GluK2-mediated excitability within the superficial layers of the entorhinal cortex

11 pages, 6 pages.-- PMID: 19440371 [PubMed].-- PMCID: PMC2679203.-- Supporting information available: Figure S1, doi:10.1371/journal.pone.0005576.s001 (0.63 MB TIF).Recent analysis of genetically modified mice deficient in different kainate receptor (KAR) subunits have strongly pointed to a role of the GluK2 subunit, mediating the vulnerability of the brain towards seizures. Research concerning this issue has focused mainly on the hippocampus. However, several studies point to a potential role of other parts of the hippocampal formation, in particular the entorhinal cortex, in the development of epileptic seizures. There is extensive cell death after such seizures in layer III of the medial entorhinal cortex (LIII mEC), making this region of special interest for investigation into related pathological conditions. We therefore characterized KAR mediated currents in LIII mEC pyramidal neurons by several different approaches. Using patch-clamp technique, in combination with glutamate uncaging in horizontal brain slices, we show that LIII mEC neurons exhibit KAR currents. Use of genetically modified mice reveal that these currents are mediated by GluK2 containing KARs. The IV curve indicates the predominant presence of a Ca2+ impermeable and edited form of the KAR. Finally, we show that GluK2 containing kainate receptors are essential for kainate-induced gamma oscillations within the entorhinal cortex.This study has been funded by the SFB 665 grant and P.B. is a member of and funded by the GRK 1123.Peer reviewe

The SCLtTAxBCR-ABL transgenic mouse model closely reflects the differential effects of dasatinib on normal and malignant hematopoiesis in chronic phase-CML patients

The second generation tyrosine kinase inhibitor (TKI) dasatinib is a clinically approved drug for chronic myeloid leukemia (CML) as well as Ph+ acute lymphoblastic leukemia. In addition to its antileukemic effects, dasatinib was shown to impact on normal hematopoiesis and cells of the immune system. Due to the fact that the murine in vivo studies so far have not been performed in a chronic-phase CML model under steady-state conditions, our aim was to study the hematopoietic effects of dasatinib (20 mg/kg p.o.) in BCR-ABL expressing SCLtTAxBCR-ABL double transgenic (dtg) mice. Dasatinib robustly antagonized the CML phenotype in vivo in our transgenic mouse model, and this effect included both mature and immature cell populations. However, similar to patients with CML, the fraction of Lin(neg)Sca-1(+)KIT(+)CD48(neg)CD150(+) hematopoietic stem cells was not reduced by dasatinib treatment, suggesting that these cells are not oncogene-addicted. Moreover, we observed differential effects of dasatinib in these animals as compared to wild-type (wt) animals: while granulocytes were significantly reduced in dtg animals, they were increased in wt mice. And Ter119(+) erythrocytic and B220(+) B cells were increased in dtg mice but decreased in wt mice. Finally, while dasatinib induced a shift from CD49b/NK1.1 positive NK cells from the bone marrow to the spleen in wt animals, there was no change in dtg mice. In conclusion, the present mouse model provides a useful tool to study mechanisms of TKI resistance and dasatinib-associated beneficial effects and adverse events.Peer reviewe

ДО ПИТАННЯ ПРО ЄДНІСТЬ ДВОРЯНСЬКОЇ ВЕРСТВИ (НА ПРИКЛАДІ КАТЕРИНОСЛАВСЬКОГО ДВОРЯНСТВА)

Встатті аналізуються внутрішньокорпоративні відносинидворянської верстви на прикладі Катеринославської губерніїCorporate Relationships ofNobility inKaterinoslavRegion are analyzed in this articl

Современные тенденции деятельности страховых компаний РФ по автострахованию (на примере ООО СБ «Коместра-Страхование»)

Объект исследования в данной работе рынок автострахования России. Целью работы было: изучить рынок автострахования России на примере компании "Коместра страхование".Основными задачами было:изучить сущность и структуру страхового рынка,дать характеристику участников страхового рынка,проанализировать состояние российского страхового рынка в части его динамики, масштабов, уровня оказываемых страховых услуг. Данная тема актуальна, так как множество различных компаний открываются и стараются конкурировать с уже устоявшимися компаниями. В данной работе предложен ряд решений которые могут увеличить уровень конкурентоспособности компании в целом.The object of research in this work is the car insurance market of Russia. The aim of the work was: to study the Russian auto insurance market using the example of the company "Comestra Insurance". The main tasks were: to study the nature and structure of the insurance market, to characterize the participants of the insurance market, to analyze the state of the Russian insurance market in terms of its dynamics, scale, level of insurance services provided. This topic is relevant, as many different companies open up and try to compete with already established companies. In this work, a number of solutions are proposed that can increase the level of competitiveness of the company as a whole