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排序方式: 共有151条查询结果,搜索用时 46 毫秒
31.
Chen-Hui Chen Alexander F. Merriman Jeremiah Savage Jason Willer Taylor Wahlig Nicholas Katsanis Viravuth P. Yin Kenneth D. Poss 《PLoS genetics》2015,11(8)
The first critical stage in salamander or teleost appendage regeneration is creation of a specialized epidermis that instructs growth from underlying stump tissue. Here, we performed a forward genetic screen for mutations that impair this process in amputated zebrafish fins. Positional cloning and complementation assays identified a temperature-sensitive allele of the ECM component laminin beta 1a (lamb1a) that blocks fin regeneration. lamb1a, but not its paralog lamb1b, is sharply induced in a subset of epithelial cells after fin amputation, where it is required to establish and maintain a polarized basal epithelial cell layer. These events facilitate expression of the morphogenetic factors shha and lef1, basolateral positioning of phosphorylated Igf1r, patterning of new osteoblasts, and regeneration of bone. By contrast, lamb1a function is dispensable for juvenile body growth, homeostatic adult tissue maintenance, repair of split fins, or renewal of genetically ablated osteoblasts. fgf20a mutations or transgenic Fgf receptor inhibition disrupt lamb1a expression, linking a central growth factor to epithelial maturation during regeneration. Our findings reveal transient induction of lamb1a in epithelial cells as a key, growth factor-guided step in formation of a signaling-competent regeneration epidermis. 相似文献
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33.
S Elements: A Family of Tc1-like Transposons in the Genome of Drosophila Melanogaster 总被引:2,自引:0,他引:2
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P. J. Merriman C. D. Grimes J. Ambroziak D. A. Hackett P. Skinner M. J. Simmons 《Genetics》1995,141(4):1425-1438
The S elements form a diverse family of long-inverted-repeat transposons within the genome of Drosophila melanogaster. These elements vary in size and sequence, the longest consisting of 1736 bp with 234-bp inverted terminal repeats. The longest open reading frame in an intact S element could encode a 345-amino acid polypeptide. This polypeptide is homologous to the transposases of the mariner-Tc1 superfamily of transposable elements. S elements are ubiquitous in D. melanogaster populations and also appear to be present in the genomes of two sibling species; however, they seem to be absent from 17 other Drosophila species that were examined. Within D. melanogaster strains, there are, on average, 37.4 cytologically detectable S elements per diploid genome. These elements are scattered throughout the chromosomes, but several sites in both the euchromatin and β heterochromatin are consistently occupied. The discovery of an S-element-insertion mutation and a reversion of this mutation indicates that S elements are at least occasionally mobile in the D. melanogaster genome. These elements seem to insert at an AT dinucleotide within a short palindrome and apparently duplicate that dinucleotide upon insertion. 相似文献
34.
Thomas GH; Newbern EC; Korte CC; Bales MA; Muse SV; Clark AG; Kiehart DP 《Molecular biology and evolution》1997,14(12):1285-1295
Many structural, signaling, and adhesion molecules contain tandemly
repeated amino acid motifs. The alpha-actinin/spectrin/dystrophin
superfamily of F-actin-crosslinking proteins contains an array of triple
alpha-helical motifs (spectrin repeats). We present here the complete
sequence of the novel beta-spectrin isoform beta(Heavy)- spectrin (beta H).
The sequence of beta H supports the origin of alpha- and beta-spectrins
from a common ancestor, and we present a novel model for the origin of the
spectrins from a homodimeric actin-crosslinking precursor. The pattern of
similarity between the spectrin repeat units indicates that they have
evolved by a series of nested, nonuniform duplications. Furthermore, the
spectrins and dystrophins clearly have common ancestry, yet the repeat unit
is of a different length in each family. Together, these observations
suggest a dynamic period of increase in repeat number accompanied by
homogenization within each array by concerted evolution. However, today,
there is greater similarity of homologous repeats between species than
there is across repeats within species, suggesting that concerted evolution
ceased some time before the arthropod/vertebrate split. We propose a
two-phase model for the evolution of the spectrin repeat arrays in which an
initial phase of concerted evolution is subsequently retarded as each new
protein becomes constrained to a specific length and the repeats diverge at
the DNA level. This evolutionary model has general applicability to the
origins of the many other proteins that have tandemly repeated motifs.
相似文献
35.
Humaira Rasheed Cushla McKinney Lisa K. Stamp Nicola Dalbeth Ruth K. Topless Richard Day Diluk Kannangara Kenneth Williams Malcolm Smith Matthijs Janssen Tim L. Jansen Leo A. Joosten Timothy R. Radstake Philip L. Riches Anne-Kathrin Tausche Frederic Lioté Leo Lu Eli A. Stahl Hyon K. Choi Alexander So Tony R. Merriman 《PloS one》2016,11(1)
Deposition of crystallized monosodium urate (MSU) in joints as a result of hyperuricemia is a central risk factor for gout. However other factors must exist that control the progression from hyperuricaemia to gout. A previous genetic association study has implicated the toll-like receptor 4 (TLR4) which activates the NLRP3 inflammasome via the nuclear factor-κB signaling pathway upon stimulation by MSU crystals. The T-allele of single nucleotide polymorphism rs2149356 in TLR4 is a risk factor associated with gout in a Chinese study. Our aim was to replicate this observation in participants of European and New Zealand Polynesian (Māori and Pacific) ancestry. A total of 2250 clinically-ascertained prevalent gout cases and 13925 controls were used. Non-clinically-ascertained incident gout cases and controls from the Health Professional Follow-up (HPFS) and Nurses Health Studies (NHS) were also used. Genotypes were derived from genome-wide genotype data or directly obtained using Taqman. Logistic regression analysis was done including age, sex, diuretic exposure and ancestry as covariates as appropriate. The T-allele increased the risk of gout in the clinically-ascertained European samples (OR = 1.12, P = 0.012) and decreased the risk of gout in Polynesians (OR = 0.80, P = 0.011). There was no evidence for association in the HPFS or NHS sample sets. In conclusion TLR4 SNP rs2143956 associates with gout risk in prevalent clinically-ascertained gout in Europeans, in a direction consistent with previously published results in Han Chinese. However, with an opposite direction of association in Polynesians and no evidence for association in a non-clinically-ascertained incident gout cohort this variant should be analysed in other international gout genetic data sets to determine if there is genuine evidence for association. 相似文献
36.
Summary The first morphological examination of the surface and internal anatomy of the kinorhynch, Echinoderes dujardini was undertaken using the scanning and transmission electron microscopes.The oral styles and at least the first ring of scalids were found to have a basal pectinate fringe that resembles the pectinate fringe found at the posterior margins of the trunk segments. In addition to the fringe, the scalids were subdivisible into at least two distinct classes which are similar in structure to the trichoscalid and type I spinocalid identified by Moritz and Storch in T. giganteus. The trichoscalid of E. dujardini however, was found to possess a unique fluted cuticle structure with spines arising only on the medial surface.Although pores are known to occur in the cuticle of homalorhagid kinorhynchs, such pores were not found in the cyclorhagid, E. dujardini.A structure, provisionally designated sensory-like structure is described. Some 60 or more compactly placed spines occur as paired circles or ellipses on all but the terminal trunk segment.An electron dense structure was seen in the subsurface of the placids that may lend mechanical support and may contribute to the Napoleon hats seen with light microscopy. Micrographs of the circumentric nerve ring, gut, epidermis and pharynx are presented. Located at the anterior of the pharynx is a peripharyngeal muscle. The muscle, composed of two membrane bounded smooth muscle strands, probably acts as a sphincter to prevent a reverse flow of food material. Finally, scanning micrographs show a single opening located dorsolaterally on the 10th segment. This opening has been interpreted as an excretory pore even though it does not occur ventrolaterally on the 11th segment as reported for other kinorhynchs.This investigation was supported in part by NIH Contract 70-4136 from the Division of Research Resources. 相似文献
37.
Carolyn J. M. Best Lee R. Tanzer Patricia C. Phelps Ronald L. Merriman George G. Boder Benjamin F. Trump Kathryn A. Elliget 《In vitro cellular & developmental biology. Animal》1999,35(4):205-214
Summary We studied the effect of the ras oncogene on the growth kinetics, morphology, cytoskeletal structure, and tumorigenicity of the widely used NRK-52E rat kidney
epithelial cell line and two H-ras oncogene-transformed cell lines, H/1.2-NRK-52E (H/1.2) and H/6.1-NRK-52E (H/6.1). Population doubling times of NRK-52E, H/1.2,
and H/6.1 cells were 28, 26, and 24 h, respectively, with the transformed cells reaching higher saturation densities than
the parent cells. NRK-52E cells had typical epithelial morphology with growth in colonies. H/1.2 and H/6.1 cell colonies were
more closely packed, highly condensed, and had increased plasma membrane ruffling compared to parent cell colonies. NRK-52E
cells showed microfilament, microtubule, and intermediate filament networks typical of epithelial cells, while H/1.2 and H/6.1
cells showed altered cytoskeleton architecture, with decreased stress fibers and increased microtubule and intermediate filament
staining at the microtubule organizing center. H/1.2 and H/6.1 cells proliferated in an in vitro soft agar transformation
assay, indicating anchorage-independence, and rapidly formed tumors in vivo with characteristics of renal cell carcinoma,
including mixed populations of sarcomatoid, granular, and clear cells, H/6.1 cells consistently showed more extensive alterations
of growth kinetics, morphology, and cytoskeleton than H/1.2 cells, and formed tumors of a more aggressive phenotype. These
data suggest that analysis of renal cell characteristics in vitro may have potential in predicting tumor behavior in vivo,
and significantly contribute to the utility of these cell lines as in vitro models for examining renal epithelial cell biology
and the role of the ras proto-oncogene in signal transduction involving the cytoskeleton. 相似文献
38.
Christopher S. Stach Bao G. Vu Joseph A. Merriman Alfa Herrera Michael P. Cahill Patrick M. Schlievert Wilmara Salgado-Pabón 《PloS one》2016,11(4)
BackgroundSuperantigens are indispensable virulence factors for Staphylococcus aureus in disease causation. Superantigens stimulate massive immune cell activation, leading to toxic shock syndrome (TSS) and contributing to other illnesses. However, superantigens differ in their capacities to induce body-wide effects. For many, their production, at least as tested in vitro, is not high enough to reach the circulation, or the proteins are not efficient in crossing epithelial and endothelial barriers, thus remaining within tissues or localized on mucosal surfaces where they exert only local effects. In this study, we address the role of TSS toxin-1 (TSST-1) and most importantly the enterotoxin gene cluster (egc) in infective endocarditis and sepsis, gaining insights into the body-wide versus local effects of superantigens.MethodsWe examined S. aureus TSST-1 gene (tstH) and egc deletion strains in the rabbit model of infective endocarditis and sepsis. Importantly, we also assessed the ability of commercial human intravenous immunoglobulin (IVIG) plus vancomycin to alter the course of infective endocarditis and sepsis.ResultsTSST-1 contributed to infective endocarditis vegetations and lethal sepsis, while superantigens of the egc, a cluster with uncharacterized functions in S. aureus infections, promoted vegetation formation in infective endocarditis. IVIG plus vancomycin prevented lethality and stroke development in infective endocarditis and sepsis.ConclusionsOur studies support the local tissue effects of egc superantigens for establishment and progression of infective endocarditis providing evidence for their role in life-threatening illnesses. In contrast, TSST-1 contributes to both infective endocarditis and lethal sepsis. IVIG may be a useful adjunct therapy for infective endocarditis and sepsis. 相似文献
39.
40.
Annemarie MM Vlaar Marinus JPG van Kroonenburgh Alfons GH Kessels Wim EJ Weber 《BMC neurology》2007,7(1):27