Температурное поле в кристалле иттрий-алюминиевого граната при двухстадийном выращивании

Установлено существование оптимального значения теплопроводности, при котором достигается наиболее равномерное распределение модуля температурного градиента на фронте кристаллизации

Visualization of Active Glucocerebrosidase in Rodent Brain with High Spatial Resolution following In Situ Labeling with Fluorescent Activity Based Probes

Bio-organic SynthesisMedical Biochemistr

Macrophages in inflammatory multiple sclerosis lesions have an intermediate activation status

BACKGROUND: Macrophages play a dual role in multiple sclerosis (MS) pathology. They can exert neuroprotective and growth promoting effects but also contribute to tissue damage by production of inflammatory mediators. The effector function of macrophages is determined by the way they are activated. Stimulation of monocyte-derived macrophages in vitro with interferon-γ and lipopolysaccharide results in classically activated (CA/M1) macrophages, and activation with interleukin 4 induces alternatively activated (AA/M2) macrophages. METHODS: For this study, the expression of a panel of typical M1 and M2 markers on human monocyte derived M1 and M2 macrophages was analyzed using flow cytometry. This revealed that CD40 and mannose receptor (MR) were the most distinctive markers for human M1 and M2 macrophages, respectively. Using a panel of M1 and M2 markers we next examined the activation status of macrophages/microglia in MS lesions, normal appearing white matter and healthy control samples. RESULTS: Our data show that M1 markers, including CD40, CD86, CD64 and CD32 were abundantly expressed by microglia in normal appearing white matter and by activated microglia and macrophages throughout active demyelinating MS lesions. M2 markers, such as MR and CD163 were expressed by myelin-laden macrophages in active lesions and perivascular macrophages. Double staining with anti-CD40 and anti-MR revealed that approximately 70% of the CD40-positive macrophages in MS lesions also expressed MR, indicating that the majority of infiltrating macrophages and activated microglial cells display an intermediate activation status. CONCLUSIONS: Our findings show that, although macrophages in active MS lesions predominantly display M1 characteristics, a major subset of macrophages have an intermediate activation status

The astrocytic cytoskeleton: Unravelling the role of GFAPδ

Glial fibrillary acidic protein (GFAP) is the main intermediate filament (IF) in astrocytes. The GFAP gene can give rise to different splice isoforms, of which GFAPα is the canonical isoform. GFAPδ is an isoform which in the human SVZ is expressed in specific astrocytes; the adult neural stem cells. Expression differences between these isoforms lead to the hypothesis that GFAPδ may play a functional role in specific subtypes of astrocytes. In overexpression studies, we investigated the effects of GFAP isoform expression on the IF network and functional features of neurogenic astrocytes. We confirmed that GFAPδ expression collapses the GFAP network which altered cell morphology but not motility or proliferation rate. Since there is a constant exchange of proteins from an insoluble form to soluble form in the cytoplasm we assessed the dynamic properties of GFAPα and GFAPδ. The exchange rate of GFAPδ was lower compared to GFAPα and the exchange rates of both isoforms were decreased in a collapsed IF network. A role for GFAPδ in both cell motility and cell adhesion was found in experiments where the endogenous GFAP isoform levels were altered with specific isoform knockdown. Moreover, the expression levels of integrins, plectin and Laminin1a were regulated in cells with a high GFAPδ:GFAPɑ ratio. The molecular mechanisms underlying the influence of GFAPδ on cell motility, adhesion, and extracellular matrix (ECM) related protein expression is still unknown. Future research should focus on the link between the IF network, the ECM, integrin signalling and the role of GFAPδ therein