In vivo quantification of neuro‐glial metabolism and glial glutamate concentration using 1H‐[13C] MRS at 14.1T

Astrocytes have recently become a major center of interest in neurochemistry with the discoveries on their major role in brain energy metabolism. An interesting way to probe this glial contribution is given by in vivo ¹³C NMR spectroscopy coupled with the infusion labeled glial‐specific substrate, such as acetate. In this study, we infused alpha‐chloralose anesthetized rats with [2‐¹³C]acetate and followed the dynamics of the fractional enrichment (FE) in the positions C4 and C3 of glutamate and glutamine with high sensitivity, using ¹H‐[¹³C] magnetic resonance spectroscopy (MRS) at 14.1T. Applying a two‐compartment mathematical model to the measured time courses yielded a glial tricarboxylic acid (TCA) cycle rate (V_g) of 0.27 ± 0.02 μmol/g/min and a glutamatergic neurotransmission rate (V_NT) of 0.15 ± 0.01 μmol/g/min. Glial oxidative ATP metabolism thus accounts for 38% of total oxidative metabolism measured by NMR. Pyruvate carboxylase (V_PC) was 0.09 ± 0.01 μmol/g/min, corresponding to 37% of the glial glutamine synthesis rate. The glial and neuronal transmitochondrial fluxes (V_x^g and V_xⁿ) were of the same order of magnitude as the respective TCA cycle fluxes. In addition, we estimated a glial glutamate pool size of 0.6 ± 0.1 μmol/g. The effect of spectral data quality on the fluxes estimates was analyzed by Monte Carlo simulations.

     

Release of antidiuretic hormone (ADH) under the influence of gastric distention in the rabbit. Demonstration by radioimmunoassay]

In this investigation, are studied in rabbits, the effects of gastric distention upon plasma concentration of vasopressin; the arginine-vasopressine is determined by a very sensitive radio-immunologic method. Increases of intragastric ballonet pressure up to 10-20 cmH2O induce significant rise in plasma vasopressin concentrations averaging 21 +/- 3,7 muU/ml (base line 6,25 +/- 2,3 muU/ml). Increase of vasopressin is associated with significantly lowered diuresis. Intravenous injections of nicotine induce similar decrease in urine flow and increase of plasma AVP concentrations up to 12,01 +/- 1,7 muU/ml.     

Short Time Scale Changes in Underwater Irradiance in a Wind-exposed Lagoon (Vaccarès Lagoon,France): Efficiency of Infrequent Field Measurements of Water Turbidity or Weather Data to Predict Irradiance in the Water Column

High frequency water sampling in the wind-exposed Vaccarès lagoon revealed frequent and rapid changes in suspended solid (SS) concentrations in the water column. SS concentrations, sometimes higher than 800 mg l⁻¹, were significantly correlated with antecedent wind conditions. Mean wind velocity during the 5–33 h before water sampling or maximal wind velocity during the previous 8.5–22 h were good predictors of SS concentrations in the water column. Underwater irradiance at canopy level was modeled (r² = 0.66, n = 7584) using the SS calculated from the relationship between SS and antecedent mean wind velocity and the surface irradiance data measured at the weather station close to the study site. On the other hand, we have shown that in this wind-exposed lagoon, mean underwater irradiance can not be effectively estimated using infrequent measurements of the optical properties of water.     

Cellulose Fermentation by an Asporogenous Mutant and an Ethanol-Tolerant Mutant of Clostridium thermocellum

Two mutants of Clostridium thermocellum were isolated after UV light mutagenesis. Mutant A1, selected as asporogenous, exhibited a fermentation pattern similar to that of the wild type. However, at pH 6.5, the mutant degraded 12% more cellulose than did the wild type, leading to enhanced ethanol production. Mutant 647, selected as ethanol tolerant, was able to grow in medium containing 4% ethanol. During the early stage of the exponential growth phase, ethanol was produced as the main product, up to a concentration of about 9 g/liter. After 3 days of culture, 48.3 g (89% of the initial amount) of degraded cellulose per liter was fermented into 12.7 g of ethanol per liter.     

Structure activity relationship and optimization of N-(3-(2-aminothiazol-4-yl)aryl)benzenesulfonamides as anti-cancer compounds against sensitive and resistant cells

We recently described a new family of bioactive molecules with interesting anti-cancer activities: the N-(4-(3-aminophenyl)thiazol-2-yl)acetamides. The lead compound of the series (1) displays significant anti-proliferative and cytotoxic activities against a panel of cancer cell lines, either sensitive or resistant to standard treatments. This molecule also shows a good pharmacological profile and high in vivo potency towards mice xenografts, without signs of toxicity on the animals. In the present article, we disclose the structure-activity relationships of this lead compound, which have provided clear information about the replacement of the acetamide function and the substitution pattern of the benzenesulfonamide ring. An improved high-yielding synthetic procedure towards these compounds has also been developed. Our drug design resulted in potency enhancement of 1, our new optimized lead compound being 19. These findings are of great interest to further improve this scaffold for the development of future clinical candidates.     

The viable but non-culturable state of wine micro-organisms during storage

Colony counting and DEFT did not give the same results when wine micro-organisms were enumerated. Both methods were used to monitor the population of acetic acid bacteria (AAB) and lactic acid bacteria (LAB) during wine storage. Results suggest that part of the populations had reached a viable but non-culturable (VBNC) state. These cells were unable to produce colonies but could hydrolyse fluorescent esters and could be counted by DEFT. For AAB, O2 deprivation quickly induced this state. Recovery from this state was very rapid as soon as O2 was available. The response was not so clear for LAB during wine storage. However, a similar state was induced by sulfiting. Moreover, filtration of wine stored in barrels and contaminated by Brettanomyces, AAB and LAB demonstrated that cell size was not homogeneous. Cells which remained in wine after several weeks could pass through a 0.45-microm membrane. However, when they re-entered a growing phase, they were again retained by membrane filtration. During and after the decline phase, wine micro-organisms might survive as smaller cells in a VBNC state.     

Mitochondrial function declines with age within individuals but is not linked to the pattern of growth or mortality risk in zebra finch

Mitochondrial dysfunction is considered a highly conserved hallmark of ageing. However, most of the studies in both model and non-model organisms are cross-sectional in design; therefore, little is known, at the individual level, on how mitochondrial function changes with age, its link to early developmental conditions or its relationship with survival. Here we manipulated the postnatal growth in zebra finches (Taeniopygia guttata) via dietary modification that induced accelerated growth without changing adult body size. In the same individuals, we examined blood cells mitochondrial functioning (mainly erythrocytes) when they were young (ca. 36 weeks) and again in mid-aged (ca. 91 weeks) adulthood. Mitochondrial function was strongly influenced by age but not by postnatal growth conditions. Across all groups, within individual ROUTINE respiration, OXPHOS and OXPHOS coupling efficiency significantly declined with age, while LEAK respiration increased. However, we found no link between mitochondrial function and the probability of survival into relatively old age (ca. 4 years). Our results suggest that the association between accelerated growth and reduced longevity, evident in this as in other species, is not attributable to age-related changes in any of the measured mitochondrial function traits.