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61.
We present a transmission electron microscopy (TEM) investigation of a coupled cobalt and silver nanoparticle system. A plan view in situ lift-out method for preparing samples for TEM using the focused ion beam (FIB) microscope was used. This technique is used to prepare high quality TEM samples with site specificity in a short time and with a high success rate. We demonstrate the ability of the plan view sample preparation technique to provide information about an ordered system of nanoparticles which could not be observed using standard FIB cross sectioning of the sample. High resolution TEM and energy dispersive X-ray spectroscopy mapping of both cross sectional and plan view samples are presented, clearly showing the significant benefit of plan view TEM analysis for certain samples  相似文献   
62.
Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder resulting from motor neuron death. Approximately 10% of cases are familial (FALS), typically with a dominant inheritance mode. Despite numerous advances in recent years, nearly 50% of FALS cases have unknown genetic aetiology. Here we show that mutations within the profilin 1 (PFN1) gene can cause FALS. PFN1 is crucial for the conversion of monomeric (G)-actin to filamentous (F)-actin. Exome sequencing of two large ALS families showed different mutations within the PFN1 gene. Further sequence analysis identified 4 mutations in 7 out of 274 FALS cases. Cells expressing PFN1 mutants contain ubiquitinated, insoluble aggregates that in many cases contain the ALS-associated protein TDP-43. PFN1 mutants also display decreased bound actin levels and can inhibit axon outgrowth. Furthermore, primary motor neurons expressing mutant PFN1 display smaller growth cones with a reduced F/G-actin ratio. These observations further document that cytoskeletal pathway alterations contribute to ALS pathogenesis.  相似文献   
63.
C R Artalejo  S Rossie  R L Perlman  A P Fox 《Nature》1992,358(6381):63-66
Bovine chromaffin cells have two components of whole-cell Ca2+ current: 'standard' Ca2+ currents that are activated by brief depolarizations, and 'facilitation' Ca2+ currents, which are normally quiescent but can be activated by large pre-depolarizations or by repetitive depolarizations to physiological potentials. The activation of protein kinase A can also stimulate Ca2+ current facilitation, indicating that phosphorylation can play a part in facilitation. Here we investigate the role of protein phosphorylation in the recruitment of facilitation Ca2+ currents by pre-pulses or repetitive depolarizations. We find that recruitment of facilitation by depolarization is a rapid first-order process which is suppressed by inhibitors of protein phosphorylation or by injection of phosphatase 2A into cells. Recruitment of facilitation Ca2+ current by voltage is normally reversible but phosphatase inhibitors render it irreversible. Our results indicate that recruitment of these Ca2+ currents by pre-pulses or repetitive depolarizations involves voltage-dependent phosphorylation of the facilitation Ca2+ channel or a closely associated regulatory protein. Voltage-dependent phosphorylation may therefore be a mechanism by which membrane potential can modulate ion channel activity.  相似文献   
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R Blake  R Fox 《Nature》1974,249(456):488-490
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66.
Summary Monochromatic Ag-Ka-radiation decreased irreversibly the peak sodium current in nodes of Ranvier. This decrease occurs only with a delay of about 1000 sec after a threshold dose of about 8 kR has been reached. Potassium current and resting potential are practically not affected.Dedicated to Prof. Dr Dres h.c. Robert Stämpfli on the occasion of his 65th birthday.Supported by Deutsche Forschungsgemeinschaft, SFB 38, Membranforschung Bonn-Bad Godesberg.  相似文献   
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Faraday demonstrated electromagnetic induction in 1831 using an iron ring wound with two wire coils; on interrupting battery current in one coil, momentary currents arose in the other. Between Faraday's ring and the induction coil, coiled instruments developed via meandering paths. This paper explores the opening phase of that work in the late 1830s, as the iron core, primary wire coil, and secondary wire coil were researched and differentiated. ‘Working knowledge’ (defined by Baird) gained with materials and phenomena was crucial to innovations. To understand these material-based interactions, I experimented with hand-wound coils, along with examining historical texts, drawings, and artefacts. My experience recovered the historical dead-end of two-wire coils and ensuing work with long-coiled single conductors initiated by Faraday and Henry. The shock and spark heightened in these coils provided feedback to the many instrumental configurations tested by Page, Callan, Sturgeon, Bachhoffner, and others. The continuous conductor differentiated into two segments soldered together: a thick short wire carrying battery current and a long thin wire for elevating shocks (voltage). The joined wires eventually separated, yet their transitional connection documents belief that the induced effects depend on continuity. These coiled instruments, with their intertwined histories, show experimental work and understandings in the process of developing. Seeing the nonlinear paths by which these instruments developed deepens our understanding of historical experiences, and of how people learn.  相似文献   
70.
1 Biology for the 21st Century In a recent article in the New York Times (3/23/05), reporting on yet another upset to received views of the ways in which cells make use of their DNA, a prominent geneticist is quoted as remarking, "biologists have gotten used to the unexpected." Indeed, they have, as indeed, they have had to. Over the last few years, our understanding of molecular and developmental genetics has mutated dramatically in response to ever more complex analyses of ever more abundant and more complex data.  相似文献   
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