Frontal increase of beta modulation during the practice of a motor task is enhanced by visuomotor learning.

Movement is accompanied by beta power changes over frontal and sensorimotor regions: a decrease during movement (event-related desynchronization, ERD), followed by an increase (event-related synchronization, ERS) after the movement end. We previously found that enhancements of beta modulation (from ERD to ERS) during a reaching test (mov) occur over frontal and left sensorimotor regions after practice in a visuo-motor adaptation task (ROT) but not after visual learning practice. Thus, these enhancements may reflect local cumulative effects of motor learning. Here we verified whether they are triggered by the learning component inherent in ROT or simply by motor practice in a reaching task without such learning (MOT). We found that beta modulation during mov increased over frontal and left areas after three-hour practice of either ROT or MOT. However, the frontal increase was greater after ROT, while the increase over the left area was similar after the two tasks. These findings confirm that motor practice leaves local traces in beta power during a subsequent motor test. As they occur after motor tasks with and without learning, these traces likely express the cost of processes necessary for both usage and engagement of long-term potentiation mechanisms necessary for the learning required by ROT.

Human cytomegalovirus-induced inhibition of cytotrophoblast invasion in a first trimester extravillous cytotrophoblast cell line.

Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection in the United States and intrauterine transmission of HCMV occurs in approximately 40% of pregnant women with primary HCMV infection. Although HCMV infection during pregnancy clearly may be detrimental to fetal development, its consequences on placentation remain largely unexplored. In this study, the effects of HCMV infection on cytotrophoblast (CTB) invasion were investigated utilizing the first trimester extravillous CTB cell line SGHPL-4. HCMV infection significantly inhibited SGHPL-4 proliferation, epidermal growth factor (EGF)- and hepatocyte growth factor (HGF)-induced migration and invasion, as well as the secretion of matrix metalloproteinase (MMP)-2 and MMP-9. Both HCMV and EGF activated the EGF receptor (EGFR), inducing receptor tyrosine phosphorylation at specific residues. Of interest, EGFR was differentially activated by HCMV, and viral gene transcription was not required for the observed inhibitory effect on CTB invasiveness. These findings demonstrate that HCMV infection impairs CTB differentiation along the invasive pathway and that the differential regulation of EGFR by HCMV may contribute to impaired CTB function. Elucidating the mechanisms by which HCMV impairs placentation may be key in understanding fetal and maternal pathologies associated with intrauterine HCMV infection.

Three-dimensional growth of extravillous cytotrophoblasts promotes differentiation and invasion.

Human trophoblast research relies on a combination of in vitro models, including isolated primary cultures, explant cultures, and trophoblast cell lines. In the present study, we have utilized the rotating wall vessel (RWV) bioreactor to generate a three-dimensional (3-D) model of human placentation for the study of cytotrophoblast (CTB) invasion. The RWV supported the growth of the human CTB cell line SGHPL-4 and allowed for the formation of complex, multilayered 3-D aggregates that were morphologically, phenotypically, and functionally distinct from SGHPL-4 monolayers. The cells cultured three-dimensionally differentiated into an aggressively invasive cell population characterized by the upregulation of matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-9 and urokinase-type plasminogen activator (uPA) secretion and activation. Microarray analysis of the 3-D and 2-D cultured cells revealed increased expression in the 3-D cells of various genes that are known mediators of invasion, including MT1-MMP, PECAM-1 and L-selectin, as well as genes not previously associated with CTB differentiation such as MMP-13 and MT5-MMP. These results were verified by quantitative real-time PCR. These findings suggest that when cultured in 3-D, SGHPL-4 cells closely mimic differentiating in utero CTBs, providing a novel approach for the in vitro study of the molecular mechanisms that regulate CTB differentiation and invasion.

Pycnogenol inhibits macrophage oxidative burst, lipoprotein oxidation, and hydroxyl radical-induced DNA damage.

Pycnogenol (procyanidins extracted from Pinus maritima) has been reputed as a potent free-radical scavenger and an antioxidant phytochemical. We previously reported that pycnogenol prevents vascular endothelial cells from injury induced by an organic oxidant t-butyl hydroperoxide. In this study, we determined the effects of pycnogenol on (a) oxidative burst of macrophages, (b) oxidation of plasma low density lipoprotein (LDL), and (c) hydroxyl radical-induced breakage of plasmid DNA. Pycnogenol was incubated with J774 murine macrophages at 37 degrees C and 5% CO2 and oxidative burst was triggered by zymosan. The intensity of fluorescence was measured. Pycnogenol exhibited a concentration-dependent inhibition of oxidative burst. CuSO4 was used to oxidize human plasma LDL and the formation of thiobarbituric acid reactive substances (TBARS) was determined. Co-incubation with pycnogenol resulted in a concentration-dependent inhibition of LDL oxidation. Exposure of pBR322 plasmid DNA to iron/ascorbic acid system resulted in cleavage/damage of DNA by hydroxyl radical, measured by agarose gel electrophoresis. Pycnogenol significantly minimized this cleavage. The results indicate that pycnogenol exhibits an extensive antioxidant effect in all three in vitro systems.

Aged garlic extract and its constituents inhibit Cu(2+)-induced oxidative modification of low density lipoprotein.

Oxygen radical injury and lipid peroxidation have been suggested as major causes of atherosclerosis, cancer, liver disease, and the aging process. More specifically, oxidative modification of low density lipoprotein (LDL) has been recognized as an important process of atherosclerosis. In this study, we determined the effects of aged garlic extract (AGE), four of its constituents, and a metabolite on Cu(2+)-induced oxidative modification of LDL using an in vitro system. All these compounds were shown to inhibit oxidative modification of LDL.