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1.
Human sickle hemoglobin in transgenic mice 总被引：21，自引：0，他引：21
T M Ryan T M Townes M P Reilly T Asakura R D Palmiter R L Brinster R R Behringer 《Science (New York, N.Y.)》1990,247(4942):566-568
DNA molecules that contain the human alpha- and beta s-globin genes inserted downstream of erythroid-specific, deoxyribonuclease I super-hypersensitive sites were coinjected into fertilized mouse eggs and a transgenic mouse line was established that synthesizes human sickle hemoglobin (Hb S). These animals were bred to beta-thalassemic mice to reduce endogenous mouse globin levels. When erythrocytes from these mice were deoxygenated, greater than 90 percent of the cells displayed the same characteristic sickled shapes as erythrocytes from humans with sickle cell disease. Compared to controls the mice have decreased hematocrits, elevated reticulocyte counts, lower hemoglobin concentrations, and splenomegaly, which are all indications of the anemia associated with human sickle cell disease. 相似文献
2.
Regulation of erythrocyte cation and water content in sickle cell anemia 总被引：25，自引：0，他引：25
The pathophysiological events in sickle cell disease are critically dependent on the intracellular concentration of hemoglobin S, which varies inversely with cell cation and water content. Erythrocytes of SS homozygotes exposed to oxygen or carbon monoxide decrease their potassium and water content through a pathway for potassium transport that is activated by both cell swelling and decrease in internal pH. This pathway is not inhibited by ouabain either with or without bumetanide. When SS erythrocytes were separated according to density, the pH- and volume-dependent potassium transport was greatest in the least dense fraction and was reduced in the densest cells. This pathway, which does not depend on polymerization of sickle hemoglobin, may be important in regulating the cation and water content of SS erythrocytes. 相似文献
3.
A disk-shaped molecule with chiral tails is shown to form long fibers of molecular diameter and micrometer length by self-assembly in chloroform. The molecules are derived from crown ethers and contain a phthalocyanine ring. In the fibers, they have a clockwise, staggered orientation that leads to an overall right-handed helical structure. These structures, in turn, self-assemble to form coiled-coil aggregates with left-handed helicity. Addition of potassium ions to the fibers leaves their structure intact but blocks the transfer of the chirality from the tails to the cores, leading to loss of the helicity of the fibers. These tunable chiral materials have potential in optoelectronic applications and as components in sensor devices. 相似文献
4.
Hyaluronic acid: a novel, double helical molecule 总被引：3，自引：0，他引：3
I C Dea R Moorhouse D A Rees S Arnott J M Guss E A Balazs 《Science (New York, N.Y.)》1973,179(73):560-562
Films prepared from a deformable gel (or putty) of hyaluronic acid show high crystallinity and orientation in their x-ray diffraction patterns. We have derived a probable structure for the molecules in these films. This is a double helix in which two identical, left-handed strands are antiparallel to one another. Each strand has four disaccharide residues per pitch length. Although the putty is prepared at pH 2.5, at which dilute solutions of hyaluronic have exaggerated rheological properties, the double helical form can also exist at physiological pH and therefore may be a biologically important form. 相似文献
5.
Delay time of hemoglobin S polymerization prevents most cells from sickling in vivo 总被引：10，自引：0，他引：10
A laser photolysis technique has been developed to assess the quantitative significance of the delay time of hemoglobin S gelation to the pathophysiology of sickle cell disease. Changes in the saturation of hemoglobin S with carbon monoxide produced by varying the intensity of a photolytic laser beam were used to simulate changes in the saturation of oxyhemoglobin S produced by variations in oxygen pressure. The presence of polymer at steady-state saturation with carbon monoxide was determined by measurement of the kinetics of gelation after complete photodissociation. The kinetics are a very sensitive probe for polymer since small amounts of polymerized hemoglobin increase the rate of nucleation sufficiently to eliminate the delay period. First, the equilibrium gelation properties of partially photodissociated carbonmonoxyhemoglobin S were shown to be the same as partially oxygenated hemoglobin S, and the method was then used to determine the effect of saturation on the formation and disappearance of polymers in individual sickle cells. The saturation at which polymers first formed upon deoxygenation was much lower than the saturation at which polymers disappeared upon reoxygenation. The results indicate that at venous saturations with oxygen, gelation takes place in most cells at equilibrium, but is prevented from occurring in vivo because the delay times are sufficiently long that most cells return to the lungs and are reoxygenated before polymerization has begun. 相似文献
6.
Two genetic sources of variation influence the percentage of sickle cell hemoglobin found in heterozygotes. One factor is strongly related to the percentage of hemoglobin S in the carrier parent and appears to be determined by sickle hemoglobin isoalleles, whereas the other is related to racial background and may well be polygenic. 相似文献
7.
Arabinosylcytosine induces fetal hemoglobin in baboons by perturbing erythroid cell differentiation kinetics 总被引：9，自引：0，他引：9
T Papayannopoulou A Torrealba de Ron R Veith G Knitter G Stamatoyannopoulos 《Science (New York, N.Y.)》1984,224(4649):617-619
Arabinosylcytosine, a compound that inhibits DNA synthesis in rapidly dividing cells, stimulates fetal hemoglobin in adult baboons and produces significant perturbations in the pools of erythroid progenitors. It appears that changes in the kinetics of erythroid cell differentiation rather than direct action on the gamma genes underlie stimulation of fetal hemoglobin in the adult animals in vivo. These results also suggest that chemotherapeutic agents selected for their low carcinogenic or mutagenic potential could be used for therapeutic induction of fetal hemoglobin in patients with sickle cell anemia. 相似文献
8.
K Moffat 《Science (New York, N.Y.)》1974,185(147):274-277
The altered gelation behavior found in mixtures of sickle cell hemoglobin with other hemoglobins is due to the formation of hybrid hemoglobin tetramers from unlike dimers. The hemoglobins need not possess the deoxy quaternary structure for gelation to occur; liganded forms are also capable of participation in gelation. 相似文献
9.
Parallel stranded DNA 总被引：13，自引：0，他引：13
J H van de Sande N B Ramsing M W Germann W Elhorst B W Kalisch E von Kitzing R T Pon R C Clegg T M Jovin 《Science (New York, N.Y.)》1988,241(4865):551-557
A series of four hairpin deoxyoligonucleotides was synthesized with a four-nucleotide central loop (either C or G) flanked by the complementary sequences d(T)10 and d(A)10. Two of the molecules contain either a 3'-p-3' or 5'-p-5' linkage in the loop, so that the strands in the stem have the same, that is, parallel (ps) polarity. The pair of reference oligonucleotides have normal phosphodiester linkages throughout and antiparallel (aps) stem regions. All the molecules adopt a duplex helical structure in that (i) the electrophoretic mobilities in polyacrylamide gels of the ps and aps oligomers are similar. (ii) The ps hairpins are substrates for T4 polynucleotide kinase, T4 DNA ligase, and Escherichia coli exonuclease III. (iii) Salt-dependent thermal transitions are observed for all hairpins, but the ps molecules denature 10 degrees C lower than the corresponding aps oligomers. (iv) The ultraviolet absorption and circular dichroism spectra are indicative of a base-paired duplex in the stems of the ps hairpins but differ systematically from those of the aps counterparts. (v) The bis-benzimidazole drug Hoechst-33258, which binds in the minor groove of B-DNA, exhibits very little fluorescence in the presence of the ps hairpins but a normal, enhanced emission with the aps oligonucleotides. In contrast, the intercalator ethidium bromide forms a strongly fluorescent complex with all hairpins, the intensity of which is even higher for the ps species. (vi) The pattern of chemical methylation is the same for both the ps and aps hairpins. The combined results are consistent with the prediction from force field analysis of a parallel stranded right-handed helical form of d(A)n.d(T)n with a secondary structure involving reverse Watson-Crick base pairs and a stability not significantly different from that of the B-DNA double helix. Models of the various hairpins optimized with force field calculations are described. 相似文献
10.
Cornelissen JJ Donners JJ de Gelder R Graswinckel WS Metselaar GA Rowan AE Sommerdijk NA Nolte RJ 《Science (New York, N.Y.)》2001,293(5530):676-680
Polymerization of isocyanopeptides results in the formation of high molecular mass polymers that fold in a proteinlike fashion to give helical strands in which the peptide chains are arranged in beta-sheets. The beta-helical polymers retain their structure in water and unfold in a cooperative process at elevated temperatures. The peptide architecture in these polymers is a different form of the beta-helix motif found in proteins. Unlike their natural counterparts, which contain arrays of large beta-sheets stacked in a helical fashion, the isocyanopeptide polymers have a central helical core that acts as a director for the beta-sheet-like arrangement of the peptide side arms. The helical structure of these isocyanopeptide polymers has the potential to be controlled through tailoring of the side branches and the hydrogen-bonding network present in the beta-sheets. 相似文献
11.
12.
Tosatti E Prestipino S Kostlmeier S Dal Corso A Di Tolla FD 《Science (New York, N.Y.)》2001,291(5502):288-290
Multishell helical gold nanowires were recently imaged by electron microscopy. We show theoretically that the contact with the gold tips at either end of the wire plays a crucial role and that local minima in the string tension rather than the total wire free energy determine the nanowire stability. Density functional electronic structure calculations of the simplest and thinnest coaxial gold and silver wires of variable radius and chirality were carried out. We found a string tension minimum for a single-tube gold nanowire that is chiral and consists of seven strands, in striking agreement with observation. In contrast, no such minimum was found for silver, where the s-d competition leading to surface reconstruction is lacking. 相似文献
13.
Helical repeat and linking number of surface-wrapped DNA 总被引：6，自引：0，他引：6
The geometric properties of duplex DNA are systematically altered when the DNA is wrapped on a protein surface. The linking number of surface-wrapped closed circular DNA is the sum of two integers: the winding number, phi, a function of the helical repeat; and the surface linking number, SLk, a newly defined geometric constant that accounts for the effects of surface geometry on the twist and writhe of DNA. Changes in the helical repeat, h, and in the winding number can be deduced solely from surface geometry and superhelix density, sigma. This treatment relates the theoretically important properties twist and writhe to the more experimentally accessible quantities phi, h, SLk, and sigma. The analysis is applied to three biologically important cases: interwinding of DNA in a plectonemic superhelix, catenated DNA, and minichromosomes. 相似文献
14.
Synthesis of functional human hemoglobin in transgenic mice 总被引：18，自引：0，他引：18
R R Behringer T M Ryan M P Reilly T Asakura R D Palmiter R L Brinster T M Townes 《Science (New York, N.Y.)》1989,245(4921):971-973
Human alpha- and beta-globin genes were separately fused downstream of two erythroid-specific deoxyribonuclease (DNase) I super-hypersensitive sites that are normally located 50 kilobases upstream of the human beta-globin gene. These two constructs were coinjected into fertilized mouse eggs, and expression was analyzed in transgenic animals that developed. Mice that had intact copies of the transgenes expressed high levels of correctly initiated human alpha- and beta-globin messenger RNA specifically in erythroid tissue. An authentic human hemoglobin was formed in adult erythrocytes that when purified had an oxygen equilibrium curve identical to the curve of native human hemoglobin A (Hb A). Thus, functional human hemoglobin can be synthesized in transgenic mice. This provides a foundation for production of mouse models of human hemoglobinopathies such as sickle cell disease. 相似文献
15.
A laser light scattering technique was used to observe the extent of hemoglobin aggregation in solitary red blood cells of sickle cell anemia. Hemoglobin aggregation was confirmed in deoxygenated cells. The light scattering technique can also be applied to cytoplasmic studies of any biological cell. 相似文献
16.
X-ray diffraction patterns of transfer RNA consistent with the presence of short parallel helices in the molecule 总被引：1，自引：0，他引：1
X-ray diffraction data of yeast formylmethionine transfer RNA, Escherichia coli phenylalanine transfer RNA, and Escherichia coli arginine transfer RNA single crystals are compared with the Fourier transform of a helix. The results are consistent with the presence of short parallel double helical segments in the transfer RNA molecules. 相似文献
17.
Events occurring after infection of bacteria with wild-type and a temperature-sensitive mutant phage indicate that there are two enzymatic activities necessary to replicate phage RNA. One converts single strands into double strands, while the other uses double strands to svnthesize viral RNA. The mutant is deficient in the first activity, probably because the mutation is in the gene specifying the requisite enzyme. On the basis of these and other results, a model is presented for the replication of phage RNA. 相似文献
18.
The replicating form of single-stranded DNA virus has been isolated in pure form by chromatography on columns of methylated albumin. Its buoyant density in CsCl and "melting temperature" are characteristic of a double stranded DNA structure containing 43 percent guanine-cytosine. The nearest neighbors to uridylate were compared in the RNA synthesized when replicating-form DNA and mature single-stranded DNA were employed as templates in an in vitro system. The mature DNA component of the replicating duplex does not serve as the sole source of complementary RNA. The results agree best with the assumption that both strands of the replicating form function as templates. It is important to note that this is contrary to the situation found in the intact cell where only one of the two strands appears to be transcribed into message. 相似文献
19.
Mizuno H Higashida C Yuan Y Ishizaki T Narumiya S Watanabe N 《Science (New York, N.Y.)》2011,331(6013):80-83
Formin homology proteins (formins) elongate actin filaments (F-actin) by continuously associating with filament tips, potentially harnessing actin-generated pushing forces. During this processive elongation, formins are predicted to rotate along the axis of the double helical F-actin structure (referred to here as helical rotation), although this has not yet been definitively shown. We demonstrated helical rotation of the formin mDia1 by single-molecule fluorescence polarization (FL(P)). FL(P) of labeled F-actin, both elongating and depolymerizing from immobilized mDia1, oscillated with a periodicity corresponding to that of the F-actin long-pitch helix, and this was not altered by actin-bound nucleotides or the actin-binding protein profilin. Thus, helical rotation is an intrinsic property of formins. To harness pushing forces from growing F-actin, formins must be anchored flexibly to cell structures. 相似文献
20.
杨树无性系木材纤维形态特征及其径向变异的研究 总被引：4，自引：0，他引：4
以生长在安徽省天长市城西林场的5种不同的杨树无性系人工林木材H22、Z9、Z3、B3和107 为对象,对木材纤维形态特征进行了研究,并分析了其径向遗传变异规律.结果表明,5个无性系杨树的纤维长度、宽度以及长宽比在幼龄期较小,但随着生长轮的增加,呈增大的趋势,并在达到一定的年龄后保持稳定波动或略有减小;腔径、双壁厚以及壁腔比的径向变化规律总体上也是随着生长轮呈增大趋势,可能受到早晚材的影响,部分无性系的双壁厚和壁腔比变化波动较大. 相似文献