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Sequential Events (sequential + event)
Selected AbstractsThe spatio-temporal and subcellular expression of the candidate Down syndrome gene Mnb/Dyrk1A in the developing mouse brain suggests distinct sequential roles in neuronal developmentEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2008Barbara Hämmerle Abstract It is widely accepted that the neurological alterations in Down syndrome (DS) are principally due to modifications in developmental processes. Accordingly, a large part of the research on DS in recent years has focused on chromosome 21 genes that influence brain development. MNB/DYRK1A is one of the genes on human chromosome 21 that has raised most interest, due to its relationship with the brain functions that are altered in DS. Although a number of interesting experimental mouse models for DS are being developed, we still know little about the expression of Mnb/Dyrk1A during mouse brain development. Here, we report that Mnb/Dyrk1A displays a rather dynamic spatio-temporal expression pattern during mouse central nervous system development. Our data indicate that Mnb/Dyrk1A is specifically expressed in four sequential developmental phases: transient expression in preneurogenic progenitors, cell cycle-regulated expression in neurogenic progenitors, transient expression in recently born neurones, and persistent expression in late differentiating neurones. Our results also suggest that the subcellular localization of MNB/DYRK1A, including its translocation to the nucleus, is finely regulated. Thus, the MNB/DYRK1A protein kinase could be a key element in the molecular machinery that couples sequential events in neuronal development. This rich repertoire of potential functions in the developing central nervous system is suitable to be linked to the neurological alterations in DS through the use of mouse experimental models. [source] Caspase-8- and JNK-dependent AP-1 activation is required for Fas ligand-induced IL-8 productionFEBS JOURNAL, Issue 9 2007Norihiko Matsumoto Despite a dogma that apoptosis does not induce inflammation, Fas ligand (FasL), a well-known death factor, possesses pro-inflammatory activity. For example, FasL induces nuclear factor ,B (NF-,B) activity and interleukin 8 (IL-8) production by engagement of Fas in human cells. Here, we found that a dominant negative mutant of c-Jun, a component of the activator protein-1 (AP-1) transcription factor, inhibits FasL-induced AP-1 activity and IL-8 production in HEK293 cells. Selective inhibition of AP-1 did not affect NF-,B activation and vice versa, indicating that their activations were not sequential events. The FasL-induced AP-1 activation could be inhibited by deleting or introducing the lymphoproliferation (lpr) -type point mutation into the Fas death domain (DD), knocking down the Fas-associated DD protein (FADD), abrogating caspase-8 expression with small interfering RNAs, or using inhibitors for pan-caspase and caspase-8 but not caspase-1 or caspase-3. Furthermore, wildtype, but not a catalytically inactive mutant, of caspase-8 reconstituted the FasL-induced AP-1 activation in caspase-8-deficient cells. Fas ligand induced the phosphorylation of two of the three major mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) but not p38 MAPK. Unexpectedly, an inhibitor for JNK but not for MAPK/ERK kinase inhibited the FasL-induced AP-1 activation and IL-8 production. These results demonstrate that FasL-induced AP-1 activation is required for optimal IL-8 production, and this process is mediated by FADD, caspase-8, and JNK. [source] Lysophosphatidic acid induces ovarian cancer cell dispersal by activating Fyn kinase associated with p120-cateninINTERNATIONAL JOURNAL OF CANCER, Issue 4 2008Ruby Yun-Ju Huang Abstract Lysophosphatidic acid (LPA), known as the "ovarian cancer activating factor," is a natural phospholipid involved in important biological functions, such as cell proliferation, wound healing and neurite retraction. LPA causes colony dispersal in various carcinoma cell lines by inducing morphological changes, including membrane ruffling, lamellipodia formation, cell,cell dissociation and single cell migration. However, its effects on cell,cell dissociation and cell,cell adhesion of ovarian cancer cells have not been studied. In our study, we showed that LPA induced sequential events of intercellular junction dispersal and "half-junction" formation in ovarian cancer SKOV3 cells and that Src-family kinases were involved in both processes, since the effects were abolished by the selective tyrosine kinase inhibitor PP2. LPA induced rapid and transient activation of Src family kinases, which were recruited to cell,cell junctions by increasing the association with the adherens junction protein p120-catenin. We identified the Src family kinase, Fyn, as the key component associated with p120-catenin after LPA stimulation in SKOV3 cells. Our study provides evidence that LPA induces junction dispersal in ovarian cancer SKOV3 cells by activating the Src family kinase Fyn and increasing its association with p120-catenin at the cell,cell junction. © 2008 Wiley-Liss, Inc. [source] Development of axonal pathways in the human fetal fronto-limbic brain: histochemical characterization and diffusion tensor imagingJOURNAL OF ANATOMY, Issue 4 2010Lana Vasung Abstract The development of cortical axonal pathways in the human brain begins during the transition between the embryonic and fetal period, happens in a series of sequential events, and leads to the establishment of major long trajectories by the neonatal period. We have correlated histochemical markers (acetylcholinesterase (AChE) histochemistry, antibody against synaptic protein SNAP-25 (SNAP-25-immunoreactivity) and neurofilament 200) with the diffusion tensor imaging (DTI) database in order to make a reconstruction of the origin, growth pattern and termination of the pathways in the period between 8 and 34 postconceptual weeks (PCW). Histological sections revealed that the initial outgrowth and formation of joined trajectories of subcortico-frontal pathways (external capsule, cerebral stalk,internal capsule) and limbic bundles (fornix, stria terminalis, amygdaloid radiation) occur by 10 PCW. As early as 11 PCW, major afferent fibers invade the corticostriatal junction. At 13,14 PCW, axonal pathways from the thalamus and basal forebrain approach the deep moiety of the cortical plate, causing the first lamination. The period between 15 and 18 PCW is dominated by elaboration of the periventricular crossroads, sagittal strata and spread of fibers in the subplate and marginal zone. Tracing of fibers in the subplate with DTI is unsuccessful due to the isotropy of this zone. Penetration of the cortical plate occurs after 24,26 PCW. In conclusion, frontal axonal pathways form the periventricular crossroads, sagittal strata and ,waiting' compartments during the path-finding and penetration of the cortical plate. Histochemistry is advantageous in the demonstration of a growth pattern, whereas DTI is unique for demonstrating axonal trajectories. The complexity of fibers is the biological substrate of selective vulnerability of the fetal white matter. [source] Effects of various implant materials on regeneration of calvarial defects in ratsPATHOLOGY INTERNATIONAL, Issue 8 2000Sung-Chul Lim The purpose of the present study was to determine the best implant material, the best conditions to substitute absorbable membrane for non-absorbable membrane, and the factors influencing guided regeneration of critical size defects using experimental rats. An 8-mm circular transosseous calvarial bony defect was made and implant materials, such as demineralized freeze-dried bone (DFDB), absorbable membrane (BioMesh; Samyang Co., Seoul Korea), non-absorbable membrane (Millipore filter; Micro Filtration System, MA, USA) or a combination of these materials, was placed on the defect. As for the results of sequential time-based guided bone regeneration, histological, histochemical, immunohistochemical and histomorphometric aspects were observed, and a statistical comparative analysis was performed, with control group of a soft tissue flap. Bone formation was significantly enhanced when DFDB was retained within the defect with a protective absorbable membrane. Inframembranous DFDB-filling was required to prevent membrane collapse and to preserve spaces for bone regeneration. The absorbable membrane which was recommended to overcome the disadvantages of the non-absorbable membrane should remain intact for more than 5 weeks in order for it to be effective. The macrophages recruited by grafts were involved partly in decreasing bone regeneration via the sequential events of releasing fibronectin, and in chemotactic effect of the fibronectin to fibroblasts and collagen lay-down. Thus, the activity of new bone formation was dependent upon the physical barrier effect of the membrane, such as the preserving ability to secure spaces and the suppression ability of early infiltration of collagen and epithelium, inducible ability of inflammation by the implant material, and potential in guiding bone regeneration of the grafts. [source] Early cortical bone healing around loaded titanium implants: a histological study in the rabbitCLINICAL ORAL IMPLANTS RESEARCH, Issue 2 2009Elke Slaets Abstract Objectives: To identify the role of immediate implant loading on the early phases of the bone healing responses. Material and methods: Implants were placed in rabbit tibial diaphyses and left to heal for 3, 7, 14, 28 or 42 days. Half of the animals received an immediate loading protocol of 2.2 N at 3 Hz for 1800 cycles and 5 days/week, whereas the others served as unloaded controls. Histological assessment was combined with histomorphometrical measurements. Results: At early time-points, an endosteal and periosteal new bone formation was found, while the cortex itself contained damaged osteocytes. At later time-points, new bone formation was also found at the cortical level itself. Differences between groups were found mainly in this new bone formation process, with larger reactions for the endosteal and periosteal bone in the loaded group after 28 and 42 days, respectively. At the end-point of the experiment, bone formation at the cortical level was reduced in the loaded group compared with the control group. Conclusions: These results show that the immediate loading protocol caused no differences in the sequential events leading to osseointegration in cortical bone. However, the processes of new bone formation originating from the endosteum and the periosteum lasted longer compared with the unloaded controls. [source] | |||||||||||||