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Nitration in neurodegeneration: deciphering the "Hows" "nYs"   总被引:3,自引:0,他引:3  
Reynolds MR  Berry RW  Binder LI 《Biochemistry》2007,46(25):7325-7336
Recent literature has ushered in a new awareness of the diverse post-translational events that can influence protein folding and function. Among these modifications, protein nitration is thought to play a critical role in the onset and progression of several neurodegenerative diseases. While previously considered a late-stage epiphenomenon, nitration of protein tyrosine residues appears to be an early event in the lesions of amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. The advent of highly specific biochemical and immunological detection methods reveals that nitration occurs in vivo with biological selectively and site specificity. In fact, nitration of only a single Tyr residue is often sufficient to induce profound changes in the activity of catalytic proteins and the three-dimensional conformation of structural proteins. Presumably, nitration modifies protein function by altering the hydrophobicity, hydrogen bonding, and electrostatic properties within the targeted protein. Most importantly, however, nitrative injury may represent a unifying mechanism that explains how genetic and environmental causes of neurological disease manifest a singular phenotype. In this review and synthesis, we first examine the pathways of protein nitration in biological systems and the factors that influence site-directed nitration. Subsequently, we turn our attention to the structural implications of site-specific nitration and how it affects the function of several neurodegeneration-related proteins. These proteins include Mn superoxide dismutase and neurofilament light subunit in amyotrophic lateral sclerosis, alpha-synuclein and tyrosine hydroxylase in Parkinson's disease, and tau in Alzheimer's disease.  相似文献   

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From "Rights" to "Ritual": AIDS Activism in South Africa   总被引:1,自引:0,他引:1  
In this article, I investigate how the moral politics of HIV/AIDS activism in South Africa is contributing toward new forms of citizenship that are concerned with both rights-based struggles and with creating collectively shared meanings of the extreme experiences of illness and stigmatization of individual HIV/AIDS sufferers. I argue that it is precisely the extremity of the "near death" experiences of full-blown AIDS, and the profound stigma and "social death" associated with the later stages of the disease, that produce the conditions for HIV/AIDS survivors' commitment to "new life" and social activism. It is the activist mediation and retelling of these traumatic experiences that facilitates HIV/AIDS activist commitment and grassroots mobilization. It is also the profound negativity of stigma and social death that animates the activist's construction of a new positive HIV-positive identity and understanding of what it means to be a citizen–activist and member of a social movement.  相似文献   

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In this article, I draw on anthropological and feminist scholarship on the body and the nature/culture divide as a framework for understanding the place of surrogate mothers in a conceptual ideology that connects motherhood with nature. I explore links between the medicalization of childbirth in Israel and the personal agency of surrogate mothers as relayed through interviews. Taking the patriarchal context of the Israeli surrogacy law of 1996 into consideration, I underscore surrogates' imaginative use of medical metaphors as tools for the subversion of surrogacy's threatening social connotations. By redefining the surrogate body as "artificial" and locating "nature" in the commissioning mother's body, surrogates adopt medical rhetoric to transform surrogacy from a transgressive act into an alternative route toward achieving normative Israeli national reproductive goals.  相似文献   

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This paper details a methodology which, when applied to magnetoencephalography (MEG) data, is capable of measuring the spatio-temporal dynamics of ‘disorder’ in the human brain. Our method, which is based upon signal entropy, shows that spatially separate brain regions (or networks) generate temporally independent entropy time-courses. These time-courses are modulated by cognitive tasks, with an increase in local neural processing characterised by localised and transient increases in entropy in the neural signal. We explore the relationship between entropy and the more established time-frequency decomposition methods, which elucidate the temporal evolution of neural oscillations. We observe a direct but complex relationship between entropy and oscillatory amplitude, which suggests that these metrics are complementary. Finally, we provide a demonstration of the clinical utility of our method, using it to shed light on aberrant neurophysiological processing in schizophrenia. We demonstrate significantly increased task induced entropy change in patients (compared to controls) in multiple brain regions, including a cingulo-insula network, bilateral insula cortices and a right fronto-parietal network. These findings demonstrate potential clinical utility for our method and support a recent hypothesis that schizophrenia can be characterised by abnormalities in the salience network (a well characterised distributed network comprising bilateral insula and cingulate cortices).  相似文献   

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Singer 《Ecology letters》2000,3(3):159-162
Ecologists and evolutionary biologists have a common interest in plant–insect interactions. Ecologists develop terminology describing patterns of association between plants and insects, while evolutionary biologists use the same words to denote potentially heritable traits of individuals. Use of the same terms to describe both traits of the interaction and traits of the organisms hinders communication. An example is "preference", often used by ecologists to denote properties of the plant–insect interaction and by behavioural or evolutionary biologists to denote insect traits. The existing term "electivity" could be incorporated into the lexicon of plant–insect interactions to supplant the ecological use of "preference". The term "preference" would then denote a behavioural trait of the insect. The mirror-image trait of the plant would be "acceptability". This could be a step towards a common terminology that would be usable by both ecologists and evolutionists.  相似文献   

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Italy's "Southern Question": Orientalism in One Country. Jane Schneider. ed. New York: Berg, 1998. 299 pp.  相似文献   

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Protists provide the opportunity to integrate analyses from a low (molecular) to a high (organism) level of complexity within a broad evolutionary framework. The perpectives they offer in the cytoskeletal field are discussed with respect to emerging concepts of cellular biology.  相似文献   

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Although Georgia is known for its wines, industrial production of beer far outstrips industrial wine production for local markets: wine consumption occurs in ritual contexts in which new wine, typically purchased from peasant producers, is preferred; bottled, aged wines are primarily for exports. Beer, therefore, is a key area in which industrial production for indigenous consumers has been elaborated. Such goods are packaged and presented as being both ecologically "pure" and following "traditional" methods, often referencing "ethnographic" materials about traditional life in brand images, even as they proclaim their reliance on Western technologies.  相似文献   

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In 1846, burdened by insecurity and self-doubt, and having been convinced that he needed to study some group of organisms closely, Darwin embarked on an eight-year odyssey in the protean and perplexing world of barnacles. At the time, he was searching for evidence in support of his theory of evolution by natural selection. In the course of his long study of barnacles, however, he was not just validating his preexisting theoretical system, but was also modifying his views on such fundamental aspects as the universality of individual variation, which is the focus of this paper. According to this notion, the members of any population of living things are expected to exhibit sufficient differences from one another for natural selection to operate. By emphasizing the theoretical value of the barnacle project, my analysis contributes to the historiographic tradition which highlights the significance of the period between the first comprehensive formulation of the theory of evolution by natural selection in 1844 and its urgent publication in the late 1850s. In the course of these years, Darwin's theory was not just accumulating empirical laurels, but was also expected to adapt to a changing conceptual landscape.  相似文献   

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"Sleeping beauty": quiescence in Saccharomyces cerevisiae.   总被引:1,自引:0,他引:1  
The cells of organisms as diverse as bacteria and humans can enter stable, nonproliferating quiescent states. Quiescent cells of eukaryotic and prokaryotic microorganisms can survive for long periods without nutrients. This alternative state of cells is still poorly understood, yet much benefit is to be gained by understanding it both scientifically and with reference to human health. Here, we review our knowledge of one "model" quiescent cell population, in cultures of yeast grown to stationary phase in rich media. We outline the importance of understanding quiescence, summarize the properties of quiescent yeast cells, and clarify some definitions of the state. We propose that the processes by which a cell enters into, maintains viability in, and exits from quiescence are best viewed as an environmentally triggered cycle: the cell quiescence cycle. We synthesize what is known about the mechanisms by which yeast cells enter into quiescence, including the possible roles of the protein kinase A, TOR, protein kinase C, and Snf1p pathways. We also discuss selected mechanisms by which quiescent cells maintain viability, including metabolism, protein modification, and redox homeostasis. Finally, we outline what is known about the process by which cells exit from quiescence when nutrients again become available.  相似文献   

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New ideas in science frequently arise from neglected or distorted antecedents. This essay deals with the idea of biochemical unity, encapsulated in Jacques Monod's well-known phrase, dating from 1954: "Anything found to be true of E. coli must also be true of elephants." An earlier version of this phrase,--"From the elephant to butyric acid bacterium--it is all the same!"--was coined in 1926 by the Dutch microbiologist Albert Jan Kluyver. In that year Kluyver and his associate Hendrick Jean Louis Donker published a celebrated paper, "Unity in Biochemistry." The concept of biochemical unity had many antecedents, but these had never caught on. The Kluyver-Donker paper has often been regarded to provide a boost to biochemical and especially to microbiological thinking. Its interpretations and misinterpretations represent an encapsulated history of biochemistry. The present paper examines the history of the concept of biochemical unity from before to beyond Kluyver, investigates the two "elephant" phrases and their possible relationships, and ends with a discussion of the attractiveness of unifying ideas in science.  相似文献   

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