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751.
Belinda U. Nwagbara Anna E. Faris Elizabeth A. Bearce Burcu Erdogan Patrick T. Ebbert Matthew F. Evans Erin L. Rutherford Tiffany B. Enzenbacher Laura Anne Lowery 《Molecular biology of the cell》2014,25(21):3350-3362
Microtubule plus end dynamics are regulated by a conserved family of proteins called plus end–tracking proteins (+TIPs). It is unclear how various +TIPs interact with each other and with plus ends to control microtubule behavior. The centrosome-associated protein TACC3, a member of the transforming acidic coiled-coil (TACC) domain family, has been implicated in regulating several aspects of microtubule dynamics. However, TACC3 has not been shown to function as a +TIP in vertebrates. Here we show that TACC3 promotes axon outgrowth and regulates microtubule dynamics by increasing microtubule plus end velocities in vivo. We also demonstrate that TACC3 acts as a +TIP in multiple embryonic cell types and that this requires the conserved C-terminal TACC domain. Using high-resolution live-imaging data on tagged +TIPs, we show that TACC3 localizes to the extreme microtubule plus end, where it lies distal to the microtubule polymerization marker EB1 and directly overlaps with the microtubule polymerase XMAP215. TACC3 also plays a role in regulating XMAP215 stability and localizing XMAP215 to microtubule plus ends. Taken together, our results implicate TACC3 as a +TIP that functions with XMAP215 to regulate microtubule plus end dynamics. 相似文献
752.
Peter Dann Leesa A. Sidhu Roz Jessop Leanne Renwick Margaret Healy Belinda Dettmann Barry Baker Edward A. Catchpole 《Ibis》2014,156(1):73-83
Tagging is essential for many types of ecological and behavioural studies, and it is generally assumed that it does not affect the fitness of the individuals being examined. However, the tagging of birds has been shown to have negative effects on some aspects of their lives. Here we investigate the influence of tagging on apparent survival. We examined the effects of flipper bands and injected transponders on the apparent survival of adult Little Penguins by comparing the survival probabilities of 2483 Little Penguins marked at Phillip Island, Australia, between 1995 and 2001 in one of three ways: with bands, with transponders or with both. The design of the study and our method of analysis allowed us to estimate tag loss and ensured that tag loss did not bias the survival estimates. Birds marked with flipper bands had lower survival probabilities than those marked with transponders (with apparent survival probabilities in the first year after tagging of 75% for banded birds and 80% for birds fitted with transponders, and in subsequent years of 87% for banded birds and 91% for birds fitted with transponders). We estimated both band and transponder loss probabilities for the first time, and found that transponder loss probabilities were substantially higher than band loss probabilities, particularly in the first year after marking when the tag loss probability was 5% for transponders and 0.7% for bands. Survival probabilities were lower in the first year after marking than in subsequent years for all birds. Studies of penguins that have used flipper bands to identify individuals may have underestimated annual adult survival probabilities, as banded penguins were likely to have lower than average survival probabilities than those of unbanded birds. The higher annual survival probabilities of individuals marked with transponders indicate that this should be the preferred marking technique for Little Penguins. However, future studies will, like ours, need to consider the higher rates of transponder loss when estimating survival, possibly by double‐tagging some birds. 相似文献
753.
Eng Kuan Moo Sang Kuy Han Salvatore Federico Scott C. Sibole Azim Jinha Noor Azuan Abu Osman Belinda Pingguan-Murphy Walter Herzog 《Journal of biomechanics》2014
Cartilage lesions change the microenvironment of cells and may accelerate cartilage degradation through catabolic responses from chondrocytes. In this study, we investigated the effects of structural integrity of the extracellular matrix (ECM) on chondrocytes by comparing the mechanics of cells surrounded by an intact ECM with cells close to a cartilage lesion using experimental and numerical methods. Experimentally, 15% nominal compression was applied to bovine cartilage tissues using a light-transmissible compression system. Target cells in the intact ECM and near lesions were imaged by dual-photon microscopy. Changes in cell morphology (Ncell=32 for both ECM conditions) were quantified. A two-scale (tissue level and cell level) Finite Element (FE) model was also developed. A 15% nominal compression was applied to a non-linear, biphasic tissue model with the corresponding cell level models studied at different radial locations from the centre of the sample in the transient phase and at steady state. We studied the Green-Lagrange strains in the tissue and cells. Experimental and theoretical results indicated that cells near lesions deform less axially than chondrocytes in the intact ECM at steady state. However, cells near lesions experienced large tensile strains in the principal height direction, which are likely associated with non-uniform tissue radial bulging. Previous experiments showed that tensile strains of high magnitude cause an up-regulation of digestive enzyme gene expressions. Therefore, we propose that cartilage degradation near tissue lesions may be due to the large tensile strains in the principal height direction applied to cells, thus leading to an up-regulation of catabolic factors. 相似文献
754.
McGrath MJ Cottle DL Nguyen MA Dyson JM Coghill ID Robinson PA Holdsworth M Cowling BS Hardeman EC Mitchell CA Brown S 《The Journal of biological chemistry》2006,281(11):7666-7683
Four and a half LIM protein 1 (FHL1/SLIM1) is highly expressed in skeletal and cardiac muscle; however, the function of FHL1 remains unknown. Yeast two-hybrid screening identified slow type skeletal myosin-binding protein C as an FHL1 binding partner. Myosin-binding protein C is the major myosin-associated protein in striated muscle that enhances the lateral association and stabilization of myosin thick filaments and regulates actomyosin interactions. The interaction between FHL1 and myosin-binding protein C was confirmed using co-immunoprecipitation of recombinant and endogenous proteins. Recombinant FHL2 and FHL3 also bound myosin-binding protein C. FHL1 impaired co-sedimentation of myosin-binding protein C with reconstituted myosin filaments, suggesting FHL1 may compete with myosin for binding to myosin-binding protein C. In intact skeletal muscle and isolated myofibrils, FHL1 localized to the I-band, M-line, and sarcolemma, co-localizing with myosin-binding protein C at the sarcolemma in intact skeletal muscle. Furthermore, in isolated myofibrils FHL1 staining at the M-line appeared to extend partially into the C-zone of the A-band, where it co-localized with myosin-binding protein C. Overexpression of FHL1 in differentiating C2C12 cells induced "sac-like" myotube formation (myosac), associated with impaired Z-line and myosin thick filament assembly. This phenotype was rescued by co-expression of myosin-binding protein C. FHL1 knockdown using RNAi resulted in impaired myosin thick filament formation associated with reduced incorporation of myosin-binding protein C into the sarcomere. This study identified FHL1 as a novel regulator of myosin-binding protein C activity and indicates a role for FHL1 in sarcomere assembly. 相似文献
755.
Belinda van Heerwaarden Carla M. Sgrò 《Evolution; international journal of organic evolution》2017,71(11):2618-2633
Phenotypic plasticity is thought to be an important mechanism for adapting to environmental heterogeneity. Nonetheless, the genetic basis of plasticity is still not well understood. In Drosophila melanogaster and D. simulans, body size and thermal stress resistance show clinal patterns along the east coast of Australia, and exhibit plastic responses to different developmental temperatures. The genetic basis of thermal plasticity, and whether the genetic effects underlying clinal variation in traits and their plasticity are similar, remains unknown. Here, we use line‐cross analyses between a tropical and temperate population of Drosophila melanogaster and D. simulans developed at three constant temperatures (18°C, 25°C, and 29°C) to investigate the quantitative genetic basis of clinal divergence in mean thermal response (elevation) and plasticity (slope and curvature) for thermal stress and body size traits. Generally, the genetic effects underlying divergence in mean response and plasticity differed, suggesting that different genetic models may be required to understand the evolution of trait means and plasticity. Furthermore, our results suggest that nonadditive genetic effects, in particular epistasis, may commonly underlie plastic responses, indicating that current models that ignore epistasis may be insufficient to understand and predict evolutionary responses to environmental change. 相似文献
756.
A novel Apaf-1-independent putative caspase-2 activation complex 总被引:12,自引:0,他引:12
Caspase activation is a key event in apoptosis execution. In stress-induced apoptosis, the mitochondrial pathway of caspase activation is believed to be of central importance. In this pathway, cytochrome c released from mitochondria facilitates the formation of an Apaf-1 apoptosome that recruits and activates caspase-9. Recent data indicate that in some cells caspase-9 may not be the initiator caspase in stress-mediated apoptosis because caspase-2 is required upstream of mitochondria for the release of cytochrome c and other apoptogenic factors. To determine how caspase-2 is activated, we have studied the formation of a complex that mediates caspase-2 activation. Using gel filtration analysis of cell lysates, we show that caspase-2 is spontaneously recruited to a large protein complex independent of cytochrome c and Apaf-1 and that recruitment of caspase-2 to this complex is sufficient to mediate its activation. Using substrate-binding assays, we also provide the first evidence that caspase-2 activation may occur without processing of the precursor molecule. Our data are consistent with a model where caspase-2 activation occurs by oligomerization, independent of the Apaf-1 apoptosome. 相似文献
757.
Marina Roussaki Belinda Hall Sofia Costa Lima Anabela Cordeiro da Silva Shane Wilkinson Anastasia Detsi 《Bioorganic & medicinal chemistry letters》2013,23(23):6436-6441
A series of novel quinolinone–chalcone hybrids and analogues were designed, synthesized and their biological activity against the mammalian stages of Trypanosoma brucei and Leishmania infantum evaluated. Promising molecular scaffolds with significant microbicidal activity and low cytotoxicity were identified. Quinolinone–chalcone 10 exhibited anti-parasitic properties against both organisms, being the most potent anti-L. infantum agent of the entire series (IC50 value of 1.3 ± 0.1 μM). Compounds 4 and 11 showed potency toward the intracellular, amastigote stage of L. infantum (IC50 values of 2.1 ± 0.6 and 3.1 ± 1.05 μM, respectively). Promising trypanocidal compounds include 5 and 10 (IC50 values of 2.6 ± 0.1 and 3.3 ± 0.1 μM, respectively) as well as 6 and 9 (both having IC50 values of <5 μM). Chemical modifications on the quinolinone–chalcone scaffold were performed on selected compounds in order to investigate the influence of these structural features on antiparasitic activity. 相似文献
758.
A common thermal niche among geographically diverse populations of the widely distributed tree species Eucalyptus tereticornis: No evidence for adaptation to climate‐of‐origin 下载免费PDF全文
John E. Drake Angelica Vårhammar Dushan Kumarathunge Belinda E. Medlyn Sebastian Pfautsch Peter B. Reich David T. Tissue Oula Ghannoum Mark G. Tjoelker 《Global Change Biology》2017,23(12):5069-5082
Impacts of climate warming depend on the degree to which plants are constrained by adaptation to their climate‐of‐origin or exhibit broad climatic suitability. We grew cool‐origin, central and warm‐origin provenances of Eucalyptus tereticornis in an array of common temperature environments from 18 to 35.5°C to determine if this widely distributed tree species consists of geographically contrasting provenances with differentiated and narrow thermal niches, or if provenances share a common thermal niche. The temperature responses of photosynthesis, respiration, and growth were equivalent across the three provenances, reflecting a common thermal niche despite a 2,200 km geographic distance and 13°C difference in mean annual temperature at seed origin. The temperature dependence of growth was primarily mediated by changes in leaf area per unit plant mass, photosynthesis, and whole‐plant respiration. Thermal acclimation of leaf, stem, and root respiration moderated the increase in respiration with temperature, but acclimation was constrained at high temperatures. We conclude that this species consists of provenances that are not differentiated in their thermal responses, thus rejecting our hypothesis of adaptation to climate‐of‐origin and suggesting a shared thermal niche. In addition, growth declines with warming above the temperature optima were driven by reductions in whole‐plant leaf area and increased respiratory carbon losses. The impacts of climate warming will nonetheless vary across the geographic range of this and other such species, depending primarily on each provenance's climate position on the temperature response curves for photosynthesis, respiration, and growth. 相似文献
759.
Boo YC Hwang J Sykes M Michell BJ Kemp BE Lum H Jo H 《American journal of physiology. Heart and circulatory physiology》2002,283(5):H1819-H1828
Shear stress stimulates nitric oxide (NO) production by phosphorylating endothelial NO synthase (eNOS) at Ser(1179) in a phosphoinositide-3-kinase (PI3K)- and protein kinase A (PKA)-dependent manner. The eNOS has additional potential phosphorylation sites, including Ser(116), Thr(497), and Ser(635). Here, we studied these potential phosphorylation sites in response to shear, vascular endothelial growth factor (VEGF), and 8-bromocAMP (8-BRcAMP) in bovine aortic endothelial cells (BAEC). All three stimuli induced phosphorylation of eNOS at Ser(635), which was consistently slower than that at Ser(1179). Thr(497) was rapidly dephosphorylated by 8-BRcAMP but not by shear and VEGF. None of the stimuli phosphorylated Ser(116). Whereas shear-stimulated Ser(635) phosphorylation was not affected by phosphoinositide-3-kinase inhibitors wortmannin and LY-294002, it was blocked by either treating the cells with a PKA inhibitor H89 or infecting them with a recombinant adenovirus-expressing PKA inhibitor. These results suggest that shear stress stimulates eNOS by two different mechanisms: 1) PKA- and PI3K-dependent and 2) PKA-dependent but PI3K-independent pathways. Phosphorylation of Ser(635) may play an important role in chronic regulation of eNOS in response to mechanical and humoral stimuli. 相似文献
760.
Timothy H. Rainer Hiu Hung Yeung Belinda J. Gabbe Kai Y. Yuen Hiu F. Ho Chak W. Kam Annice Chang Wai S. Poon Peter A. Cameron Colin A. Graham 《PloS one》2014,9(8)