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1.
The effects of mispair and nonpair correction in hybrid DNA on base ratios (G + C content) and total amounts of DNA 总被引:1,自引:0,他引:1
Base ratios and total DNA amounts can vary substantially between and within
higher taxa and genera, and even within species. Gene conversion is one of
several mechanisms that could cause such changes. For base substitutions,
disparity in conversion direction is accompanied by an equivalent disparity
in base ratio at the heterozygous site. Disparity in the direction of gene
conversion at meiosis is common and can be extreme. For transitions (which
give purine [R]/pyrimidine [Y] mispairs) and for transversions giving
unlike R/R and Y/Y mispairs in hybrid DNA, this disparity could give slow
but systematic changes in G + C percentage. For transversions giving like
R/R and Y/Y mispairs, it could change AT/TA and CG/GC ratios. From the
extent of correction direction disparity, one can deduce properties of
repair enzymes, such as the ability (1) to excise preferentially the purine
from one mispair and the pyrimidine from the other for two different R/Y
mispairs from a single heterozygous site and (2) to excise one base
preferentially from unlike R/R or Y/Y mispairs. Frame-shifts usually show
strong disparity in conversion direction, with preferential cutting of the
nonlooped or the looped-out strand of the nonpair in heterozygous h-DNA.
The opposite directions of disparity for frame-shifts and their intragenic
suppressors as Ascobolus suggest that repair enzymes have a strong,
systematic bias as to which strand is cut. The conversion spectra of
mutations induced with different mutagens suggest that the nonlooped strand
is preferentially cut, so that base additions generally convert to mutant
and deletions generally convert to wild-type forms. Especially in
nonfunctional or noncoding DNA, this could cause a general increase in DNA
amounts. Conversion disparity, selection, mutation, and other processes
interact, affecting rates of change in base ratios and total DNA.
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In the post-natal growth plate, chondrocytes are arranged in columns parallel to the long axis of the bone. Chondrocytes divide perpendicular to this axis and then move into position one on top of another in a process called "rotation" that maintains columnar organization. Primary cilia are non-motile microtubule base appendages extending from the surface of almost all vertebrate cells. Primary cilia were described on chondrocytes almost 40 years ago but the function of these structures in cartilage biology is not known. Intraflagellar transport (IFT) is the process by which primary cilia are generated and maintained. This study tested the hypothesis that IFT plays an important role in post-natal skeletal development. Kif3a, a subunit of the Kinesin II motor complex, that is required for intraflagellar transport and the formation of cilia, was deleted in mouse chondrocytes via Col2a-Cre-mediated recombination. Disruption of IFT resulted in subsequent depletion of cilia and post-natal dwarfism due to premature loss of the growth plate likely a result of reduced proliferation and accelerated hypertrophic differentiation of chondrocytes. Cell shape and columnar orientation in the growth plate were also disrupted suggesting a defect in the process of rotation. Alterations in chondrocyte rotation were accompanied by disruption of the actin cytoskeleton and alterations in the localization of activated FAK to focal adhesion-like structures on chondrocytes. This is the first report indicating a role for IFT and primary cilia in the development of the post-natal growth plate. The results suggest a model in which IFT/cilia act to maintain the columnar organization of the growth plate via the process of chondrocyte rotation. 相似文献
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CABYR, a novel calcium-binding tyrosine phosphorylation-regulated fibrous sheath protein involved in capacitation 总被引:8,自引:0,他引:8
Naaby-Hansen S Mandal A Wolkowicz MJ Sen B Westbrook VA Shetty J Coonrod SA Klotz KL Kim YH Bush LA Flickinger CJ Herr JC 《Developmental biology》2002,242(2):236-254
To reach fertilization competence, sperm undergo an incompletely understood series of morphological and molecular maturational processes, termed capacitation, involving, among other processes, protein tyrosine phosphorylation and increased intracellular calcium. Hyperactivated motility and an ability to undergo the acrosome reaction serve as physiological end points to assess successful capacitation. We report here that acidic (pI 4.0) 86-kDa isoforms of a novel, polymorphic, testis-specific protein, designated calcium-binding tyrosine phosphorylation-regulated protein (CABYR), were tyrosine phosphorylated during in vitro capacitation and bound (45)Ca on 2D gels. Acidic 86-kDa calcium-binding forms of CABYR increased during in vitro capacitation, and calcium binding to these acidic forms was abolished by dephosphorylation with alkaline phosphatase. Six variants of CABYR containing two coding regions (CR-A and CR-B) were cloned from human testis cDNA libraries, including five variants with alternative splice deletions. A motif homologous to the RII dimerization domain of PK-A was present in the N-terminus of CR-A in four CABYR variants. A single putative EF handlike motif was noted in CR-A at aas 197-209, while seven potential tyrosine phosphorylation-like sites were noted in CR-A and four in CR-B. Pro-X-X-Pro (PXXP) modules were identified in the N- and C-termini of CR-A and CR-B. CABYR localizes to the principal piece of the human sperm flagellum in association with the fibrous sheath and is the first demonstration of a sperm protein that gains calcium-binding capacity when phosphorylated during capacitation. 相似文献
7.
Telomere shortening impairs organ regeneration by inhibiting cell cycle re-entry of a subpopulation of cells 下载免费PDF全文
Satyanarayana A Wiemann SU Buer J Lauber J Dittmar KE Wüstefeld T Blasco MA Manns MP Rudolph KL 《The EMBO journal》2003,22(15):4003-4013
Telomere shortening limits the regenerative capacity of primary cells in vitro by inducing cellular senescence characterized by a permanent growth arrest of cells with critically short telomeres. To test whether this in vitro model of cellular senescence applies to impaired organ regeneration induced by telomere shortening in vivo, we monitored liver regeneration after partial hepatectomy in telomerase-deficient mice. Our study shows that telomere shortening is heterogeneous at the cellular level and inhibits a subpopulation of cells with critically short telomeres from entering the cell cycle. This subpopulation of cells with impaired proliferative capacity shows senescence-associated beta-galactosidase activity, while organ regeneration is accomplished by cells with sufficient telomere reserves that are capable of additional rounds of cell division. This study provides experimental evidence for the existence of an in vivo process of cellular senescence induced by critical telomere shortening that has functional impact on organ regeneration. 相似文献
8.
Changes in Hechtian strands in cold-hardened cells measured by optical microsurgery 总被引:1,自引:0,他引:1 下载免费PDF全文
Optical microsurgical techniques were employed to investigate the mechanical properties of Hechtian strands in tobacco (Nicotiana tabacum) and Ginkgo biloba callus cells. Using optical tweezers, a 1. 5-microm diameter microsphere coated with concanavalin A was inserted though an ablated hole in the cell wall of a plasmolyzed cell and attached to a Hechtian strand. By displacing the adhered microsphere from equilibrium using the optical trapping force, the tensions of individual strands were determined. Measurements were made using both normal and cold-hardened cells, and in both cases, tensions were on the order of 10(-12) N. Significant differences were found in the binding strengths of cold-hardened and normal cultured cells. An increased number density of strands in cold-hardened G. biloba compared with normal cultured cells was also observed. Although no Hechtian strands were detected in any Arabidopsis callus cells, strands were present in leaf epidermal cells. Finally, the movement of attached microspheres was monitored along the outside of a strand while cycling the osmotic pressure. 相似文献
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Daniela Beisser Julia Kolter Anna M Sigmund Jörg Steinmann Simon Schäfer Hubertus Hochrein Sven Rahmann Hermann Wagner Philipp Henneke Veit Hornung Jan Buer Carsten J Kirschning 《EMBO reports》2015,16(12):1656-1663
Toll‐like receptor (TLR) 13 and TLR2 are the major sensors of Gram‐positive bacteria in mice. TLR13 recognizes Sa19, a specific 23S ribosomal (r) RNA‐derived fragment and bacterial modification of Sa19 ablates binding to TLR13, and to antibiotics such as erythromycin. Similarly, RNase A‐treated Staphylococcus aureus activate human peripheral blood mononuclear cells (PBMCs) only via TLR2, implying single‐stranded (ss) RNA as major stimulant. Here, we identify human TLR8 as functional TLR13 equivalent that promiscuously senses ssRNA. Accordingly, Sa19 and mitochondrial (mt) 16S rRNA sequence‐derived oligoribonucleotides (ORNs) stimulate PBMCs in a MyD88‐dependent manner. These ORNs, as well as S. aureus‐, Escherichia coli‐, and mt‐RNA, also activate differentiated human monocytoid THP‐1 cells, provided they express TLR8. Moreover, Unc93b1
−/−‐ and Tlr8
−/−‐THP‐1 cells are refractory, while endogenous and ectopically expressed TLR8 confers responsiveness in a UR/URR RNA ligand consensus motif‐dependent manner. If TLR8 function is inhibited by suppression of lysosomal function, antibiotic treatment efficiently blocks bacteria‐driven inflammatory responses in infected human whole blood cultures. Sepsis therapy might thus benefit from interfering with TLR8 function. 相似文献
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M Matsuda A Tazumi S Kagawa T Sekizuka O Murayama JE Moore BC Millar 《BMC veterinary research》2006,2(1):1-4