BURIAL HISTORY AND THERMAL MATURITY EVOLUTION OF THE TERMIT BASIN,NIGER

Reconstruction of the burial history and thermal evolution of the Cretaceous – Tertiary Termit Basin, a sub‐basin within the larger Eastern Niger Basin of Niger, indicates spatially and temporally variable conditions for organic matter maturation during the basin's multi‐phased evolution. Three episodes of tectonic subsidence which correspond to the observed fault mechanical stratigraphy within the Termit Basin are identified: Late Cretaceous, Maastrichtian to early Paleocene, and Oligocene. These episodes fall within the regional tectonic phases of the West African Rift System delineated by previous studies. The basin exhibits substantial heterogeneity in the magnitude of the tectonic episodes and in consequent thermal maturities. For this paper, 1D burial and thermal histories of eight widely dispersed wells in the Agadem permit area in the SW of the Termit Graben were modelled to investigate the maturation of organic matter in source rocks ranging from Santonian to Oligocene in age. The kinetic modelled maturities match with maturities based on Rock‐Eval T_max values for four wells if present‐day heat flows are elevated. Future exploration strategies in the Termit Basin should take into consideration these heterogeneities in thermal histories and tectonic pulses, which may lead to the development of hydrocarbon accumulations with different oil‐gas compositions in different reservoir compartments.     

Exposure to antibiotics induces expression of the Mycobacterium tuberculosis sigF gene: implications for chemotherapy against mycobacterial persistors

BACKGROUND: Although many studies have investigated macromolecular uptake in the stomach and small intestine, little is known about macromolecular uptake in the colon. AIMS: To investigate the mechanisms involved in the transport of large antigenically intact macromolecules across the proximal and distal colonic epithelium in the rabbit. METHODS: The mucosal to serosal movement of bovine serum albumin (BSA) was examined in modified Ussing chambers under short circuited conditions. The mucosal surface was exposed to varying concentrations of BSA, and after a 50 minute equilibration period, the mucosal to serosal flux of immunologically intact BSA was determined by ELISA. Total BSA flux was determined by the transport of radiolabelled 125I-BSA. RESULTS: Intact BSA transport in proximal and distal colonic tissue showed saturable kinetics. Intact BSA transport in the proximal and distal segment was 7% and 2% of the total 125I-BSA flux respectively. Immunologically intact BSA transport in the distal segment was significantly less than that in the proximal segment. Intact BSA transport in the proximal colon was significantly reduced following treatment with sodium fluoride, colchicine, and tetrodotoxin. Cholinergic blockade had no effect on the uptake of intact BSA. Conclusion: The findings indicate that the transport of intact macromolecules across the proximal and distal large intestine is a saturable process. Further, intact BSA transport in the proximal colon is an energy dependent process that utilises microtubules and is regulated by the enteric nervous system.     

Sacrosidase therapy for congenital sucrase-isomaltase deficiency

BACKGROUND: The purpose of this study was to determine if sacrosidase, a liquid produced from Saccharomyces cerevisiae containing 6000 IU of sucrase activity per mg protein, prevented symptoms of diarrhea, abdominal cramps, gas, and bloating in patients with congenital sucrase-isomaltase deficiency (CSID) consuming a normal sucrose and carbohydrate-containing diet. METHODS: Twenty-eight children (aged 5 months to 11 years) underwent a randomized, double-blind trial consisting of two phases: 1) three sucrose breath H2 tests with three single-dose treatments (placebo, sacrosidase, and sacrosidase plus milk), and 2) a dose-response phase consisting of four multidose treatments, each for 10 days of full-strength sacrosidase, 1:10 dilution, 1:100 dilution, and 1:1000 dilution. Patients who weighed less than or equal to 15 kg received a dose of sacrosidase and those who weighed more than 15 kg received 2 ml. For the dose-response phase each patient consumed a normal diet. The number of stools and severity of symptoms were recorded daily for each concentration of sacrosidase administered and compared to a baseline period during which the patient took no sacrosidase and consumed a sucrose/starch-free diet. Data were analyzed using an ANOVA model and the nonparameter Wilcoxon signed-rank test. RESULTS: Breath H2 excretion decreased significantly when patients received sacrosidase or sacrosidase plus milk compared to placebo during sucrose breath tests. During the dose-response phase significant treatment differences were observed between the two higher concentrations and the two lower concentrations of sacrosidase for both total stools (p < 0.001) and total symptom score (p = 0.003). Higher concentrations of sacrosidase were associated with fewer stools and a greater number of formed or hard stools compared to lower concentrations and compared to the baseline period. Higher concentrations were also associated with fewer symptoms of gas, abdominal cramps, or bloating, but no differences in vomiting. The only significant adverse event was wheezing in one child with a history of asthma. CONCLUSIONS: Sacrosidase is a safe, effective, well-accepted treatment to prevent gastrointestinal symptoms in patients with CSID consuming a normal diet.     

Regional variation in the lamina propria T cell receptor V beta repertoire in normal human colon

The Ewing's sarcoma cell line RD-ES, which carries the EWS/FLI-1 fusion gene, responded to the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin with growth arrest. Replenishment of mevalonate (MVA) to the arrested cells restored cell growth. However, if tunicamycin (TM), which is an inhibitor of N-linked glycosylation, was present together with MVA the cells remained arrested, indicating that N-linked glycosylation is of importance for growth of Ewing's sarcoma cells. Inhibition of the biosynthesis of EWS/FLI-1 fusion protein by treatment with antisense oligonucleotides also led to growth arrest, suggesting that this protein is of importance for cell growth. We investigated whether MVA synthesis and N-linked glycosylation could be involved in regulation of the expression of the EWS/FLI-1 fusion protein, which in fact contains four potential sites for N-linked glycosylation. We found that inhibition of both HMG-CoA reductase and N-linked glycosylation drastically decreased the expression of the fusion protein, which mainly appears in the cell nuclei. There was no significant difference in the inhibitory effect on the fusion protein between the cytoplasm and the cell nuclei, indicating that the transport of the fusion protein to the cell nucleus is not affected. The fusion protein did not exhibit any gel electrophoretic mobility shift after treatment of the cells with lovastatin or TM, and it did not incorporate [3H]glucosamine. Therefore we can conclude that the fusion protein is not a glycoprotein. The decreased expression of the fusion protein following lovastatin or TM treatment was found to be due to a lowered stability of de novo-synthesized fusion protein. The down-regulation of the fusion protein was correlated to growth arrest. Furthermore, the kinetics between the expression of EWS/FLI-1 fusion protein and the initiation of DNA synthesis in MVA-stimulated cells were similar. Taken together, our data suggest that the regulatory role of N-linked glycosylation in the expression of the EWS/FLI-1 fusion protein is important for growth of Ewing's sarcoma cells. Possible mechanisms underlying TM-induced decrease in EWS/FLI-1 expression may involve the breaking of growth factor receptor pathways.     

Effects of temperature and volatile anesthetics on GABA(A) receptors

BACKGROUND: Potentiation of the activity of the gamma-aminobutyric acid type A (GABA(A)) receptor channel by volatile anesthetic agents is usually studied in vitro at room temperature. Systematic variation of temperature can be used to assess the relevance of this receptor to general anesthesia and to characterize the modulation of its behavior by volatile agents at normal body temperature. METHODS: Potentiation of the GABA(A) receptor by halothane, sevoflurane, isoflurane, and methoxyflurane was studied at six temperatures in the range 10-37 degrees C using the whole-cell patch-clamp technique and mouse fibroblast cells stably transfected with defined GABA(A) receptor subunits. RESULTS: Control GABA concentration-response plots showed small and physically reasonable changes in the GABA concentration required for a half-maximal effect, the Hill coefficient, and maximal response over the range 10-30 degrees C. Potentiations of GABA (1 microM) responses by aqueous minimum alveolar concentrations of the volatile anesthetic agents decreased with increasing temperature from 10-37 degrees C in an agent-specific manner (methoxyflurane > isoflurane > sevoflurane > halothane) but tended to equalize at normal body temperature (37 degrees C). These findings are in line with published results on the temperature dependence of anesthetic potencies in animals. CONCLUSIONS: These results are consistent with direct binding of volatile anesthetic agents to the GABA(A) receptor channel playing an important role in general anesthesia. The finding that the degree of anesthetic potentiation was agent-specific at low temperatures but not at 37 degrees C emphasizes the importance of doing in vitro experiments at normal body temperature.