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32.
This paper reports reconstitution of 5'-nick-directed mismatch repair using purified human proteins. The reconstituted system includes MutSalpha or MutSbeta, MutLalpha, RPA, EXO1, HMGB1, PCNA, RFC, polymerase delta, and ligase I. In this system, MutSbeta plays a limited role in repair of base-base mismatches, but it processes insertion/deletion mispairs much more efficiently than MutSalpha, which efficiently corrects both types of heteroduplexes. MutLalpha reduces the processivity of EXO1 and terminates EXO1-catalyzed excision upon mismatch removal. In the absence of MutLalpha, mismatch-provoked excision by EXO1 occurs extensively. RPA and HMGB1 play similar but complementary roles in stimulating MutSalpha-activated, EXO1-catalyzed excision in the presence of a mismatch, but RPA has a distinct role in facilitating MutLalpha-mediated excision termination past mismatch. Evidence is provided that efficient repair of a single mismatch requires multiple molecules of MutSalpha-MutLalpha complex. These data suggest a model for human mismatch repair involving coordinated initiation and termination of mismatch-provoked excision. 相似文献
33.
Axillary clearance provides important prognostic information but is associated with significant morbidity. Sentinel node biopsy can provide staging .141 patients with node negative early breast cancers-tumour size less than 1.5 cm measured clinically or by imaging had guided axillary sampling (sentinel lymph node biopsy in combination with axillary sampling). Four node axillary sampling improved the detection rate of axillary node metastases by 13.6% as compared to blue dye sentinel node biopsy alone. Positive sampled nodes strongly indicated the likelihood of further metastatic being revealed by axillary dissection (67%). Negative sampled nodes in combination with a positive sentinel node biopsy were associated with a much lower rate of further nodal involvement in the axillary clearance (8%). 相似文献
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35.
Experimental and theoretical studies of the three-dimensional structure of human interleukin-4 总被引:2,自引:0,他引:2
B M Curtis S R Presnell S Srinivasan H Sassenfeld R Klinke E Jeffery D Cosman C J March F E Cohen 《Proteins》1991,11(2):111-119
The structure of human interleukin 4 (IL-4) was predicted utilizing a series of experimental and theoretical techniques. Circular Dichroism (CD) spectroscopy indicated that IL-4 belonged to the all alpha-helix class of protein structures. Secondary structure prediction, site-directed mutagenesis, and CD spectroscopy suggested a predominantly alpha-helical structure, consistent with a four-helix bundle structural motif. A human/mouse IL-4 chimera was constructed to qualitatively evaluate alternative secondary structure predictions. The four predicted helices were assembled into tertiary structures using established algorithms. The mapping of three disulfide bridges in IL-4 provided additional constraints on possible tertiary structures. Using accessible surface contact area as a criterion, the most suitable structures were right handed all antiparallel four-helix bundles with two overhand loop connections. Successful loop closure and incorporation of the three disulfide constraints were possible while maintaining the expected shape, solvent accessibility, and steric interactions between loops and helices. Lastly, energy minimization was used to regularize the chain. 相似文献
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The efficiencies of two 24-hr elevated-temperature tests to recover Escherichia coli from estaurine water were compared simultaneously with the 72-hr standard methods procedure of the American Public Health Association (APHA). From 1,710 tubes, E. coli was recovered 222 times in lauryl tryptose medium incubated at 44 ± 0.2 C for 24 hr, 261 times in an experimental medium incubated at 44.5 ± 0.2 C for 24 hr, and 257 times by the 72-hr APHA method. The number of false positives enumerated was similar in all three tests. The data indicated that E. coli in raw seawater could be determined in 24 hr without a significant loss of accuracy. 相似文献
38.
V?Srinivasan GJM?Maestroni DP?Cardinali AI?Esquifino SR?Pandi?Perumal SC?MillerEmail author 《Immunity & ageing : I & A》2005,2(1):17
Aging is associated with a decline in immune function (immunosenescence), a situation known to correlate with increased incidence
of cancer, infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration
with age. A decrease in functional competence of individual natural killer (NK) cells is found with advancing age. Macrophages
and granulocytes show functional decline in aging as evidenced by their diminished phagocytic activity and impairment of superoxide
generation. There is also marked shift in cytokine profile as age advances, e.g., CD3+ and CD4+ cells decline in number whereas
CD8+ cells increase in elderly individuals. A decline in organ specific antibodies occurs causing reduced humoral responsiveness.
Circulating melatonin decreases with age and in recent years much interest has been focused on its immunomodulatory effect.
Melatonin stimulates the production of progenitor cells for granulocytes-macrophages. It also stimulates the production of
NK cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from NK cells and T-helper
lymphocytes also are enhanced by melatonin. Melatonin presumably regulates immune function by acting on the immune-opioid
network, by affecting G protein-cAMP signal pathway and by regulating intracellular glutathione levels. Melatonin has the
potential therapeutic value to enhance immune function in aged individuals and in patients in an immunocompromised state. 相似文献
39.
MCWHINNIE MARY A.; CAHOON MARY ODILE SR.; JOHANNECK ROSEMARIE 《Integrative and comparative biology》1969,9(3):841-855
Cyclic shifts of calcium in the exoskeleton and soft tissues,as they are related to the intermolt cycle in crayfish, arereviewed. Regulatory factors, derived from the eyestalk, influencelevels of exoskeletal calcium; eyestalk extracts prepared fromanimals in premolt decrease shell calcium, while reciprocallyextracts from animals in intermolt increase it when these hormonalsources are injected into animals in the premolt stage (D0-D4). In addition, premolt eyestalk extract results in an increasein gastrolith calcium. In the exchange of calcium between theanimal and its environment there is evidence for differentialdepositionof recently available calcium in the exoskeleton. Further, intermoltand early premolt animals maintained in Ca45-labelled waterfor 15 days concentrate it 4 and 3fold in the exoskeletonand stomach, respectively. However, removal of a molt-inhibitingfactor through ablation of eyestalks results in a 20 and 40foldincrease in incorporation inthese same sites relative to environmentalconcentrations. Treatment with mammalian parathyroid extract mobilizes bothexoskeletal and gastric calciumand leads to a rise in bloodcalcium. However, there is little or no effect on levels ofexoskeletal citric acid. Further, citric acid is higher in thecrayfish carapace during stage C, the period of mineralization,than in stage D, the period of demineralization. There are both similarities and differences between the effectsof crustacean and mammalianregulating factors with respect tothe direction and extent of mineralization. Biochemical studiesshould elucidate the mechanisms regulated by these hormones. 相似文献
40.
The partition matrix: exploring variable phylogenetic signals along nucleotide sequence alignments 总被引:6,自引:2,他引:4
The partition matrix is a graphical tool for comparative analysis of
nucleotide sequences following alignment. It is particularly useful for
investigating the divergent phylogenies of sequence regions undergoing
reticulate evolution. A partition matrix is generated by determining the
consistency of the parsimoniously informative sites in a set of aligned
sequences with the binary partitions inferred from the sequences. Since the
linear order of sites is maintained, the matrix can be used to assess
whether the distribution of sites either supporting or conflicting with
particular partitions changes along the length of the alignment. The
usefulness of the matrix in allowing visual identification of differences
in evolutionary history among regions depends on the order in which
partitions are shown; several suitable ordering schemes are proposed. We
demonstrate the use of the partition matrix in interpreting the evolution
of the pseudoautosomal boundary region on the sex chromosome of catarrhine
primates. Its routine use should help to avoid attempts to derive single
phylogenies from sequences whose evolution has been reticulate and to
identify the gene conversion or recombination events underlying the
reticulation. The method is relatively fast. It is exploratory, and it can
form the basis for more formal analysis, which we discuss.
相似文献