral sequence to the insert (p>0.30). Interpretation: Despite evidence of anamnestic responses, the sieve effect was not well explained by available measures of T-cell immunogenicity. Sequence divergence from the vaccine was not significantly associated with acute viral load. While point estimates suggested weak vaccine suppression of viral load, the result was not significant and more viral load data would be needed to detect suppression.

Geochronological constraints on the age of a Permo-Triassic impact event: U-Pb and Ar-40/Ar-39 results for the 40 km Araguainha structure of central Brazil

Impact cratering has been a fundamental geological process in Earth history with major ramifications for the biosphere. The complexity of shocked and melted rocks within impact structures presents difficulties for accurate and precise radiogenic isotope age determination, hampering the assessment of the effects of an individual event in the geological record. We demonstrate the utility of a multi-chronometer approach in our study of samples from the 40 km diameter Araguainha impact structure of central Brazil. Samples of uplifted basement granite display abundant evidence of shock deformation, but U/Pb ages of shocked zircons and the Ar-40/Ar-39 ages of feldspar from the granite largely preserve the igneous crystallization and cooling history. Mixed results are obtained from in situ Ar-40/Ar-39 spot analyses of shocked igneous biotites in the granite, with deformation along kink-bands resulting in highly localized, partial resetting in these grains. Likewise, spot analyses of perlitic glass from pseudotachylitic breccia samples reflect a combination of argon inheritance from wall rock material, the age of the glass itself, and post-impact devitrification. The timing of crater formation is better assessed using samples of impact-generated melt rock where isotopic resetting is associated with textural evidence of melting and in situ crystallization. Granular aggregates of neocrystallized zircon form a cluster of ten U-Pb ages that yield a "Concordia" age of 247.8 +/- 3.8 Ma. The possibility of Pb loss from this population suggests that this is a minimum age for the impact event. The best evidence for the age of the impact comes from the U-Th-Pb dating of neocrystallized monazite and Ar-40/Ar-39 step heating of three separate populations of post-impact, inclusion-rich quartz grains that are derived from the infill of miarolitic cavities. The Pb-206/U-238 age of 254.5 +/- 3.2 Ma (2 sigma error) and Pb-208/Th-232 age of 255.2 +/- 4.8 Ma (2 sigma error) of monazite, together with the inverse, 18 point isochron age of 254 +/- 10 Ma (MSWD = 0.52) for the inclusion-rich quartz grains yield a weighted mean age of 254.7 +/- 2.5 Ma (0.99%, 2 sigma error) for the impact event. The age of the Araguainha crater overlaps with the timing of the Permo-Triassic boundary, within error, but the calculated energy released by the Araguainha impact is insufficient to be a direct cause of the global mass extinction. However, the regional effects of the Araguainha impact event in the Parana-Karoo Basin may have been substantial. (C) 2012 Elsevier Ltd. All rights reserved.

Use of Demonstrably Effective Therapies in the Treatment of Acute Coronary Syndromes: Comparison between Different Brazilian Regions. Analysis of the Brazilian Registry on Acute Coronary Syndromes (BRACE)

Background: Little is known in our country about regional differences in the treatment of acute coronary disease. Objective: To analyze the behavior regarding the use of demonstrably effective regional therapies in acute coronary disease. Methods: A total of 71 hospitals were randomly selected, respecting the proportionality of the country in relation to geographic location, among other criteria. In the overall population was regionally analyzed the use of aspirin, clopidogrel, ACE inhibitors / AT1 blocker, beta-blockers and statins, separately and grouped by individual score ranging from 0 (no drug used) to 100 (all drugs used). In myocardial infarction with ST elevation (STEMI) regional differences were analyzed regarding the use of therapeutic recanalization (fibrinolytics and primary angioplasty). Results: In the overall population, within the first 24 hours of hospitalization, the mean score in the North-Northeast (70.5 +/- 22.1) was lower (p < 0.05) than in the Southeast (77.7 +/- 29.5), Midwest (82 +/- 22.1) and South (82.4 +/- 21) regions. At hospital discharge, the score of the North-Northeast region (61.4 +/- 32.9) was lower (p < 0.05) than in the Southeast (69.2 +/- 31.6), Midwest (65.3 +/- 33.6) and South (73.7 +/- 28.1) regions; additionally, the score of the Midwest was lower (p < 0.05) than the South region. In STEMI, the use of recanalization therapies was highest in the Southeast (75.4%, p = 0.001 compared to the rest of the country), and lowest in the North-Northeast (52.5%, p < 0.001 compared to the rest of the country). Conclusion: The use of demonstrably effective therapies in the treatment of acute coronary disease is much to be desired in the country, with important regional differences.

Underlying Factors Associated with Anemia in Amazonian Children: A Population-Based, Cross-Sectional Study

Background: Although iron deficiency is considered to be the main cause of anemia in children worldwide, other contributors to childhood anemia remain little studied in developing countries. We estimated the relative contributions of different factors to anemia in a population-based, cross-sectional survey. Methodology: We obtained venous blood samples from 1111 children aged 6 months to 10 years living in the frontier town of Acrelandia, northwest Brazil, to estimate the prevalence of anemia and iron deficiency by measuring hemoglobin, erythrocyte indices, ferritin, soluble transferrin receptor, and C-reactive protein concentrations. Children were simultaneously screened for vitamin A, vitamin B-12, and folate deficiencies; intestinal parasite infections; glucose-6-phosphate dehydrogenase deficiency; and sickle cell trait carriage. Multiple Poisson regression and adjusted prevalence ratios (aPR) were used to describe associations between anemia and the independent variables. Principal Findings: The prevalence of anemia, iron deficiency, and iron-deficiency anemia were 13.6%, 45.4%, and 10.3%, respectively. Children whose families were in the highest income quartile, compared with the lowest, had a lower risk of anemia (aPR, 0.60; 95% CI, 0.37-0.98). Child age (<24 months, 2.90; 2.01-4.20) and maternal parity (>2 pregnancies, 2.01; 1.40-2.87) were positively associated with anemia. Other associated correlates were iron deficiency (2.1; 1.4-3.0), vitamin B-12 (1.4; 1.0-2.2), and folate (2.0; 1.3-3.1) deficiencies, and C-reactive protein concentrations (>5 mg/L, 1.5; 1.1-2.2). Conclusions: Addressing morbidities and multiple nutritional deficiencies in children and mothers and improving the purchasing power of poorer families are potentially important interventions to reduce the burden of anemia.

Spin-glass-like behavior of uncompensated surface spins in NiO nanoparticulated powder

Nickel oxide nonoparticles successfully synthesized by a polymer percursor method are studied in this work. The analysis of X-ray powder diffraction data provides a mean crystallite size of 22 +/- 2 nm which is in a good agreement with the mean size estimated from transmission electron microscopy images. Whereas the magnetization (M) vs. magnetic field (H) curve obtained at 5 K is consistent with a ferromagnetic component which coexists with an antiferromagnetic component, the presence of two peaks in the zero-field-cooled trace suggests the occurrence of two blocking process. The broad maximum at high temperature was associated with the thermal relaxation of uncompensated spins at the particle core and the low temperature peak was assigned to the freeze of surface spins clusters. Static and dynamic magnetic results suggest that the correlations of surface spins clusters show a spin-glass-like below T-g = 7.3 +/- 0.1 K with critical exponents zv = 9.7 +/- 0.5 and beta = 0.7 +/- 0.1, which are consistent with typical reported for spin-glass systems. (C) 2012 Elsevier B.V. All rights reserved.

Evaluation of physiologic complexity in time series using generalized sample entropy and surrogate data analysis

Complexity in time series is an intriguing feature of living dynamical systems, with potential use for identification of system state. Although various methods have been proposed for measuring physiologic complexity, uncorrelated time series are often assigned high values of complexity, errouneously classifying them as a complex physiological signals. Here, we propose and discuss a method for complex system analysis based on generalized statistical formalism and surrogate time series. Sample entropy (SampEn) was rewritten inspired in Tsallis generalized entropy, as function of q parameter (qSampEn). qSDiff curves were calculated, which consist of differences between original and surrogate series qSampEn. We evaluated qSDiff for 125 real heart rate variability (HRV) dynamics, divided into groups of 70 healthy, 44 congestive heart failure (CHF), and 11 atrial fibrillation (AF) subjects, and for simulated series of stochastic and chaotic process. The evaluations showed that, for nonperiodic signals, qSDiff curves have a maximum point (qSDiff(max)) for q not equal 1. Values of q where the maximum point occurs and where qSDiff is zero were also evaluated. Only qSDiff(max) values were capable of distinguish HRV groups (p-values 5.10 x 10(-3); 1.11 x 10(-7), and 5.50 x 10(-7) for healthy vs. CHF, healthy vs. AF, and CHF vs. AF, respectively), consistently with the concept of physiologic complexity, and suggests a potential use for chaotic system analysis. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4758815]

Is a Genome a Codeword of an Error-Correcting Code?

Since a genome is a discrete sequence, the elements of which belong to a set of four letters, the question as to whether or not there is an error-correcting code underlying DNA sequences is unavoidable. The most common approach to answering this question is to propose a methodology to verify the existence of such a code. However, none of the methodologies proposed so far, although quite clever, has achieved that goal. In a recent work, we showed that DNA sequences can be identified as codewords in a class of cyclic error-correcting codes known as Hamming codes. In this paper, we show that a complete intron-exon gene, and even a plasmid genome, can be identified as a Hamming code codeword as well. Although this does not constitute a definitive proof that there is an error-correcting code underlying DNA sequences, it is the first evidence in this direction.

Hydrogen production and consumption of organic acids by a phototrophic microbial consortium

Alternative fuel sources have been extensively studied. Hydrogen gas has gained attention because its combustion releases only water, and it can be produced by microorganisms using organic acids as substrates. The aim of this study was to enrich a microbial consortium of photosynthetic purple non-sulfur bacteria from an Upflow Anaerobic Sludge Blanket reactor (UASB) using malate as carbon source. After the enrichment phase, other carbon sources were tested, such as acetate (30 mmol l(-1)), butyrate (17 mmol l(-1)), citrate (11 mmol l(-1)), lactate (23 mmol l(-1)) and malate (14.5 mmol l(-1)). The reactors were incubated at 30 degrees C under constant illumination by 3 fluorescent lamps (81 mu mol m(-2) s(-1)). The cumulative hydrogen production was 7.8, 9.0, 7.9, 5.6 and 13.9 mmol H-2 l(-1) culture for acetate, butyrate, citrate, lactate and malate, respectively. The maximum hydrogen yield was 0.6, 1.4, 0.7, 0.5 and 0.9 mmol H-2 mmol(-1) substrate for acetate, butyrate, citrate, lactate and malate, respectively. The consumption of substrates was 43% for acetate, 37% for butyrate, 100% for citrate, 49% for lactate and 100% for malate. Approximately 26% of the clones obtained from the Phototrophic Hydrogen-Producing Bacterial Consortium (PHPBC) were similar to Rhodobacter, Rhodospirillum and Rhodopseudomonas, which have been widely cited in studies of photobiological hydrogen production. Clones similar to the genus Sulfurospirillum (29% of the total) were also found in the microbial consortium. Copyright (C) 2012, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.

VALIDATION OF THE LAND WATER STORAGE FROM GRAVITY RECOVERY AND CLIMATE EXPERIMENT (GRACE) WITH GAUGE DATA IN THE AMAZON BASIN

The Amazon basin is a region of constant scientific interest due to its environmental importance and its biodiversity and climate on a global scale. The seasonal variations in water volume are one of the examples of topics studied nowadays. In general, the variations in river levels depend primarily on the climate and physics characteristics of the corresponding basins. The main factor which influences the water level in the Amazon Basin is the intensive rainfall over this region as a consequence of the humidity of the tropical climate. Unfortunately, the Amazon basin is an area with lack of water level information due to difficulties in access for local operations. The purpose of this study is to compare and evaluate the Equivalent Water Height (Ewh) from GRACE (Gravity Recovery And Climate Experiment) mission, to study the connection between water loading and vertical variations of the crust due to the hydrologic. In order to achieve this goal, the Ewh is compared with in-situ information from limnimeter. For the analysis it was computed the correlation coefficients, phase and amplitude of GRACE Ewh solutions and in-situ data, as well as the timing of periods of drought in different parts of the basin. The results indicated that vertical variations of the lithosphere due to water mass loading could reach 7 to 5 cm per year, in the sedimentary and flooded areas of the region, where water level variations can reach 10 to 8 m.

Multivariate analysis in the maximum strength performance

This study performed an exploratory analysis of the anthropometrical and morphological muscle variables related to the one-repetition maximum (1RM) performance. In addition, the capacity of these variables to predict the force production was analyzed. 50 active males were submitted to the experimental procedures: vastus lateralis muscle biopsy, quadriceps magnetic resonance imaging, body mass assessment and 1RM test in the leg-press exercise. K-means cluster analysis was performed after obtaining the body mass, sum of the left and right quadriceps muscle cross-sectional area (Sigma CSA), percentage of the type II fibers and the 1RM performance. The number of clusters was defined a priori and then were labeled as high strength performance (HSP1RM) group and low strength performance (LSP1RM) group. Stepwise multiple regressions were performed by means of body mass, Sigma CSA, percentage of the type II fibers and clusters as predictors' variables and 1RM performance as response variable. The clusters mean +/- SD were: 292.8 +/- 52.1 kg, 84.7 +/- 17.9 kg, 19249.7 +/- 1645.5 mm(2) and 50.8 +/- 7.2% for the HSP1RM and 254.0 +/- 51.1 kg, 69.2 +/- 8.1 kg, 15483.1 +/- 1 104.8 mm(2) and 51.7 +/- 6.2 %, for the LSP1RM in the 1RM, body mass, Sigma CSA and muscle fiber type II percentage, respectively. The most important variable in the clusters division was the Sigma CSA. In addition, the Sigma CSA and muscle fiber type II percentage explained the variance in the 1RM performance (Adj R-2 = 0.35, p = 0.0001) for all participants and for the LSP1RM (Adj R-2 = 0.25, p = 0.002). For the HSP1RM, only the Sigma CSA was entered in the model and showed the highest capacity to explain the variance in the 1RM performance (Adj R-2 = 0.38, p = 0.01). As a conclusion, the muscle CSA was the most relevant variable to predict force production in individuals with no strength training background.

Trypanosoma cruzi Adjuvants Potentiate T Cell-Mediated Immunity Induced by a NY-ESO-1 Based Antitumor Vaccine

Immunological adjuvants that induce T cell-mediate immunity (TCMI) with the least side effects are needed for the development of human vaccines. Glycoinositolphospholipids (GIPL) and CpGs oligodeoxynucleotides (CpG ODNs) derived from the protozoa parasite Trypanosoma cruzi induce potent pro-inflammatory reaction through activation of Toll-Like Receptor (TLR) 4 and TLR9, respectively. Here, using mouse models, we tested the T. cruzi derived TLR agonists as immunological adjuvants in an antitumor vaccine. For comparison, we used well-established TLR agonists, such as the bacterial derived monophosphoryl lipid A (MPL), lipopeptide (Pam3Cys), and CpG ODN. All tested TLR agonists were comparable to induce antibody responses, whereas significant differences were noticed in their ability to elicit CD4(+) T and CD8(+) T cell responses. In particular, both GIPLs (GTH, and GY) and CpG ODNs (B344, B297 and B128) derived from T. cruzi elicited interferon-gamma (IFN-gamma) production by CD4(+) T cells. On the other hand, the parasite derived CpG ODNs, but not GIPLs, elicited a potent IFN-gamma response by CD8(+) T lymphocytes. The side effects were also evaluated by local pain (hypernociception). The intensity of hypernociception induced by vaccination was alleviated by administration of an analgesic drug without affecting protective immunity. Finally, the level of protective immunity against the NY-ESO-1 expressing melanoma was associated with the magnitude of both CD4+ T and CD8+ T cell responses elicited by a specific immunological adjuvant.

MYLIP p.N342S polymorphism is not associated with lipid profile in the Brazilian population

Background: A recent study investigated the MYLIP region in the Mexican population in order to fine-map the actual susceptibility variants of this locus. The p.N342S polymorphism was identified as the underlying functional variant accounting for one of the previous signals of genome-wide association studies and the N342 allele was associated with higher cholesterol concentrations in Mexican dyslipidemic individuals. To date, there is no further evaluation on this genotype-phenotype association in the literature. In this scenario, and because of a possible pharmacotherapeutic target of dyslipidemia, the main aim of this study was to assess the influence of the MYLIP p.N342S polymorphism on lipid profile in Brazilian individuals. Methods: 1295 subjects of the general population and 1425 consecutive patients submitted to coronary angiography were selected. General characteristics, biochemical tests, blood pressures, pulse wave velocity, and coronary artery disease scores were analyzed. Genotypes for the MYLIP rs9370867 (p.N342S, c.G1025A) polymorphism were detected by high resolution melting analysis. Results: No association of the MYLIP rs9370867 genotypes with lipid profile, hemodynamic data, and coronary angiographic data was found. Analysis stratified by hyperlipidemia, gender, and ethnicity was also performed and the sub-groups presented similar results. In both general population and patient samples, the MYLIP rs9370867 polymorphism was differently distributed according to ethnicity. In the general population, subjects carrying GG genotypes had higher systolic blood pressure (BP), diastolic BP, and mean BP values (129.0 +/- 23.3; 84.9 +/- 14.6; 99.5 +/- 16.8 mmHg) compared with subjects carrying AA genotypes (123.7 +/- 19.5; 81.6 +/- 11.8; 95.6 +/- 13.6 mmHg) (p = 0.01; p = 0.02; p = 0.01, respectively), even after adjustment for covariates. However, in analysis stratified by ethnicity, this finding was not found and there is no evidence that the polymorphism influences BP. Conclusion: Our findings indicate that association studies involving this MYLIP variant can present distinct results according to the studied population. In this moment, further studies are needed to reaffirm if the MYLIP p.N342S polymorphism is functional or not, and to identify other functional markers within this gene.

Experimental gestational hypothyroidism evokes hypertension in adult offspring rats

Gestational hypothyroidism is a prevalent disorder in pregnant women. We aimed to investigate the impact of experimental gestational hypothyroidism (EGH) on cardiovascular and autonomic nervous systems (ANS) in the offspring of rats. EGH was induced with methimazole (MMI) 0.02% in drinking water from day 9 of gestation until birth. Sixty day old offspring from MMI-treated dams (OMTD, n = 13) or water-treated dams (OWTD, n = 13) had femoral arteries surgically assessed for the measurements of heart rate (HR), mean (MAP), systolic (SAP) and diastolic arterial pressure (DAP), and spontaneous baroreflex sensitivity (BRS). To investigate the balance of ANS, we established the high (HF) and low frequency (LF) bands of pulse interval (PI) and LF band of SAP spectrum. OMTD had increased MAP (130.2 +/- 2.0 vs 108.8 +/- 3.0 mm Hg, p<0.001), SAP (157.3 +/- 2.9 vs 135.7 +/- 4.5 mm Hg, p<0.001) and DAP (109.7 +/- 1.9 vs 88.4 +/- 2.6 mm Hg, p<0.001) when compared to OWED, and had lower HR (355.1 +/- 8.9 vs 386.8 +/- 9.2 bpm, p<0.05). After spectral analysis of PI and SAP, only LF band of SAP spectrum was higher (7.2 +/- 0.8 vs 4.0 +/- 0.6 mm Hg-2, p<0.01) in OMTD under spontaneous condition. Despite bradycardia, EGH promotes spontaneous hypertension in 60 day old offspring, probably due to increased sympathetic modulation of vessels, which is suggested by the higher LF of SAP. These findings suggest a critical role of maternal THs in the development of fetal cardiovascular and autonomic nervous systems. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.

Using Prior Information from the Medical Literature in GWAS of Oral Cancer Identifies Novel Susceptibility Variant on Chromosome 4-the AdAPT Method

Background: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS. Methods: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts, and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the phenotype of interest - the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and subsequently applied it in a two-phase GWAS of oral cancer. Results: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (per-rare-allele log additive p-value [p(trend)] = 2.5 x 10(-3)). The combined OR for having one additional rare allele was 0.83 (95% CI: 0.76-0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper aerodigestive tract (UADT), but no additional association signal was found. Conclusion: This study highlights the potential utility of systematically incorporating prior knowledge from the medical literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/lld/gwas/service/config).