Topiramate Reduces Energy and Fat Gains in Lean (Fa/?) and Obese (fa/fa) Zucker Rats

Objective: This study examined the effects of topiramate (TPM), a novel neurotherapeutic agent reported to reduce body weight in humans, on the components of energy balance in female Zucker rats. Research Methods and Procedures: A 2 × 3 factorial experiment was performed in which two cohorts of Zucker rats differing in their phenotype (phenotype: lean, Fa/?; obese, fa/fa) were each divided into three groups defined by the dose of TPM administered (dose: TPM 0, vehicle; TPM 15, 15 mg/kg; TPM 60, 60 mg/kg). Results: The reduction in body weight gain induced by TPM in both lean and obese rats reflected a decrease in total body energy gain, which was more evident in obese than in lean rats. Whereas TPM administration did not influence the intake of digestible energy in lean rats, it induced a reduction in food intake in obese animals. In lean, but not in obese rats, apparent energy expenditure (as calculated by the difference between energy intake and energy gain) was higher in rats treated with TPM than in animals administered the vehicle. The low dose of TPM decreased fat gain (with emphasis on subcutaneous fat) without affecting protein gain, whereas the high dose of the drug induced a reduction in both fat and protein gains. The effects of TPM on muscle and fat depot weights were representative of the global effects of TPM on whole body fat and protein gains. The calculated energetic efficiency (energy gain/energy intake) was decreased in both lean and obese rats after TPM treatment. TPM dose independently reduced hyperinsulinemia of obese rats, but it did not alter insulinemia of lean animals. Discussion: The present results provide sound evidence for the ability of TPM to reduce fat and energy gains through reducing energetic efficiency in both lean and obese Zucker rats.     

Comparison of the activities of Bacillus thuringiensis mosquitocidal crystal proteins on mosquito cell lines (Diptera,Culicidae), using two colorimetric methods

Two colorimetric methods were compared for assaying the cell toxicity of soluble crystal proteins from five mosquitocidal serovarieties of Bacillus thuringiensis: israelensis, jegathesan, medellin, darmstadiensis and fukuokaensis. In mosquitoes cell lines from Culex quinquefasciatus, Aedes aegypti and Anopheles gambiae, all the crystal proteins were equally toxic. Both colorimetric methods MTT (tetrazolium salt) and Alamar Blue gave similar results, but the Alamar Blue method was simpler, faster, cheaper, and could be used to take readings from the same cell population at various time points. The most active crystal proteins were those of B. thuringiensis israelensis, followed by those of B. thuringiensis jegathesan, and B. thuringiensis medellin, which were much less active.     

Maintenance and Integrity of the Mitochondrial Genome: a Plethora of Nuclear Genes in the Budding Yeast

Instability of the mitochondrial genome (mtDNA) is a general problem from yeasts to humans. However, its genetic control is not well documented except in the yeast Saccharomyces cerevisiae. From the discovery, 50 years ago, of the petite mutants by Ephrussi and his coworkers, it has been shown that more than 100 nuclear genes directly or indirectly influence the fate of the rho⁺ mtDNA. It is not surprising that mutations in genes involved in mtDNA metabolism (replication, repair, and recombination) can cause a complete loss of mtDNA (rho⁰ petites) and/or lead to truncated forms (rho⁻) of this genome. However, most loss-of-function mutations which increase yeast mtDNA instability act indirectly: they lie in genes controlling functions as diverse as mitochondrial translation, ATP synthase, iron homeostasis, fatty acid metabolism, mitochondrial morphology, and so on. In a few cases it has been shown that gene overexpression increases the levels of petite mutants. Mutations in other genes are lethal in the absence of a functional mtDNA and thus convert this petite-positive yeast into a petite-negative form: petite cells cannot be recovered in these genetic contexts. Most of the data are explained if one assumes that the maintenance of the rho⁺ genome depends on a centromere-like structure dispensable for the maintenance of rho⁻ mtDNA and/or the function of mitochondrially encoded ATP synthase subunits, especially ATP6. In fact, the real challenge for the next 50 years will be to assemble the pieces of this puzzle by using yeast and to use complementary models, especially in strict aerobes.     

A dual lanthanide probe suitable for optical (Tb3+ luminescence) and magnetic resonance imaging (Gd3+ relaxometry)

A new polyaminocarboxylate ligand derived from N,C-pyrazolylpyridine was synthesized. The luminescence and relaxometry properties of its Tb(3+) and Gd(3+) chelates were investigated in aqueous solutions. The Tb(3+) chelate is strongly luminescent having remarkable lifetime and quantum yield (tau=1.82ms and Phi=0.42). The 1/T(1) proton relaxivity at 20MHz and 25 degrees C (5.3s(-1)mM(-1)) of the Gd(3+) chelate was found to be comparable to that of the clinically used Gd-DTPA.     

Translation initiation by non-AUG codons in Arabidopsis thaliana transgenic plants

The efficiency of translation initiation at codons differing at one or two nucleotides from AUG was tested as initiation codons for the phosphinotricin-acetyltransferase gene in T-DNA plant transformation in Arabidopsis thaliana. With the exception of UUA codon that differs from AUG at two nucleotides and does not permit any detectable activity, all the other codons (AUC, GUG, ACG, and CUG) present a phosphinotrycin acetyltransferase activity that varies between 5 and 10% of the AUG activity. This low activity is sufficient to confer glufosinate resistance to some of the plants. These results indicate that, in plants as is the case in animals, non-AUG initiating codons may be used for translation initiation, namely when a low expression rate is needed.     

Coagulation factor mutations and thrombosis

The coagulation system is governed by a subtle balance between clotting activators and inhibitors. Many genes can contribute to the overall phenotype, and polymorphisms may act to up regulate or down regulate the generation of thrombin, the coagulation-key enzyme. An increase in coagulation factor (gain function) or/and a decrease in coagulation inhibitors (loss of function) may favor venous thromboembolism (VTE). It has been observed since a long time that VTE may be a familial disease, but it was only in 1965 that Egeberg published the first case of inherited antithrombin (AT) deficiency. This was followed by similar reports of protein C (PC) and protein S (PS) deficiencies. Hereditary thrombophilia was thus initially considered as a rare monogenic disorder with incomplete penetrance. AT, PC and PS deficiencies are due to multiple and mostly private mutations of the corresponding genes. Most patients are heterozygous and experience VTE at adult age. Homozygosity associated with severe thrombosis at birth has been observed in newborns with undetectable PC or PS concentrations. The discovery of factor (F) V Leiden and F2 g.20210 G>A, two gain of function mutations, challenged the view of thrombophilia as a rare monogenic disorder. FV Leiden and F2 g.20210 G>A are due to a founder effect and affect populations of European descent with frequencies at 5% and 3% respectively. These two mutations are moderate of risk factor for thrombosis and paved the way for gene-gene and gene-environment interactions. Patients carrying more than one genetic risk factor are at higher risk to develop VTE. The exposition to acquired risk factors such as estrogen based oral contraception may also have a synergistic effect favoring thrombosis in patients with FV Leiden or other genetic risk factors.     

Influence of polyelectrolyte chemical structure on their interaction with lipid membrane of zwitterionic liposomes

In this paper we extend our previous experimental work on interaction between polyelectrolytes and liposomes. First, the adsorption of chitosan and alkylated chitosan (cationic polyelectrolytes) with different alkyl chain lengths on lipid membranes of liposomes is examined. The amount of both chitosans adsorbed remains the same even if more alkylated polysaccharide has to be added to get saturation if compared with unmodified chitosan. It is demonstrated that alkyl chains do not specifically interact with the lipid bilayer and that electrostatic interaction mechanism governs the chitosan adsorption. The difference observed between unmodified and alkylated chitosans behavior to reach the plateau can be interpreted in terms of a competition between electrostatic polyelectrolyte adsorption on lipid bilayer and hydrophobic autoassociation in solution (which depends on the alkyl chain length). Second, interaction of liposomes with hyaluronan (HA) and alkylated hyaluronan (anionic polyelectrolytes) is analyzed. The same types of results as discussed for chitosan are obtained, but in this case, autoassociation of alkylated HA only occurs in the presence of salt excess. Finally, a first positive layer of chitosan is adsorbed on the lipid membrane, followed by a second negative layer of HA at three different pHs. This kind of multilayer decoration allows the control of the net charge of the composite vesicles. A general conclusion is that whatever the pH and, consequently, the initial charge of the liposomes, chitosan adsorption gives positively charged composite systems, which upon addition of hyaluronan, give rise to negatively charged composite vesicles.     

Ecosystem and Seasonal Control of Stream Dissolved Organic Carbon Along a Gradient of Land Use

We examined the influence of watershed land use and morphology on dissolved organic carbon (DOC) concentration in 32 south-central Ontario streams having varying agricultural land-use intensities in their catchments. For streams in this region, both univariate and multivariate regression models identify the proportion of the watershed with poorly drained soils (r ² up to 0.67) as a better predictor of stream DOC concentrations than any other landscape characteristic, including the proportion of the watershed as wetland. Agricultural land use did not strongly influence DOC concentrations in our study area; however, we do show that land-use changes could significantly alter the delivery of DOC to streams in the region. We also identify how landscape–DOC relationships change over a 2-year time period, as related to season, regional climatic conditions, soil moisture, and hydrology. Our results indicate that the relationships between landscape predictors and stream DOC concentrations are temporally dynamic. Strong temporal trends are shown seasonally and in association with climate, through its control of modelled soil moisture conditions. During periods of positive and negative deviation from normal soil moisture conditions, the relationships of DOC concentrations with landscape characteristics become less predictable. We show that these dominant patterns are likely a function of varying flow paths and that anthropogenic changes that affect soil moisture conditions or flow path will in turn strongly influence DOC dynamics. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.