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1.
Dyskeratosis congenita is an inherited skin and bone marrow failure syndrome. There are X-linked, autosomal dominant and autosomal recessive forms of the disease. The X-linked form is due to mutations in the DKC1 gene at Xq28. The encoded protein, dyskerin, is a component of both small nucleolar ribonuclear protein particles and the telomerase complex. Mutations in DKC1 mainly lead to amino acid substitutions. The autosomal dominant form of the disease is due to mutations in hTR, the RNA component of telomerase, making it likely that the disease is due to defective telomerase activity. Mutations in hTR are predicted to either disrupt secondary structure or alter the template region. The gene or genes involved in the recessive forms of the disease remain elusive, though genes whose products are required for telomere maintenance are strong candidates. 相似文献
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The Marfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue with highly variable clinical manifestations including aortic dilatation and dissection, ectopia lentis, and a range of skeletal anomalies. Mutations in the gene for fibrillin-1 (FBN1) cause MFS and other related disorders of connective tissue collectively termed type-1 fibrillinopathies. Fibrillin-1 is a main component of the 10- to 12-nm extracellular microfibrils that are important for elastogenesis, elasticity, and homeostasis of elastic fibers. Mutations in fibrillin-1 are hypothesized to exert their effects by dominant negative mechanisms, but recent work has also emphasized the potential role of proteases and disturbances in tissue homeostasis in the pathogenesis of the MFS. This article provides an overview of the clinical aspects of the MFS and current thinking on the pathogenesis of this disorder. 相似文献
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The correct repair of double-strand breaks (DSBs) is essential for the genomic integrity of a cell, as inappropriate repair
can lead to chromosomal rearrangements such as translocations. In many hematologic cancers and sarcomas, translocations are
the etiological factor in tumorigenesis, resulting in either the deregulation of a proto-oncogene or the expression of a fusion
protein with transforming properties. Mammalian cells are able to repair DSBs by pathways involving homologous recombination
and nonhomologous end-joining. The analysis of translocation breakpoints in a number of cancers and the development of model
translocation systems are beginning to shed light on specific DSB repair pathway(s) responsible for the improper repair of
broken chromosomes.
Received 19 June 2001; received after revision 6 September 2001; accepted 11 September 2001 相似文献
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Apaf1 has been described as the core of the apoptosome. Deficiency in murine Apaf1 leads to embryonic lethality with a phenotype affecting many aspects of developmental apoptosis. In the developing brain,
Apaf1 is a death regulator of the neuronal founder cells. Combined intercrosses of mouse lines mutant for members of the mitochondrial
death pathway are providing us with some clues about the relative regulation existing among neuronal cell populations. Apaf1-deficient embryos display an interesting phenotype in the inner ear and in limb development, which involves different caspase-dependent
and -independent pathways. Moreover, APAF1 is mutated in human melanomas, and its depletion contributes to malignant transformation in a mouse model of cancer. This
review has a double aim: the analysis of the alternatives taken by the embryo to bring into the suicidal program different
cells at different stages, and the relevance of APAF1 in the onset and progression of cancer.
Received 5 March 2001; received after revision 19 April 2001; accepted 4 May 2001 相似文献
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Peroxisomes are single-membrane-bound organelles present in virtually all eukaryotic cells. They are involved in numerous
metabolic processes, both catabolic and anabolic, including β-oxidation of very long chain fatty acids, metabolism of hydrogen
peroxide, plasmalogen biosynthesis and bile acid synthesis. In several genetic diseases, there is either isolated deficiency
of a specific peroxisomal protein (single-protein deficiencies) or a defect in the formation of the organelle with loss of
multiple peroxisomal functions (peroxisome biogenesis disorders). X-linked adrenoleukodystrophy is an example of the former,
and the Zellweger spectrum of the latter. Peroxisome biogenesis disorders are inherited in an autosomal recessive manner and
result from mutations in any of at least 12 PEX genes that encode peroxins. This article reviews the peroxisomal system, the clinical, biochemical and molecular aspects
of peroxisomal disorders, and discusses recent scientific advances in the understanding of peroxisome biogenesis.
Received 16 October 2001; received after revision 2 January 2002; accepted 3 January 2002 相似文献
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Contributions in the domain of cancer research: Review¶Human papillomaviruses and their role in cervical cancer 总被引:17,自引:0,他引:17
Human papillomaviruses (HPVs) have been linked to a variety of human diseases, most notably cancer of the cervix, a disease responsible for at least 200,000 deaths per year worldwide. Over 100 different types of HPV have been identified and these can be divided into two groups. Low-risk HPV types are the causative agent of benign warts. High-risk HPV types are associated with cancer. This review focuses on the role of high-risk HPV types in cervical tumorigenesis. Recent work has uncovered new cellular partners for many of the HPV early proteins and thrown light on many of the pathways and processes in which these viral proteins intervene. At the same time, structural and biochemical studies are revealing the molecular details of viral protein function. Several of these new avenues of research have the potential to lead to new approaches to the treatment and prevention of cervical cancer. 相似文献
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Contributions in the domain of cancer research: Review¶Negative regulators of cyclin-dependent kinases and their roles in cancers 总被引:25,自引:0,他引:25
In the past decade, the discovery and characterization of cyclin-dependent kinases (CDKs), the engine cores of the cell cycle machinery, have advanced our understanding of the cell cycle. Both positive and negative regulators of CDKs have been characterized, accelerating the important research to unravel the mechanisms of the cell cycle disease--cancer. Cancer can originate from overexpression of positive regulators, such as cyclins, or from underexpression of negative regulators, such as CDK inhibitors (CKIs). CKIs are the focus of much cancer research because they are capable of controlling cell cycle proliferation--the Holy Grail for cancer treatment. CDKs can be inactivated by several mechanisms:, (i) by association with CKIs including p16 (INK4a), p15 (INK4b), p21 (Cip1), p27 (Kip1), and p57 (Kip2), (ii) by disassociation from their cyclin regulatory unit, (iii) by dephosphorylation of a conserved threonine residue in the T-loop, and (iv) by adding inhibitory phosphate. Here we discuss what is known about each mechanism with a hope that these insights will become useful in developing strategies to eliminate cancer in the future. 相似文献
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Summary The C-terminal amino acid sequences of human and of porcine antithrombin III have been determined as Gly-Arg-Val-Ala-Asn-Pro-Cys-Val-Lys and Gly-Arg-Val-Ala-Asn-Pro-Cys, respectively. These sequences are highly homologous with the C-terminal sequence of human -1-proteinase inhibitor. 相似文献
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Hu QD Lu H Huo K Ying K Li J Xie Y Mao Y Li YY 《Cellular and molecular life sciences : CMLS》2003,60(8):1725-1732
The Saccharomyces cerevisiae TPT1 gene plays a role in removing the 2-phosphate from ligated tRNA during the maturation of pre-tRNA. Here we reported the cloning and characterization of the human TRPT1 gene as a homolog of yeast TPT1. The TRPT1 gene is located at human chromosome 11q13 and encodes a polypeptide of 253 amino acids. BLAST searches with its amino acid sequence revealed the ubiquitous occurrence of TRPT1 homologs and their functional relationships with the presence of the DUF60/KptA domain. Northern analysis demonstrated that the gene is primarily expressed in heart and skeletal muscle, with lower or undetectable levels in other tissues studied. A plasmid-shuffling experiment showed that the human TRPT1 gene could complement the tpt1 mutation in S. cerevisiaeReceived 19 March 2003; received after revision 25 April 2003; accepted 22 May 2003 相似文献
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M. Oimomi F. Hata N. Igaki T. Nakamichi S. Baba H. Kato 《Cellular and molecular life sciences : CMLS》1989,45(5):463-466
Summary Alfa-ketoaldehyde dehydrogenase, which was extracted and purified from human livers, may act on carbonyl compounds, such as 3-deoxyglucosone, and be involved in the control of glycation (Maillard reaction) in the body. 相似文献
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Hui Feng 《Journal of forecasting》2009,28(3):183-193
In this paper we investigate the impact of data revisions on forecasting and model selection procedures. A linear ARMA model and nonlinear SETAR model are considered in this study. Two Canadian macroeconomic time series have been analyzed: the real‐time monetary aggregate M3 (1977–2000) and residential mortgage credit (1975–1998). The forecasting method we use is multi‐step‐ahead non‐adaptive forecasting. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
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Sergio Porté Agrin Moeini Irene Reche Naeem Shafqat Udo Oppermann Jaume Farrés Xavier Parés 《Cellular and molecular life sciences : CMLS》2011,68(6):1065-1077
Human ζ-crystallin is a Zn2+-lacking medium-chain dehydrogenase/reductase (MDR) included in the quinone oxidoreductase (QOR) family because of its activity
with quinones. In the present work a novel enzymatic activity was characterized: the double bond α,β-hydrogenation of medium-chain
2-alkenals and 3-alkenones. The enzyme is especially active with lipid peroxidation products such as 4-hydroxyhexenal, and
a role in their detoxification is discussed. This specificity is novel in the QOR family, and it is similar to that described
in the distantly related alkenal/one reductase family. Moreover, we report the X-ray structure of ζ-crystallin, which represents
the first structure solved for a tetrameric Zn2+-lacking MDR, and which allowed the identification of the active-site lining residues. Docking simulations suggest a role
for Tyr53 and Tyr59 in catalysis. The kinetics of Tyr53Phe and Tyr59Phe mutants support the implication of Tyr53 in binding/catalysis
of alkenal/one substrates, while Tyr59 is involved in the recognition of 4-OH-alkenals. 相似文献
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Sidney Dancoff׳s paper “On Radiative Corrections for Electron Scattering” is generally viewed in the secondary literature as a failed attempt to develop renormalized quantum electrodynamics (QED) a decade early, an attempt that failed because of a mistake that Dancoff made. I will discuss Dancoff׳s mistake and try to reconstruct why it occurred, by relating it to the usual practices of the quantum field theory of his time. I will also argue against the view that Dancoff was on the verge of developing renormalized QED and will highlight the conceptual divides that separate Dancoff׳s work from the QED of the late 1940s. I will finally discuss how the established view of Dancoff׳s paper came to be and how the reading of this specific anecdote relates to more general assessments of the conceptual advances of the late 1940s (covariant techniques, renormalization), in particular to their assessment as being conservative rather than revolutionary. 相似文献
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Patricio Atanes Inmaculada Ruz-Maldonado Attilio Pingitore Ross Hawkes Bo Liu Min Zhao Guo Cai Huang Shanta J. Persaud Stefan Amisten 《Cellular and molecular life sciences : CMLS》2018,75(4):715-726