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  • 1
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    A high yield cellulose extraction system for small whole wood samples and dual measurement of carbon and oxygen stable isotopes (2019)
    In:  Chemical Geology
    Details
    Publikationsdatum: 2021-03-11
    Beschreibung: This paper describes devices to extract α-cellulose from small whole wood samples developed at the Lamont-Doherty Earth Observatory Tree-Ring Lab and explains the procedures for chemical extractions and for the dual analysis of carbon (δ13C) and oxygen (δ18O) stable isotopes. Here, we provide the necessary steps and guidelines for constructing a cellulose extraction system for small amounts of wood and leaves. The system allows the simultaneous extraction of cellulose from 150 samples by means of in-house filter tubes, where chemicals used for the cellulose extraction are exchanged and eliminated in batches. This new implementation diminishes the processing time, minimizes physical sample manipulation and potential errors, increases sample throughput, and reduces the amount of chemicals and analytic costs. We also describe the dual measurement of δ13C and δ18O ratios in tree-ring cellulose using high-temperature pyrolysis in a High Temperature Conversion Elemental Analyzer (TC/EA) interfaced with a Thermo Delta V plus mass spectrometer.
    Materialart: info:eu-repo/semantics/article
    Format: application/pdf
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  • 2
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    IL-4 abrogates TH17 via IL-23 silencing [Immunology and Inflammation] (2015)
    National Academy of Sciences
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    Publikationsdatum: 2015-02-18
    Beschreibung: Interleukin 4 (IL-4) can suppress delayed-type hypersensitivity reactions (DTHRs), including organ-specific autoimmune diseases in mice and humans. Despite the broadly documented antiinflammatory effect of IL-4, the underlying mode of action remains incompletely understood, as IL-4 also promotes IL-12 production by dendritic cells (DCs) and IFN-γ–producing TH1 cells in vivo. Studying...
    Print ISSN: 0027-8424
    Digitale ISSN: 1091-6490
    Thema: Biologie , Medizin , Allgemeine Naturwissenschaft
    Publiziert von National Academy of Sciences
    Standort Signatur Einschränkungen Verfügbarkeit
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    PAPER CURRENT
  • 3
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    Hedgehog Pathway Inhibitors Effect on Basal Cell Carcinoma (2015)
    The American Association for Cancer Research (AACR)
    Details
    Publikationsdatum: 2015-03-14
    Beschreibung: Purpose: Basal cell carcinomas (BCCs) are tumors ignored by immune surveillance. Activated Hedgehog (Hh) signaling within primary cilia is a key driver in the pathogenesis of BCCs. We examined immune alterations during treatment with systemic Hh inhibitors. Experimental Design: We investigated biopsies from patients with BCC before (23 patients) and after 4 weeks of treatment (5 patients) with Hh signaling inhibitor. Ber-Ep4, BCL-2, Ki-67, CD4, CD8, MHC class I, HLA-DR-class II, and SOX9 were analyzed by immunohistochemistry. Primary cilia were analyzed by double immunofluorescence of acetylated tubulin and SOX9. Differential gene expression for 84 cytokines and chemokines was analyzed in 3 patients. Results: After 4 weeks of treatment, we found reduction of Ki-67, SOX9, Ber-EP4, and BCL-2 expression in tumors associated with morphologic signs of squamous differentiation. In addition, the number of cilia-positive BCC cells was significantly decreased. An upregulation of MHC I expression on the cell membranes of residual tumor cells and an influx of CD4 + , HLA-DR-class II + , and CD8 + cells with invasion into the tumor cell nests were found. Finally, qPCR arrays showed the differential expression of genes involved in modulating immune responses. Conclusions: We show that Hh pathway inhibitor–induced tumor regression is accompanied by a dynamic change of the microenvironment with a disruption of immune privilege involving an influx of cytotoxic T cells, activation of the adaptive immune functions, and a profound alteration of the local chemokine/cytokine network. Clin Cancer Res; 21(6); 1289–97. ©2015 AACR .
    Print ISSN: 1078-0432
    Digitale ISSN: 1557-3265
    Thema: Medizin
    Publiziert von The American Association for Cancer Research (AACR)
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
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    Lmx1a/b regulate survival of dopamine neurons [Neuroscience] (2016)
    National Academy of Sciences
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    Publikationsdatum: 2016-07-28
    Beschreibung: The LIM-homeodomain transcription factors Lmx1a and Lmx1b play critical roles during the development of midbrain dopaminergic progenitors, but their functions in the adult brain remain poorly understood. We show here that sustained expression of Lmx1a and Lmx1b is required for the survival of adult midbrain dopaminergic neurons. Strikingly, inactivation of...
    Print ISSN: 0027-8424
    Digitale ISSN: 1091-6490
    Thema: Biologie , Medizin , Allgemeine Naturwissenschaft
    Publiziert von National Academy of Sciences
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    Romidepsin and Azacitidine Synergize in CTCL (2016)
    The American Association for Cancer Research (AACR)
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    Publikationsdatum: 2016-04-16
    Beschreibung: Purpose: Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of malignancies that despite available therapies commonly relapse. The emergence of combination epigenetic therapies in other hematologic malignancies have made investigation of such combinations in CTCL a priority. Here, we explore the synergistic antiproliferative effects of romidepsin, an HDAC inhibitor, and azacitidine, a demethylating agent, combination in CTCL. Experimental Design: The growth inhibition under combination treatment and single agent was explored by the MTT cell viability assay and the Annexin V/propidium iodide (PI) apoptosis assay in different CTCL cell lines and tumor cells derived from Sézary syndrome patients. Quantitative analysis of a dose–effect relationship of romidepsin and azacitidine was done by the CompuSyn software. Investigation of mechanism of action was performed by flow cytometry, immunoblotting, qRT-PCR arrays, and chromatin immunoprecipitation. Global CpG methylation sequencing was utilized to study genome methylation alteration under the treatment modalities. Results: The combination of romidepsin and azacitidine exerts synergistic antiproliferative effects and induction of apoptosis involving activation of the caspase cascade in CTCL cell lines and tumor cells derived from Sézary syndrome patients. We identified genes that were selectively induced by the combination treatment, such as the tumor suppressor gene RhoB that is linked to enhanced histone acetylation at its promoter region in parallel with pronounced expression of p21. Global CpG methylation sequencing in a CTCL cell line and tumor cells demonstrated a subset of genes with a unique change in methylation profile in the combination treatment. Conclusions: The synergistic antiproliferative effects of romidepsin and azacitidine combination treatment justify further exploration in clinical trials for advanced CTCL. Clin Cancer Res; 22(8); 2020–31. ©2015 AACR .
    Print ISSN: 1078-0432
    Digitale ISSN: 1557-3265
    Thema: Medizin
    Publiziert von The American Association for Cancer Research (AACR)
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
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    Unexpected contribution of lymphatic vessels to promotion of distant metastatic tumor spread (2018)
    American Association for the Advancement of Science (AAAS)
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    Publikationsdatum: 2018-08-09
    Beschreibung: Tumor lymphangiogenesis is accompanied by a higher incidence of sentinel lymph node metastasis and shorter overall survival in several types of cancer. We asked whether tumor lymphangiogenesis might also occur in distant organs with established metastases and whether it might promote further metastatic spread of those metastases to other organs. Using mouse metastasis models, we found that lymphangiogenesis occurred in distant lung metastases and that some metastatic tumor cells were located in lymphatic vessels and draining lymph nodes. In metastasis-bearing lungs of melanoma patients, a higher lymphatic density within and around metastases and lymphatic invasion correlated with poor outcome. Using a transgenic mouse model with inducible expression of vascular endothelial growth factor C (VEGF-C) in the lung, we found greater growth of lung metastases, with more abundant dissemination to other organs. Our findings reveal unexpected contributions of lymphatics in distant organs to the promotion of growth of metastases and their further spread to other organs, with potential clinical implications for adjuvant therapies in patients with metastatic cancer.
    Digitale ISSN: 2375-2548
    Thema: Allgemeine Naturwissenschaft
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
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    Large magnetoresistance by Pauli blockade in hydrogenated graphene (2018)
    American Physical Society (APS)
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    Publikationsdatum: 2018-04-19
    Beschreibung: Author(s): J. Guillemette, N. Hemsworth, A. Vlasov, J. Kirman, F. Mahvash, P. L. Lévesque, M. Siaj, R. Martel, G. Gervais, S. Studenikin, A. Sachrajda, and T. Szkopek We report the observation of a giant positive magnetoresistance in millimeter-scale hydrogenated graphene with the magnetic field oriented in the plane of the graphene sheet. A positive magnetoresistance in excess of 200% at a temperature of 300 mK was observed in this configuration, reverting to ne... [Phys. Rev. B 97, 161402(R)] Published Wed Apr 18, 2018
    Schlagwort(e): Surface physics, nanoscale physics, low-dimensional systems
    Print ISSN: 1098-0121
    Digitale ISSN: 1095-3795
    Thema: Physik
    Publiziert von American Physical Society (APS)
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
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    Inhibition of Age-Related Therapy Resistance in Melanoma by Rosiglitazone-Mediated Induction of Klotho (2017)
    The American Association for Cancer Research (AACR)
    Details
    Publikationsdatum: 2017-06-16
    Beschreibung: Purpose: Aging is a poor prognostic factor for melanoma. We have shown that melanoma cells in an aged microenvironment are more resistant to targeted therapy than identical cells in a young microenvironment. This is dependent on age-related secreted factors. Klotho is an age-related protein whose serum levels decrease dramatically by age 40. Most studies on klotho in cancer have focused on the expression of klotho in the tumor cell. We have shown that exogenous klotho inhibits internalization and signaling of Wnt5A, which drives melanoma metastasis and resistance to targeted therapy. We investigate here whether increasing klotho in the aged microenvironment could be an effective strategy for the treatment of melanoma. Experimental Design: PPAR increases klotho levels and is increased by glitazones. Using rosiglitazone, we queried the effects of rosiglitazone on Klotho/Wnt5A cross-talk, in vitro and in vivo , and the implications of that for targeted therapy in young versus aged animals. Results: We show that rosiglitazone increases klotho and decreases Wnt5A in tumor cells, reducing the burden of both BRAF inhibitor–sensitive and BRAF inhibitor–resistant tumors in aged, but not young mice. However, when used in combination with PLX4720, tumor burden was reduced in both young and aged mice, even in resistant tumors. Conclusions: Using glitazones as adjuvant therapy for melanoma may provide a new treatment strategy for older melanoma patients who have developed resistance to vemurafenib. As klotho has been shown to play a role in other cancers too, our results may have wide relevance for multiple tumor types. Clin Cancer Res; 23(12); 3181–90. ©2017 AACR .
    Print ISSN: 1078-0432
    Digitale ISSN: 1557-3265
    Thema: Medizin
    Publiziert von The American Association for Cancer Research (AACR)
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
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    Nrf2 and Skin Cancer (2015)
    The American Association for Cancer Research (AACR)
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    Publikationsdatum: 2015-11-17
    Beschreibung: Pharmacologic activation of the transcription factor NRF2 has been suggested to offer a strategy for cancer prevention. In this study, we present evidence from murine tumorigenesis experiments suggesting there may be limitations to this possibility, based on tumorigenic effects of Nrf2 in murine keratinocytes that have not been described previously. In this setting, Nrf2 expression conferred metabolic alterations in keratinocytes that were protumorigenic in nature, affecting enzymes involved in glutathione biosynthesis or in the oxidative pentose phosphate pathway and other NADPH-producing enzymes. Under stress conditions, coordinate increases in NADPH, purine, and glutathione levels promoted the survival of keratinocytes harboring oncogenic mutations, thereby promoting tumor development. The protumorigenic activity of Nrf2 in keratinocytes was particularly significant in a mouse model of skin tumorigenesis that did not rely upon chemical carcinogenesis. In exploring the clinical relevance of our findings, we confirm that NRF2 and protumorigenic NRF2 target genes were activated in some actinic keratoses, the major precancerous lesion in human skin. Overall, our results reveal an unexpected tumor-promoting activity of activated NRF2 during early phases of skin tumorigenesis. Cancer Res; 75(22); 4817–29. ©2015 AACR.
    Print ISSN: 0008-5472
    Digitale ISSN: 1538-7445
    Thema: Medizin
    Publiziert von The American Association for Cancer Research (AACR)
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
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    Three-Dimensional Vascular Network Assembly From Diabetic Patient-Derived Induced Pluripotent Stem Cells [Translational Sciences] (2015)
    American Heart Association (AHA)
    Details
    Publikationsdatum: 2015-11-26
    Beschreibung: Objective— In diabetics, hyperglycemia results in deficient endothelial progenitors and cells, leading to cardiovascular complications. We aim to engineer 3-dimensional (3D) vascular networks in synthetic hydrogels from type 1 diabetes mellitus (T1D) patient–derived human-induced pluripotent stem cells (hiPSCs), to serve as a transformative autologous vascular therapy for diabetic patients. Approach and Results— We validated and optimized an adherent, feeder-free differentiation procedure to derive early vascular cells (EVCs) with high portions of vascular endothelial cadherin-positive cells from hiPSCs. We demonstrate similar differentiation efficiency from hiPSCs derived from healthy donor and patients with T1D. T1D-hiPSC–derived vascular endothelial cadherin-positive cells can mature to functional endothelial cells–expressing mature markers: von Willebrand factor and endothelial nitric oxide synthase are capable of lectin binding and acetylated low-density lipoprotein uptake, form cords in Matrigel and respond to tumor necrosis factor-α. When embedded in engineered hyaluronic acid hydrogels, T1D-EVCs undergo morphogenesis and assemble into 3D networks. When encapsulated in a novel hypoxia-inducible hydrogel, T1D-EVCs respond to low oxygen and form 3D networks. As xenografts, T1D-EVCs incorporate into developing zebrafish vasculature. Conclusions— Using our robust protocol, we can direct efficient differentiation of T1D-hiPSC to EVCs. Early endothelial cells derived from T1D-hiPSC are functional when mature. T1D-EVCs self-assembled into 3D networks when embedded in hyaluronic acid and hypoxia-inducible hydrogels. The capability of T1D-EVCs to assemble into 3D networks in engineered matrices and to respond to a hypoxic microenvironment is a significant advancement for autologous vascular therapy in diabetic patients and has broad importance for tissue engineering.
    Schlagwort(e): Vascular Biology, Diabetes, Type 1
    Print ISSN: 1079-5642
    Digitale ISSN: 1524-4636
    Thema: Medizin
    Publiziert von American Heart Association (AHA)
    Standort Signatur Einschränkungen Verfügbarkeit
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