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61.
Peter S. Levi Jennifer L. Tank Janine Rüegg David J. Janetski Scott D. Tiegs Dominic T. Chaloner Gary A. Lamberti 《Ecosystems》2013,16(2):269-283
Pacific salmon (Oncorhynchus spp.) perform important ecological roles in stream ecosystems by provisioning nutrients as resource subsidies and modifying their physical habitat as ecosystem engineers. These contrasting roles result in concurrent nutrient enrichment and benthic disturbance, where local environmental characteristics potentially determine which effect predominates. Whole-stream metabolism quantifies the functional response to salmon and may identify patterns in enrichment and disturbance not apparent from structural measurements alone. We measured ecosystem respiration (ER) and gross primary production (GPP), along with chemical and physical characteristics, in seven Southeast Alaska streams and two Michigan streams, before and during the salmon run. These streams in the native and introduced ranges of salmon differed in environmental characteristics, from geomorphology at the reach scale to climate at the biome scale. Salmon consistently increased ER across streams and biomes, from an average (±SE) of 1.92 ± 0.23 g O2 m?2 d?1 before salmon to 6.30 ± 1.08 g O2 m?2 d?1 during the run. In the cobble-bottom streams of Southeast Alaska, GPP doubled from 0.29 ± 0.05 g O2 m?2 d?1 before salmon to 0.66 ± 0.16 g O2 m?2 d?1 during the run. In contrast, GPP responded inconsistently to salmon in the sand-bottom Michigan streams, increasing in one and decreasing in the other. Patterns in ER and GPP among streams and time periods were predicted by stream water nutrients (for example, ammonium, soluble reactive phosphorus) rather than by physical characteristics (for example, light, sediment size, and so on). This study demonstrates that salmon can periodically override physical controls on ER and GPP and enhance whole-stream metabolism via their dual ecological roles as both resource subsidies and ecosystem engineers. 相似文献
62.
Marijke Frederix Kimmo Hütter Jessica Leu Tanveer S. Batth William J. Turner Thomas L. Rüegg Harvey W. Blanch Blake A. Simmons Paul D. Adams Jay D. Keasling Michael P. Thelen Mary J. Dunlop Christopher J. Petzold Aindrila Mukhopadhyay 《PloS one》2014,9(7)
The ability to solubilize lignocellulose makes certain ionic liquids (ILs) very effective reagents for pretreating biomass prior to its saccharification for biofuel fermentation. However, residual IL in the aqueous sugar solution can inhibit the growth and function of biofuel-producing microorganisms. In E. coli this toxicity can be partially overcome by the heterologous expression of an IL efflux pump encoded by eilA from Enterobacter lignolyticus. In the present work, we used microarray analysis to identify native E. coli IL-inducible promoters and develop control systems for regulating eilA gene expression. Three candidate promoters, PmarR’, PydfO’, and PydfA’, were selected and compared to the IPTG-inducible PlacUV5 system for controlling expression of eilA. The PydfA’ and PmarR’ based systems are as effective as PlacUV5 in their ability to rescue E. coli from typically toxic levels of IL, thereby eliminating the need to use an IPTG-based system for such tolerance engineering. We present a mechanistic model indicating that inducible control systems reduce target gene expression when IL levels are low. Selected-reaction monitoring mass spectrometry analysis revealed that at high IL concentrations EilA protein levels were significantly elevated under the control of PydfA’ and PmarR’ in comparison to the other promoters. Further, in a pooled culture competition designed to determine fitness, the strain containing pPmarR’-eilA outcompeted strains with other promoter constructs, most significantly at IL concentrations above 150 mM. These results indicate that native promoters such as PmarR’ can provide effective systems for regulating the expression of heterologous genes in host engineering and simplify the development of industrially useful strains. 相似文献
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Cilengitide is a high-affinity cyclic pentapeptdic αV integrin antagonist previously reported to suppress angiogenesis by inducing anoikis of endothelial cells adhering through αVβ3/αVβ5 integrins. Angiogenic endothelial cells express multiple integrins, in particular those of the β1 family, and little is known on the effect of cilengitide on endothelial cells expressing αVβ3 but adhering through β1 integrins. Through morphological, biochemical, pharmacological and functional approaches we investigated the effect of cilengitide on αVβ3-expressing human umbilical vein endothelial cells (HUVEC) cultured on the β1 ligands fibronectin and collagen I. We show that cilengitide activated cell surface αVβ3, stimulated phosphorylation of FAK (Y397 and Y576/577), Src (S418) and VE-cadherin (Y658 and Y731), redistributed αVβ3 at the cell periphery, caused disappearance of VE-cadherin from cellular junctions, increased the permeability of HUVEC monolayers and detached HUVEC adhering on low-density β1 integrin ligands. Pharmacological inhibition of Src kinase activity fully prevented cilengitide-induced phosphorylation of Src, FAK and VE-cadherin, and redistribution of αVβ3 and VE-cadherin and partially prevented increased permeability, but did not prevent HUVEC detachment from low-density matrices. Taken together, these observations reveal a previously unreported effect of cilengitide on endothelial cells namely its ability to elicit signaling events disrupting VE-cadherin localization at cellular contacts and to increase endothelial monolayer permeability. These effects are potentially relevant to the clinical use of cilengitide as anticancer agent. 相似文献
66.
Adrian Zumsteg Vanessa Baeriswyl Natsuko Imaizumi Reto Schwendener Curzio Rüegg Gerhard Christofori 《PloS one》2009,4(9)
The formation of new blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis) promotes tumor outgrowth and metastasis. Previously, it has been demonstrated that bone marrow-derived cells (BMDC) can contribute to tumor angiogenesis. However, the role of BMDC in lymphangiogenesis has largely remained elusive. Here, we demonstrate by bone marrow transplantation/reconstitution and genetic lineage-tracing experiments that BMDC integrate into tumor-associated lymphatic vessels in the Rip1Tag2 mouse model of insulinoma and in the TRAMP-C1 prostate cancer transplantation model, and that the integrated BMDC originate from the myelomonocytic lineage. Conversely, pharmacological depletion of tumor-associated macrophages reduces lymphangiogenesis. No cell fusion events are detected by genetic tracing experiments. Rather, the phenotypical conversion of myeloid cells into lymphatic endothelial cells and their integration into lymphatic structures is recapitulated in two in vitro tube formation assays and is dependent on fibroblast growth factor-mediated signaling. Together, the results reveal that myeloid cells can contribute to tumor-associated lymphatic vessels, thus extending the findings on the previously reported role of hematopoietic cells in lymphatic vessel formation. 相似文献
67.
The regulation of benzene degradation by Ralstonia pickettii PKO1 in the presence of the alternative substrate succinate was investigated in batch and continuous culture. In batch culture,
R. pickettii PKO1 achieved a maximum specific growth rate with benzene of 0.18 h−1, while succinate allowed much faster growth (μmax = 0.5 h−1). Under carbon excess conditions succinate repressed benzene consumption resulting in diauxic growth whereas under carbon-limited
conditions in the chemostat both substrates were used simultaneously. Moreover, the effect of succinate on the adaptation
towards growth with benzene was investigated in carbon-limited continuous culture at a dilution rate of 0.1 h−1 by changing the inflowing carbon substrate from succinate to different mixtures of benzene and succinate. The adaptation
process towards utilisation of benzene was rather complex. Three to seven hours after the medium shift biomass production
from benzene started. Higher proportions of succinate in the mixture had a positive effect on both the onset of biomass production
and on the time required for induction of benzene utilisation. Strikingly, after the initial increase in biomass and benzene-catabolising
activities, the culture collapsed regularly and wash-out of biomass was observed. After a transient phase of low biomass concentrations
growth on benzene resumed so that finally rather stable and high biomass concentrations were reached. The decrease in biomass
and degradative activities cannot be explained so far, but the possibilities of either intoxication of the cells by benzene
itself, or of inhibition by degradation intermediates were ruled out. 相似文献
68.
John L. Bixby Kristine Baerwald‐De La Torre Cong Wang Fritz G. Rathjen Markus A. Rüegg 《Developmental neurobiology》2002,50(2):164-179
Agrin is required for appropriate pre‐ and postsynaptic differentiation of neuromuscular junctions. While agrin's ability to orchestrate postsynaptic differentiation is well documented, more recent experiments have suggested that agrin is also a “stop signal” for the presynaptic neuron, and that agrin has actions on neurons in the CNS. To elucidate the neuronal activities of agrin and to define the receptor(s) responsible for these functions, we have examined adhesions of neurons and their neurite‐outgrowth responses to purified agrin in vitro. We find that both full‐length agrin and the C‐terminal 95 kDa of agrin (agrin c95), which is sufficient to induce postsynaptic differentiation, are adhesive for chick ciliary ganglion (CG) and forebrain neurons. Consistent with previous findings, our results show that N‐CAM binds to full‐length agrin, and suggest that α‐dystroglycan is a neuronal receptor for agrin c95. In neurite outgrowth assays, full‐length agrin inhibited both laminin‐ and N‐cadherin–induced neurite growth from CG neurons. The N‐terminal 150 kDa fragment of agrin, but not agrin c95, inhibited neurite outgrowth, indicating that domains in the N‐terminal portion of agrin are sufficient for this function. Adhesion assays using protein‐coated beads and agrin‐expressing cells revealed differential interactions of agrin with members of the immunoglobulin superfamily of cell adhesion molecules. However, none of these, including N‐CAM, appeared to be critical for neuronal adhesion. In summary, our results suggest that the N‐terminal half of agrin is involved in agrin's ability to inhibit neurite outgrowth. Our results further suggest that neither α‐dystroglycan nor N‐CAM, two known binding proteins for agrin, mediate this effect. © 2002 Wiley Periodicals, Inc. J Neurobiol 50: 164–179, 2002; DOI 10.1002/neu.10025 相似文献
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Agrin is a key organizer of acetylcholine receptor (AChR) clustering at the neuromuscular junction. The binding of agrin to laminin is required for its localization to synaptic basal lamina and other basement membranes. The high-affinity interaction with the coiled-coil domain of laminin is mediated by the N-terminal domain of agrin. We have adopted a structurally guided site-directed mutagenesis approach to map the laminin-binding site of NtA. Mutations of L117 and V124 in the C-terminal helix 3 showed that they are crucial for binding. Both residues are located in helix 3 and face the groove between the beta-barrel and the C-terminal helical segment of NtA. Remarkably, the distance between both residues matches a heptad repeat distance of two aliphatic residues which are solvent exposed in the coiled-coil domain of laminin. A lower but significant contribution originates from R43 and a charged cluster (E23, E24 and R40) at the open face of the beta-barrel structure. We propose that surface-exposed, conserved residues of the laminin gamma1 chain interact with NtA via hydrophobic and ionic interactions. 相似文献