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71.
Phenotypic characterization of Bbs4 null mice reveals age-dependent penetrance and variable expressivity 总被引:1,自引:0,他引:1
Eichers ER Abd-El-Barr MM Paylor R Lewis RA Bi W Lin X Meehan TP Stockton DW Wu SM Lindsay E Justice MJ Beales PL Katsanis N Lupski JR 《Human genetics》2006,120(2):211-226
Bardet-Biedl syndrome (BBS) is a rare oligogenic disorder exhibiting both clinical and genetic heterogeneity. Although the BBS phenotype is variable both between and within families, the syndrome is characterized by the hallmarks of developmental and learning difficulties, post-axial polydactylia, obesity, hypogenitalism, renal abnormalities, retinal dystrophy, and several less frequently observed features. Eleven genes mutated in BBS patients have been identified, and more are expected to exist, since about 20–30% of all families cannot be explained by the known loci. To investigate the etiopathogenesis of BBS, we created a mouse null for one of the murine homologues, Bbs4, to assess the contribution of one gene to the pleiotropic murine Bbs phenotype. Bbs4 null mice, although initially runted compared to their littermates, ultimately become obese in a gender-dependent manner, females earlier and with more severity than males. Blood chemistry tests indicated abnormal lipid profiles, signs of liver dysfunction, and elevated insulin and leptin levels reminiscent of metabolic syndrome. As in patients with BBS, we found age-dependent retinal dystrophy. Behavioral assessment revealed that mutant mice displayed more anxiety-related responses and reduced social dominance. We noted the rare occurrence of birth defects, including neural tube defects and hydrometrocolpos, in the null mice. Evaluations of these null mice have uncovered phenotypic features with age-dependent penetrance and variable expressivity, partially recapitulating the human BBS phenotype.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at . 相似文献
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73.
ISABELLA URRU JOHANNES STÖKL JEANINE LINZ TAMARA KRÜGEL MARCUS C. STENSMYR BILL S. HANSSON 《Biological journal of the Linnean Society. Linnean Society of London》2010,101(4):991-1001
Flowers of the genus Arum are known to attract dung‐breeding flies and beetles through olfactory deceit. In addition to this strategy, the genus has evolved several other pollination mechanisms. The present study aimed to characterize the pollination strategies of the Cretan Arum species by investigating the flowering phenology, thermogeny, inflorescence odours, and the pollinating fauna. The results obtained show that Arum cyrenaicum and Arum concinnatum emit a strong dung smell and exhibit the distinctive features associated with this pollination syndrome. Both species are highly thermogenic, have a similar odour profile and attract small‐bodied Diptera. Although sharing the same habitat, these two plant species are never found growing sympatrically as a result of the early blooming period of A. cyrenaicum. By contrast, Arum creticum and Arum idaeum have evolved a more traditional and mutually beneficial pollination mechanism. The stinking smell has been replaced by a more flower‐like odour that attracts bees (Lasioglossum sp.) and, occasionally, bugs (Dionconotus cruentatus). Although attracting the same pollinator, the main compound present in the odour of A. creticum is different from that of A. idaeum. Principal component analysis (PCA), based on physiologically active components of the flower odours determined by testing on the antenna of the Lasioglossum bee, revealed two different clusters, indicating that pollinators can potentially discriminate between the odours of the two species. A further PCA on the main floral odour volatiles as identified by gas chroatography‐mass spectroscopy from all the Arum species under investigation displayed odour‐based similarities and differences among the species. The PCA‐gas chomotography‐electroantennographic detection active peaks analysis showed that the two species, A. creticum and A. idaeum, form two groups and are clearly separated from A. cyrenaicum and A. concinnatum, which, conversely, cluster together. The evolutionary forces and selective pressures leading to diversification of pollination mechanisms in the Cretan Arum spp. are discussed. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 101 , 991–1001. 相似文献
74.
BACKGROUND: PBMC can be expanded ex vivo into aggressive cytotoxic effector cells (CEC) comprising T, NK and NKT cells. We identified the phenotype, cytotoxicity and mechanisms of killing of these CEC. METHODS: CY- and G-CSF-mobilized PBMC from myeloma patients were placed in Aim-V serum-free medium, IL-2 (50 IU/mL) and OKT-3 (50 ng/mL). Cytotoxicity was evaluated by selectively blocking the TCR, MHC class I or NKG2D receptor. RESULTS: The CEC expanded three-fold by day 7 and aggressively lysed myeloma cells (41.9%) compared with day 0 (4%; P=0.012). CD8+ CD56+ NKT cells performed the majority of lysis. The CD8+ cells greatly increased NKG2D expression during culture (P=0.005). Cytotoxicity correlated with target NKG2D ligand expression (P=0.0002). Blocking the TCR or MHC class I did not affect cytotoxicity (P>0.22). CD8+ cell-mediated lysis dropped 48% when the NKG2D receptor was blocked. Day 7 CEC aggressively lysed myeloma cells in an MHC- and non-MHC-restricted fashion, through the NKG2D receptor. DISCUSSION: Because MHC expression is often down-regulated on tumor cells and the NKG2D ligands are generally specific to malignant cells, the adoptive transfer of CEC that kill through different pathways may circumvent tumor-resistant mechanisms and improve outcomes. 相似文献
75.
Meehan TD 《Physiological and biochemical zoology : PBZ》2006,79(5):878-884
Metabolic scaling theory provides a framework for modeling the combined mass and temperature dependence of metabolic rate. The theory predicts that whole-organism metabolic rate should scale with body mass raised to the 3/4 power as a consequence of the physical characteristics of internal distribution networks. Metabolic rate is predicted to vary with absolute body temperature, T, according to the Boltzmann factor, e(-E/kT), where E is the apparent activation energy of biochemical reactions, 0.2-1.2 eV, and k is Boltzmann's constant. I evaluated those predictions, using a compilation of published data on the metabolic rates of litter- and soil-dwelling earthworms, isopods, oribatid mites, springtails, and spiders. Earthworms, oribatid mites, springtails, and spiders had mass-scaling exponents that were statistically indistinguishable from the expected value of 0.75. The scaling exponent for terrestrial isopods, 0.91, was significantly greater than expected. All taxa had apparent activation energies within the predicted range of 0.2-1.2 eV. Activation energies for isopods, oribatid mites, springtails, and spiders were not significantly different from the average expected value of 0.6 eV, while the activation energy for earthworms, 0.25 eV, was significantly lower than 0.6 eV. Updated equations for estimating metabolic rate from body mass and environmental temperature are given for investigations into the ecological energetics of litter and soil animals. 相似文献
76.
A total of 1479 recombinant clones were obtained from a Sau3A-digested genomic library of Penaeus (Litopenaeus) vannamei and used for probe hybridization. Of the 251 clones that tested positive to one or more of the probes and were sequenced, 173 (69%) contained 573 simple sequence repeats, or microsatellites, with 3 or more repeats. The frequency of microsatellites with 3, 5, and 10 or more repeats was 1 in 0.94 kb, 1 in 2.78 kb, and 1 in 5.94 kb, respectively. To increase the number of polymorphic markers for mapping, 136 primer sets that flanked microsatellites containing single or multiple motifs with 3 or more repeats were designed and tested. Of the 136 primers, 93 (68.0%) were polymorphic in cultured shrimp, with polymorphism information content (PIC) values ranging from 0.195 to 0.873, and observed heterozygosities ranging from 10% to 100%. These markers are being used along with other markers to construct a linkage map for P. vannamei. 相似文献
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N. A. Quaderi R. R. Meehan P. H. Tate S. H. Cross A. P. Bird A. Chatterjee G. E. Herman S. D. M. Brown 《Genomics》1994,22(3)
The methyl CpG binding proteins (MeCP1 and MeCP2) are a class of proteins that bind to templates containing symmetrically methylated CpGs. Using an interspecific backcross segregating a number of X-linked markers, we have localized the Mecp2 gene in mouse to the X chromosome close to the microsatellite marker DXMit1. Detailed physical mapping utilizing an available YAC contig encompassing the DXMit1 locus has localized the Mecp2 gene to a 40-kb region between the L1cam and the Rsvp loci, indicating the probable position of a homologue on the human X chromosome. 相似文献
79.
Interaction of antibody-bearing small unilamellar liposomes with antigencoated cells. The effect of antibody and antigen concentration on the liposomal and cell surface respectively 下载免费PDF全文
Human blood lymphocytes were coated with increasing amounts of human kappa chain (2–85μg/107 cells) through the linking reagent CrCl3. These cells were then exposed to small unilamellar liposomes composed of egg phosphatidylcholine, cholesterol and phosphatidic acid (molar proportions 7:7:1) containing carboxyfluorescein and/or 111In-labelled bleomycin and bearing 131I-labelled affinity chromatography-purified or non-purified anti-(kappa-chain) immunoglobulin G (IgG) [see the preceding paper, Gregoriadis, Meehan & Mah (1981) Biochem. J. 200, 203–210]. In some experiments liposomes contained [14C]phosphatidylcholine. (1) Lymphocytes (107) coated with 2–85μg of kappa chain and exposed to liposomes devoid of IgG or bearing non-purified anti-(kappa chain) IgG bound only a small proportion of the liposomal markers. Even with liposomes bearing the purified anti-(kappa chain) IgG, uptake of the labels improved only slightly for cells coated with up to 10μg of kappa chain. However, with higher concentrations of the antigen on the cell surface, binding was improved considerably to reach values of 31% (111In-labelled bleomycin) and 43% (131I-labelled IgG) of added liposomes for cells coated with 85μg of kappa chain. (2) Lymphocytes coated with kappa chain were exposed to liposomes bearing increasing amounts (0–180μg/0.9mg of egg phosphatidylcholine) of purified anti-(kappa chain) IgG. It was found that under the present conditions, binding of all three markers (111In-labelled bleomycin, 131I-labelled IgG and [14C]phosphatidylcholine) was directly proportional to the concentration of IgG on the liposomal surface. However, uptake values remained unchanged above 90μg of IgG. (3) Antibody-mediated uptake of liposomes by cells coated with the corresponding antigen without loss of their metabolic activities may provide a method of efficient targeting. 相似文献
80.
Susan P. Hawkes Thomas D. Meehan Mina J. Bissell 《Biochemical and biophysical research communications》1976,68(4):1226-1233
A rapid method was developed to label the outer surface of chick embryo fibroblasts with fluorescamine without disruption of the cell monolayer. Polyacrylamide gel electrophoresis resolved two distinct areas of fluorescence: a group of high molecular weight polypeptides and several rapidly migrating species. The latter were demonstrated by tlc to be phospholipids. Fluorescamine did not label internal components of the cell as evidenced by two intracellular proteins which were found to be non-fluorescent. Intact normal cells were labeled 3-fold more than transformed cells, indicating a possible loss of exposed sites at the surface, while disrupted cells, subsequently labeled, yielded similar amounts of fluorescence. 相似文献