Unexpected dimerization of a tripeptide comprising a β,γ‐diamino acid

We have previously reported the synthesis of enantiopure β,γ‐diamino acids and relevant short α/γ‐peptide containing such building blocks. Complete nuclear magnetic resonance (NMR) studies, together with molecular modeling, highlighted the ability of a β,γ‐diamino acid to induce various intramolecular turns. In this paper, we describe for the first time the formation of a dimeric structure constituted by α/γ/α‐tripeptide and stabilized by intermolecular interactions. A structural model is proposed based on extensive NMR measurements.     

Normal progression of testicular size in boys with idiopathic short stature and isolated growth hormone deficiency treated with growth hormone: experience from the KIGS

BACKGROUND: The aim of this retrospective analysis was to evaluate the effects of growth hormone (GH) treatment on testicular development in boys with idiopathic short stature (ISS) and isolated GH deficiency (IGHD) followed in the KIGS (Pharmacia International Growth Database). METHODS: For inclusion in the study, the patients had to have received more than 1 year of prepubertal GH treatment, at least 4 consecutive years of GH treatment in total, and to have attained their final height, defined as a height velocity of less than 2 cm/year. Data on 107 boys in the KIGS database have been analyzed. RESULTS: No significant differences in duration of GH treatment and testicular volume at the start of treatment or at final height were found between the boys with ISS and those with IGHD. The progression of testicular volume in boys with ISS or IGHD during GH treatment did not differ from the reference population. CONCLUSIONS: This analysis shows that GH treatment does not alter testicular growth in boys with ISS or IGHD. However, prospective controlled studies are needed to rule out moderate attenuating or stimulating effects.     

Trophic and steroidogenic effects of water deprivation on the adrenal gland of the adult female rat

The effects of a 3-day water deprivation were studied in adult female rats in order to know what are the different zones of the adrenal gland and the hormonal factors involved in the growth and the activity of the adrenal gland. Water deprivation significantly increased plasma renin activity (PRA), plasma Angiotensin II (AII), vasopressin (AVP), epinephrine, aldosterone and corticosterone concentrations but did not modify the plasma adrenocorticotropin hormone (ACTH) level. Water deprivation significantly increased the absolute weight of the adrenal capsule containing the zona glomerulosa without modification of the density of cells per area unit suggesting that the growth of the adrenal capsule was due to a cell hyperplasia of the zona glomerulosa. Water deprivation significantly increased the density of AII type 1 (AT₁) receptors in the adrenal capsule but did not modify the density of AII type 2 (AT₂) receptors in the adrenal capsule and core containing the zona fasciculata, the zona reticularis and the medulla. The treatment of dehydrated female rats with captopril, which inhibits the angiotensin converting enzyme (ACE) in order to block the production of AII, significantly decreased the absolute weight of the adrenal capsule, plasma aldosterone and the density of AT₁ receptors in the adrenal capsule. The concentration of corticosterone in the plasma, the density of AT₂ receptors and the density of cells per unit area in the zona glomerulosa of the adrenal capsule were not affected by captopril-treatment. In conclusion, these results suggest that AII seems to be the main factor involved in the stimulation of the growth and the secretion of aldosterone by the adrenal capsule containing the zona glomerulosa during water deprivation. The low level of plasma ACTH is not involved in the growth of the adrenal gland but is probably responsible for the secretion of corticosterone by the zona fasciculata.     

Spatio-temporal growth dynamics of a subAlpine Pinus uncinata stand in the French Alps

Natural forests are characterised by a high level of both spatial and temporal heterogeneity. The major processes involved in the creation and maintenance of forest heterogeneity in temperate climates are small-sized canopy disturbances. The resulting openings also modify the growth conditions for the remaining trees. The analysis of tree growth responses using dendrochronological techniques allows the reconstruction of the time sequence of the disturbances. The radial growth analysis is coupled here with both a spatial analysis and a demographic analysis of the forest structure. The age classes are temporally organised in cohorts and spatially distributed in spatial aggregates. The analysis of the most documented disturbance event allowed us to determine the size of the disturbance response patch (between 0.036 and 0.073 ha) and the duration of the disturbance (six years). We considered that this small-scale disturbance event may have been caused by the fall of a single tree and has freed the surrounding trees of its competition.     

Engineering tolerance and accumulation of lead and cadmium in transgenic plants

We have studied the utility of the yeast protein YCF1, which detoxifies cadmium by transporting it into vacuoles, for the remediation of lead and cadmium contamination. We found that the yeast YCF1-deletion mutant DTY167 was hypersensitive to Pb(II) as compared with wild-type yeast. DTY167 cells overexpressing YCF1 were more resistant to Pb(II) and Cd(II) than were wild-type cells, and accumulated more lead and cadmium. Analysis of transgenic Arabidopsis thaliana plants overexpressing YCF1 showed that YCF1 is functionally active and that the plants have enhanced tolerance of Pb(II) and Cd(II) and accumulated greater amounts of these metals. These results suggest that transgenic plants expressing YCF1 may be useful for phytoremediation of lead and cadmium.     

Light scattering studies of the solution properties of chitosans of varying degrees of acetylation

The use of two techniques, differential interferometry and quasi-elastic light scattering (QELS), allowed us to study solutions of chitosan varying in degree of acetylation (DA), degree of dissociation (alpha), and concentration (C(p)). With the first technique, we demonstrated the modification of the electric polarizability of the polymer chains, through a law of behavior of the variation of the refractive index increment dn/dC with DA and alpha. This brought us information on the various kinds of interactions (H-bonds, electrostatic, and hydrophobic) involved in the evolution of the solution properties. QELS experiments performed in dilute regime showed the presence of supramolecular structures depending on DA and alpha. The topology and the nature of these objects are discussed. The typical presence of aggregates and their evolution with concentration was also demonstrated in semidilute regime.     

Acute inflammation increases selective uptake of HDL cholesteryl esters into adrenals of mice overexpressing human sPLA2

The acute-phase protein secretory phospholipase A2 (sPLA2) influences the metabolism of high-density lipoproteins (HDL). The adrenals are known to utilize HDL cholesterol as a source of sterols. The aim of the present study was to test the hypothesis that sPLA2 enhances the selective uptake of HDL into the adrenals in response to acute inflammation as a possible physiological role for the sPLA2-HDL interaction. Human sPLA2-transgenic mice, in which sPLA2 expression is upregulated by inflammatory stimuli, were used. Ten hours after induction of the acute-phase response (APR) by injection of bacterial lipopolysaccharide (LPS), plasma levels of HDL cholesterol decreased significantly in sPLA2-transgenic mice (-18%, P < 0.05) but remained unchanged in wild-type mice. The fractional catabolic rates of both 125I-labeled tyraminecellobiose (TC)-HDL and [3H]cholesteryl ether increased significantly in the sPLA2-transgenic mice after induction of the APR (0.18 +/- 0.01 vs. 0.21 +/- 0.01 pool/h, P < 0.05, and 0.31 +/- 0.02 vs. 0.42 +/- 0.05 pool/h, P < 0.05, respectively) but remained unchanged in the wild-type mice (0.10 +/- 0.01 vs. 0.22 +/- 0.02 pool/h, respectively). After induction of the APR, in both groups HDL holoparticle uptake by the liver was increased (P < 0.001). sPLA2-transgenic mice had 2.4-fold higher selective uptake into the adrenals after induction of the APR than wild-type mice (156 +/- 6 vs. 65 +/- 5%/ micro g tissue protein, P < 0.001). In summary, upregulation of sPLA2 expression during the APR specifically increases the selective uptake of HDL cholesteryl ester into the adrenals. These data suggest a novel metabolic role for sPLA2: modification of HDL during the APR to promote increased adrenal uptake of HDL cholesteryl ester to serve as source for steroid hormone synthesis.     

A quantitative assay for the non-covalent association between apolipoprotein[a] and apolipoprotein B: an alternative measure of Lp[a] assembly

Increasing evidence suggests that the assembly of lipoprotein[a] (Lp[a]) proceeds in two steps. In the first step, non-covalent interactions between apolipoprotein[a] (apo[a]) and apolipoprotein B (apoB) of low density lipoprotein (LDL) form a dissociable apo[a]:LDL complex. In the second step, a covalent disulfide linkage forms the stable Lp[a] particle. Several methods are currently used to study the assembly of Lp[a], however, these methods are laborious, time-consuming, and not suitable for a high throughput screening. We report here the development of a rapid and simple assay based on the binding of labeled LDL to a Lp[a]/apo[a] substrate which is immobilized on the surface of a microtiter plate. Quantification of bound LDL provides a measure of the extent of complex formation. Labeled LDL bound to both Lp[a] and apo[a] substrates with similar affinity. Plasma lipoproteins containing apoB as well as free apo[a] were capable of competing with LDL binding. The binding of LDL to Lp[a]/apo[a] was inhibited by L-proline and lysine analogs, which are known to inhibit the non-covalent association between apo[a] and apoB. Using this method we have found that nicotinic acid and captopril are able to inhibit the association of apo[a] with apoB. This method is compatible with automation and can be applied to a high throughput screening of inhibitors of Lp[a] formation.     

Rapid <Emphasis Type="Italic">Leptospira</Emphasis> identification by direct sequencing of the diagnostic PCR products in New Caledonia

Background  

Most of the current knowledge of leptospirosis epidemiology originates from serological results obtained with the reference Microscopic Agglutination Test (MAT). However, inconsistencies and weaknesses of this diagnostic technique are evident. A growing use of PCR has improved the early diagnosis of leptospirosis but a drawback is that it cannot provide information on the infecting Leptospira strain which provides important epidemiologic data. Our work is aimed at evaluating if the sequence polymorphism of diagnostic PCR products could be used to identify the infecting Leptospira strains in the New Caledonian environment.     

The in vitro chronotropic and inotropic effects of vasoactive intestinal peptide (VIP) on the atria and ventricular papillary muscle from Cynomolgus monkey heart

The in vitro chronotropic and inotropic effects of vasoactive intestinal peptide (VIP) and of isoproterenol, two agents known to stimulate cardiac adenylate cyclase were compared on the heart from Cynomolgus monkey using the spontaneously beating right atrium, the electrically stimulated left atrium, and the electrically-stimulated ventricular papillary muscle. VIP increased concentration-dependently the rate of beating of the right atrium as well as the contractility of both atria but its efficiency was lower than that of D,L-isoproterenol. VIP also stimulated concentration-dependently, and this time as efficiently as D,L-isoproterenol, the contractility of papillary muscle. These VIP effects were unaltered by the neuronal blocker tetrodotoxin. In addition, the moderate inhibition exerted by the beta-adrenergic blocker D,L-propranolol on VIP effects argued against the implication of beta-adrenergic receptors in VIP effects. These results indicate that VIP exerts a direct stimulatory influence on the rate and contractility of Cynomolgus monkey heart.