Experimentelle Untersuchungen zur Pathogenese des Kontaktekzems

Summary The mechanism of development of contact eczema, which might serve as a working hypothesis for other clinical forms of eczema, is not yet fully understood. An attempt was made, by means of sensitization with Dinitrochlorobenzol in guinea-pigs, to determine the time and place of the pathogenetic phenomena, as well as the organs and tissues affected. Experiments on skin-explants permitted the separate investigation of the different systems, i.e. the blood, nerve and lymphe, presumed to be involved.It was ascertained that the lymphatic system is absolutely essential for the development of sensitization, and the blood path for its generalized spread.

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Ausführliche Publikation erscheint demnächst in Dermatologica, Basel.     

Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin

Membrane phosphoinositides control a variety of cellular processes through the recruitment and/or regulation of cytosolic proteins. One mechanism ensuring spatial specificity in phosphoinositide signalling is the targeting of enzymes that mediate their metabolism to specific subcellular sites. Phosphatidylinositol phosphate kinase type 1 gamma (PtdInsPKI gamma) is a phosphatidylinositol-4-phosphate 5-kinase that is expressed at high levels in brain, and is concentrated at synapses. Here we show that the predominant brain splice variant of PtdInsPKI gamma (PtdInsPKI gamma-90) binds, by means of a short carboxy-terminal peptide, to the FERM domain of talin, and is strongly activated by this interaction. Talin, a principal component of focal adhesion plaques, is also present at synapses. PtdInsPKI gamma-90 is expressed in non-neuronal cells, albeit at much lower levels than in neurons, and is concentrated at focal adhesion plaques, where phosphatidylinositol-4,5-bisphosphate has an important regulatory role. Overexpression of PtdInsPKI gamma-90, or expression of its C-terminal domain, disrupts focal adhesion plaques, probably by local disruption of normal phosphoinositide balance. These findings define an interaction that has a regulatory role in cell adhesion and suggest new similarities between molecular interactions underlying synaptic junctions and general mechanisms of cell adhesion.     

SNX3-dependent regulation of epidermal growth factor receptor (EGFR) trafficking and degradation by aspirin in epidermoid carcinoma (A-431) cells

Since being introduced globally as aspirin in 1899, acetylsalicylic acid has been widely used as an analgesic, anti-inflammation, anti-pyretic, and anti-thrombotic drug for years. Aspirin had been reported to down-regulate surface expression of CD40, CD80, CD86, and MHCII in myeloid dendritic cells (DC), which played essential roles in regulating the immune system. We hypothesized that the down-regulation of these surface membrane proteins is partly due to the ability of aspirin in regulating trafficking/sorting of endocytosed surface membrane proteins. By using an established epidermoid carcinoma cell line (A-431), which overexpresses the epidermal growth factor receptor (EGFR) and transferrin receptor (TfnR), we show that aspirin (1) reduces cell surface expression of EGFR and (2) accumulates endocytosed-EGFR and -TfnR in the early/sorting endosome (ESE). Further elucidation of the mechanism suggests that aspirin enhances recruitment of SNX3 and SNX5 to membranes and consistently, both SNX3 and SNX5 play essential roles in the aspirin-mediated accumulation of endocytosed-TfnR at the ESE. This study sheds light on how aspirin may down-regulate surface expression of EGFR by inhibiting/delaying the exit of endocytosed-EGFR from the ESE and recycling of endocytosed-EGFR back to the cell surface.     

低碳锰钢中周期性带状组织

用扫描电镜和电子探针研究了低碳锰钢中的周期性带状组织，结果表明，在全部研究用钢中，钢锭经热轧后均出现这种组织，其严重程度随钢的成分而异，并随坯带加工顺序而增加，带状组织与锰的显微偏析等因素有关，适当的调整碳锰以及形成模跨铁素体带的转变产物可降低带状组织的严重程度。     

A simple method for the collection of leucocytes from rat blood

Zusammenfassung Blutleukozyten von Ratten wurden mit menschlichem (normalem) Serum behandelt. Die Viabilität dieser Präparationen konnte dadurch demonstriert werden, dass die Zellen durch Phytohemagglutinin in «blast» Formen umgewandelt wurden.     

Impaired PtdIns(4,5)P2 synthesis in nerve terminals produces defects in synaptic vesicle trafficking

Phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) has an important function in cell regulation both as a precursor of second messenger molecules and by means of its direct interactions with cytosolic and membrane proteins. Biochemical studies have suggested a role for PtdIns(4,5)P2 in clathrin coat dynamics, and defects in its dephosphorylation at the synapse produce an accumulation of coated endocytic intermediates. However, the involvement of PtdIns(4,5)P2 in synaptic vesicle exocytosis remains unclear. Here, we show that decreased levels of PtdIns(4,5)P2 in the brain and an impairment of its depolarization-dependent synthesis in nerve terminals lead to early postnatal lethality and synaptic defects in mice. These include decreased frequency of miniature currents, enhanced synaptic depression, a smaller readily releasable pool of vesicles, delayed endocytosis and slower recycling kinetics. Our results demonstrate a critical role for PtdIns(4,5)P2 synthesis in the regulation of multiple steps of the synaptic vesicle cycle.     

The plastic deformation of iron at pressures of the Earth's inner core

Soon after the discovery of seismic anisotropy in the Earth's inner core, it was suggested that crystal alignment attained during deformation might be responsible. Since then, several other mechanisms have been proposed to account for the observed anisotropy, but the lack of deformation experiments performed at the extreme pressure conditions corresponding to the solid inner core has limited our ability to determine which deformation mechanism applies to this region of the Earth. Here we determine directly the elastic and plastic deformation mechanism of iron at pressures of the Earth's core, from synchrotron X-ray diffraction measurements of iron, under imposed axial stress, in diamond-anvil cells. The epsilon-iron (hexagonally close packed) crystals display strong preferred orientation, with c-axes parallel to the axis of the diamond-anvil cell. Polycrystal plasticity theory predicts an alignment of c-axes parallel to the compression direction as a result of basal slip, if basal slip is either the primary or a secondary slip system. The experiments provide direct observations of deformation mechanisms that occur in the Earth's inner core, and introduce a method for investigating, within the laboratory, the rheology of materials at extreme pressures.     

Texturing of the Earth's inner core by Maxwell stresses.

Elastic anisotropy in the Earth's inner core has been attributed to a preferred lattice orientation, which may be acquired during solidification of the inner core or developed subsequent to solidification as a result of plastic deformation. But solidification texturing alone cannot explain the observed depth dependence of anisotropy, and previous suggestions for possible deformation processes have all relied on radial flow, which is inhibited by thermal and chemical stratification. Here we investigate the development of anisotropy as the inner core deforms plastically under the influence of electromagnetic (Maxwell) shear stresses. We estimate the flow caused by a representative magnetic field using polycrystal plasticity simulations for epsilon-iron, where the imposed deformation is accommodated by basal and prismatic slip. We find that individual grains in an initially random polycrystal become preferentially oriented with their c axes parallel to the equatorial plane. This pattern is accentuated if deformation is accompanied by recrystallization. Using the single-crystal elastic properties of epsilon-iron at core pressure and temperature, we average over the simulated orientation distribution to obtain a pattern of elastic anisotropy which is similar to that observed seismologically.