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51.
Kerry Bohl Stricker Philip F. Harmon Erica M. Goss Keith Clay S. Luke Flory 《Ecology letters》2016,19(4):469-477
Emerging pathogens are a growing threat to human health, agriculture and the diversity of ecological communities but may also help control problematic species. Here we investigated the diversity, distribution and consequences of emerging fungal pathogens infecting an aggressive invasive grass that is rapidly colonising habitats throughout the eastern USA. We document the recent emergence and accumulation over time of diverse pathogens that are members of a single fungal genus and represent multiple, recently described or undescribed species. We also show that experimental suppression of these pathogens increased host performance in the field, demonstrating the negative effects of emerging pathogens on invasive plants. Our results suggest that invasive species can facilitate pathogen emergence and amplification, raising concerns about movement of pathogens among agricultural, horticultural, and wild grasses. However, one possible benefit of pathogen accumulation is suppression of aggressive invaders over the long term, potentially abating their negative impacts on native communities. 相似文献
52.
Adam J. Golman Kerry A. Danelson 《Computer methods in biomechanics and biomedical engineering》2016,19(7):717-732
This study developed a parametric methodology to robustly predict occupant injuries sustained in real-world crashes using a finite element (FE) human body model (HBM). One hundred and twenty near-side impact motor vehicle crashes were simulated over a range of parameters using a Toyota RAV4 (bullet vehicle), Ford Taurus (struck vehicle) FE models and a validated human body model (HBM) Total HUman Model for Safety (THUMS). Three bullet vehicle crash parameters (speed, location and angle) and two occupant parameters (seat position and age) were varied using a Latin hypercube design of Experiments. Four injury metrics (head injury criterion, half deflection, thoracic trauma index and pelvic force) were used to calculate injury risk. Rib fracture prediction and lung strain metrics were also analysed. As hypothesized, bullet speed had the greatest effect on each injury measure. Injury risk was reduced when bullet location was further from the B-pillar or when the bullet angle was more oblique. Age had strong correlation to rib fractures frequency and lung strain severity. The injuries from a real-world crash were predicted using two different methods by (1) subsampling the injury predictors from the 12 best crush profile matching simulations and (2) using regression models. Both injury prediction methods successfully predicted the case occupant's low risk for pelvic injury, high risk for thoracic injury, rib fractures and high lung strains with tight confidence intervals. This parametric methodology was successfully used to explore crash parameter interactions and to robustly predict real-world injuries. 相似文献
53.
Kentaro Ohkuni Yoshimitsu Takahashi Alyona Fulp Josh Lawrimore Wei-Chun Au Nagesh Pasupala Reuben Levy-Myers Jack Warren Alexander Strunnikov Richard E. Baker Oliver Kerscher Kerry Bloom Munira A. Basrai 《Molecular biology of the cell》2016,27(9):1500-1510
Centromeric histone H3, CENP-ACse4, is essential for faithful chromosome segregation. Stringent regulation of cellular levels of CENP-ACse4 restricts its localization to centromeres. Mislocalization of CENP-ACse4 is associated with aneuploidy in yeast and flies and tumorigenesis in human cells; thus defining pathways that regulate CENP-A levels is critical for understanding how mislocalization of CENP-A contributes to aneuploidy in human cancers. Previous work in budding yeast shows that ubiquitination of overexpressed Cse4 by Psh1, an E3 ligase, partially contributes to proteolysis of Cse4. Here we provide the first evidence that Cse4 is sumoylated by E3 ligases Siz1 and Siz2 in vivo and in vitro. Ubiquitination of Cse4 by the small ubiquitin-related modifier (SUMO)-targeted ubiquitin ligase (STUbL) Slx5 plays a critical role in proteolysis of Cse4 and prevents mislocalization of Cse4 to euchromatin under normal physiological conditions. Accumulation of sumoylated Cse4 species and increased stability of Cse4 in slx5∆ strains suggest that sumoylation precedes ubiquitin-mediated proteolysis of Cse4. Slx5-mediated Cse4 proteolysis is independent of Psh1, since slx5∆ psh1∆ strains exhibit higher levels of Cse4 stability and mislocalization than either slx5∆ or psh1∆ strains. Our results demonstrate a role for Slx5 in ubiquitin-mediated proteolysis of Cse4 to prevent its mislocalization and maintain genome stability. 相似文献
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55.
Wang Yu Liu Di Crowell Laura E. Love Kerry R. Wu Shiaw-lin Hancock William S. 《Amino acids》2019,51(9):1353-1363
Amino Acids - Interferons are signaling proteins that belong to the large class of cytokines and human interferons which are classified based on the type of receptor interactions: type I, II and... 相似文献
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58.
Miller KA Barrow J Collinson JM Davidson S Lear M Hill RE Mackenzie A 《Developmental biology》2007,311(2):665-678
The product of the Msx1 gene is a potent inhibitor of muscle differentiation. Msx1 is expressed in muscle precursor cells of the limb bud that also express Pax3. It is thought that Msx1 may facilitate distal migration by delaying myogenesis in these cells. Despite the role played by Msx1 in inhibiting muscle differentiation, nothing is known of the mechanisms that support the expression of the Msx1 gene within limb bud muscle precursor cells. In the present study we have used a combination of comparative genomics, mouse transgenic analysis, in situ hybridisation and immunohistochemistry to identify a highly conserved and tissue-specific regulatory sub-domain within the previously characterised Msx1 gene proximal enhancer element that supports the expression of the Msx1 gene in Pax3-expressing mouse limb pre-muscle masses. Furthermore, using a combination of in situ hybridisation, in vivo ChIP assay and transgenic explant culture analysis we provide evidence that Msx1 expression in limb bud muscle precursor cells is dependent on the canonical Wnt/TCF signalling pathway that is important in muscle shape formation. The results of these studies provide evidence of a mechanistic link between the Wnt/TCF and the Msx1/Pax3/MyoD pathways within limb bud muscle precursor cells. 相似文献
59.
Lucas KA Filley JR Erb JM Graybill ER Hawes JW 《The Journal of biological chemistry》2007,282(34):24980-24989
The subcellular sites of branched-chain amino acid metabolism in plants have been controversial, particularly with respect to valine catabolism. Potential enzymes for some steps in the valine catabolic pathway are clearly present in both mitochondria and peroxisomes, but the metabolic functions of these isoforms are not clear. The present study examined the possible function of these enzymes in metabolism of isobutyryl-CoA and propionyl-CoA, intermediates in the metabolism of valine and of odd-chain and branched-chain fatty acids. Using (13)C NMR, accumulation of beta-hydroxypropionate from [2-(13)C]propionate was observed in seedlings of Arabidopsis thaliana and a range of other plants, including both monocots and dicots. Examination of coding sequences and subcellular targeting elements indicated that the completed genome of A. thaliana likely codes for all the enzymes necessary to convert valine to propionyl-CoA in mitochondria. However, Arabidopsis mitochondria may lack some of the key enzymes for metabolism of propionyl-CoA. Known peroxisomal enzymes may convert propionyl-CoA to beta-hydroxypropionate by a modified beta-oxidation pathway. The chy1-3 mutation, creating a defect in a peroxisomal hydroxyacyl-CoA hydrolase, abolished the accumulation of beta-hydroxyisobutyrate from exogenous isobutyrate, but not the accumulation of beta-hydroxypropionate from exogenous propionate. The chy1-3 mutant also displayed a dramatically increased sensitivity to the toxic effects of excess propionate and isobutyrate but not of valine. (13)C NMR analysis of Arabidopsis seedlings exposed to [U-(13)C]valine did not show an accumulation of beta-hydroxypropionate. No evidence was observed for a modified beta-oxidation of valine. (13)C NMR analysis showed that valine was converted to leucine through the production of alpha-ketoisovalerate and isopropylmalate. These data suggest that peroxisomal enzymes for a modified beta-oxidation of isobutyryl-CoA and propionyl-CoA could function for metabolism of substrates other than valine. 相似文献
60.
Manton KJ Haupt LM Vengadasalam K Nurcombe V Cool SM 《Journal of molecular histology》2007,38(5):415-424
Summary Understanding the complex mechanisms underlying bone remodeling is crucial to the development of novel therapeutics. Glycosaminoglycans
(GAGs) localised to the extracellular matrix (ECM) of bone are thought to play a key role in mediating aspects of bone development.
The influence of isolated GAGs was studied by utilising in vitro murine calvarial monolayer and organ culture model systems.
Addition of GAG preparations extracted from the cell surface of human osteoblasts at high concentrations (5 μg/ml) resulted
in decreased proliferation of cells and decreased suture width and number of bone lining cells in calvarial sections. When
we investigated potential interactions between the growth factors fibroblast growth factor-2 (FGF2), bone morphogenic protein-2
(BMP2) and transforming growth factor-β1 (TGFβ1) and the isolated cell surface GAGs, differences between the two model systems
emerged. The cell culture system demonstrated a potentiating role for the isolated GAGs in the inhibition of FGF2 and TGFβ1
actions. In contrast, the organ culture system demonstrated an enhanced stimulation of TFGβ1 effects. These results emphasise
the role of the ECM in mediating the interactions between GAGs and growth factors during bone development and suggest the
GAG preparations contain potent inhibitory or stimulatory components able to mediate growth factor activity.
Kerry J. Manton and Larisa M. Haupt—Co-first authors. 相似文献