A biphasic model of limb venous compliance: a comparison with linear and exponential models.

Compliance is not linear within the physiological range of pressures, and linear modeling may not describe venous physiology adequately. Forearm and calf venous compliance were assessed in nine subjects. Venous compliance was modeled by using a biphasic model with high- and low-pressure linear phases separated by a breakpoint. This model was compared with a linear model and several exponential models. The biphasic, linear, and two-parameter exponential models best represented the data. The mean coefficient of determination for the biphasic model was greater than for the linear and exponential models in the calf (biphasic 0.94 +/- 0.04, exponential 0.81 +/- 0.16, P = not significant; and linear 0.54 +/- 0.05, P < 0.05) and forearm (biphasic 0.83 +/- 0.17, exponential 0.79 +/- 0.15, P = not significant; and linear 0.51 +/- 0.06, P < 0.05). The breakpoint pressure in the biphasic model was higher in the calf than the forearm, 34.4 +/- 3.9 vs. 29.1 +/- 4.5 mmHg, P < 0.05. A biphasic model can describe limb venous compliance and delineate differences in venous physiology at high and low pressures. The steep low-pressure phase of the compliance curve extends to higher pressures in the calf than in the forearm, thereby enlarging the range of pressures over which hemodynamic regulation by the calf venous circulation occurs.     

Mesoscopic gel at low agarose concentration in water: a dynamic light scattering study.

Previous work in our laboratory has shown that at very low agarose concentration in water gelation still occurs within mutually disconnected, high concentration regions generated by spinodal demixing. The freely diffusing particles obtained in these conditions are studied in the present work by depolarized dynamic light scattering and probe diffusion experiments. These particles are found to behave as large (in fact, mesoscopic) polymer fibers entangled in a continuously rearranged mesh with scaling parameters typical of partially flexible, neutral chains. The present results allow specifying the notion of mesoscopic gelation. They also reveal that the same symmetry-breaking mechanism that allows macroscopic gelation at polymer concentrations well below the threshold for random cross-link percolation generates additional and unexpected phenomena.     

Temperature dependence of the effects of some monohydric alcohols on the oxygen affinity of hemoglobin: Determination and analysis of thermodynamic parameters

We studied the effects of methanol, ethanol, iso-propanol, and n-propanol on the reaction of hemoglobin with oxygen at various temperatures. The analysis of the results in terms of the Monod-Wyman-Changeux model allowed determination of the overall contribution of the alcohols to the standard enthalpy and entropy differences between the T and R states of hemoglobin. A phenomenological approach allowed us to obtain separately the contributions related to the variations of the bulk dielectric constant of the solvent (bulk electrostatic contributions) and the contributions related to other effects (non-bulk-electrostatic contributions). The values of non-bulk-electrostatic contributions to ΔΔH and ΔΔS supported the suggestion that these contributions are mainly related to protein-solvent hydrophobic interactions.     

Novel role for E4 region genes in protection of adenovirus vectors from lysis by cytotoxic T lymphocytes

Target cells infected with adenovirus (Ad) vectors containing intact E3 and E4 regions were found to be relatively resistant to lysis by Ad-specific cytotoxic T lymphocytes. Elements from both the E3 and the E4 regions were required for this effect, leading to the identification of a previously undescribed role for E4 gene products in resistance to cytolysis.     

The COUP-TF nuclear receptors regulate cell migration in the mammalian basal forebrain

Cells migrate via diverse pathways and in different modes to reach their final destinations during development. Tangential migration has been shown to contribute significantly to the generation of neuronal diversity in the mammalian telencephalon. GABAergic interneurons are the best-characterized neurons that migrate tangentially, from the ventral telencephalon, dorsally into the cortex. However, the molecular mechanisms and nature of these migratory pathways are only just beginning to be unravelled. In this study we have first identified a novel dorsal-to-ventral migratory route, in which cells migrate from the interganglionic sulcus, located in the basal telencephalon between the lateral and medial ganglionic eminences, towards the pre-optic area and anterior hypothalamus in the diencephalon. Next, with the help of transplantations and gain-of-function studies in organotypic cultures, we have shown that COUP-TFI and COUP-TFII are expressed in distinct and non-overlapping migratory routes. Ectopic expression of COUP-TFs induces an increased rate of cell migration and cell dispersal, suggesting roles in cellular adhesion and migration processes. Moreover, cells follow a distinct migratory path, dorsal versus ventral, which is dependent on the expression of COUP-TFI or COUP-TFII, suggesting an intrinsic role of COUP-TFs in guiding migrating neurons towards their target regions. Therefore, we propose that COUP-TFs are directly involved in tangential cell migration in the developing brain, through the regulation of short- and long-range guidance cues.     

Biochemical characterization of a CDC6-like protein from the crenarchaeon Sulfolobus solfataricus

Cdc6 proteins play an essential role in the initiation of chromosomal DNA replication in Eukarya. Genes coding for putative homologs of Cdc6 have been also identified in the genomic sequence of Archaea, but the properties of the corresponding proteins have been poorly investigated so far. Herein, we report the biochemical characterization of one of the three putative Cdc6-like factors from the hyperthermophilic crenarchaeon Sulfolobus solfataricus (SsoCdc6-1). SsoCdc6-1 was overproduced in Escherichia coli as a His-tagged protein and purified to homogeneity. Gel filtration and glycerol gradient ultracentrifugation experiments indicated that this protein behaves as a monomer in solution (molecular mass of about 45 kDa). We demonstrated that SsoCdc6-1 binds single- and double-stranded DNA molecules by electrophoretic mobility shift assays. SsoCdc6-1 undergoes autophosphorylation in vitro and possesses a weak ATPase activity, whereas the protein with a mutation in the Walker A motif (Lys-59 --> Ala) is completely unable to hydrolyze ATP and does not autophosphorylate. We found that SsoCdc6-1 strongly inhibits the ATPase and DNA helicase activity of the S. solfataricus MCM protein. These findings provide the first in vitro biochemical evidence of a functional interaction between a MCM complex and a Cdc6 factor and have important implications for the understanding of the Cdc6 biological function.     

Tauroursodeoxycholic acid reduces damaging effects of taurodeoxycholic acid on fundus gastric mucosa

We investigated the effects of tauroursodeoxycholic acid (TUDCA) to assess whether this acid may also have "protective" effects similar to those found with ursodeoxycholic acid (UDCA). We used a well-known amphibian model of gastric mucosa, and studied the effects of taurodeoxycholic acid (TDCA) on electrical transepithelial parameters, acid secretion and histology in absence or in presence of TUDCA. Mucosal exposure to TDCA, after stimulation with histamine, caused a reduction in transepithelial potential difference (V(t)) and transepithelial resistance (R(t)) and a decrease in acid secretion while mucosal exposure to TUDCA did not cause a significant change in the electrical parameters. Moreover, TDCA primarily affected the neck cells, while TUDCA affected only oxyntic cells, causing a similar degree of injury to that observed in controls. Mucosal exposure to TUDCA plus TDCA caused a reduction in short circuit current (I(sc)) and R(t), whereas acid secretion did not change. These results suggest that: (1) TUDCA reduces the damaging effects of TDCA on fundus gastric mucosa; (2) TUDCA may play an important role in the treatment of gastritis associated with bile reflux.     

Improved pulmonary artery buffering function during phenylephrine-induced pulmonary hypertension

The goal of this study was to determine the in vivo pulmonary arterial buffering function (BF) during acute and moderate pulmonary hypertension achieved by phenylephrine-induced smooth muscle activation.Pulmonary pressure (Konigsberg P7) and diameter (sonomicrometry) were measured in nine anesthetized sheep. Transit pulmonary arterial hypertension was induced by mechanical occlusion of the pulmonary artery (HP) and by phenylephrine infusion (5 g/kg/min) (PHE). A viscoelastic Kelvin-Voigt model was used. By increasing the values of the viscous modulus, the pressure-diameter hysteresis area was reduced to a minimum in order to obtain the purely elastic pressure-diameter relationship. The elastic index (E) was calculated as the first derivative of the exponential model of the purely elastic pressure-diameter relationship at the mean pressure point.Systolic, diastolic, mean and pulse pressures were similar during HP and PHE, but significantly higher with regard to control steady state. In HP, E and arterial diameter (both its minimum and maximum values) increased significantly. In contrast, when pulmonary hypertension was induced by VSM activation, E was maintained concomitantly with pulmonary artery vasoconstriction.Pulmonary hypertension produced by occlusion of the pulmonary artery increases elasticity. Smooth muscle activation may offset the deleterious effect of pulmonary hypertension on arterial wall elasticity by reducing E and impeding arterial dilatation and collagen recruitment, maintaining BF during pulmonary hypertension.