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A 63-year-old white man of Ecuadorian origin had a subarachnoid hemorrhage at age 57 followed by numbness and paresthesia in his lower extremities. He subsequently developed sexual impotence, alternating constipation and diarrhea, urinary frequency, and difficulty in walking. Rectal biopsy revealed amyloid deposits immunohistochemically reactive with antitransthyretin antisera. Direct DNA sequencing of the transthyretin gene of the patient showed a trinucleotide deletion in exon 4. This deletion resulted in the loss of one of two valines at position 121 or 122. DNA analysis on 11 family members at risk revealed four mutant gene carriers. Plasma transthyretin levels in the mutant gene carriers measured by nephelometry were very low. Peptide sequence analysis revealed that most of plasma transthyretin was normal with only a small amount of variant protein. This is the first report of a DNA deletion in the transthyretin gene. We speculate that the loss of valine in the carboxyl terminal region of the transthyretin monomer alters stability of the tetrameric protein, which leads to rapid clearance from the plasma and amyloid deposition in the tissue. 相似文献
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CATH--a hierarchic classification of protein domain structures 总被引:1,自引:0,他引:1
CA Orengo AD Michie S Jones DT Jones MB Swindells JM Thornton 《Canadian Metallurgical Quarterly》1997,5(8):1093-1108
BACKGROUND: Protein evolution gives rise to families of structurally related proteins, within which sequence identities can be extremely low. As a result, structure-based classifications can be effective at identifying unanticipated relationships in known structures and in optimal cases function can also be assigned. The ever increasing number of known protein structures is too large to classify all proteins manually, therefore, automatic methods are needed for fast evaluation of protein structures. RESULTS: We present a semi-automatic procedure for deriving a novel hierarchical classification of protein domain structures (CATH). The four main levels of our classification are protein class (C), architecture (A), topology (T) and homologous superfamily (H). Class is the simplest level, and it essentially describes the secondary structure composition of each domain. In contrast, architecture summarises the shape revealed by the orientations of the secondary structure units, such as barrels and sandwiches. At the topology level, sequential connectivity is considered, such that members of the same architecture might have quite different topologies. When structures belonging to the same T-level have suitably high similarities combined with similar functions, the proteins are assumed to be evolutionarily related and put into the same homologous superfamily. CONCLUSIONS: Analysis of the structural families generated by CATH reveals the prominent features of protein structure space. We find that nearly a third of the homologous superfamilies (H-levels) belong to ten major T-levels, which we call superfolds, and furthermore that nearly two-thirds of these H-levels cluster into nine simple architectures. A database of well-characterised protein structure families, such as CATH, will facilitate the assignment of structure-function/evolution relationships to both known and newly determined protein structures. 相似文献
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MB Blecher 《Canadian Metallurgical Quarterly》1997,71(7):96, 98-96, 99
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Hartmann and Hasher (1991) used a garden-path task in which younger and older adults generated the final word for each of a series of high-cloze sentences. Under instructions to remember the final word, the experiment included critical sentences for which the generated word was replaced by a new, to-be-remembered target. Using an implicit priming task, the first experiment replicated a basic finding: Younger adults showed priming only for the target words, whereas older adults showed priming for both the generated and target words. Two experiments explored the boundary conditions. One showed that an additional sentence that interpreted the new target word enabled older adults to narrow access to only the target word. The provision of additional time following the introduction of the new target word did not. Specific information, not more time, is required for inefficient inhibitory mechanisms to clear the recent past from memory. 相似文献
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A microwave field-detecting element based on the pyroelectric effect in polyvinylidene fluoride (PVDF) has been developed. Characterisation of the response of a half-wavelength structure etched on 25 ?m PVDF film has been modelled and validated by measurements. The sensitivity, linearity and dynamic range are sufficient for array applications. 相似文献
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