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311.
312.
Jahoda CA Kljuic A O'Shaughnessy R Crossley N Whitehouse CJ Robinson M Reynolds AJ Demarchez M Porter RM Shapiro L Christiano AM 《Genomics》2004,83(5):747-756
Desmosomal cadherins are essential cell adhesion molecules present throughout the epidermis and other organs, whose major function is to provide mechanical integrity and stability to epithelial cells in a wide variety of tissues. We recently identified a novel desmoglein family member, Desmoglein 4 (Dsg4), using a positional cloning approach in two families with localized autosomal recessive hypotrichosis (LAH) and in the lanceolate hair (lah) mouse. In this study, we report cloning and identification of the rat Dsg4 gene, in which we discovered a missense mutation in a naturally occurring lanceolate hair (lah) rat mutant. Phenotypic analysis of lah/lah mutant rats revealed a striking hair shaft defect with the appearance of a lance head within defective hair shafts. The mutation disrupts a critical calcium binding site bridging the second and third extracellular domains of Dsg4, likely disrupting extracellular interactions of the protein. 相似文献
313.
Elmasri H Winkler C Liedtke D Sasado T Morinaga C Suwa H Niwa K Henrich T Hirose Y Yasuoka A Yoda H Watanabe T Deguchi T Iwanami N Kunimatsu S Osakada M Loosli F Quiring R Carl M Grabher C Winkler S Del Bene F Wittbrodt J Abe K Takahama Y Takahashi K Katada T Nishina H Kondoh H Furutani-Seiki M 《Mechanisms of development》2004,121(7-8):659-671
The metameric structure of the vertebrate trunk is generated by repeated formation of somites from the unsegmented presomitic mesoderm (PSM). We report the initial characterization of nine different mutants affecting segmentation that were isolated in a large-scale mutagenesis screen in Medaka (Oryzias latipes). Four mutants were identified that show a complete or partial absence of somites or somite boundaries. In addition, five mutations were found that cause fused somites or somites with irregular sizes and shapes. In situ hybridization analysis using specific markers involved in the segmentation clock and antero-posterior (A-P) polarity of somites revealed that the nine mutants can be compiled into two groups. In group 1, mutants exhibit defects in tailbud formation and PSM prepatterning, whereas A-P identity in the somites is defective in group 2 mutants. Three mutants (planlos, pll; schnelles ende, sne; samidare, sam) have characteristic phenotypes that are similar to those in zebrafish mutants affected in the Delta/Notch signaling pathway. The majority of mutants, however, exhibit somitic phenotypes distinct from those found in zebrafish, such as individually fused somites and irregular somite sizes. Thus, these Medaka mutants can be expected to provide clues to uncovering novel components essential for somitogenesis. 相似文献
314.
Wingert RA Brownlie A Galloway JL Dooley K Fraenkel P Axe JL Davidson AJ Barut B Noriega L Sheng X Zhou Y Zon LI 《Development (Cambridge, England)》2004,131(24):6225-6235
Iron is a crucial metal for normal development, being required for the production of heme, which is incorporated into cytochromes and hemoglobin. The zebrafish chianti (cia) mutant manifests a hypochromic, microcytic anemia after the onset of embryonic circulation, indicative of a perturbation in red blood cell hemoglobin production. We show that cia encodes tfr1a, which is specifically expressed in the developing blood and requisite only for iron uptake in erythroid precursors. In the process of isolating zebrafish tfr1, we discovered two tfr1-like genes (tfr1a and tfr1b) and a single tfr2 ortholog. Abrogation of tfr1b function using antisense morpholinos revealed that this paralog was dispensable for hemoglobin production in red cells. tfr1b morphants exhibited growth retardation and brain necrosis, similar to the central nervous system defects observed in the Tfr1 null mouse, indicating that tfr1b is probably used by non-erythroid tissues for iron acquisition. Overexpression of mouse Tfr1, mouse Tfr2, and zebrafish tfr1b partially rescued hypochromia in cia embryos, establishing that each of these transferrin receptors are capable of supporting iron uptake for hemoglobin production in vivo. Taken together, these data show that zebrafish tfr1a and tfr1b share biochemical function but have restricted domains of tissue expression, and establish a genetic model to study the specific function of Tfr1 in erythroid cells. 相似文献
315.
Bani-Yaghoub M Kendall SE Moore DP Bellum S Cowling RA Nikopoulos GN Kubu CJ Vary C Verdi JM 《Development (Cambridge, England)》2004,131(17):4287-4298
Reports of non-neural differentiation of neural stem cells (NSCs) have been challenged by alternative explanations for expanded differentiation potentials. In an attempt to demonstrate the plasticity of NSC, neurospheres were generated from single retrovirally labeled embryonic cortical precursors. In a defined serum-free insulin-containing media, 40% of the neurospheres contained both myogenic and neurogenic differentiated progeny. The number of NSCs displaying multilineage differentiation potential declines through gestation but does exist in the adult animal. In this system, insulin appears to function as a survival and dose-dependent myogenic differentiation signal for multilineage NSCs (MLNSC). MLNSC-derived cardiomyocytes contract synchronously, respond to sympathetic and parasympathetic stimulation, and regenerate injured heart tissues. These studies provide support for the hypothesis that MLNSCs exist throughout the lifetime of the animal, and potentially provide a population of stem cells for cell-based regenerative medicine strategies inside and outside of the nervous system. 相似文献
316.
A modified method for determining protein binding capacity of plant polyphenolics using radiolabelled protein 总被引:1,自引:0,他引:1
Henson GL Niemeyer L Ansong G Forkner R Makkar HP Hagerman AE 《Phytochemical analysis : PCA》2004,15(3):159-163
A modified radiochemical protein binding method for determining the protein binding capacity of plant polyphenolics (tannins) is described. Purified tannin or unfractionated plant extracts were immobilised on filter paper discs and incubated with the 125I-labelled bovine serum albumin. Protein bound to the disc was proportional to the amount of tannin applied to the disc, although at high concentrations of polyphenolics the discs became saturated and the relationship was no longer applicable. The method was validated using purified procyanidin from Sorghum grain and has been applied to crude polyphenolic extracts from maple, white oak, black oak, walnut and tulip poplar leaves. Specific chemical assays for the determination of proanthocyanidins (acid butanol method) and hydrolysable tannins (modified potassium iodate method) were employed to validate the new protein binding method with the complex plant extracts. 相似文献
317.
5-lipoxygenase and cyclooxygenase regulate wound closure in NIH/3T3 fibroblast monolayers 总被引:1,自引:0,他引:1
Green JA Stockton RA Johnson C Jacobson BS 《American journal of physiology. Cell physiology》2004,287(2):C373-C383
Wound healing involves multiple cell signaling pathways, including those regulating cell-extracellular matrix adhesion. Previous work demonstrated that arachidonate oxidation to leukotriene B4 (LTB4) by 5-lipoxygenase (5-LOX) signals fibroblast spreading on fibronectin, whereas cyclooxygenase-2 (COX-2)-catalyzed prostaglandin E2 (PGE2) formation facilitates subsequent cell migration. We investigated arachidonate metabolite signaling in wound closure of perturbed NIH/3T3 fibroblast monolayers. We found that during initial stages of wound closure (0120 min), all wound margin cells spread into the wound gap perpendicularly to the wound long axis. At regular intervals, between 120 and 300 min, some cells elongated to project across the wound and meet cells from the opposite margin, forming distinct cell bridges spanning the wound that act as foci for later wound-directed cell migration and resulting closure. 5-LOX inhibition by AA861 demonstrated a required LTB4 signal for initial marginal cell spreading and bridge formation, both of which must precede wound-directed cell migration. 5-LOX inhibition effects were reversible by exogenous LTB4. Conversely, COX inhibition by indomethacin reduced directed migration into the wound but enhanced early cell spreading and bridge formation. Exogenous PGE2 reversed this effect and increased cell migration into the wound. The differential effects of arachidonic acid metabolites produced by LOX and COX were further confirmed with NIH/3T3 fibroblast cell lines constitutively over- and underexpressing the 5-LOX and COX-2 enzymes. These data suggest that two competing oxidative enzymes in arachidonate metabolism, LOX and COX, differentially regulate sequential aspects of fibroblast wound closure in vitro. leukotriene B4; prostaglandin E2; spreading; migration; bridges 相似文献
318.
Five pigeons performed in a delayed matching-to-sample (DMTS) procedure with five delay durations (0.5, 2.5, 5, 10 and 20 s) mixed within sessions. Contrary to the predictions of need probability theory, discriminability decreased when fewer short than long delays were included in each session. To test whether the decrease in discriminability was due to a decrease in obtained reinforcement at short delays, the number of trials at each delay was held constant and reinforcer probability was increased with increasing delay. This manipulation produced a similar decrease in discriminability as when the frequency of delays was manipulated. It was concluded that the effect of delay frequency on the forgetting function is mediated by the effect of the reinforcer distribution, which influences discriminability by weakening stimulus control. 相似文献
319.
Overexpression of phytochelatin synthase in Arabidopsis leads to enhanced arsenic tolerance and cadmium hypersensitivity 总被引:1,自引:0,他引:1
Li Y Dhankher OP Carreira L Lee D Chen A Schroeder JI Balish RS Meagher RB 《Plant & cell physiology》2004,45(12):1787-1797
Phytochelatin synthase (PCS) catalyzes the final step in the biosynthesis of phytochelatins, which are a family of cysteine-rich thiol-reactive peptides believed to play important roles in processing many thiol-reactive toxicants. A modified Arabidopsis thaliana PCS sequence (AtPCS1) was active in Escherichia coli. When AtPCS1 was overexpressed in Arabidopsis from a strong constitutive Arabidopsis actin regulatory sequence (A2), the A2::AtPCS1 plants were highly resistant to arsenic, accumulating 20-100 times more biomass on 250 and 300 microM arsenate than wild type (WT); however, they were hypersensitive to Cd(II). After exposure to cadmium and arsenic, the overall accumulation of thiol-peptides increased to 10-fold higher levels in the A2::AtPCS1 plants compared with WT, as determined by fluorescent HPLC. Whereas cadmium induced greater increases in traditional PCs (PC2, PC3, PC4), arsenic exposure resulted in the expression of many unknown thiol products. Unexpectedly, after arsenate or cadmium exposure, levels of the dipeptide substrate for PC synthesis, gamma-glutamyl cysteine (gamma-EC), were also dramatically increased. Despite these high thiol-peptide concentrations, there were no significant increases in concentrations of arsenic and cadmium in above-ground tissues in the AtPCS1 plants relative to WT plants. The potential for AtPCS1 overexpression to be useful in strategies for phytoremediating arsenic and to compound the negative effects of cadmium are discussed. 相似文献
320.
Experimentally intrauterine (IU) viral inoculation has been commonly used to circumvent maternal interference with transplacental infection of fetuses and to assess the effect of viral infection on fetal development or reproductive parameters. However, IU inoculation requires surgical procedures such as laparatomy and surgical incision of the uterus. Post-surgical complications, that frequently result in abortion or fetal death, have been a major disadvantage. An animal trial was conducted to evaluate the non-surgical procedure of ultrasound needle-guided transabdominal injection for IU inoculation of porcine circovirus type 2 (PCV2) since this virus has been reported to cause reproductive failure in pigs. Two groups of seven pregnant sows at mid- and late-gestation, respectively, were inoculated with PCV2 using an ultrasound needle-guided technique that delivered PCV2 directly into one of the fluid-filled fetal compartments. The effect of transabdominal in utero virus challenge on fetuses and sows was assessed until term. While five of six sham-inoculated control sows had no or minimal adverse affects from in utero injection, 10 of 14 virus-inoculated sows had dead and/or stillborn piglets and PCV2 infection was evident by polymerase chain reaction and/or immunohistochemistry. These results supported previous field and experimental observations that PCV2 may cause reproductive failure. In conclusion, ultrasound needle-guided transabdominal injection was a safe and efficient method for IU inoculation of virus in pigs. 相似文献