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The formation of amyloid fibrils, protofibrils and oligomers from the β-amyloid (Aβ) peptide represents a hallmark of Alzheimer's disease. Aβ-peptide-derived assemblies might be crucial for disease onset, but determining their atomic structures has proven to be a major challenge. Progress over the past 5 years has yielded substantial new data obtained with improved methodologies including electron cryo-microscopy and NMR. It is now possible to resolve the global fibril topology and the cross-β sheet organization within protofilaments, and to identify residues that are crucial for stabilizing secondary structural elements and peptide conformations within specific assemblies. These data have significantly enhanced our understanding of the mechanism of Aβ aggregation and have illuminated the possible relevance of specific conformers for neurodegenerative pathologies.  相似文献   

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China's Free ART Program was initiated in 2002 as an emergency response to save and improve the lives of AIDS patients living mainly in impoverished rural regions of central China. With little experience in HIV/AIDS treatment and care and resource limitations, China's efforts to provide widespread access to free antiretroviral therapy has been a process fraught with difficulty. However, the Free ART Program is progressing from an emergency response to a standardized treatment and care system. The development of national guidelines, training programs, a laboratory support network, a national patient database, programs for special populations such as children and patients living with coinfections, and operational research has improved the scope and quality of the free treatment program. As of June 30, 2005, a total of 19,456 patients in 28 provinces, autonomous regions, and special municipalities had received free ART. Challenges stemming from the nature of China's health system and patient population persist, but with strong government support and a diverse set of resources, China has the capacity to overcome these challenges and to provide nationwide access to high quality treatment and care.  相似文献   

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The amount of comparative data for phylogenetic analyses is constantly increasing. Data come from different directions such as morphology, molecular genetics, developmental biology and paleontology. With the increasing diversity of data and of analytical tools, the number of competing hypotheses on phylogenetic relationships rises, too. The choice of the phylogenetic tree as a basis for the interpretation of new data is important, because different trees will support different evolutionary interpretations of the data investigated. I argue here that, although many problematic aspects exist, there are several phylogenetic relationships that are supported by the majority of analyses and may be regarded as something like a robust backbone. This accounts, for example, for the monophyly of Metazoa, Bilateria, Deuterostomia, Protostomia (= Gastroneuralia), Gnathifera, Spiralia, Trochozoa and Arthropoda and probably also for the branching order of diploblastic taxa (“Porifera”, Trichoplax adhaerens, Cnidaria and Ctenophora). Along this “backbone”, there are several problematic regions, where either monophyly is questionable and/or where taxa “rotate” in narrow regions of the tree. This is illustrated exemplified by the probable paraphyly of Porifera and the phylogenetic relationships of basal spiralian taxa. Two problems span wider regions of the tree: the position of Arthropoda either as the sister taxon of Annelida (= Articulata) or of Cycloneuralia (= Ecdysozoa) and the position of tentaculate taxa either as sister taxa of Deuterostomia (= Radialia) or within the taxon Spiralia. The backbone makes it possible to develop a basic understanding of the evolution of genes, molecules and structures in metazoan animals.  相似文献   

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Attempts through somatic cell nuclear transfer to expand wild populations that have shrunk to critical numbers is a logical extension of the successful cloning of mammals. However, although the first mammal was cloned 10 years ago, nuclear reprogramming remains phenomenological, with abnormal gene expression and epigenetic deregulation being associated with the cloning process. In addition, although cloning of wild animals using host oocytes from different species has been successful, little is known about the implication of partial or total mitochondrial DNA heteroplasmy in cloned embryos, fetuses and offspring. Finally, there is a need for suitable foster mothers for inter-intra specific cloned embryos. Considering these issues, the limited success achieved in cloning endangered animals is not surprising. However, optimism comes from the rapid gain in the understanding of the molecular clues underlying nuclear reprogramming. If it is possible to achieve a controlled reversal of the differentiated state of a cell then it is probable that other issues that impair the cloning of endangered animals, such as the inter-intra species oocyte or womb donor, will be overcome in the medium term.  相似文献   

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Current progress of China’s free ART program   总被引:5,自引:0,他引:5  
INTRODUCTION At the end of 2003, there were an estimated 840,000 people in China infected with HIV, among whom 80,000 were in need of antiretroviral therapy (ART) [1]. Since 1999, the annual rate of increase in reported HIV infec- tions has been around 30%, with growing numbers of females becoming infected [1]. The transmission of HIV/ AIDS in China has been through intravenous drug use (43. 2%) in the south, southwest, and western provinces; prior commercial blood and plasma selli…  相似文献   

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Due to their potent ability to activate the immune system, dendritic cells (DC) are showing promise as potential adjuvants for tumour immunotherapy of cancer patients. However, little is known about the effect tumour cells can have on DC function. Indeed, the discovery of different DC subsets with different immunological functions indicates that the relationship between tumour cells and tumour-infiltrating DC subtypes is likely to be complex. There remains a lot to be understood about the effects of tumours on DC before we can expect to benefit from DC-based tumour immunotherapy of cancer patients. Here we review the recent advances being made in understanding DC phenotype and function in relation to interactions with different types of tumours.  相似文献   

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Current progress of China‘s free ART program   总被引:2,自引:1,他引:1  
China‘s Free ART Program was initiated in 2002 as an emergency response to save and improve the lives of AIDS patients living mainly in impoverished rural regions of central China. With little experience in HIV/AIDS treatment and care and resource limitations, China‘s efforts to provide widespread access to free antiretroviral therapy has been a process fraught with difficulty. However, the Free ART Program is progressing from an emergency response to a standardized treatment and care system. The development of national guidelines, training programs, a laboratory support network, a national patient database, programs for special populations such as children and patients living with coinfections, and operational research has improved the scope and quality of the free treatment program. As of June 30,2005, a total of 19,456 patients in 28 provinces, autonomous regions, and special municipalities had received free ART.Challenges stemming from the nature of China‘s health system and patient population persist, but with strong government support and a diverse set of resources, China has the capacity to overcome these challenges and to provide nationwide access to high quality treatment and care.  相似文献   

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There is a severe shortage of trained microbiologists in Brazil which is hampering the development and expansion of microbiology/biotechnology research, the development of the biotechnology industries and environmental control agencies. Even some medical areas are affected. The reason for this situation lies in the deficient teaching of microbiology, where undergraduate courses in the biological sciences contain little or no microbiology, and in the low number of professionals that are produced. There are a few post-graduates courses in microbiology but these have high costs and little capacity for expansion. There is a need for incentives for the establishment of more undergraduate university courses, more practical training in specific areas, courses for retraining or updating of professionals already at work and specific programmes by the funding agencies.The objective of this article is to encourage discussion about the present state and the future of the teaching of Microbiology in Brazil. It may also be useful for other countries in the same situation.J.R. Jardim Freire is with the Department of Soil Science, Federal University of Rio Grande do Sul, Av. Bento Gonçalves 7712, 91540-000 Porto Alegre, RS, Brazil; W. Gambale is with the Department of Microbiology, Institute of Biomedical Science, University of São Paulo, Av. Lineu Prestes 1374, 05508-900, São Paulo, SP, Brazil.  相似文献   

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Much of the apparent progress in community ecology amounts to little more than re-inventing the wheel, albeit with technical improvements. Many central ideas in the field were stated by A.K. Cajander at the turn of the century. Thereafter, community ecology has moved back and forth between competition-centered and individualistic views of community structure. The chief problems have probably been inappropriate methodology (lack of rigorous formulation and/or critical experimental testing of theories) and a tendency to work only on subcommunities that are delimited by taxonomic criteria. Although these problems are beginning to be remedied, a new one has emerged: ignorance of history and a tendency to re-invent old ideas under new, flashy names. This problem is potentially as dangerous as the old ones and must be tackled by improving our first-hand contact with the classics in our field.  相似文献   

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Harvey is generally accepted as the patron saint of cardiology. Some shading is not amiss because a medical history canon is by definition an instantaneous photograph. Therefore De Motu Cordis is set in a historic perspective and portrayed as the result of genuine scientific progress. Nevertheless Harvey symbolises the watershed between ancient medicine and modern medicine based on observational and experimental research. We too seem to witness a transitional zone between modern medicine and a new customised medicine, individualised and integrative, firmly based on a further expanding technology. (Neth Heart J 2008;16:143-6.)  相似文献   

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Ventricular hypertrophy develops in response to numerous forms of cardiac stress, including pressure or volume overload, loss of contractile mass from prior infarction, neuroendocrine activation, and mutations in genes encoding sarcomeric proteins. Hypertrophic growth is believed to have a compensatory role that diminishes wall stress and oxygen consumption, but Framingham and other studies established ventricular hypertrophy as a marker for increased risk of developing chronic heart failure, suggesting that hypertrophy may have maladaptive features. However, the relative contribution of comorbid disease to hypertrophy-associated systolic failure is unknown. For instance, coronary artery disease is induced by many of the same risk factors that cause hypertrophy and can itself lead to systolic dysfunction. It is uncertain, therefore, whether ventricular hypertrophy commonly progresses to systolic dysfunction without the contribution of intervening ischemia or infarction. In this review, we summarize findings from epidemiologic studies, preclinical experiments in animals, and clinical trials to lay out what is known-and not known-about this important question.  相似文献   

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Twenty years since the inception of the agricultural biotechnology era, only two products have had a significant impact in the market place: herbicide-resistant and insect-resistant crops. Additional products have been pursued but little success has been achieved, principally because of limited understanding of key genetic intervention points. Genomics tools have fueled a new strategy for identifying candidate genes. Primarily thanks to the application of functional genomics in Arabidopsis and other plants, the industry is now overwhelmed with candidate genes for transgenic intervention points. This success necessitates the application of genomics to the rapid validation of gene function and mode of action. As one example, the development of C-box binding factors (CBFs) for enhanced freezing and drought tolerance has been rapidly advanced because of the improved understanding generated by genomics technologies.  相似文献   

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