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

The role of chronic muscle (in)activity on carnosine homeostasis: a study with spinal-cord injured athletes

To examine the role of chronic (in)activity on muscle carnosine (MCarn) and how chronic (in)activity affects MCarn responses to β-alanine supplementation in spinal-cord injured athletes, sixteen male athletes with paraplegia were randomized (2:1 ratio) to receive β-alanine (n=11) or placebo (PL, n=5). They consumed 6.4 g‧d-1 of β-alanine or PL for 28 days. Muscle biopsies of the active deltoid and the inactive vastus lateralis (VL) were taken before and after supplementation. MCarn in the VL was also compared with the VL of a group of individuals without paraplegia (n=15). MCarn was quantified in whole muscle and in pools of individual fibers by High-performance Liquid Chromatography. MCarn was higher in chronically inactive VL vs. well-trained deltoid (32.0±12.0 vs. 20.5±6.1 mmol‧kg-1 DM; p=0.018). MCarn was higher in inactive vs. active VL (32.0±12.0 vs. 21.2±7.5 mmol‧kg-1 DM; p=0.011). In type-I fibers, MCarn was significantly higher in the inactive VL than in the active deltoid (38.3±4.7 vs. 27.3±11.8 mmol‧kg-1 DM, p=0.014). MCarn increased similarly between inactive VL and active deltoid in the β-alanine group (VL: 68.9±55.1%, p=0.0002; deltoid: 90.5±51.4%, p<0.0001), with no changes in the PL group. MCarn content was higher in the inactive VL than in the active deltoid and the active VL, but this is probably a consequence of fiber type shift (type I to type II) that occurs with chronic inactivity. Chronically inactive muscle showed an increase in MCarn after BA supplementation equally to the active muscle, suggesting that carnosine accretion following β-alanine supplementation is not influenced by muscle inactivity

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

The Bacterium Endosymbiont of Crithidia deanei Undergoes Coordinated Division with the Host Cell Nucleus

In trypanosomatids, cell division involves morphological changes and requires coordinated replication and segregation of the nucleus, kinetoplast and flagellum. In endosymbiont-containing trypanosomatids, like Crithidia deanei, this process is more complex, as each daughter cell contains only a single symbiotic bacterium, indicating that the prokaryote must replicate synchronically with the host protozoan. In this study, we used light and electron microscopy combined with three-dimensional reconstruction approaches to observe the endosymbiont shape and division during C. deanei cell cycle. We found that the bacterium replicates before the basal body and kinetoplast segregations and that the nucleus is the last organelle to divide, before cytokinesis. In addition, the endosymbiont is usually found close to the host cell nucleus, presenting different shapes during the protozoan cell cycle. Considering that the endosymbiosis in trypanosomatids is a mutualistic relationship, which resembles organelle acquisition during evolution, these findings establish an excellent model for the understanding of mechanisms related with the establishment of organelles in eukaryotic cells