Apolipoprotein C-I reduces cholesteryl esters selective uptake from LDL and HDL by binding to HepG2 cells and lipoproteins

Plasma cholesterol from low- and high-density lipoproteins (LDL and HDL) are cleared from the circulation by specific receptors that either totally degrade lipoproteins as the LDL receptor or selectively take up their cholesteryl esters (CE) like the scavenger receptor class B type I (SR-BI). The aim of the present study was to define the effect of apoC-I on the uptake of LDL and HDL₃ by HepG2 cells. In experiments conducted with exogenously added purified apoC-I, no significant effect was observed on lipoprotein–protein association and degradation; however, LDL- and HDL₃-CE selective uptake was significantly reduced in a dose-dependent manner. This study also shows that apoC-I has the ability to associate with HepG2 cells and with LDL and HDL₃. Moreover, pre-incubation of HepG2 cells with apoC-I reduces HDL₃-CE selective uptake and pre-incubation of LDL and HDL₃ with apoC-I decreases their CE selective uptake by HepG2 cells. Thus, apoC-I can accomplish its inhibitory effect on SR-BI activity by either binding to SR-BI or lipoproteins. We conclude that by reducing hepatic lipoprotein-CE selective uptake, apoC-I has an atherogenic character.     

The relation between salinity and copper complexing capacity of natural estuarine waters and the uptake of dissolved 64Cu by Macoma balthica

Abstract

The radiotracer ⁶⁴Cu was used to assess the influence of natural organic ligands on the bioavailability of copper. Biological availability of the ⁶⁴Cu-complexes was measured by accumulation in the bivalve Macoma balthica. The experiments were carried out in April as well as in February with water from the relatively clean Oosterschelde Sea arm and the relatively polluted Westerschelde estuary. Adsorption onto shells, as well as uptake in tissues was assessed at salinities of 10‰ and 30‰. Simultaneously with the exposure experiments, ligand characteristics of the natural waters were assessed. High ligand concentrations, as occurring in the Westerschelde around February, reduced ⁶⁴Cu (320 nM) uptake by more than 50%, in spite of the much lower salinity in the Westerschelde water. At the low salinity, uptake was increased slightly in Westerschelde water, but considerably in Oosterschelde water. This implies that at low ambient ligand concentrations (during the whole year in Oosterschelde water and in the summer period also in Westerschelde water) the influence of salinity on ⁶⁴Cu uptake is more pronounced.     

Interactions between age,sex, and hormones in experimental ischemic stroke

Age, sex, and gonadal hormones have profound effects on ischemic stroke outcomes, although how these factors impact basic stroke pathophysiology remains unclear. There is a plethora of inconsistent data reported throughout the literature, primarily due to differences in the species examined, the timing and methods used to evaluate injury, the models used, and confusion regarding differences in stroke incidence as seen in clinical populations vs. effects on acute neuroprotection or neurorepair in experimental stroke models. Sex and gonadal hormone exposure have considerable independent impact on stroke outcome, but these factors also interact with each other, and the contribution of each differs throughout the lifespan. The contribution of sex and hormones to experimental stroke will be the focus of this review. Recent advances and our current understanding of age, sex, and hormone interactions in ischemic stroke with a focus on inflammation will be discussed.     

Three-dimensional structure of phosphorylase kinase at 22 A resolution and its complex with glycogen phosphorylase b.

Phosphorylase kinase (PhK) integrates hormonal and neuronal signals and is a key enzyme in the control of glycogen metabolism. PhK is one of the largest of the protein kinases and is composed of four types of subunit, with stoichiometry (alphabetagammadelta)(4) and a total MW of 1.3 x 10(6). PhK catalyzes the phosphorylation of inactive glycogen phosphorylase b (GPb), resulting in the formation of active glycogen phosphorylase a (GPa) and the stimulation of glycogenolysis. We have determined the three-dimensional structure of PhK at 22 A resolution by electron microscopy with the random conical tilt method. We have also determined the structure of PhK decorated with GPb at 28 A resolution. GPb is bound toward the ends of each of the lobes with an apparent stoichiometry of four GPb dimers per (alphabetagammadelta)(4) PhK. The PhK/GPb model provides an explanation for the formation of hybrid GPab intermediates in the PhK-catalyzed phosphorylation of GPb.     

Early Syllabic Segmentation of Fluent Speech by Infants Acquiring French

Word form segmentation abilities emerge during the first year of life, and it has been proposed that infants initially rely on two types of cues to extract words from fluent speech: Transitional Probabilities (TPs) and rhythmic units. The main goal of the present study was to use the behavioral method of the Headturn Preference Procedure (HPP) to investigate again rhythmic segmentation of syllabic units by French-learning infants at the onset of segmentation abilities (around 8 months) given repeated failure to find syllabic segmentation at such a young age. The second goal was to explore the interaction between the use of TPs and syllabic units for segmentation by French-learning infants. The rationale was that decreasing TP cues around target syllables embedded in bisyllabic words would block bisyllabic word segmentation and facilitate the observation of syllabic segmentation. In Experiments 1 and 2, infants were tested in a condition of moderate TP decrease; no evidence of either syllabic or bisyllabic word segmentation was found. In Experiment 3, infants were tested in a condition of more marked TP decrease, and a novelty syllabic segmentation effect was observed. Therefore, the present study first establishes early syllabic segmentation in French-learning infants, bringing support from a syllable-based language to the proposal that rhythmic units are used at the onset of segmentation abilities. Second, it confirms that French-learning infants are sensitive to TP cues. Third, it demonstrates that they are sensitive to the relative weight of TP and rhythmic cues, explaining why effects of syllabic segmentation are not observed in context of high TPs. These findings are discussed in relation to theories of word segmentation bootstrapping, and the larger debate about statistically- versus prosodically-based accounts of early language acquisition.