Regulation and butanol inhibition of D-xylose and D-glucose uptake in Clostridium acetobutylicum.

Clostridium acetobutylicum exhibited diauxie growth in the presence of mixtures of glucose and xylose. Both glucose- and xylose-grown cells had a glucose uptake activity. On the other hand, growth on xylose was associated with the induction of a xylose permease activity, which was repressed by glucose in xylose-induced cells. The rate of sugar uptake with increasing sugar concentrations showed saturation kinetics with an apparent Km of 1.25 X 10(-5) M for glucose and 5 X 10(-3) M for xylose. Concomitant with the production of solvents, the activities of the glucose and xylose transport systems decreased. Among the main products of fermentation, butanol was shown to be a potent inhibitor of the growth of the organism and of the rate of sugar uptake as well as of sugar incorporation into cell materials. These inhibitory effects of butanol were more pronounced in xylose-grown cells than in glucose-grown cells. Butanol completely inhibited growth at a concentration of 14 g/liter for cultures growing on glucose and 8 g/liter for cultures growing on xylose. Concentrations of 7 and 10.5 g/liter of butanol caused a 50% inhibition of the xylose and glucose incorporations into cell materials. These inhibitory levels of butanol were found in typical glucose or xylose fermentation.     

Structure of the MORN4/Myo3a Tail Complex Reveals MORN Repeats as Protein Binding Modules

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Synthesis and biological evaluation of some 5-ethoxycarbonyl-6-isopropylamino-4-(substitutedphenyl)aminopyrimidines as potent analgesic and anti-inflammatory agents

Synthesis and biological evaluation of some 5-ethoxycarbonyl-6-isopropylamino-4-(substitutedphenyl)aminopyrimidines have been achieved by cyclization of N-[2-ethoxycarbonyl-2-cyano-1-(isopropylamino)vinyl] formamidine in presence of dry HCl in dioxane followed by nucleophilic substitution of 4-chloro group with substituted aromatic amine or phenoxide. Target compounds were evaluated for their analgesic and anti-inflammatory potential by known experimental models. Some of the compounds emerged out as more potent than standard drugs. Very low ulcer index was observed for the potent compounds.     

Phospholipid asymmetry in the membranes of intact human erythrocytes and in spectrin-free microvesicles derived from them

Phospholipase A₂ from bee venom and Naja naja has been used to study the orientation of phospholipids present in the membrane of intact human erythrocytes and in spectrin-free microvesicles derived from the cells by treatment with Ca²⁺ and A23187. Little difference between the cells and microvesicles was observed in the apparent accessibility of phospholipids to the enzyme, suggesting that the original lipid asymmetry was maintained in the absence of spectrin. However, incubation of the microvesicles for 16 h at 37°C did lead to partial loss of asymmetry in the transmembrane distribution of phosphatidylcholine and phosphatidylethanolamine but not of phosphatidylserine. Despite the similarity of lipid asymmetry in cells and fresh microvesicles, the latter were about 40-fold more sensitive to phospholipase treatment than were cells. Although they retained the lipid asymmetry of intact cells, the microvesicles resembled ghosts in their great sensitivity to phospholipase A₂ attack, suggesting that the lipid packing in microvesicles and ghosts was similar. This conclusion was supported by the results of experiments with a fluorescent probe Merocyanine 540.     

First myocardial infarctions in Asian and white men.

OBJECTIVE--To compare the presentation and natural course of first myocardial infarctions in immigrant Asians and the indigenous white population in Britain and the subsequent risk states of the two groups. DESIGN--Prospective ethnic comparison of consecutive patients with first myocardial infarctions. SETTING--Secondary referrals to a coronary care unit of a district general hospital. PATIENTS--128 Men (77 white, 54 Asian) presenting consecutively with a first myocardial infarction diagnosed on the basis of clinical, biochemical, and electrocardiographic findings. END POINT--Identification of mechanisms accounting for the increased rate of ischaemic heart disease in Asians. MEASUREMENTS AND MAIN RESULTS--Infarct size was assessed by measuring the release of creatine phosphokinase (all patients), radionuclide ventriculography (50), and contrast ventriculography (103). Risk states after infarction were assessed from the degree of ventricular dysfunction as determined by exercise electrocardiography (82 patients) and from the extent of coronary atheroma as determined by coronary arteriography (103). Glucose state was measured in fasting venous blood samples. Overall the relative rate of infarction was 4.9 times higher in Asians (95% confidence interval 3.4 to 6.9) than in the white population. Moreover, the relative rate of infarction was higher in Asians in all 10 year age groups, the greatest difference being in 30-39 year olds. The mean age of the Asian denominator population was 47.1 years compared with 49.5 years in the white population. Age at infarction was less in Asians (50.2 years) than in white patients (55.5 years; mean difference 5.5 years (95% confidence interval 2.5 to 7.1]. In Asians the mean creatine phosphokinase activity was 777 (95% confidence interval 155 to 1399) U/1 higher, radionuclide ejection fraction 8.9% (1.0% to 16.9%) lower, and left ventricular fractional shortening 4.8% (1.4% to 8.2%) lower than in white patients. The extent of coronary atheroma was significantly greater in Asians. The mean numbers of plaques in vessels not associated with infarction were 3.66 (median 3.0, range 0-10) in Asians compared with 1.97 (median 2.0, range 0-6) in white patients (p less than 0.001), and a higher proportion of Asians had three vessel coronary artery disease (p less than 0.001). Asians with diabetes or impaired glucose tolerance did not differ from those with normal blood glucose values. CONCLUSIONS--Atherogenesis arises earlier in Asians, contributing to premature first myocardial infarctions. The increased incidence of diabetes in Asians may not in itself be relevant in the greater propensity to coronary atheroma in Asians.     

Variations du taux d'amp cyclique et des activités spécifiques de l'adénylate cyclase et de l'amp cyclique-phosphodiestérase pendant le cycle cellulaire d'un actinomycète

The variations in the concentrations of intra- and extracellular cyclic AMP and in the specific activities of adenylate cyclase (EC 4.6.1.1) and cyclic AMP phosphodiesterase (EC 3.1.4.17) have been monitored in synchronized culture of Nocardia restricta, a prokaryote belonging to the group of Actinomycetes. At the beginning of the cell cycel, during a first period of RNA and protein synthesis, there is an increasing synthesis of adenylate cyclase which can be suppressed in the presence of chloramphenicol or rifampicin. Simultaneously, the specific activity of cyclic AMP phosphodiesterase decreases and the concentrations of intra- and extracellular cyclic AMP rise. After the end of DNA replication, during a second period of RNA and protein synthesis, the specific activity of cyclic AMP phosphodiesterase increases; during the same time, the specific activity of adenylate cyclase and the level of intracellular cyclic AMP drop. It appears that the overall metabolism of cyclic AMP is coordinated so that the cyclic AMP level will be high at the beginning of DNA replication and will fall thereafter. The results are discussed in comparison with known data about the variations of cyclic AMP during the cell cycle of mammalian cells in cultures.     

Neuroprotective properties of marrow-isolated adult multilineage-inducible cells in rat hippocampus following global cerebral ischemia are enhanced when complexed to biomimetic microcarriers

Cell-based therapies for global cerebral ischemia represent promising approaches for neuronal damage prevention and tissue repair promotion. We examined the potential of marrow-isolated adult multilineage-inducible (MIAMI) cells, a homogeneous subpopulation of immature human mesenchymal stromal cell, injected into the hippocampus to prevent neuronal damage induced by global ischemia using rat organotypic hippocampal slices exposed to oxygen-glucose deprivation and rats subjected to asphyxial cardiac arrest. We next examined the value of combining fibronectin-coated biomimetic microcarriers (FN-BMMs) with epidermal growth factor (EGF)/basic fibroblast growth factor (bFGF) pre-treated MIAMI compared to EGF/bFGF pre-treated MIAMI cells alone, for their in vitro and in vivo neuroprotective capacity. Na?ve and EGF/bFGF pre-treated MIAMI cells significantly protected the Cornu Ammonis layer 1 (CA1) against ischemic death in hippocampal slices and increased CA1 survival in rats. MIAMI cells therapeutic value was significantly increased when delivering the cells complexed with FN-BMMs, probably by increasing stem cell survival and paracrine secretion of pro-survival and/or anti-inflammatory molecules as concluded from survival, differentiation and gene expression analysis. Four days after oxygen and glucose deprivation and asphyxial cardiac arrest, few transplanted cells administered alone survived in the brain whereas stem cell survival improved when injected complexed with FN-BMMs. Interestingly, a large fraction of the transplanted cells administered alone or in complexes expressed βIII-tubulin suggesting that partial neuronal transdifferentiation may be a contributing factor to the neuroprotective mechanism of MIAMI cells.