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11.
Presynaptic inhibition at mammalian peripheral synapse?   总被引:5,自引:0,他引:5  
G D Hirst  H C McKirdy 《Nature》1974,250(465):430-431
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Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries. Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present. There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation. Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous. There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-d-proline compound CPHPC, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis.  相似文献   
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Whitney D  Westwood DA  Goodale MA 《Nature》2003,423(6942):869-873
One of the most important functions of vision is to direct actions to objects. However, every time that vision is used to guide an action, retinal motion signals are produced by the movement of the eye and head as the person looks at the object or by the motion of other objects in the scene. To reach for the object accurately, the visuomotor system must separate information about the position of the stationary target from background retinal motion signals-a long-standing problem that is poorly understood. Here we show that the visuomotor system does not distinguish between these two information sources: when observers made fast reaching movements to a briefly presented stationary target, their hand shifted in a direction consistent with the motion of a distant and unrelated stimulus, a result contrary to most other findings. This can be seen early in the hand's trajectory (approximately 120 ms) and occurs continuously from programming of the movement through to its execution. The visuomotor system might make use of the motion signals arising from eye and head movements to update the positions of targets rapidly and redirect the hand to compensate for body movements.  相似文献   
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The intergalactic medium was not completely reionized until approximately a billion years after the Big Bang, as revealed by observations of quasars with redshifts of less than 6.5. It has been difficult to probe to higher redshifts, however, because quasars have historically been identified in optical surveys, which are insensitive to sources at redshifts exceeding 6.5. Here we report observations of a quasar (ULAS?J112001.48+064124.3) at a redshift of 7.085, which is 0.77 billion years after the Big Bang. ULAS?J1120+0641 has a luminosity of 6.3 × 10(13)L(⊙) and hosts a black hole with a mass of 2 × 10(9)M(⊙) (where L(⊙) and M(⊙) are the luminosity and mass of the Sun). The measured radius of the ionized near zone around ULAS?J1120+0641 is 1.9?megaparsecs, a factor of three smaller than is typical for quasars at redshifts between 6.0 and 6.4. The near-zone transmission profile is consistent with a Lyα damping wing, suggesting that the neutral fraction of the intergalactic medium in front of ULAS?J1120+0641 exceeded 0.1.  相似文献   
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Understanding trends and changes in the circumstances of couples separated by death is important for policy initiatives to reduce vulnerabilities associated with end of life care and for those who live on. This article uses widow(er)hood statistics and census data from the Office for National Statistics Longitudinal Study. It examines changes in couples' living arrangements and households at four successive censuses from 1971 to 2001 and shows how these differ by age and gender on the death of a spouse or partner. Findings draw attention to the effects of ageing and mortality improvements as well as wider social and economic trends in family and household formation, residential independence in older age, and policy developments on long-term care provision for older people.  相似文献   
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