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511.
In Parkinson's disease, brain dopamine neurons degenerate most prominently in the substantia nigra. Neurotrophic factors promote survival, differentiation and maintenance of neurons in developing and adult vertebrate nervous system. The most potent neurotrophic factor for dopamine neurons described so far is the glial-cell-line-derived neurotrophic factor (GDNF). Here we have identified a conserved dopamine neurotrophic factor (CDNF) as a trophic factor for dopamine neurons. CDNF, together with its previously described vertebrate and invertebrate homologue the mesencephalic-astrocyte-derived neurotrophic factor, is a secreted protein with eight conserved cysteine residues, predicting a unique protein fold and defining a new, evolutionarily conserved protein family. CDNF (Armetl1) is expressed in several tissues of mouse and human, including the mouse embryonic and postnatal brain. In vivo, CDNF prevented the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons in a rat experimental model of Parkinson's disease. A single injection of CDNF before 6-OHDA delivery into the striatum significantly reduced amphetamine-induced ipsilateral turning behaviour and almost completely rescued dopaminergic tyrosine-hydroxylase-positive cells in the substantia nigra. When administered four weeks after 6-OHDA, intrastriatal injection of CDNF was able to restore the dopaminergic function and prevent the degeneration of dopaminergic neurons in substantia nigra. Thus, CDNF was at least as efficient as GDNF in both experimental settings. Our results suggest that CDNF might be beneficial for the treatment of Parkinson's disease.  相似文献   
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One of the most important current scientific paradoxes is the economy with which nature uses genes. In all higher animals studied, we have found many fewer genes than we would have previously expected. The functional outputs of the eventual products of genes seem to be far more complex than the more restricted blueprint. In higher organisms, the functions of many proteins are modulated by post-translational modifications (PTMs). These alterations of amino-acid side chains lead to higher structural and functional protein diversity and are, therefore, a leading contender for an explanation for this seeming incongruity. Natural protein production methods typically produce PTM mixtures within which function is difficult to dissect or control. Until now it has not been possible to access pure mimics of complex PTMs. Here we report a chemical tagging approach that enables the attachment of multiple modifications to bacterially expressed (bare) protein scaffolds: this approach allows reconstitution of functionally effective mimics of higher organism PTMs. By attaching appropriate modifications at suitable distances in the widely-used LacZ reporter enzyme scaffold, we created protein probes that included sensitive systems for detection of mammalian brain inflammation and disease. Through target synthesis of the desired modification, chemistry provides a structural precision and an ability to retool with a chosen PTM in a manner not available to other approaches. In this way, combining chemical control of PTM with readily available protein scaffolds provides a systematic platform for creating probes of protein-PTM interactions. We therefore anticipate that this ability to build model systems will allow some of this gene product complexity to be dissected, with the aim of eventually being able to completely duplicate the patterns of a particular protein's PTMs from an in vivo assay into an in vitro system.  相似文献   
514.
Chirality is a fascinating phenomenon that can manifest itself in subtle ways, for example in biochemistry (in the observed single-handedness of biomolecules) and in particle physics (in the charge-parity violation of electroweak interactions). In condensed matter, magnetic materials can also display single-handed, or homochiral, spin structures. This may be caused by the Dzyaloshinskii-Moriya interaction, which arises from spin-orbit scattering of electrons in an inversion-asymmetric crystal field. This effect is typically irrelevant in bulk metals as their crystals are inversion symmetric. However, low-dimensional systems lack structural inversion symmetry, so that homochiral spin structures may occur. Here we report the observation of magnetic order of a specific chirality in a single atomic layer of manganese on a tungsten (110) substrate. Spin-polarized scanning tunnelling microscopy reveals that adjacent spins are not perfectly antiferromagnetic but slightly canted, resulting in a spin spiral structure with a period of about 12 nm. We show by quantitative theory that this chiral order is caused by the Dzyaloshinskii-Moriya interaction and leads to a left-rotating spin cycloid. Our findings confirm the significance of this interaction for magnets in reduced dimensions. Chirality in nanoscale magnets may play a crucial role in spintronic devices, where the spin rather than the charge of an electron is used for data transmission and manipulation. For instance, a spin-polarized current flowing through chiral magnetic structures will exert a spin-torque on the magnetic structure, causing a variety of excitations or manipulations of the magnetization and giving rise to microwave emission, magnetization switching, or magnetic motors.  相似文献   
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516.
Non-volcanic tremor driven by large transient shear stresses   总被引:2,自引:0,他引:2  
Non-impulsive seismic radiation or 'tremor' has long been observed at volcanoes and more recently around subduction zones. Although the number of observations of non-volcanic tremor is steadily increasing, the causative mechanism remains unclear. Some have attributed non-volcanic tremor to the movement of fluids, while its coincidence with geodetically observed slow-slip events at regular intervals has led others to consider slip on the plate interface as its cause. Low-frequency earthquakes in Japan, which are believed to make up at least part of non-volcanic tremor, have focal mechanisms and locations that are consistent with tremor being generated by shear slip on the subduction interface. In Cascadia, however, tremor locations appear to be more distributed in depth than in Japan, making them harder to reconcile with a plate interface shear-slip model. Here we identify bursts of tremor that radiated from the Cascadia subduction zone near Vancouver Island, Canada, during the strongest shaking from the moment magnitude M(w) = 7.8, 2002 Denali, Alaska, earthquake. Tremor occurs when the Love wave displacements are to the southwest (the direction of plate convergence of the overriding plate), implying that the Love waves trigger the tremor. We show that these displacements correspond to shear stresses of approximately 40 kPa on the plate interface, which suggests that the effective stress on the plate interface is very low. These observations indicate that tremor and possibly slow slip can be instantaneously induced by shear stress increases on the subduction interface-effectively a frictional failure response to the driving stress.  相似文献   
517.
A fundamental question in nuclear physics is what combinations of neutrons and protons can make up a nucleus. Many hundreds of exotic neutron-rich isotopes have never been observed; the limit of how many neutrons a given number of protons can bind is unknown for all but the lightest elements, owing to the delicate interplay between single particle and collective quantum effects in the nucleus. This limit, known as the neutron drip line, provides a benchmark for models of the atomic nucleus. Here we report a significant advance in the determination of this limit: the discovery of two new neutron-rich isotopes--40Mg and 42Al--that are predicted to be drip-line nuclei. In the past, several attempts to observe 40Mg were unsuccessful; moreover, the observation of 42Al provides an experimental indication that the neutron drip line may be located further towards heavier isotopes in this mass region than is currently believed. In stable nuclei, attractive pairing forces enhance the stability of isotopes with even numbers of protons and neutrons. In contrast, the present work shows that nuclei at the drip line gain stability from an unpaired proton, which narrows the shell gaps and provides the opportunity to bind many more neutrons.  相似文献   
518.
Fryxell JM  Mosser A  Sinclair AR  Packer C 《Nature》2007,449(7165):1041-1043
Theoretical ecology is largely founded on the principle of mass action, in which uncoordinated populations of predators and prey move in a random and well-mixed fashion across a featureless landscape. The conceptual core of this body of theory is the functional response, predicting the rate of prey consumption by individual predators as a function of predator and/or prey densities. This assumption is seriously violated in many ecosystems in which predators and/or prey form social groups. Here we develop a new set of group-dependent functional responses to consider the ecological implications of sociality and apply the model to the Serengeti ecosystem. All of the prey species typically captured by Serengeti lions (Panthera leo) are gregarious, exhibiting nonlinear relationships between prey-group density and population density. The observed patterns of group formation profoundly reduce food intake rates below the levels expected under random mixing, having as strong an impact on intake rates as the seasonal migratory behaviour of the herbivores. A dynamical system model parameterized for the Serengeti ecosystem (using wildebeest (Connochaetes taurinus) as a well-studied example) shows that grouping strongly stabilizes interactions between lions and wildebeest. Our results suggest that social groups rather than individuals are the basic building blocks around which predator-prey interactions should be modelled and that group formation may provide the underlying stability of many ecosystems.  相似文献   
519.
520.
South-polar features on Venus similar to those near the north pole   总被引:1,自引:0,他引:1  
Venus has no seasons, slow rotation and a very massive atmosphere, which is mainly carbon dioxide with clouds primarily of sulphuric acid droplets. Infrared observations by previous missions to Venus revealed a bright 'dipole' feature surrounded by a cold 'collar' at its north pole. The polar dipole is a 'double-eye' feature at the centre of a vast vortex that rotates around the pole, and is possibly associated with rapid downwelling. The polar cold collar is a wide, shallow river of cold air that circulates around the polar vortex. One outstanding question has been whether the global circulation was symmetric, such that a dipole feature existed at the south pole. Here we report observations of Venus' south-polar region, where we have seen clouds with morphology much like those around the north pole, but rotating somewhat faster than the northern dipole. The vortex may extend down to the lower cloud layers that lie at about 50 km height and perhaps deeper. The spectroscopic properties of the clouds around the south pole are compatible with a sulphuric acid composition.  相似文献   
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