Adaptation of endoplasmic reticulum exit sites to acute and chronic increases in cargo load

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102229/1/emboj2008136.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102229/2/emboj2008136-sup-0001.pd

Use of Imatinib in the Prevention of Heterotopic Ossification

Background: Heterotopic ossification (HO) is a common complication following orthopedic and trauma surgery, which may have substantial negative effects on the postoperative outcome. Angiogenesis appears to play a critical role in heterotopic ossification. One of the involved signaling molecules is platelet-derived growth factor (PDGF) which may be inhibited by imatinib. Questions/Purposes: Our goal was to prevent HO by pharmacologically interfering with the molecular signaling pathways involved in the developmental process. We hypothesized that by administering a proven inhibitor of PDGF expression, heterotopic bone formation may be prevented. Methods: The effect of imatinib on HO formation was studied in a murine model which reliably produces islets of HO within the soft tissue following Achilles tenotomy. The control group underwent Achilles tenotomy only. The imatinib group received imatinib mesylate. After trial completion, the limbs were harvested and scanned by micro-CT. Heterotopic bone volume was then identified and quantified. Results: The mean volume of heterotopic bone formed in the control group was 0.976mm3 compared to 0.221mm3 in the imatinib group. The volume of HO in the treatment group was reduced by 85% compared to the control group. Conclusions: The administration of imatinib was associated with a significantly reduced volume of HO. This may be due to the inhibitory effect of imatinib on the PDGF signaling pathway during development of HO. Clinical Relevance: The successful reduction of HO formation following imatinib administration has led to further insight concerning the pathogenesis of HO which in the future may lead to new clinical approaches towards the prevention of H

Wind-driven mixing causes a reduction in the strength of the continental shelf carbon pump in the Chukchi Sea

The Chukchi Sea is thought to be a globally important sink of atmospheric CO2 due to the summertime drawdown of surface pCO2 by phytoplankton and subsequent shelf-to-basin transport of CO2-enriched subsurface waters into the upper halocline of the Arctic Ocean. Here we show that annually occurring storm-induced mixing events during autumn months disrupt water column stratification and stir up remineralized carbon from subsurface waters to the surface, leading to CO2 outgassing to the atmosphere. Our analysis provides a new understanding of the dynamics of carbon cycling in the region and suggests that late season wind events are strong and frequent enough to significantly decrease the carbon sink strength of the Chukchi Sea on a scale of relevance to the global carbon cycle. These results highlight the importance of obtaining data with more complete seasonal and spatial coverage in order to accurately constrain regional to basin-scale carbon flux budgets

MAPK signaling to the early secretory pathway revealed by kinase/phosphatase functional screening

An RNAi screen determines that the early secretory pathway is subject to phosphoregulation via a variety of signaling pathways, including a link between growth factor signaling and ER export

The Apical Submembrane Cytoskeleton Participates in the Organization of the Apical Pole in Epithelial Cells

In a previous publication (Rodriguez, M.L., M. Brignoni, and P.J.I. Salas. 1994. J. Cell Sci. 107: 3145–3151), we described the existence of a terminal web-like structure in nonbrush border cells, which comprises a specifically apical cytokeratin, presumably cytokeratin 19. In the present study we confirmed the apical distribution of cytokeratin 19 and expanded that observation to other epithelial cells in tissue culture and in vivo. In tissue culture, subconfluent cell stocks under continuous treatment with two different 21-mer phosphorothioate oligodeoxy nucleotides that targeted cytokeratin 19 mRNA enabled us to obtain confluent monolayers with a partial (40–70%) and transitory reduction in this protein. The expression of other cytoskeletal proteins was undisturbed. This downregulation of cytokeratin 19 resulted in (a) decrease in the number of microvilli; (b) disorganization of the apical (but not lateral or basal) filamentous actin and abnormal apical microtubules; and (c) depletion or redistribution of apical membrane proteins as determined by differential apical–basolateral biotinylation. In fact, a subset of detergent-insoluble proteins was not expressed on the cell surface in cells with lower levels of cytokeratin 19. Apical proteins purified in the detergent phase of Triton X-114 (typically integral membrane proteins) and those differentially extracted in Triton X-100 at 37°C or in n-octyl-β-d-glycoside at 4°C (representative of GPIanchored proteins), appeared partially redistributed to the basolateral domain. A transmembrane apical protein, sucrase isomaltase, was found mispolarized in a subpopulation of the cells treated with antisense oligonucleotides, while the basolateral polarity of Na+– K+ATPase was not affected. Both sucrase isomaltase and alkaline phosphatase (a GPI-anchored protein) appeared partially depolarized in A19 treated CACO-2 monolayers as determined by differential biotinylation, affinity purification, and immunoblot. These results suggest that an apical submembrane cytoskeleton of intermediate filaments is expressed in a number of epithelia, including those without a brush border, although it may not be universal. In addition, these data indicate that this structure is involved in the organization of the apical region of the cytoplasm and the apical membrane

Wind-driven mixing causes a reduction in the strength of the continental shelf carbon pump in the Chukchi Sea

The Chukchi Sea is thought to be a globally important sink of atmospheric CO₂ due to the summertime drawdown of surface pCO₂ by phytoplankton and subsequent shelf-to-basin transport of CO₂-enriched subsurface waters into the upper halocline of the Arctic Ocean. Here we show that annually occurring storm-induced mixing events during autumn months disrupt water column stratification and stir up remineralized carbon from subsurface waters to the surface, leading to CO₂ outgassing to the atmosphere. Our analysis provides a new understanding of the dynamics of carbon cycling in the region and suggests that late season wind events are strong and frequent enough to significantly decrease the carbon sink strength of the Chukchi Sea on a scale of relevance to the global carbon cycle. These results highlight the importance of obtaining data with more complete seasonal and spatial coverage in order to accurately constrain regional to basin-scale carbon flux budgets.Keywords: CO₂ flux, Vertical mixing, Remineralization, Chukchi Sea, Carbon dioxid

Insights into crustal assimilation by Icelandic basalts from boron isotopes in melt inclusions from the 1783–1784 Lakagígar eruption

Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 94 (2012): 164-180, doi:10.1016/j.gca.2012.07.002.The boron isotope system has great potential for tracing alteration and assimilation in basaltic systems due to the very low concentrations of B in mantle-derived melts and the strong isotopic contrast between the mantle and surface materials. However, variability in B concentrations and isotope ratios in basalts can also be interpreted to reflect inputs from enriched regions of the mantle, as the extent of mantle heterogeneity with respect to boron remains poorly delineated. We have determined boron concentrations and isotope ratios in fresh, glassy, plagioclase-hosted melt inclusions and unaltered scoriaceous matrix glasses from four localities associated with the 1783-1784 Lakagígar (Laki Fissure) eruption, Iceland. Boron concentrations range from 0.59-1.25 ppm in the melt inclusions, and from 1.25-1.65 ppm in the matrix glasses, while δ11BNBS-951 ranges from - 7.8‰ to -16.5‰ in the melt inclusions and -10.5‰ to -16.9‰ in the matrix glasses. In contrast to previous studies of boron in basaltic melt inclusions from other fissure swarms in Iceland (Gurenko and Chaussidon, 1997, Chem. Geol. 135, 21-34), the Lakagígar melt inclusions display a significant range of boron concentrations and isotope ratios at constant K2O wt.%, which is more consistent with B addition by assimilation of altered basalt than it is with mixing between depleted and enriched mantle sources. Assimilation of freshwater-altered crustal materials at depth may impart a light δ11B signature such as that observed in the Lakagígar melt inclusions and tephra host glasses. Considering boron concentrations and isotope ratios in the Lakagígar glasses and previously studied altered Icelandic basalts, together with volatile equilibration depths of the Lakagígar melt inclusions, we propose that a) mantle-derived magmas formed beneath Lakagígar assimilated ~5-20% altered crust at a depth of ~3-4 km or more, probably during magma accumulation in sills formed at the boundaries of low-density hyaloclastite layers; and b) the magma subsequently underwent extensive mixing and homogenization prior to eruption, quite possibly within the magma chamber beneath the Grímsvötn central volcano, assimilating an additional ~10% of altered crust at that time, for a total of up to 30% crustal assimilation. We hypothesize that volatiles including H2O, CO2, S, F, and Cl, which were responsible for the majority of the considerable casualties attributed to the Lakagígar eruption, were added together with isotopically light B by assimilation of hydrothermally altered crustal materials.This work was supported by a PSU-EMS Miller Award to MDF, NSF 761 EAR 09117456 to PCL, and awards to MNB by the GSA Northeast Division Grant for Undergraduate Research, the Dept. of Geosciences Undergraduate Senior Thesis Grant, and PSU Undergraduate Research Discovery Grant

MPI-DING reference glasses for in situ microanalysis: New reference values for element concentrations and isotope ratios

We present new analytical data of major and trace elements for the geological MPI-DING glasses KL2-G, ML3B-G, StHs6/80-G, GOR128-G, GOR132-G, BM90/21-G, T1-G, and ATHO-G. Different analytical methods were used to obtain a large spectrum of major and trace element data, in particular, EPMA, SIMS, LA-ICPMS, and isotope dilution by TIMS and ICPMS. Altogether, more than 60 qualified geochemical laboratories worldwide contributed to the analyses, allowing us to present new reference and information values and their uncertainties (at 95% confidence level) for up to 74 elements. We complied with the recommendations for the certification of geological reference materials by the International Association of Geoanalysts (IAG). The reference values were derived from the results of 16 independent techniques, including definitive (isotope dilution) and comparative bulk (e.g., INAA, ICPMS, SSMS) and microanalytical (e.g., LA-ICPMS, SIMS, EPMA) methods. Agreement between two or more independent methods and the use of definitive methods provided traceability to the fullest extent possible. We also present new and recently published data for the isotopic compositions of H, B, Li, O, Ca, Sr, Nd, Hf, and Pb. The results were mainly obtained by high-precision bulk techniques, such as TIMS and MC-ICPMS. In addition, LA-ICPMS and SIMS isotope data of B, Li, and Pb are presented. Copyright 2006 by the American Geophysical Union

Shelled pteropods in peril: Assessing vulnerability in a high CO2 ocean

The impact of anthropogenic ocean acidification (OA) on marine ecosystems is a vital concern facing marine scientists and managers of ocean resources. Euthecosomatous pteropods (holoplanktonic gastropods) represent an excellent sentinel for indicating exposure to anthropogenic OA because of the sensitivity of their aragonite shells to the OA conditions less favorable for calcification. However, an integration of observations, experiments and modelling efforts is needed to make accurate predictions of how these organisms will respond to future changes to their environment. Our understanding of the underlying organismal biology and life history is far from complete and must be improved if we are to comprehend fully the responses of these organisms to the multitude of stressors in their environment beyond OA. This review considers the present state of research and understanding of euthecosomatous pteropod biology and ecology of these organisms and considers promising new laboratory methods, advances in instrumentation (such as molecular, trace elements, stable isotopes, palaeobiology alongside autonomous sampling platforms, CT scanning and high-quality video recording) and novel field-based approaches (i.e. studies of upwelling and CO2 vent regions) that may allow us to improve our predictive capacity of their vulnerability and/or resilience. In addition to playing a critical ecological and biogeochemical role, pteropods can offer a significant value as an early-indicator of anthropogenic OA. This role as a sentinel species should be developed further to consolidate their potential use within marine environmental management policy making