New detrital petrographic and thermochronologic constraints on the Late Cretaceous-Neogene erosional history of the equatorial margin of Brazil: Implications for the surface evolution of a complex rift margin

The equatorial margin of Brazil is an example of a rift margin with a complex landscape, dominated by an escarpment perpendicular to the continental margin, which testifies to an equally complex rift and post-rift surface and tectonic evolution. This has been the focus of a long debate on the driving mechanism for post-rift tectonics and on the amount of exhumation. This study contributes to this debate with new petrographic and thermochronologic data on 152 samples from three basins, Para-Maranhao, Barreirinhas and Ceara, on the offshore continental platform. Our detrital record goes back to the rift time at ca. 100 Ma ago and outlines three major evolutionary phases of a changing landscape: a rift phase, with the erosion of a moderate rift escarpment, a Late Cretaceous-Palaeogene post-rift phase of major drainage reorganization and significant vertical erosion and a Late Oligocene-to-Recent post-rift phase of moderate vertical erosion and river headwater migration. We estimate that along the equatorial margin of Brazil, over a large onshore area, exhumation since the Late Cretaceous has totalled locally up to 2-2.5 km and since the late Oligocene did not exceed 1 km

Twenty-four weeks of β-alanine supplementation on carnosine content, related genes, and exercise

Introduction: Skeletal muscle carnosine content can be increased through [beta]-alanine supplementation, but the maximum increase achievable with supplementation is unknown. No study has investigated the effects of prolonged supplementation on carnosine-related genes or exercise capacity. Purpose: To investigate the effects of 24-weeks of [beta]-alanine supplementation on muscle carnosine content, gene expression and high-intensity cycling capacity (CCT110%). Methods: Twenty-five active males were supplemented with 6.4 g[middle dot]day-1 of sustained release [beta]-alanine (BA) or placebo (PL) over a 24-week period. Every 4 weeks participants provided a muscle biopsy and performed the CCT110%. Biopsies were analysed for muscle carnosine content and gene expression (CARNS, TauT, ABAT, CNDP2, PHT1, PEPT2 and PAT1). Results: Carnosine content was increased from baseline at every time point in BA (all P<0.0001; Week 4: +11.37+/-7.03 mmol[middle dot]kg-1dm, Week 8: +13.88+/-7.84 mmol[middle dot]kg-1dm, Week 12: +16.95+/-8.54 mmol[middle dot]kg-1dm, Week 16: +17.63+/-8.42 mmol[middle dot]kg-1dm, Week 20: +21.20+/-7.86 mmol[middle dot]kg-1dm, Week 24: +20.15+/-7.63 mmol[middle dot]kg-1dm), but not PL (all P=1.00). Maximal changes were +25.66+/-7.63 mmol[middle dot]kg-1dm (range: +17.13 to +41.32 mmol[middle dot]kg-1dm), and absolute maximal content was 48.03+/-8.97 mmol[middle dot]kg-1dm (range: 31.79 to 63.92 mmol[middle dot]kg-1dm). There was an effect of supplement (P=0.002) on TauT; no further differences in gene expression were shown. Exercise capacity was improved in BA (P=0.05) with possible to almost certain improvements across all weeks. Conclusions: Twenty-four weeks of [beta]-alanine supplementation increased muscle carnosine content and improved high-intensity cycling capacity. Downregulation of TauT suggests it plays an important role in muscle carnosine accumulation with [beta]-alanine supplementation, while the variability in changes in muscle carnosine content between individuals suggests that other determinants other than the availability of [beta]-alanine may also bear a major influence on muscle carnosine content

Pre-validation of the WHO organ dysfunction based criteria for identification of maternal near miss

<p>Abstract</p> <p>Background</p> <p>To evaluate the performance of the WHO criteria for defining maternal near miss and identifying deaths among cases of severe maternal morbidity (SMM) admitted for intensive care.</p> <p>Method</p> <p>Between October 2002 and September 2007, 673 women with SMM were admitted, and among them 18 died. Variables used for the definition of maternal near miss according to WHO criteria and for the SOFA score were retrospectively evaluated. The identification of at least one of the WHO criteria in women who did not die defined the case as a near miss. Organ failure was evaluated through the maximum SOFA score above 2 for each one of the six components of the score, being considered the gold standard for the diagnosis of maternal near miss. The aggregated score (Total Maximum SOFA score) was calculated using the worst result of the maximum SOFA score. Sensitivity, specificity, positive and negative predictive values of these WHO criteria for predicting maternal death and also for identifying cases of organ failure were estimated.</p> <p>Results</p> <p>The WHO criteria identified 194 cases of maternal near miss and all the 18 deaths. The most prevalent criteria among cases of maternal deaths were the use of vasoactive drug and the use of mechanical ventilation (≥1 h). For the prediction of maternal deaths, sensitivity was 100% and specificity 70.4%. These criteria identified 119 of the 120 cases of organ failure by the maximum SOFA score (Sensitivity 99.2%) among 194 case of maternal near miss (61.34%). There was disagreement in 76 cases, one organ failure without any WHO criteria and 75 cases with no failure but with WHO criteria. The Total Maximum SOFA score had a good performance (area under the curve of 0.897) for prediction of cases of maternal near miss according to the WHO criteria.</p> <p>Conclusions</p> <p>The WHO criteria for maternal near miss showed to be able to identify all cases of death and almost all cases of organ failure. Therefore they allow evaluation of the severity of the complication and consequently enable clinicians to build a plan of care or to provide an early transfer for appropriate reference centers.</p

Appropriate criteria for identification of near-miss maternal morbidity in tertiary care facilities: A cross sectional study

<p>Abstract</p> <p>Background</p> <p>The study of severe maternal morbidity survivors (near miss) may be an alternative or a complement to the study of maternal death events as a health care indicator. However, there is still controversy regarding the criteria for identification of near-miss maternal morbidity. This study aimed to characterize the near miss maternal morbidity according to different sets of criteria.</p> <p>Methods</p> <p>A descriptive study in a tertiary center including 2,929 women who delivered there between July 2003 and June 2004. Possible cases of near miss were daily screened by checking different sets of criteria proposed elsewhere. The main outcome measures were: rate of near miss and its primary determinant factors, criteria for its identification, total hospital stay, ICU stay, and number and kind of special procedures performed.</p> <p>Results</p> <p>There were two maternal deaths and 124 cases of near miss were identified, with 102 of them admitted to the ICU (80.9%). Among the 126 special procedures performed, the most frequent were central venous access, echocardiography and invasive mechanical ventilation. The mean hospital stay was 10.3 (± 13.24) days. Hospital stay and the number of special procedures performed were significantly higher when the organ dysfunction based criteria were applied.</p> <p>Conclusion</p> <p>The adoption of a two level screening strategy may lead to the development of a consistent severe maternal morbidity surveillance system but further research is needed before worldwide near miss criteria can be assumed.</p

Phosphoenolpyruvate carboxylase dentified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism

Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in thePlasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10Δpepc), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10Δpepc had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using 13C-U-D-glucose and 13C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10Δpepc and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of 13C,15N-U-glutamine was similar in both parasite lines, although the flux was lower in D10Δpepc; it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery

Bacteria-Killing Type IV Secretion Systems

Bacteria have been constantly competing for nutrients and space for billions of years. During this time, they have evolved many different molecular mechanisms by which to secrete proteinaceous effectors in order to manipulate and often kill rival bacterial and eukaryotic cells. These processes often employ large multimeric transmembrane nanomachines that have been classified as types I–IX secretion systems. One of the most evolutionarily versatile are the Type IV secretion systems (T4SSs), which have been shown to be able to secrete macromolecules directly into both eukaryotic and prokaryotic cells. Until recently, examples of T4SS-mediated macromolecule transfer from one bacterium to another was restricted to protein-DNA complexes during bacterial conjugation. This view changed when it was shown by our group that many Xanthomonas species carry a T4SS that is specialized to transfer toxic bacterial effectors into rival bacterial cells, resulting in cell death. This review will focus on this special subtype of T4SS by describing its distinguishing features, similar systems in other proteobacterial genomes, and the nature of the effectors secreted by these systems and their cognate inhibitor