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121.
Ori Elkayam Refael Segal Daniele Bendayan Robert van Uitert Carla Onnekink Ger JM Pruijn 《Arthritis research & therapy》2010,12(1):R12
Introduction
Patients with tuberculosis (TB) frequently produce anti-citrullinated protein antibodies (ACPA). The objective of this study is to characterize the citrulline-dependence of the ACPA reactivity in sera of patients with mycobacterium infections. 相似文献122.
Swank DM Knowles AF Kronert WA Suggs JA Morrill GE Nikkhoy M Manipon GG Bernstein SI 《The Journal of biological chemistry》2003,278(19):17475-17482
We integratively assessed the function of alternative versions of a region near the N terminus of Drosophila muscle myosin heavy chain (encoded by exon 3a or 3b). We exchanged the alternative exon 3 regions between an embryonic isoform and the indirect flight muscle isoform. Each chimeric myosin was expressed in Drosophila indirect flight muscle, in the absence of other myosin isoforms, allowing for purified protein analysis and whole organism locomotory studies. The flight muscle isoform generates higher in vitro actin sliding velocity and solution ATPase rates than the embryonic isoform. Exchanging the embryonic exon 3 region into the flight muscle isoform decreased ATPase rates to embryonic levels but did not affect actin sliding velocity or flight muscle ultrastructure. Interestingly, this swap only slightly impaired flight ability. Exchanging the flight muscle-specific exon 3 region into the embryonic isoform increased actin sliding velocity 3-fold and improved indirect flight muscle ultrastructure integrity but failed to rescue the flightless phenotype of flies expressing embryonic myosin. These results suggest that the two structural versions of the exon 3 domain independently influence the kinetics of at least two steps of the actomyosin cross-bridge cycle. 相似文献
123.
Morrill PR Millington RB Lowe CR 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,793(2):229-251
A surface plasmon resonance (SPR) system for screening ligands for application in affinity chromatography is described. A combinatorial library of 13 ligands was synthesised, characterised and immobilised to agarose beads and gold SPR devices. Binding and elution behaviour and a range of K(AX) values (10(3) to 10(5) M(-1)) were measured against two target proteins, an insulin analogue (MI3) and a recombinant clotting factor (rFVIIa), in order to create a relational database between the traditional chromatographic format and the new SPR screening system. The SPR transducer surface was fabricated with affinity ligands in a two-dimensional, spatially addressable format, which was durable (>100 cycles) and stable over 6 months. The imaging SPR system comprised a direct optical, CCD-based, instrument capable of imaging the change in refractive index created by biochemical interactions and allowed affinity ligands to be evaluated 15-fold faster with 130-fold less target protein than conventional chromatographic methods. The binding and elution data from both the SPR and chromatographic systems for both target proteins were comparable, with the K(AX) value generating a nearly linear correlation (R(2)=0.875) and a slope bias of approximately 2.5+/-0.25-fold higher for the SPR system. The imaging SPR system has proven capable of screening and evaluating affinity ligands for potential use in the recovery of biopharmaceutical proteins. 相似文献
124.
Cross-adaptation and molecular modeling study of receptor mechanisms common to four taste stimuli in humans 总被引:2,自引:2,他引:0
Psychophysical cross-adaptation experiments were performed with two
carbohydrates, sucrose (SUC) and fructose (FRU), and two sweeteners,
acesulfame-K (MOD) and dulcin (DUL). Seven subjects were asked to match
concentrations that elicited the same intensity as a sucrose reference (30
g/l). Cross-adaptation levels were calculated as the ratio of isointense
concentrations measured for a given stimulus before and under adaptation.
On average, cross-adaptation between SUC and FRU is low and apparently
reciprocal. By contrast, cross-adaptation between SUC and MOD is clearly
non-reciprocal: SUC adapts MOD significantly (24%, P < 0.005), but MOD
fails to adapt SUC (2%, P < 0.79). Significant and reciprocal
cross-enhancement is observed between DUL and MOD (approximately -20%, P
< 0.03), and also between SUC and DUL (approximately -15%, P < 0.08).
In parallel, molecular modeling of the four tastants was performed in order
to look for the 12 common binding motifs that were isolated on 14 other
tastants in a previous study. SUC and FRU each display 10 out of the 12
binding motifs, whereas DUL and MOD only display four and five distinct
motifs respectively and do not have any motif in common. Experimental
cross-adaptation levels seem to correlate well with the number of motifs
that molecules have in common. FRU and SUC share a majority of binding
motifs and correlatively show mutual cross-adaptation. Four motifs of MOD
are found among the 10 motifs of SUC, which may explain why SUC
cross-adapts MOD but not vice versa. By contrast, DUL and MOD do not share
any motif and do not cross- adapt. The various molecular mechanisms that
may be responsible for cross-adaptation and/or cross-enhancement are
discussed in light of our results.
相似文献
125.
The evolutionary analysis of the Tnt1 retrotransposon in Nicotiana species reveals the high variability of its regulatory sequences 总被引:2,自引:0,他引:2
We studied the evolution of the tobacco Tnt1 retrotransposon by analyzing
Tnt1 partial sequences containing both coding domains and U3 regulatory
sequences obtained from a number of Nicotiana species. We detected three
different subfamilies of Tnt1 elements, Tnt1A, Tnt1B, and Tnt1C, that
differ completely in their U3 regions but share conserved flanking coding
and LTR regions. U3 divergence between the three subfamilies is found in
the region that contains the regulatory sequences that control the
expression of the well-characterized Tnt1-94 element. This suggests that
expression of the three Tnt1 subfamilies might be differently regulated.
The three Tnt1 subfamilies were present in the Nicotiana genome at the time
of species divergence, but have evolved independently since then in the
different genomes. Each Tnt1 subfamily seems to have conserved its ability
to transpose in a limited and different number of Nicotiana species. Our
results illustrate the high variability of Tnt1 regulatory sequences. We
propose that this high sequence variability could allow these elements to
evolve regulatory mechanisms in order to optimize their coexistence with
their host genome.
相似文献
126.
The growth and division of mitochondria during the cell cycle was investigated by a morphometric analysis of electron micrographs of synchronized HeLa cells. The ratio of total outer membrane contour length to cytoplasmic area did not vary significantly during the cell cycle, implying a continuous growth of the mitochondrial outer membrane. The mean fraction of cytoplasmic area occupied by mitochondrial profiles was likewise found to remain constant, indicating that the increase in total mitochondrial volume per cell occurs continuously during interphase, in such a way that the mitochondrial complement occupies a constant fraction( approximately 10-11(percent)) of the volume of the cytoplasm. The mean area, outer membrane contour length, and axis ratio of the mitochondrial profiles also did not vary appreciably during the cell cycle; furthermore, the close similarity of the frequency distributions of these parameters for the six experimental time-points suggested a stable mitochondrial shape distribution. The constancy of both the mean mitochondrial profile area and the number of mitochondrial profiles per unit of cytoplasmic area was interpreted to indicate the continuous division of mitochondria at the level of the cell population. Furthermore, no evidence was found for the occurrence of synchronous mitochondrial growth and division within individual cells. Thus, it appears that, in HeLa cells, there is no fixed temporal relationship between the growth and division of mitochondria and the events of the cell cycle. A number of statistical methods were developed for the purpose of making numerical estimates of certain three-dimensional cellular and mitochondrial parameters. Mean cellular and cytoplasmic volumes were calculated for the six time-points; both exhibited a nonlinear, approx. twofold increase. A comparison of the axis ratio distributions of the mitochondrial profiles with theoretical distributions expected from random sectioning of bodies of various three-dimensional shapes allowed the derivation of an "average" mitochondrial shape. This, in turn, permitted calculations to be made which expressed the two-dimensional results in three-dimensional terms. Thus, the estimated values for the number of mitochondria per unit of cytoplasmic volume and for the mean mitochondrial volume were found to remain constant during the cell cycle, while the estimated number of mitochondria per cell increase approx. twofold in an essentially continuous manner. 相似文献
127.
We have shown previously that the β-adrenergic agonist isoproterenol (2μM) and the phosphodiesterase inhibitor isobutylmethylxanthine (1 mM) produce a much greater increase in cyclic AMP in human leukocytes that have been pretreated with colchicine (or with other agents that affect microtubule assembly) than in control leukocytes. The effects of colchicines were both time- and dose-dependant. These and other data suggested that the generation of cyclic AMP is normally restricted by an intact system of cytoplasmic microtubules. If so, then the same time and dose dependencies might apply to other colchicines-induced changes in leukocyte function. We have now assayed the distribution of concanavalin A (Con A)-receptor complexes on the leukocyte membrane, taking into account that leukocytes competent to assemble microtubules show a uniform distribution of surface- bound Con A whereas microtubule-deficient cells accumulate Con A in surface caps. We have found that the effect of colchicine on capping is also both time- and dose dependent, and that the dose-response relationships conform to those required to increase cyclic AMP levels. These findings provide further evidence that both colchicine-induced Con-A capping and colchicine- induced cyclic AMP generation depend upon the relaxation of constraints normally imposed by cytoplasmic microtubules upon the plasma membrane, which limit, respectively, lateral mobility of the lectin-receptor complexes, and expression of hormone-sensitive adenylate cyclase. Moreover, colchicine-induced Con-A cap formation is not affected even by very large changes in leukocyte cyclic AMP levels. Thus, elevated cyclic AMP levels do not appear to promote the dissolution of microtubules; rather, the dissolution of microtubules permits the generation of increased amounts of cyclic AMP. 相似文献
128.
Mating patterns in the population of St. Barthélémy, French West Indies, are examined to evaluate the expected genetic consequences of consanguinity avoidance and of failure to mate due to celibacy and emigration. Nearly 60% of all individuals reaching mating age on "St. Bart" never contribute to the gene pool of succeeding generations. This greatly reduces the effective population size and, therefore, increases genetic drift or random inbreeding. The consequent loss of heterozygosity is partially countered by the fact that the individuals who fail to reproduce within the population tend to be more closely related to the population than are those who do reproduce. This nonrandom failure to mate results in nonrandom inbreeding, which reduces total pedigree inbreeding. Total inbreeding is also reduced by consanguinity avoidance. However, the effect of avoiding close consanguineous matings is, to some extent, reversed by an apparent preference for more distant relationships, especially with second cousins. Generally similar results are found for the related Northside French population of St. Thomas. U.S. Virgin Islands. A recently developed mathematical model predicts the expected effect on heterozygosity of partial or complete avoidance of, or preference for, any combination of consanguineous matings, and also takes into account nonrandom failure to mate. Application of this model to these two populations suggests that under some circumstances nonrandomness in celibacy and emigration may have a greater influence on genotype distributions than does consanguinity avoidance. 相似文献
129.
130.