Metabotropic Glutamate Receptors Protect Oligodendrocytes from Acute Ischemia in the Mouse Optic Nerve.

Studies by Bruce Ransom and colleagues have made a major contribution to show that white matter is susceptible to ischemia/hypoxia. White matter contains axons and the glia that support them, notably myelinating oligodendrocytes, which are highly vulnerable to ischemic-hypoxic damage. Previous studies have shown that metabotropic GluRs (mGluRs) are cytoprotective for oligodendrocyte precursor cells and immature oligodendrocytes, but their potential role in adult white matter was unresolved. Here, we report that group 1 mGluR1/5 and group 2 mGluR3 subunits are expressed in optic nerves from mice aged postnatal day (P)8-12 and P30-35. We demonstrate that activation of group 1 mGluR protects oligodendrocytes against oxygen-glucose deprivation (OGD) in developing and young adult optic nerves. In contrast, group 2 mGluR are shown to be protective for oligodendrocytes against OGD in postnatal but not young adult optic nerves. The cytoprotective effect of group 1 mGluR requires activation of PKC, whilst group 2 mGluR are dependent on negatively regulating adenylyl cyclase and cAMP. Our results identify a role for mGluR in limiting injury of oligodendrocytes in developing and young adult white matter, which may be useful for protecting oligodendrocytes in neuropathologies involving excitoxicity and ischemia/hypoxia

Caenorhabditis elegans Myotubularin MTM-1 Negatively Regulates the Engulfment of Apoptotic Cells

During programmed cell death, apoptotic cells are recognized and rapidly engulfed by phagocytes. Although a number of genes have been identified that promote cell corpse engulfment, it is not well understood how phagocytosis of apoptotic cells is negatively regulated. Here we have identified Caenorhabditis elegans myotubularin MTM-1 as a negative regulator of cell corpse engulfment. Myotubularins (MTMs) constitute a large, highly conserved family of lipid phosphatases. MTM gene mutations are associated with various human diseases, but the cellular functions of MTM proteins are not clearly defined. We found that inactivation of MTM-1 caused significant reduction in cell corpses in strong loss-of-function mutants of ced-1, ced-6, ced-7, and ced-2, but not in animals deficient in the ced-5, ced-12, or ced-10 genes. In contrast, overexpression of MTM-1 resulted in accumulation of cell corpses. This effect is dependent on the lipid phosphatase activity of MTM-1. We show that loss of mtm-1 function accelerates the clearance of cell corpses by promoting their internalization. Importantly, the reduction of cell corpses caused by mtm-1 RNAi not only requires the activities of CED-5, CED-12, and CED-10, but also needs the functions of the phosphatidylinositol 3-kinases (PI3Ks) VPS-34 and PIKI-1. We found that MTM-1 localizes to the plasma membrane in several known engulfing cell types and may modulate the level of phosphatidylinositol 3-phosphate (PtdIns(3)P) in vivo. We propose that MTM-1 negatively regulates cell corpse engulfment through the CED-5/CED-12/CED-10 module by dephosphorylating PtdIns(3)P on the plasma membrane

Characterisation and expression analysis of the Atlantic halibut (Hippoglossus hippoglossus L.) cytokines: IL-1β, IL-6, IL-11, IL-12β and IFNγ

Genes encoding the five Atlantic halibut (Hippoglossus hippoglossus L.) cytokines; interleukin (IL)-1β, IL-6, IL-11b, IL-12βc, and interferon (IFN) γ, were cloned and characterised at a molecular level. The genomic organisation of the halibut cytokine genes was similar to that seen in mammals and/or other fish species. Several mRNA instability motifs were found within the 3′-untranslated region (UTR) of all cytokine cDNA sequences. The putative cytokine protein sequences showed a low sequence identity with the corresponding homologues in mammals, avian and other fish species. Nevertheless, important structural features were presumably conserved such as the presence, or absence in the case of IL-1β, of a signal peptide, secondary structure and family signature motifs. The relative expression pattern of the cytokine genes was analyzed in several halibut organs, revealing a constitutive expression in both lymphoid and non-lymphoid organs. Interestingly, the gills showed a relatively high expression of IL-1β, IL-12βc and IFNγ. The real time RT-PCR data also showed that the mRNA level of IL-1β, IL-6, IL-12βc and IFNγ was high in the thymus, while IL-11b was relatively highly expressed in the posterior kidney and posterior gut. Moreover, the halibut brain showed a relatively high level of IL-6 transcripts. Anterior kidney leucocytes in vitro stimulated with imiquimod showed a significant increase in mRNA level of the five halibut cytokine genes. The sequence and characterisation data presented here will be useful for further investigation of both innate and adaptive immune responses in halibut, and be helpful in the design of vaccines for the control of various infectious diseases

ICAR: endoscopic skull‐base surgery

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Kaffillari - kahvilapyörän suunnittelu

Opinnäytetyön tavoitteena oli suunnitella polkupyörän päällä toimiva liikkuva kahvila eli kahvilapyörä turkulaissyntyisen yrityksen Kaffillarin käyttöön. Kahvilapyörän piti ulkoasullaan ilmentää Kaffillarin kahvintäyteistä maailmankuvaa sekä kyetä tarjoamaan edellytykset kahvin valmistamiseen itsenäisesti paikasta rippumatta. Suunnittelun tueksi vertailtiin tehtyjä tavarapyörärakennelmia sekä määriteltiin moodboardin avulla tunnelmaa, johon pyrittiin. Suunnittelun pohjaksi kartoitettiin ja määriteltiin mahdollisuuksia ja rajoituksia. Liikkuvaan kahvilatoimintaan tutustuttiin prototyyppien ja havainnoinnin kautta kahvilapyörän oikeassa ympäristössä. 3D-mallintaminen toimi suunnittelun päätyökaluna yhdessä hahmomallien kanssa, joilla näyttöruudun toisinaan harhaanjohtavia mittasuhteita tuotiin fyysiseen maailmaan. Rakenteiden tukevuutta testattiin ja tuotannollisuutta kehitettiin yhdessä valmistajan kanssa. Tuloksena saatiin toimiva prototyyppi, jota käytettiin Kaffillarin toiminnassa ensimmäisellä kesäkaudella sekä valmiit suunnitelmat Kaffillarin ensimmäiseen varsinaiseen tuotannolliseen versioon, jota jo rakennettiin opinnäytetyön loppuvaiheessa.The aim of the thesis was to design a fully functional café bicycle for a company in Turku called Kaffillari. The appearance of the café bicycle should represent the coffee filled worldview of Kaffillari and enable the best ground for making outstanding coffee self-reliantly anywhere. Benchmarking was conducted with already existing cargo bicycle creations and moodboard was used for defining the desired atmosphere. Functional possibilities and limitations were defined for the basis of the design. Prototypes were used to explore and observe the mobile café working in the real future environment of the café bicycle. 3D-modeling was the key tool for the entire project. It was used hand in hand with mock-ups to ensure the real life scale which sometimes may become blurry when only seen in the computer screen. The stability of the structure and producibility was developed with the manufacturer. The end results of the project were a working prototype which was used by Kaffillari for its first high season summer and ready plans for the actual first production model which is already under construction