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101.
Short interfering RNA-mediated gene targeting in the zebrafish 总被引:12,自引:0,他引:12
Short interfering RNAs (siRNAs) have proved to be a useful tool in studying gene function in plants, invertebrates and mammalian systems. Here we report the use of siRNAs for targeting the zebrafish dystrophin gene. This study demonstrates the efficacy of siRNA-based gene silencing in this vertebrate model species, and illustrates the potential of this approach for determining the roles of multiple protein products expressed by a single gene during the early stages of development. In addition this study illustrates the usefulness of zebrafish as a model for muscle disease, and highlights the potential of siRNA-based gene targeting for disease analysis in this model organism. 相似文献
102.
Mary M. Nishimoto Libe Washburn Robert R. Warner Milton S. Love Georges L. Paradis 《Environmental Biology of Fishes》2010,89(3-4):341-356
We examined variability in otolith chemistry of wild caught fish in relation to in situ temperature and salinity within the California Current System. Barium, magnesium, and iron from the most recent growth zone in otoliths differentiated pelagic juvenile shortbelly rockfish (Sebastes jordani) residing in water masses with distinct temperature and salinity properties from central and southern California spanning nearly 500 km of coastline. The 3-element signature also discriminated fish that resided in different water masses that were associated with mesoscale cyclonic eddy circulation in the Santa Barbara Channel. Variability in otolith chemistry reflected the spatial patterns of both horizontal gradients and vertical gradients in water mass properties related to circulation. Although we found that the concentrations of particular elements in otoliths were correlated to ambient temperature or salinity, we suggest that these parameters are more useful as an identifying signature of distinct water masses associated with unique otolith signatures rather than as factors directly affecting otolith chemistry. Other factors varying among the water masses or among the fish populations residing in the water masses may also affect otolith chemistry. We discuss how oceanographic phenomena associated with the 1997–1998 El Niño and the persistent, recirculating eddy in the Channel may have affected coastal ocean conditions and variation in otolith chemistry of fish in the study area. 相似文献
103.
Dietary ω3-polyunsaturated fatty acids are thought to influence the risk of Alzheimer’s disease (AD), and supplemental docosahexaenoic
acid (DHA; 22:6n-3) has been reported to reduce neurodegeneration in mouse models of AD. We have analysed the fatty acid composition
of frontal, temporal and parietal neocortex in 58 normal and 114 AD brains. Significant reductions were found for stearic
acid (18:0) in frontal and temporal cortex and arachidonic acid (20:4n-6) in temporal cortex in AD, and increases in oleic
acid in frontal and temporal cortex (18:1n-9) and palmitic acid (16:0) in parietal cortex. DHA level varied more in AD than
controls but the mean values were not significantly different. Fatty acid composition was not related to APOE genotype, age, gender or post-mortem delay. Further research is needed to distinguish between alterations that are secondary
to AD and those that contribute to the disease process. 相似文献
104.
Sekine O Love DC Rubenstein DS Hanover JA 《The Journal of biological chemistry》2010,285(49):38684-38691
A dynamic cycle of O-linked GlcNAc (O-GlcNAc) addition and removal is catalyzed by O-GlcNAc transferase and O-GlcNAcase, respectively, in a process that serves as the final step in a nutrient-driven "hexosamine-signaling pathway." Evidence points to a role for O-GlcNAc cycling in diabetes and insulin resistance. We have used Drosophila melanogaster to determine whether O-GlcNAc metabolism plays a role in modulating Drosophila insulin-like peptide (dilp) production and insulin signaling. We employed transgenesis to either overexpress or knock down Drosophila Ogt(sxc) and Oga in insulin-producing cells (IPCs) or fat bodies using the GAL4-UAS system. Knockdown of Ogt decreased Dilp2, Dilp3, and Dilp5 production, with reduced body size and decreased phosphorylation of Akt in vivo. In contrast, knockdown of Oga increased Dilp2, Dilp3, and Dilp5 production, increased body size, and enhanced phosphorylation of Akt in vivo. However, knockdown of either Ogt(sxc) or Oga in the IPCs increased the hemolymph carbohydrate concentration. Furthermore, phosphorylation of Akt stimulated by extraneous insulin in an ex vivo cultured fat body of third instar larvae was diminished in strains subjected to IPC knockdown of Ogt or Oga. Knockdown of O-GlcNAc cycling enzymes in the fat body dramatically reduced neutral lipid stores. These results demonstrate that altered O-GlcNAc cycling in Drosophila IPCs modulates insulin production and influences the insulin responsiveness of peripheral tissues. The observed phenotypes in O-GlcNAc cycling mimic pancreatic β-cell dysfunction and glucose toxicity related to sustained hyperglycemia in mammals. 相似文献
105.
106.
Alan C. Love 《Theorie in den Biowissenschaften》2006,124(3-4):317-333
Although the role of morphology in evolutionary theory remains a subject of debate, assessing the contributions of morphological investigation to evolutionary developmental biology (Evo-devo) is a more circumscribed issue of direct relevance to ongoing research. Historical studies of morphologically oriented researchers and the formation of the Modern Synthesis in the Anglo-American context identify a recurring theme: the synthetic theory of evolution did not capture multiple levels of biological organization. When this feature is incorporated into a philosophical framework for explaining the origin of evolutionary innovations and novelties (a core domain of inquiry in Evo-devo) two specific roles for morphology can be described: (1) the conceptualization and operational identification of the targets of explanation; and (2) the elucidation of causal interactions at higher levels of organization during ontogeny and through evolutionary time. These roles are critical components of any adequate explanation of innovation and novelty though not exhaustive of the parts played by morphology in evolutionary investigation. They also invite reflection on what counts as an evolutionary cause in contemporary evolutionary biology. 相似文献
107.
108.
Saxena M Soni LK Gupta AK Wakode SR Saxena AK Kaskhedikar SG 《Indian journal of biochemistry & biophysics》2006,43(1):32-36
Quantitative structure-activity relationship (QSAR) has been established on a series of thirty-eight compounds of four different sets of condensed pyridine and pyrimidine analogs, for their hydroxymethyl glutaryl coenzyme (HMG-CoA) reductase inhibitor activity, in order to understand the essential structural requirement for binding with receptor, in terms of common biophoric and secondary sites employing APEX-3D software. Among several 3D pharmacophoric models with different sizes and arrangements, one model was selected based on r2 = 0.8, chance<0.001, match equivalent to 0.38 and all the 38 compounds were considered. The results suggest that hydrophobicity, hydrogen acceptor and optimum steric refractivity play a dominant role in the inhibition of HMG-CoA reductase. The information obtained from the present study can be used to design and predict more potent molecules as HMG-CoA reductase inhibitors, prior to their synthesis. 相似文献
109.
Blanchard TL Thompson JA Love CC Brinsko SP Ramsey J O'Meara A Varner DD 《Theriogenology》2012,77(7):1290-1296
Records (years 2005-2007) were analyzed from a Thoroughbred stud farm in central Kentucky. Data from all breeding cycles of foaling mares were tabulated (3184 cycles of 2003 foaling mares bred between 7 and 163 days postpartum). A multiple logistic regression model employing Bayesian statistics was used to adjust for factors that significantly affected outcome; odds ratios (ORs) for pregnancy rate, pregnancy loss rate, and foaling rate were determined to examine the influence of day of postpartum breeding on these parameters. Mares bred before Day 22 (Day 0 = day of foaling) postpartum had a decreased OR for becoming pregnant (P < 0.05); the median OR for becoming pregnant (1.00) was not reached until Day 46 postpartum. Mares bred before Day 13 postpartum had an increased OR for pregnancy loss (P < 0.05). The median OR for pregnancy loss did not decline below 1.00 until Day 78 postpartum. Mares bred before Day 20 postpartum had a decreased OR for producing a foal (P < 0.05). The median OR for producing a foal (1.00) was not reached until Day 75 postpartum. We concluded that fertility (in terms of a higher OR for becoming pregnant and a lower OR for pregnancy loss, resulting in a higher OR for producing a foal) continued to improve in Thoroughbred mares for approximately 2.5 mo postpartum. These findings are of importance to management strategies directed at early postpartum breeding, and explain some of the reported drift in subsequent foaling dates of Thoroughbred mares, despite management practices that employ early postpartum breeding. 相似文献
110.