High frequency repetitive transcranial magnetic stimulation over the motor cortex: No diagnostic value for narcolepsy/cataplexy

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Cell Death or Survival Promoted by Alternative Isoforms of ErbB4

The report demonstrates that two distinct isoforms of the ErbB4 receptor tyrosine kinase stimulate either proliferation or apoptosis by mechanisms involving differential transcriptional regulation of the PDGFRA gene. These data have implications for developing approaches to target ErbB4 signaling in cancer

Brain Abnormalities and Glioma-Like Lesions in Mice Overexpressing the Long Isoform of PDGF-A in Astrocytic Cells

BACKGROUND: Deregulation of platelet-derived growth factor (PDGF) signaling is a hallmark of malignant glioma. Two alternatively spliced PDGF-A mRNAs have been described, corresponding to a long (L) and a short (S) isoform of PDGF-A. In contrast to PDGF-A(S), the PDGF-A(L) isoform has a lysine and arginine rich carboxy-terminal extension that acts as an extracellular matrix retention motif. However, the exact role of PDGF-A(L) and how it functionally differs from the shorter isoform is not well understood.\ud \ud METHODOLOGY/PRINCIPAL FINDINGS: We overexpressed PDGF-A(L) as a transgene under control of the glial fibrillary acidic protein (GFAP) promoter in the mouse brain. This directs expression of the transgene to astrocytic cells and GFAP expressing neural stem cells throughout the developing and adult central nervous system. Transgenic mice exhibited a phenotype with enlarged skull at approximately 6-16 weeks of age and they died between 1.5 months and 2 years of age. We detected an increased number of undifferentiated cells in all areas of transgene expression, such as in the subependymal zone around the lateral ventricle and in the cerebellar medulla. The cells stained positive for Pdgfr-α, Olig2 and NG2 but this population did only partially overlap with cells positive for Gfap and the transgene reporter. Interestingly, a few mice presented with overt neoplastic glioma-like lesions composed of both Olig2 and Gfap positive cell populations and with microvascular proliferation, in a wild-type p53 background.\ud \ud CONCLUSIONS: Our findings show that PDGF-A(L) can induce accumulation of immature cells in the mouse brain. The strong expression of NG2, Pdgfr-α and Olig2 in PDGF-A(L) brains suggests that a fraction of these cells are oligodendrocyte progenitors. In addition, accumulation of fluid in the subarachnoid space and skull enlargement indicate that an increased intracranial pressure contributed to the observed lethality.\ud \u

Laboratoriumonderzoek aan een ATAG HR-ketel, voorzien van een nageschakelde membraanmodule -vervolgonderzoek-

Door Atag verwarming BV is aan TNO-ME afdeling Warmte- en Koudetechniek opdracht verleend een laboratoriumonderzoek uit te voeren aan een ATAG-CV-ketel voorzien van een mebraanmodule. Het onderzoek had tot doel het effect van de toepassing van de membraammodule ten aanzien van de rendementen, de energiebalans, emissies en drukval over de module bij verschillende bedrijfscondities vast te stellen. De aanleiding van het vervolgonderzoek was het niet gasdicht zijn van de ketel in het voorafgaande onderzoek, waardoor het effect van de membraammodule niet volledig kon worden vastgesteld. In dit rapport worden de resultaten weergegeven van het vervolgonderzoek naar het effect van de membraanmodule gekoppeld aan een bestaande HR-ketel.

Onderzoek aan de ketelinstallatie in het gewestelijk arbeidsbureau te Arnhem

Dit rapport beschrijft samenvattend uitvoering en resultaten van een onderzoek an de ketelinstallatie in het Gewestelijk Arbeidsbureau te Arnhem. Het doel van dit onderzoek was om door meting vast te stellen welke regelstrategie het hoogste rendement van de ketelinstallatie oplevert en welke installatie-uitvoering de meest optimale is ten aanzien van het energieverbruik en investering.

Onderzoek aan een afvoerloze keukengeiser RINNAI RUS-5RX

In het laboratorium van IMET-TNO afdeling Warmte- en Koudetechniek is de keukengeiser Rinnai RUS-5RX serienummer 93.4-130004 onderzocht op het functioneren van de atmosfeerbeveiliging en zijn de toestelparameters vastgesteld ten behoeve van het simulatiemodel TAPSIM.

Platelet-derived growth factor receptor-alpha in ventricular zone cells and in developing neurons

Cells in the early neuroepithelium differentiate and give rise to all cells in the central nervous system (CNS). The ways from a multipotent CNS stem cell to specialized neurons and glia are not fully understood. Using immunohistochemistry we found that neuroepithelial cells express the platelet-derived growth factor receptor-alpha (PDGFR-alpha) in the neural plate at embryonic day 8.5 and onwards in the neural tube. The protein was polarized to ventricular endfeet. Furthermore, PDGFR-alpha expression was localized to cells undergoing early neuronal development. We also found PDGFR-alpha expression in developing granule cells in the postnatal cerebellum, in Purkinje cells in the adult cerebellum and on processes of developing dorsal root ganglion cells. Previous reports mainly describe PDGFR-alpha expression in oligodendrocyte precursors and glial cells. We believe, in line with a few previous reports, that the PDGFR-alpha in addition marks a pool of undifferentiated cells, which are able to differentiate into neuron

Immunohistochemical and DNA sequencing analysis on human mismatch repair gene MLH1 in cervical squamous cell carcinoma with LOH of this gene

BACKGROUND: The human MLH1 gene (hMLH1) is one of the DNA mismatch repair genes. Defects in these genes are believed to be the underlying cause of microsatellite instability (MSI). MSI has been demonstrated in many human cancers such as colon cancer and some female-specific tumors. The hMLH1 gene can be inactivated by genetic mutation or by hypermethylation of its promoter region, which often causes cessation of hMLH1 protein production. We were prompted by our previous finding of 43% of cervical cancers and their precursors with a loss of heterozygosity (LOH) of the hMLH1 gene to investigate whether it is inactivated during the carcinogenesis of cervical cancer. MATERIALS AND METHODS: hMLH1 protein production was assessed by immunohistochemistry, and nucleotide sequence analysis were performed on all exons of the hMLH1 gene. RESULTS: In 11 cases of invasive cervical cancer, among which 7 had LOH of the hMLH1 gene, immunohistochemistry provided no evidence for cessation of hMLH1 protein production. In addition, no mutations were found in any of the 19 hMLH1 gene exons. CONCLUSIONS: The activity of hMLH1 gene might not be disturbed in the development of cervical cancer although a proportion of the cases had lost one of its hMLH1 gene copie