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1.
Oxidative stress has been implicated in numerous pathophysiological conditions and also aging. The tools for studying oxidative stress are now expanding as a result of the human genome effort and, in particular, expanding knowledge on human genetic variation. A few genetic variants, mostly in the form of single nucleotide polymorphisms of relevance to oxidative stress are already studied by a molecular epidemiologic approach. A review of the current knowledge on variant human genes that are directly implicated in human protection against oxidative stress is presented. 相似文献
2.
Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. 总被引:26,自引:0,他引:26
K Ueda N Okamura M Hirai Y Tanigawara T Saeki N Kioka T Komano R Hori 《The Journal of biological chemistry》1992,267(34):24248-24252
We expressed human MDR1 cDNA isolated from the human adrenal gland in porcine LLC-PK1 cells. A highly polarized epithelium formed by LLC-GA5-COL300 cells that expressed human P-glycoprotein specifically on the apical surface showed a multidrug-resistant phenotype and had 8.3-, 3.4-, and 6.5-fold higher net basal to apical transport of 3H-labeled cortisol, aldosterone, and dexamethasone, respectively, compared with host cells. But progesterone was not transported, although it inhibited azidopine photoaffinity labeling of human P-glycoprotein and increased the sensitivity of multidrug-resistant cells to vinblastine. An excess of progesterone inhibited the transepithelial transport of cortisol by P-glycoprotein. These results suggest that cortisol and aldosterone are physiological substrates for P-glycoprotein in the human adrenal cortex and that substances that efficiently bind to P-glycoprotein are not necessarily transported by P-glycoprotein. 相似文献
3.
人与大猩猩,黑猩猩和猩猩亲缘关系的探讨 总被引:3,自引:0,他引:3
有关人锆超科的系统发育仍然存在刍议。争论焦点在与大猩猩和黑猩猩哪 个关系更近一点。酪氨酸酶是黑色素合成中的关键酶,酪氨酶基因的突变将导致白化病。测定了人猿科中大猩猩,黑猩猩、猩猩和长臂锆产基因全部5个外显子的DNA序列。 相似文献
4.
The two major apolipoproteins of marmoset serum have been isolated and characterized, and on the basis of physicochemical and immunological criteria are homologous with the human AI and B-100 proteins. Marmoset apolipoprotein AI was the principal protein of high-density lipoproteins (HDL) and was purified by gel filtration chromatography and electrophoresis in alkaline-urea polyacrylamide gel followed by electrophoretic elution. Purified marmoset apolipoprotein AI displayed an Mr of approx. 27000, was polymorphic (five forms) on isoelectric focussing, with pI values in the range 4.8-5.0, and migrated similarly to human apolipoprotein AI in alkaline-urea gels. An overall resemblance was seen in the amino acid composition of marmoset apolipoprotein AI and that of its human counterpart with the notable exception that marmoset AI contained 1 isoleucine residue/mole. An immunological reaction of partial identity between the human and monkey proteins was seen upon immunodiffusion of their HDLs against antiserum to human apolipoprotein AI. Marmoset B-100 was the predominant apoprotein of VLDL and LDL, resembling the human protein in its elution profile on gel filtration chromatography in anionic detergent, and in its high apparent Mr (approx. 520000). The marmoset and human B-100 proteins were alike in amino acid composition and carbohydrate content. Moreover, their immunological behaviour with an antiserum to marmoset apolipoprotein B showed them to share certain antigenic determinant(s). We conclude that the physicochemical properties of the principle apolipoproteins of Callithrix jacchus, a New World primate, markedly resemble those of the human AI and B-100 proteins, suggesting therefore that they may function similarly in lipid transport and metabolism. Counterparts to human apolipoproteins AII, E, CII and CIII have also been tentatively identified. 相似文献
5.
The adenylyl cyclases (AC) act as second messengers in regulatory processes in the central nervous system. They might be involved in the pathophysiology of diseases, but their biological function is unknown, except for AC type I, which has been implicated in learning and memory. We previously mapped the gene encoding AC I to human Chromosome (Chr) 7p12. In this study we report the mapping of the adenylyl cyclase genes type I–VI to mouse chromosomes by fluorescence in situ hybridization (FISH): Adcy1 to Chr 11A2, Adcy2 to 13C1, Adcy3 to 12A-B, Adcy4 to 14D3, Adcy5 to 16B5, and Adcy6 to 15F. We also confirmed previously reported mapping results of the corresponding human loci ADCY2, ADCY3, ADCY5, and ADCY6 to human chromosomes and, in addition, determined the chromosomal location of ADCY4 to human Chr 14q11.2. The mapping data confirm known areas of conservation between mouse and human chromosomes. 相似文献
6.
P. Lieberman 《Human Evolution》1988,3(1-2):3-18
The evolution of human speech and syntax, which appear to be the defining characteristics of modern human beings, is discussed. Speech depends on the morphology of the mouth, tongue, and larynx which yield the human «vocal tract», and neural mechanisms that facilitate the perception of speech and make possible the control of the articulatory gestures that underly speech. The neural mechanisms that underly human syntax may have derived by means of the Darwinian process of preadaption from the structures of the brain that first evolved to facilitate speech motor control. Recent data consistent with this theory are presented; deficits in the comprehension of syntax of normal aged people are correlated with a slowdown in speech rate. 相似文献
7.
Fiermonte G Dolce V Palmieri L Ventura M Runswick MJ Palmieri F Walker JE 《The Journal of biological chemistry》2001,276(11):8225-8230
In Saccharomyces cerevisiae, the genes ODC1 and ODC2 encode isoforms of the oxodicarboxylate carrier. They both transport C5-C7 oxodicarboxylates across the inner membranes of mitochondria and are members of the family of mitochondrial carrier proteins. Orthologs are encoded in the genomes of Caenorhabditis elegans and Drosophila melanogaster, and a human expressed sequence tag (EST) encodes part of a closely related protein. Information from the EST has been used to complete the human cDNA sequence. This sequence has been used to map the gene to chromosome 14q11.2 and to show that the gene is expressed in all tissues that were examined. The human protein was produced by overexpression in Escherichia coli, purified, and reconstituted into phospholipid vesicles. It has similar transport characteristics to the yeast oxodicarboxylate carrier proteins (ODCs). Both the human and yeast ODCs catalyzed the transport of the oxodicarboxylates 2-oxoadipate and 2-oxoglutarate by a counter-exchange mechanism. Adipate, glutarate, and to a lesser extent, pimelate, 2-oxopimelate, 2-aminoadipate, oxaloacetate, and citrate were also transported by the human ODC. The main differences between the human and yeast ODCs are that 2-aminoadipate is transported by the former but not by the latter, whereas malate is transported by the yeast ODCs but not by the human ortholog. In mammals, 2-oxoadipate is a common intermediate in the catabolism of lysine, tryptophan, and hydroxylysine. It is transported from the cytoplasm into mitochondria where it is converted into acetyl-CoA. Defects in human ODC are likely to be a cause of 2-oxoadipate acidemia, an inborn error of metabolism of lysine, tryptophan, and hydroxylysine. 相似文献
8.
Hardy A 《Perspectives in biology and medicine》2003,46(2):200-215
The intricate causal relationships between disease in man and disease in animals first began to be elucidated in the mid-19th century. Although the connections between animal and human disease are now generally understood, individuals as well as societies remain slow to act on this knowledge. This paper examines the gradual recognition of these disease connections and explores the parallel theme of man's reluctance to appreciate the implications of these connections. It identifies factors that have inhibited the realization of the links between disease in man and animals, and discusses several milestones in the scientific elucidation of these links. Beginning with emerging concerns over the relationship between bovine and human tuberculosis in the 1860s, it follows the discovery of insect vectors, animal reservoirs, and the links between animals, influenza, and man. Despite warnings of the potential significance for human disease of patterns of changes in the relationship with animals and the natural world, scientists have continued to treat human and animal health as largely independent disciplines, while historians too have neglected this important aspect of human disease. 相似文献
9.
Summary A computer-based statistical evaluation of the optimal alignments of the kringle domains of human plasminogen, human prothrombin, human tissue plasminogen activator, human urokinase, and human coagulation Factor XIIa, as well as the putative kringle of human haptoglobin, has been performed. A variety of different alignments has been examined and scores calculated in terms of the number of standard deviations (SD) of a given match from randomness. With the exception of human haptoglobin, it was found that very high alignment scores (8.9–23.0 SD from randomness) were obtained between each of the kringles, with the kringle 1 and kringle 5 regions of human plasminogen displaying the highest similarity, and the S kringle of human prothrombin and the human Factor XII kringle showing the least similarity. The relationships obtained were employed to construct an evolutionary tree for the kringles. The predicted alignments have also allowed nucleotide mutations in these regions to be evaluated more accurately. For those regions for which nucleotide sequences are known, we have employed the maximal alignments from the protein sequences to assess nucleotide sequence similarities. It was found that a range of approximately 40–55% of the nucleotide bases were placed at identical positions in the kringles, with the highest number found in the alignment of the two kringles of human tissue plasminogen activator and the lowest number in the alignment of the S kringle of prothrombin with the second kringle of tissue plasminogen activator. From both protein and nucleotide alignments, we conclude that haptoglobin is not statistically homologous to any other kringle.Secondary structural comparisons of the kringle regions have been predicted by a combination of the Burgess and Chou-Fasman methods. In general, the kringles display a very high number of -turns, and very low -helical contents. From analysis of the predicted structures in relationship to the functional properties of these domains, it appears as though many of their functional differences can be related to possible conformational alterations resulting from amino acid substitutions in the kringles. 相似文献
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Pullman D 《Journal of bioethical inquiry》2010,7(4):353-364
Feticide, the practice of terminating the life of an otherwise viable fetus in utero, has become an increasingly common practice in obstetric centres around the globe, a concomitant of antenatal screening technologies. This paper examines this expanding practice in light of the concept of human dignity. Although it is assumed from the outset that even viable human fetuses are not persons and as such do not enjoy full membership in the moral community, it is argued that the fact that these are nevertheless human fetuses affords them prima facie moral status. Thus even those who accept a liberal position with regard to therapeutic abortion, should be concerned about these more recent developments. Indeed, how we treat viable human fetuses has implications for our prospective treatment of other human non-persons and could undermine the common human dignity we all share. 相似文献
13.
MacEachern S 《Current anthropology》2000,41(3):357-384
Over the past 40 years, traditional perspectives on the constitution of human groups have been subjected to stringent critique within anthropology. This began with the dismantling of accepted "race" divisions after World War II and continued with analyses of the meaning and reality of African "tribal" distinctions from the 1960s until the present. Archaeologists, ethnographers, linguists, and historians of Africa now work within a research milieu where social interactions, cultural exchange, and the dynamic nature of group identifications are accepted as a normal part of the human experience. At the same time, new techniques have been developed for the examination of human history, techniques based upon an expanding repertoire of tools for the analysis of genetic variability in human populations. Perhaps the most striking result of this research has been Cavalli-Sforza, Menozzi, and Piazza's The History and Geography of Human Genes. Rather less attention has been paid, however, to the conceptual relationships between the human groups defined through such analyses, in Africa and elsewhere, and those defined through other kinds of research. This paper is a preliminary examination of the fit between genetic, archaeological, and ethnographic data on the African past. 相似文献
14.
Expression, purification, and characterization of stable, recombinant human adenylosuccinate lyase 总被引:4,自引:0,他引:4
The full length human adenylosuccinate lyase gene was generated by a PCR method using a plasmid encoding a truncated human enzyme as template, and was cloned into a pET-14b vector. Human adenylosuccinate lyase was overexpressed in Escherichia coli Rosetta 2(DE3)pLysS as an N-terminal histidine-tagged protein and was purified to homogeneity by a nickel-nitriloacetic acid column at room temperature. The histidine tag was removed from the human enzyme by thrombin digestion and the adenylosuccinate lyase was purified by Sephadex G-100 gel filtration. The histidine-tagged and non-tagged adenylosuccinate lyases exhibit similar values of Vmax and Km for S-AMP. Analytical ultracentrifugation and circular dichroism revealed, respectively, that the histidine-tagged enzyme is in tetrameric form with a molecular weight of 220 kDa and contains predominantly alpha-helical structure. This is the first purification procedure to yield a stable form of human adenylosuccinate lyase. The enzyme is stable for at least 5 days at 25 degrees C, and upon rapid freezing and thawing. Temperature as well as reducing agent (DTT) play critical roles in determining the stability of the human adenylosuccinate lyase. 相似文献
15.
Activation of a novel human transforming gene, ret, by DNA rearrangement 总被引:53,自引:0,他引:53
A novel transforming gene was detected by transfection of NIH 3T3 cells with human lymphoma DNA. The tumor DNA induced a single focus in primary transfections, whereas DNAs of transformed NIH cells induced transformation with high efficiencies in secondary and tertiary assays. Molecular clones spanning about 37 kb of human sequence were isolated from tertiary transformant DNA. Blot hybridization indicated that the transforming gene consisted of two segments that were unlinked in both normal human and primary lymphoma DNAs. The two segments of human DNA were cotranscribed in transformed NIH cells but not in any human cells examined. The transforming gene thus appeared to be activated by recombination between two unlinked human DNA segments, possibly by cointegration during transfection. 相似文献
16.
MacEachern S 《Current anthropology》2000,999(1):000357-000384
Over the past 40 years, traditional perspectives on the constitution of human groups have been subjected to stringent critique within anthropology. This began with the dismantling of accepted "race" divisions after World War II and continued with analyses of the meaning and reality of African "tribal" distinctions from the 1960s until the present. Archaeologists, ethnographers, linguists, and historians of Africa now work within a research milieu where social interactions, cultural exchange, and the dynamic nature of group identifications are accepted as a normal part of the human experience. At the same time, new techniques have been developed for the examination of human history, techniques based upon an expanding repertoire of tools for the analysis of genetic variability in human populations. Perhaps the most striking result of this research has been Cavalli-Sforza, Menozzi, and Piazza's The History and Geography of Human Genes. Rather less attention has been paid, however, to the conceptual relationships between the human groups defined through such analyses, in Africa and elsewhere, and those defined through other kinds of research. This paper is a preliminary examination of the fit between genetic, archaeological, and ethnographic data on the African past. 相似文献
17.
G Windholz 《The Pavlovian journal of biological science》1990,25(2):48-53
Pavlov's discovery of experiment neurosis was serendipitous, yet it was made under the influence of Breuer and Freud's case of Anna O. In 1914, Pavlov's disciple N. R. Shenger-Krestovnikova, exploring the limits of visual discrimination in dogs, noticed that when the discrimination was difficult, the dogs' behavior became disorganized. Pavlov drew an analogy between the condition of Shenger-Krestovnikova's dogs and their disorganized behavior with Anna O.'s situation and her neurotic reaction. Pavlov concluded that he had demonstrated in the laboratory the elements of neurosis in animals and human alike. Schilder's criticism of his position, his later study of human neuroses in clinical settings, and the views of Janet may have induced Pavlov to differentiate between animal and human neuroses. 相似文献
18.
MacEachern S 《Current anthropology》2000,999(2):000357-000384
Over the past 40 years, traditional perspectives on the constitution of human groups have been subjected to stringent critique within anthropology. This began with the dismantling of accepted "race" divisions after World War II and continued with analyses of the meaning and reality of African "tribal" distinctions from the 1960s until the present. Archaeologists, ethnographers, linguists, and historians of Africa now work within a research milieu where social interactions, cultural exchange, and the dynamic nature of group identifications are accepted as a normal part of the human experience. At the same time, new techniques have been developed for the examination of human history, techniques based upon an expanding repertoire of tools for the analysis of genetic variability in human populations. Perhaps the most striking result of this research has been Cavalli-Sforza, Menozzi, and Piazza's The History and Geography of Human Genes. Rather less attention has been paid, however, to the conceptual relationships between the human groups defined through such analyses, in Africa and elsewhere, and those defined through other kinds of research. This paper is a preliminary examination of the fit between genetic, archaeological, and ethnographic data on the African past. 相似文献
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J.C. Leonard H.L. Drwinga C.H. Kim L.H. Toji P.K. Bender R.A. Mulivor J.C. Beck 《Genomics》1997,46(3):530
The NIGMS Human Genetic Mutant Cell Repository collects and distributes well-characterized human/rodent somatic cell hybrid regional mapping panels for human chromosomes 3, 4, 5, 11, 15, 17, 18, and X. Each regional mapping panel consists of 4 to 11 hybrids that divide the chromosome into 5 to 11 intervals. These panels have been extensively characterized by the submitters and the NIGMS Repository. 相似文献