Heart rate deflection point as a strategy to defend stroke volume during incremental exercise.

The purpose of this study was to examine whether the heart rate (HR) deflection point (HRDP) in the HR-power relationship is concomitant with the maximal stroke volume (SV(max)) value achievement in endurance-trained subjects. Twenty-two international male cyclists (30.3 +/- 7.3 yr, 179.7 +/- 7.2 cm, 71.3 +/- 5.5 kg) undertook a graded cycling exercise (50 W every 3 min) in the upright position. Thoracic impedance was used to measure continuously the HR and stroke volume (SV) values. The HRDP was estimated by the third-order curvilinear regression method. As a result, 72.7% of the subjects (HRDP group, n = 16) presented a break point in their HR-work rate curve at 89.9 +/- 2.8% of their maximal HR value. The SV value increased until 78.0 +/- 9.3% of the power associated with maximal O(2) uptake (Vo(2 max)) in the HRDP group, whereas it increased until 94.4 +/- 8.6% of the power associated with Vo(2 max) in six other subjects (no-HRDP group, P = 0.004). Neither SV(max) (ml/beat or ml.beat(-1).m(-2)) nor Vo(2 max) (ml/min or ml.kg(-1).min(-1)) were different between both groups. However, SV significantly decreased before exhaustion in the HRDP group (153 +/- 44 vs. 144 +/- 40 ml/beat, P = 0.005). In the HRDP group, 62% of the variance in the power associated with the SV(max) could also be predicted by the power output at which HRDP appeared. In conclusion, in well-trained subjects, the power associated with the SV(max)-HRDP relationship supposed that the HR deflection coincided with the optimal cardiac work for which SV(max) was attained.     

Water permeability and revolving movement in Phaseolus vulgaris L. twining shoots

Osmotic water permeability (Pos) was measured in protoplasts isolated from different tissues of Phaseolus vulgaris twining shoot. Parenchyma protoplasts exhibited more frequently high Pos values than epidermis protoplasts did. Water channels could facilitate water movement between parenchyma cells whereas cell-to-cell water transport mostly occurs through plasmodesmata in epidermis.     

Synthesis and aminoacyl-tRNA synthetase inhibitory activity of aspartyl adenylate analogs

Three nonhydrolyzable aspartyl adenylate analogs have been prepared and tested as inhibitors of E. coli aspartyl-tRNA synthetase. 5'-O-[N-(L-Aspartyl)sulfamoyl]adenosine is a potent competitive inhibitor (K(i) = 15 nM) whereas L-aspartol adenylate is a weaker inhibitor (K(i) = 45 microM) with respect to aspartic acid. The corresponding ketomethylphosphonate (a novel isosteric replacement) is also a strong inhibitor (K(i) = 123 nM).     

Serum increases CYP1A1 induction by 3-methylcholanthrene

Mice with a targeted null mutation of the serotonin 5-HT(2C) receptor gene exhibit hyperphagia that leads to a late-onset obesity. Here we show that oxygen consumption was decreased in fed and fasted obese mutants. No phenotypic differences were observed in uncoupling protein-1 (UCP-1) mRNA levels in brown adipose tissues and UCP-3 mRNA in skeletal muscle. UCP-2 mRNA levels were significantly increased in white adipose tissue (4-fold) and skeletal muscle (47%) in older obese mutant mice, whereas UCP-2 mRNA in liver are significantly increased in both young lean (54% increase) and older obese (52% increase) mutant mice. In contrast, 5-HT(2C) receptor mutants displayed age-dependent decreases in beta 3-adrenergic receptor (beta 3-AR) mRNA levels in white adipose tissue, however, no such changes were observed in brown adipose tissue. These results indicate that a mutation of 5-HT(2C) receptor gene leads to a secondary decrease in beta 3-AR gene expression that is related to enhanced adiposity.     

Laminin-induced capping and receptor expression at cell surface in a rat rhabdomyosarcoma cell line: Involvement in cell adhesion and migration on laminin substrates

The present study reveals the dynamic distribution of membrane laminin receptors induced by laminin binding in a rat rhabdomyosarcoma cell line RMS S4. The treatment of the cells with soluble laminin did not modify cell adhesion to laminin-coated substrates in in vitro attachment assays. Fluorescent labeling of membrane-bound laminin revealed that occupied receptors were induced to cluster and cap. New free membrane binding sites were made evident after capping of bound laminin by a double labeling technique. Cytochalasin D (CD) treatment prevented the capping process. The adhesion of CD-treated cells to laminin-coated substrates was inhibited by cell preincubation with soluble laminin. Cycloheximide treatment had no effect on the ability of RMS S4 cells to adhere to adsorbed laminin after preincubation in the presence of soluble laminin. These results taken as a whole suggest that free receptors may arise from an intracellular pool that could be maintained by membrane receptor recycling. Since capping and motility seem related events, migration of RMS S4 cells on laminin was studied in the agarose drop assay. Immobilized laminin stimulated basic cell motility by more than 200%. E8 laminin fragment retained partially the motility stimulating property of laminin while P1 pepsinic fragment had no effect. The presence of constantly available receptors at the cell surface could be determinant in the ability of cells to migrate on laminin substrates.     

Molecular Mapping of 21 Features Associated with Partial Monosomy 21: Involvement of the APP-SOD1 Region

We compared the phenotypes, karyotypes, and molecular data for six cases of partial monosomy 21. Regions of chromosome 21, the deletion of which corresponds to particular features of monosomy 21, were thereby defined. Five such regions were identified for 21 features. Ten of the features could be assigned to the region flanked by genes APP and SOD1: six facial features, transverse palmar crease, arthrogryposis-like symptoms, hypertonia, and contribution to mental retardation. This region, covering the interface of bands 21q21-21q22.1, is 4.7–6.4 Mb long and contains the gene encoding the glutamate receptor subunit GluR5 (GRIK1).     

Increased SOD1 enzymatic activity and gene modifications in orangutans: evolutionary implications

Summary Superoxide dismutase CuZn (SOD1) enzymatic activity was measured in five orangutans (Pongo pygmaeus, PPY) and compared to that of man, chimpanzee, and gorilla. It was found to be increased by a factor of two in one orangutan (Ralfina) and by a factor of 1.5 in the four others. In situ hybridization of the SOD1 cDNA human probe showed a heterozygous intrachromosomal rearrangement of pair PPY XXI, possibly an insertion, in Ralfina. Southern blotting showed that the SOD1 gene is modified in the three orangutans that were investigated and that a further modification of the 5-end of the gene had occurred in Ralfina. The evolutionary implications of these observations are discussed.     

Cytogenetic and molecular analysis of a de novo tandem duplication of chromosome 21

Summary We have characterised by cytogenetic and molecular analysis a de novo tandem duplication of chromosome 21. High resolution chromosome examination of lymphocytes revealed the following karyotype in 90% of the cells: 46,XY,dir dup (21)(pterq22.300::q11.205 qter). Of these cells, 10% showed a normal karyotype. Gene dosage of chromosome 21 sequences by a slot blot method indicated that the duplication extends from D21S16 to D21S55. In situ hybridization with probes close to the borders of the duplicated segment confirmed the gene dosage data and gave results consistent with a true tandem duplication of chromosome 21. Pulsed field gel electrophoresis of the patient's DNA showed an abnormal restriction band common to D21S55 and D21S16, confirming that the junction point between the two homologous parts of the tandem chromosome brings these two sequences into proximity. Restriction fragment length polymorphism analysis indicated that the abnormal chromosome was maternal in origin and that the rearrangement of chromosome 21 could not have occurred at a post-zygotic stage of development but resulted from a recombination event during maternal gametogenesis. The possible mechanisms of formation of the abnormal chromosome are discussed, as is the presence of cells with normal chromosomes 21, in the patient.