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Sample records for abundant myxoid stroma

  1. Recurrent BCOR internal tandem duplication and BCOR or BCL6 expression distinguish primitive myxoid mesenchymal tumor of infancy from congenital infantile fibrosarcoma.

    PubMed

    Santiago, Teresa; Clay, Michael R; Allen, Sariah J; Orr, Brent A

    2017-03-03

    Primitive myxoid mesenchymal tumor of infancy is a rare sarcoma that preferentially affects infants. It can be locally aggressive and rarely metastasizes, but the long-term outcome of children with this tumor is mostly unknown. Histologically, it is characterized by primitive cells with abundant myxoid stroma. Internal tandem duplication of B-cell CLL/lymphoma 6 (BCL6)-interacting co-repressor (BCOR) exon 15 has recently been described in clear cell sarcoma of kidney, central nervous system high-grade neuroepithelial tumor with BCOR alteration, and primitive myxoid mesenchymal tumor of infancy. Herein, we report five cases of primitive myxoid mesenchymal tumor of infancy: three girls and two boys with mean age of 6.5 months. The tumors were located in the paraspinal region (n=3), back (n=1), or foot (n=1) and ranged in size from 2.5 to 10.2 cm. BCOR internal tandem duplication was confirmed by PCR and sequencing in all five cases. The minimally duplicated region consisted of nine residues, which is shorter than was previously reported in other BCOR-associated tumors. To assess the clinical value and specificity of the BCOR internal tandem duplication, a group of 11 ETV6-rearranged congenital infantile fibrosarcomas were evaluated and no BCOR internal tandem duplication was identified in any case. Though not detected in congenital infantile fibrosarcomas, BCOR and BCL6 immunoreactivity was present in >90% of the nuclei of tumor cells in each of the five primitive myxoid mesenchymal tumor of infancy. The presence of BCOR internal tandem duplication in all five primitive myxoid mesenchymal tumors of infancy provides evidence that it is a recurrent somatic abnormality and substantiates the concept that this tumor is a unique sarcoma of infancy. Our findings indicate that identification of BCOR internal tandem duplication and/or nuclear immunoreactivity for BCOR or BCL6 can aid in the diagnosis of primitive myxoid mesenchymal tumor of infancy and help to differentiate

  2. Reticular schwannoma mimicking myxoid sarcoma.

    PubMed

    Chaurasia, Jai Kumar; Afroz, Nishat; Sahoo, Biswajit; Naim, Mohammed

    2014-02-20

    Reticular/microcystic schwannoma is a recently described rare distinctive variant of schwannoma with a predilection for gastrointestinal tract. Its occurrence in soft tissue is extremely rare. We report a case of reticular/microcystic variant of schwannoma in a 55-year-old Indian woman who presented with a painless slow-growing swelling in the right forearm for the past 6 months. MRI findings suggested myxoid sarcoma. However, histological and immunohistochemical findings in the excised specimen were consistent with reticular/microcystic variant of schwannoma. This case report emphasises that the diagnosis of reticular/microcystic schwannoma should always be considered in cases where myxoid sarcomas are suspected as it can mimic malignant myxoid sarcomas, clinically and radiologically, thereby avoiding aggressive intervention and overtreatment.

  3. Primary myxoid chondrosarcoma of the breast.

    PubMed

    Farahat, A; Magdy, N; Elaffandi, A

    2014-01-01

    Primary breast chondrosarcoma has been rarely reported in the literature. Conservative breast surgery has never been part of the management of previously reported cases. Surgery remains the mainstay management of such a disease as it is resistant to chemotherapy and radiotherapy. In this report, we present a case of rare primary myxoid chondrosarcoma of the breast that was managed successfully with a conservative approach.

  4. Endometrial Endometrioid Carcinoma With Large Cystic Growth Configuration and Deceptive Pattern of Invasion Associated With Abundant Nodular Fasciitis-like Stroma: A Unique Hitherto Unreported Histology in Endometrioid Carcinoma.

    PubMed

    Švajdler, Marián; Michal, Michael; Dubinský, Pavol; Švajdler, Peter; Ondič, Ondrej; Michal, Michal

    2016-11-01

    We describe a case of an unusual endometrial endometrioid carcinoma occurring in a 67-year-old woman. The tumor involved uterine corpus as well as lower uterine segment and presented as polypoid tumor protruding through the cervical orifice. Microscopically, the tumor was characterized by broad zones of cytologically bland fibromyxoid stroma resembling nodular fasciitis, showing vaguely nodular architecture. Neoplastic glands were characterized by interconnected elongated slit-like and large cystic profiles, mostly lined by flattened epithelium with variable squamous differentiation, whereas typical columnar endometrioid cells were only focally present. Voluminous nodules of the stroma produced phyllodes-like appearance of the tumor. The tumor showed some resemblance to the microcystic, elongated, and fragmented (MELF) glands growth pattern, but in contrast with MELF pattern, where fibromyxoid change occurs focally, in the presented case abundant myofibroblastic proliferation was present throughout the tumor and the neoplastic glands showed anastomosing "large cystic" rather than "small cystic" profiles. Some of the neoplastic glands presented almost complete or complete squamous differentiation, with relatively bland-looking squamous cells and no hint of endometrioid differentiation, which resulted in initial misdiagnosis of Müllerian adenofibroma. We believe that nodular fasciitis-like pattern represents yet undescribed, and diagnostically challenging pattern of invasion in endometrial endometrioid carcinoma.

  5. Curious case of extraskeletal myxoid chondrosarcoma

    PubMed Central

    Gupta, Sushilkumar Satish; Khanna, Neha; Jacobi, Adam

    2017-01-01

    Extraskeletal myxoid chondrosarcomas (EMC) are a rare entity of soft tissue tumors that have slow growth with metastatic potential. We discuss here a case of EMC presenting with right upper extremity pain and hemoptysis. Computed tomography scans chest showed diffuse metastatic numerous lung nodules bilaterally. Biopsy confirmed the diagnosis of the tumor. Chemotherapy was a bigger challenge for our patient due to sparse research and data in the literature about the disease. PMID:28360467

  6. Primary myxoid chondrosarcoma of the breast

    PubMed Central

    Magdy, N; Elaffandi, A

    2014-01-01

    Primary breast chondrosarcoma has been rarely reported in the literature. Conservative breast surgery has never been part of the management of previously reported cases. Surgery remains the mainstay management of such a disease as it is resistant to chemotherapy and radiotherapy. In this report, we present a case of rare primary myxoid chondrosarcoma of the breast that was managed successfully with a conservative approach. PMID:24417859

  7. Pericardial myxoid liposarcoma in a common eland (Taurotragus oryx).

    PubMed

    Foster, A P; Johnston, P E; Duignan, P J; Schock, A

    2011-07-01

    A pericardial myxoid liposarcoma was diagnosed in a common eland (Taurotragus oryx) based on gross, microscopical and immunohistochemical findings. The pericardial and epicardial tissues were soft and uniformly thickened. Microscopically, the neoplastic mass consisted of stellate cells embedded in a myxoid matrix. These cells contained cytoplasmic vacuoles stained by oil red O. Immunohistochemical analysis showed the neoplastic cells to express vimentin and S-100.

  8. Axitinib Has Antiangiogenic and Antitumorigenic Activity in Myxoid Liposarcoma

    PubMed Central

    Donoghue, Jacqueline F.; Wilding, Alexander L.

    2016-01-01

    Myxoid liposarcoma is a rare form of soft-tissue sarcoma. Although most patients initially respond well to treatment, approximately 21% relapse, highlighting the need for alternative treatments. To identify novel treatment regimens and gain a better understanding of myxoid liposarcoma tumor biology, we screened various candidate and approved targeted therapeutics and chemotherapeutics against myxoid liposarcoma cell lines. Therapeutics that target angiogenesis showed antitumor activity. The small molecule inhibitor axitinib, which targets angiogenesis by inhibiting the VEGFR and PDGFR families and c-Kit, inhibited cell cycle progression and induced apoptosis in vitro, as well as having significant antitumor activity against MLS 1765 myxoid liposarcoma xenografts in mice. Axitinib also displayed synergistic antitumor activity in vitro when combined with the potassium channel ionophore salinomycin or the BH3 mimetic ABT-737. Another angiogenesis-targeting therapeutic, 4EGI-1, which targets the oncoprotein eIF4E, significantly decreased angiogenic ligand expression by myxoid liposarcoma cells and reduced tumor cell growth. To verify this oncogenic addiction to angiogenic pathways, we utilized VEGFR-derived ligand traps and found that autocrine VEGFR signaling was crucial to myxoid liposarcoma cell survival. Overall, these findings suggest that autocrine angiogenic signaling through the VEGFR family is critical to myxoid liposarcoma cell survival and that further study of axitinib as a potential anticancer therapy is warranted. PMID:27822137

  9. Myxoid Leiomyosarcoma of Ovary-A Rare Case Report

    PubMed Central

    V, Srinivasamurthy

    2014-01-01

    Primary pure myxoid leiomyosarcoma of the ovary is extremely rare, comprising of only 1% of the ovarian tumours. Patient presented with a mass in the right iliac fossa since three months. Radiological diagnosis of broad ligament fibroid was given. Right salphingo-oophorectomy with enucleation of ischial fossa and wedge biopsy of left ovary was carried out. Based on gross, microscopy and immunohistochemistry a diagnosis of primary myxoid leiomyosarcoma of ovary was made. We report a rare case of primary pure myxoid leiomyosarcoma of the ovary with metastasis to ischial fossa emphasising on reliable prognostic markers. Ovarian leiomyosarcomas are highly aggressive tumours with poor prognosis. PMID:25120990

  10. Myxoid stroma and delicate vasculature of a superficial angiomyxoma give rise to the red planet sign.

    PubMed

    Green, Margaret; Logemann, Nichola; Sulit, Daryl J

    2014-09-16

    Superficial angiomyxomas are uncommon benign mesenchymal tumors. They often recur locally if partially removed. This case report demonstrates not only the characteristic pathological findings of a superficial angiomyxoma in a 33- year-old man, but also shows a unique dermatoscopic image, which in our estimation resembles a celestial red planet such as the blood moon seen during a lunar eclipse. We propose to call this the "red planet" sign for a superficial angiomyxoma on dermoscopic examination.

  11. Fine needle aspiration biopsy of metastatic malignant mesothelioma with myxoid change and signet ring cells: A case report and review of the literature

    PubMed Central

    Mishra, Manisha M.; Farver, Carol F.; Chute, Deborah J.

    2016-01-01

    Malignant mesothelioma (MM) is a rare neoplasm, which is most commonly encountered in cytology through effusion specimens. Fine needle aspiration biopsy of MM, particularly the epithelioid subtype, can be a source of diagnostic difficulty and may mimic sampling of an adenocarcinoma. This is the first case report to demonstrate abundant extracellular myxoid material and numerous intracellular vacuoles, including signet ring cells, in a fine needle aspirate of metastatic MM. A review of the literature for myxoid change and vacuoles in fine needle aspiration biopsies of MM discloses that vacuoles are found in up to 35% of aspirates of MM, but myxoid change is very rare, reported in <5% of the cases. Cytologists should be aware of this rare morphologic pattern of metastatic epithelioid MM. PMID:27014364

  12. Polypeptides of the Maize Amyloplast Stroma1

    PubMed Central

    Yu, Ying; He Mu, Helen; Mu-Forster, Chen; Wasserman, Bruce P.

    1998-01-01

    In the developing endosperm of monocotyledonous plants, starch granules are synthesized and deposited within the amyloplast. A soluble stromal fraction was isolated from amyloplasts of immature maize (Zea mays L.) endosperm and analyzed for enzyme activities and polypeptide content. Specific activities of starch synthase and starch-branching enzyme (SBE), but not the cytosolic marker alcohol dehydrogenase, were strongly enhanced in soluble amyloplast stromal fractions relative to soluble extracts obtained from homogenized kernels or endosperms. Immunoblot analysis demonstrated that starch synthase I, SBEIIb, and sugary1, the putative starch-debranching enzyme, were each highly enriched in the amyloplast stroma, providing direct evidence for the localization of starch-biosynthetic enzymes within this compartment. Analysis of maize mutants shows the deficiency of the 85-kD SBEIIb polypeptide in the stroma of amylose extender cultivars and that the dull mutant lacks a >220-kD stromal polypeptide. The stromal fraction is distinguished by differential enrichment of a characteristic group of previously undocumented polypeptides. N-terminal sequence analysis revealed that an abundant 81-kD stromal polypeptide is a member of the Hsp70 family of stress-related proteins. Moreover, the 81-kD stromal polypeptide is strongly recognized by antibodies specific for an Hsp70 of the chloroplast stroma. These findings are discussed in light of implications for the correct folding and assembly of soluble, partially soluble, and granule-bound starch-biosynthetic enzymes during import into the amyloplast. PMID:9536063

  13. NY-ESO-1 is a sensitive and specific immunohistochemical marker for myxoid and round cell liposarcomas among related mesenchymal myxoid neoplasms.

    PubMed

    Hemminger, Jessica A; Iwenofu, O Hans

    2013-09-01

    Myxoid and round cell liposarcomas constitute approximately one-third of all liposarcomas, a relatively common group of fat-derived soft tissue sarcomas. The histomorphology is a continuum between highly differentiated myxoid and poorly differentiated round cell components. The gold standard of diagnosis is dependent on histomorphology and/or identification of t(12;16)(q13;p11) translocation by cytogenetics or demonstration of DDIT3 rearrangements by fluorescence in situ hybridization. There are currently no diagnostic immunohistochemical stains available. The broad range of myxoid neoplasms in the differential diagnosis includes a variety of sarcomas. Given the notable differences in disease biology among myxoid neoplasms, which range from benign to aggressive, an accurate diagnosis is imperative for proper treatment and prognostication. Prompted by our recent study showing frequent expression of the cancer testis antigen NY-ESO-1 in myxoid and round cell liposarcomas, we sought to evaluate the utility of NY-ESO-1 as an immunohistochemical marker for myxoid and round cell liposarcoma among mesenchymal myxoid neoplasms within the differential diagnosis. Formalin-fixed, paraffin-embedded blocks were obtained for the following mesenchymal myxoid neoplasms (n=138): myxoid and round cell liposarcoma (n=38); well-differentiated liposarcoma (n=12); lipoma (n=20; 4 with myxoid change); extra-cardiac soft tissue myxoma (n=39); extraskeletal myxoid chondrosarcoma (n=12); myxofibrosarcoma (n=10: 5 low grade, 2 intermediate grade, 3 high grade); and low-grade fibromyxoid sarcoma (n=7). Utilizing standard immunohistochemistry protocols, full sections were stained with NY-ESO-1 (clone E978), and staining was assessed for intensity (1-2+), percentage of tumor positivity, and location. In all, 36/38 (95%) of the myxoid and round cell liposarcomas demonstrated NY-ESO-1 immunoreactivity. The majority of the positive cases (34/36; 94%) showed strong, homogenous staining (>50% tumor

  14. Corneal Stroma Microfibrils

    PubMed Central

    Hanlon, Samuel D.; Behzad, Ali R.; Sakai, Lynn Y.; Burns, Alan R.

    2015-01-01

    Elastic tissue was first described well over a hundred years ago and has since been identified in nearly every part of the body. In this review, we examine elastic tissue in the corneal stroma with some mention of other ocular structures which have been more thoroughly described in the past. True elastic fibers consist of an elastin core surrounded by fibrillin microfibrils. However, the presence of elastin fibers is not a requirement and some elastic tissue is comprised of non-elastin-containing bundles of microfibrils. Fibers containing a higher relative amount of elastin are associated with greater elasticity and those without elastin, with structural support. Recently it has been shown that the microfibrils, not only serve mechanical roles, but are also involved in cell signaling through force transduction and the release of TGF-β. A well characterized example of elastin-free microfibril bundles (EFMBs) is found in the ciliary zonules which suspend the crystalline lens in the eye. Through contraction of the ciliary muscle they exert enough force to reshape the lens and thereby change its focal point. It is believed that the molecules comprising these fibers do not turn-over and yet retain their tensile strength for the life of the animal. The mechanical properties of the cornea (strength, elasticity, resiliency) would suggest that EFMBs are present there as well. However, many authors have reported that, although present during embryonic and early postnatal development, EFMBs are generally not present in adults. Serial-block-face imaging with a scanning electron microscope enabled 3D reconstruction of elements in murine corneas. Among these elements were found fibers that formed an extensive network throughout the cornea. In single sections these fibers appeared as electron dense patches. Transmission electron microscopy provided additional detail of these patches and showed them to be composed of fibrils (∼10nm diameter). Immunogold evidence clearly

  15. Pancreatic cancer: Stroma and its current and emerging targeted therapies.

    PubMed

    Kota, Janaiah; Hancock, Julie; Kwon, Jason; Korc, Murray

    2017-04-10

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies with a 5-year survival rate of 8%. Dense, fibrotic stroma associated with pancreatic tumors is a major obstacle for drug delivery to the tumor bed and plays a crucial role in pancreatic cancer progression. Targeting stroma is considered as a potential therapeutic strategy to improve anti-cancer drug efficacy and patient survival. Although numerous stromal depletion therapies have reached the clinic, they add little to overall survival and are often associated with toxicity. Furthermore, increasing evidence suggests the anti-tumor properties of stroma. Its complete ablation enhanced tumor progression and reduced survival. Consequently, efforts are now focused on developing stromal-targeted therapies that normalize the reactive stroma and avoid the extremes: stromal abundance vs. complete depletion. In this review, we summarized the state of current and emerging anti-stromal targeted therapies, with major emphasis on the role of miRNAs in PDAC stroma and their potential use as novel therapeutic agents to modulate PDAC tumor-stromal interactions.

  16. Validation of immature adipogenic status and identification of prognostic biomarkers in myxoid liposarcoma using tissue microarrays.

    PubMed

    Cheng, Hongwei; Dodge, Jim; Mehl, Erika; Liu, Shuzhen; Poulin, Neal; van de Rijn, Matt; Nielsen, Torsten O

    2009-09-01

    Myxoid liposarcoma displays variably aggressive behavior and responds poorly to available systemic therapies. Expression profiling followed by tissue microarray validation linked to patient outcome is a powerful approach for validating biological mechanisms and identifying prognostic biomarkers. We applied these techniques to independent series of primary myxoid liposarcomas in an effort to assess markers of adipose differentiation in myxoid liposarcoma and to identify prognostic markers that can be efficiently assessed by immunohistochemistry. Candidate genes were selected based on analysis of expression profiles from 9 primary myxoid/round liposarcomas and 45 other soft tissue tumors, and by reference to publicly available data sets. Protein products were validated on an adipose neoplasm tissue microarray, including 32 myxoid liposarcomas linked to patient outcome. Results were scored visually and correlated with clinical outcome by Kaplan-Meier and Cox regression analyses. In the study, by examining expression patterns of several lipogenic regulatory gene products, an immature adipogenic status was verified in myxoid liposarcomas. We also found that expression levels of the ret proto-oncogene, insulin-like growth factor 1 receptor, and insulin-like growth factor 2 correlate with poor metastasis-free survival, supporting a role for ERK/MAPK and PI3K/AKT pathways in clinically aggressive myxoid liposarcomas.

  17. Primary retroperitoneal myxoid/round cell liposarcoma is a nonexisting disease: an immunohistochemical and molecular biological analysis.

    PubMed

    de Vreeze, Ronald S A; de Jong, Daphne; Tielen, Ivon H G; Ruijter, Henrique J; Nederlof, Petra M; Haas, Rick L; van Coevorden, Frits

    2009-02-01

    Almost all primary retroperitoneal liposarcomas can be classified as well-/dedifferentiated liposarcoma. Rarely, however, primary retroperitoneal liposarcoma is classified as myxoid/round cell liposarcoma, based on the presence of myxoid areas and vascular crow's feet pattern, which has resulted in a debate on the classification of liposarcoma in the retroperitoneum. Genetically, myxoid/round cell liposarcoma and well-/dedifferentiated liposarcoma are different diseases. Myxoid/round cell liposarcoma is characterized by a translocation causing FUS-CHOP or EWSR1-CHOP fusion, whereas well-/dedifferentiated liposarcoma is characterized by an amplification of the 12q13-15 region, including MDM2 and CDK4 genes. As myxoid/round cell liposarcoma is highly radio- and chemosensitive, differentiation between subtypes is important to optimize treatment. We studied whether primary retroperitoneal liposarcomas diagnosed as myxoid/round cell liposarcoma represent molecularly true myxoid/round cell liposarcoma or are histopathological mimics and represent well-/dedifferentiated liposarcoma. Primary retroperitoneal myxoid/round cell liposarcoma (n=16) were compared to primary extremity myxoid/round cell liposarcoma (n=20). Histopathological and immunohistochemical features were studied. Amplification status of the 12q13-15 region was studied using a multiplex ligation-dependent probe amplification analysis, and FUS-CHOP or EWS-CHOP translocations were studied using RT-PCR. In primary retroperitoneal myxoid/round cell liposarcoma, MDM2 and CDK4 staining was both positive in 12 of 15 cases. In primary extremity myxoid/round cell liposarcoma, MDM2 was negative in 18/20 and CDK4 was negative in all cases. Multiplex ligation-dependent probe amplification showed the amplification of 12q13-15 region in 16/16 primary retroperitoneal myxoid/round cell liposarcomas and in 1/20 primary extremity myxoid/round cell liposarcomas. Translocation was present in all (18/18) primary extremity myxoid

  18. Stroma in Breast Development and Disease

    PubMed Central

    Arendt, Lisa M.; Rudnick, Jenny A.; Keller, Patricia J.; Kuperwasser, Charlotte

    2009-01-01

    It is increasingly apparent that normal and malignant breast tissues require complex local and systemic stromal interactions for development and progression. During development, mammary cell fate specification and differentiation require highly regulated contextual signals derived from the stroma. Likewise, during breast carcinoma development, the tissue stroma can provide tumor suppressing and tumor-promoting environments that serve to regulate neoplastic growth of the epithelium. This review focuses on the role of the stroma as a mediator of normal mammary development, as well as a critical regulator of malignant conversion and progression in breast cancer. Recognition of the important role of the stroma during the progression of breast cancers leads to the possibility of new targets for treatment of the initial breast cancer lesion as well as prevention of recurrence. PMID:19857593

  19. Unresectable Extraskeletal Myxoid Chondrosarcoma of the Neck: Early Tumor Response to Chemoradiotherapy

    PubMed Central

    Laszewski, Pam; Robinette, Natasha; Saleh, Husain; Raza, Naweed; Sukari, Ammar; Kim, Harold

    2015-01-01

    Extraskeletal myxoid chondrosarcoma (EMC) rarely occurs in the head and neck and is generally managed with primary surgery. To our knowledge, no cases of unresectable EMC of the neck have been reported. We present a case of an unresectable EMC treated with chemotherapy and radiation, and highlight the exceptional early response to therapy.  PMID:26848421

  20. Unresectable Extraskeletal Myxoid Chondrosarcoma of the Neck: Early Tumor Response to Chemoradiotherapy.

    PubMed

    Zaki, Mark; Laszewski, Pam; Robinette, Natasha; Saleh, Husain; Raza, Naweed; Sukari, Ammar; Kim, Harold

    2015-12-24

    Extraskeletal myxoid chondrosarcoma (EMC) rarely occurs in the head and neck and is generally managed with primary surgery. To our knowledge, no cases of unresectable EMC of the neck have been reported. We present a case of an unresectable EMC treated with chemotherapy and radiation, and highlight the exceptional early response to therapy.

  1. Diagnostic pitfalls associated with fine-needle aspiration biopsy in a patient with the myxoid variant of monophasic fibrous synovial sarcoma.

    PubMed

    Bergman, Simon; Brownlee, Noel A; Geisinger, Kim R; Ward, William G; Pettenati, Mark J; Koty, Patrick; Ellis, Ezra; Beaty, Michael W; Kilpatrick, Scott E

    2006-11-01

    Synovial sarcoma (SS) is one of the most common soft tissue tumors that typically presents in the extremities of young adults, but may occur at any site and affect children during the first decade. Herein we discuss a 12-yr-old male who complained of left foot pain and plantar mass. A fine-needle aspiration biopsy of an 8 cm subcutaneous mass was performed revealing a myxoid spindle cell neoplasm. The cytologic differential diagnosis included a myxoid neurofibroma, neurothekeoma, and a myxoid sarcoma. Subsequent excision of the mass revealed a monophasic fibrous SS with myxoid features. Examination of the tissue by fluorescence in situ hybridization confirmed the presence of characteristic SS SYT gene rearrangement at chromosome 18q11.2. This case underscores that the cytologic distinction of mxyoid spindle cell tumors may be challenging. We report the cytologic features of a myxoid monophasic fibrous SS, and discuss its distinction from other benign and malignant myxoid soft tissue neoplasms.

  2. Discal cyst associated with myxoid change and apoptosis of herniated disc materials: a case report.

    PubMed

    Okada, Kyoji; Saito, Hajime; Nishida, Jun; Miyakoshi, Naohisa; Takahashi, Shu; Nagasawa, Hiroyuki; Suzuki, Norio; Chida, Shuichi

    2007-01-01

    Discal cyst is a lumbar intraspinal cyst communicating with intervertebral disc, and previously reported series described the wall of these cysts as consisting of dense fibrous connective tissue. We report a 29-year-old Japanese male with discal cyst showing unusual histological features. Clinical symptoms in the current case as well as imaging features including discography were similar to those previously reported.However, the wall of the cyst consisted of disc material with myxoid degeneration. In addition, apoptosis of chondrocytes was diffusely observed in the herniated disc material. The current case was considered a histological variant of discal cyst. Myxoid degeneration of herniated disc material with diffuse apoptotic change of chondrocytes was probably associated with the formation of discal cyst.

  3. Myxoid Chondrosarcoma of Maxilla in a Pediatric Patient: A Rare Case Report

    PubMed Central

    Nimonkar, Pranali; Bhola, Nitin; Jadhav, Anendd; Jain, Anuj; Borle, Rajiv; Ranka, Rajul; Chaudhary, Minal

    2016-01-01

    Myxoid variant of chondrosarcoma is an uncommon potentially lethal malignant tumor which is even rare in pediatric age group. In the present paper, we report one such case of intermediate grade myxoid chondrosarcoma of left side of maxilla in a 12-year-old girl. The present case had a firm, painless, and lobulated growth in premolar-molar region which was associated with bicortical expansion. Maxillofacial imaging showed ill-defined radiolucency with displaced maxillary molars. Osteolytic changes were evident with the alveolus and walls of maxillary sinus. Owing to the age of the patient, surgical excision was selected as the modality of management followed by postoperative radiotherapy. This report encompasses the entire gamut of clinicopathological, radiological, and treatment modalities employed for chondrosarcoma. PMID:26904332

  4. A novel type of EWS-CHOP fusion gene in myxoid liposarcoma

    SciTech Connect

    Matsui, Yoshito . E-mail: ymatsui@sb4.so-net.ne.jp; Ueda, Takafumi; Kubo, Takahiro; Hasegawa, Tadashi; Tomita, Yasuhiko; Okamoto, Mina; Myoui, Akira; Kakunaga, Shigeki; Yasui, Natsuo; Yoshikawa, Hideki

    2006-09-22

    The cytogenetic hallmark of myxoid type and round cell type liposarcoma consists of reciprocal translocation of t(12;16)(q13;p11) and t(12;22)(q13;q12), which results in fusion of TLS/FUS and CHOP, and EWS and CHOP, respectively. Nine structural variations of the TLS/FUS-CHOP chimeric transcript have been reported, however, only two types of EWS-CHOP have been described. We describe here a case of myxoid liposarcoma containing a novel EWS-CHOP chimeric transcript and identified the breakpoint occurring in intron 13 of EWS. Reverse transcription-polymerase chain reaction and direct sequence showed that exon 13 of EWS was in-frame fused to exon 2 of CHOP. Genomic analysis revealed that the breaks were located in intron 13 of EWS and intron 1 of CHOP.

  5. Deep stroma investigation by confocal microscopy

    NASA Astrophysics Data System (ADS)

    Rossi, Francesca; Tatini, Francesca; Pini, Roberto; Valente, Paola; Ardia, Roberta; Buzzonetti, Luca; Canovetti, Annalisa; Malandrini, Alex; Lenzetti, Ivo; Menabuoni, Luca

    2015-03-01

    Laser assisted keratoplasty is nowadays largely used to perform minimally invasive surgery and partial thickness keratoplasty [1-3]. The use of the femtosecond laser enables to perform a customized surgery, solving the specific problem of the single patient, designing new graft profiles and partial thickness keratoplasty (PTK). The common characteristics of the PTKs and that make them eligible respect to the standard penetrating keratoplasty, are: the preservation of eyeball integrity, a reduced risk of graft rejection, a controlled postoperative astigmatism. On the other hand, the optimal surgical results after these PTKs are related to a correct comprehension of the deep stroma layers morphology, which can help in the identification of the correct cleavage plane during surgeries. In the last years some studies were published, giving new insights about the posterior stroma morphology in adult subjects [4,5]. In this work we present a study performed on two groups of tissues: one group is from 20 adult subjects aged 59 +/- 18 y.o., and the other group is from 15 young subjects, aged 12+/-5 y.o.. The samples were from tissues not suitable for transplant in patients. Confocal microscopy and Environmental Scanning Electron Microscopy (ESEM) were used for the analysis of the deep stroma. The preliminary results of this analysis show the main differences in between young and adult tissues, enabling to improve the knowledge of the morphology and of the biomechanical properties of human cornea, in order to improve the surgical results in partial thickness keratoplasty.

  6. Giant cell tumor of the tendon sheath: a rare periungual location simulating myxoid cyst*

    PubMed Central

    Minotto, Renan; Rodrigues, Camila Britto; Grill, Aline Barcellos; Furian, Roque

    2017-01-01

    Giant cell tumor of the tendon sheath is a benign soft tissue tumor most frequent between the third and fifth decades of life. It can mimic and make differential diagnoses with several hand tumors. Definitive diagnosis and the treatment of choice are reached with complete resection and histopathological examination. Here we describe a case with clinical presentation similar to that of a myxoid cyst. PMID:28225971

  7. Cancer-testis antigens PRAME and NY-ESO-1 correlate with tumour grade and poor prognosis in myxoid liposarcoma.

    PubMed

    Iura, Kunio; Kohashi, Kenichi; Hotokebuchi, Yuka; Ishii, Takeaki; Maekawa, Akira; Yamada, Yuichi; Yamamoto, Hidetaka; Iwamoto, Yukihide; Oda, Yoshinao

    2015-07-01

    Myxoid liposarcoma is the second most common liposarcoma. Although myxoid liposarcoma is relatively chemosensitive and thus a good candidate for chemotherapy, cases with relapsed or metastatic disease still have poor outcome. Here, we performed a gene microarray analysis to compare the gene expression profiles in six clinical myxoid liposarcoma samples and three normal adipose tissue samples, and to identify molecular biomarkers that would be useful as diagnostic markers or treatment targets in myxoid liposarcoma. This showed that the cancer-testis antigen PRAME was up-regulated in myxoid liposarcoma. We then performed immunohistochemical, western blotting and real-time polymerase chain reaction analyses to quantify the expression of PRAME and another cancer-testis antigen, NY-ESO-1, in clinical samples of myxoid liposarcoma (n = 93), dedifferentiated (n = 46), well-differentiated (n = 32) and pleomorphic liposarcomas (n = 14). Immunohistochemically, positivity for PRAME and NY-ESO-1 was observed in 84/93 (90%) and 83/93 (89%) of the myxoid liposarcomas, and in 20/46 (43%) and 3/46 (7%) of the dedifferentiated, 3/32 (9%) and 1/32 (3%) of the well-differentiated and 7/14 (50%) and 3/21 (21%) of the pleomorphic liposarcomas, respectively. High immunohistochemical expression of PRAME and/or NY-ESO-1 was significantly correlated with tumour diameter, the existence of tumour necrosis, a round-cell component of >5%, higher histological grade and advanced clinical stage. High PRAME and NY-ESO-1 expression correlated significantly with poor prognosis in a univariate analysis. The myxoid liposarcomas showed significantly higher protein and mRNA expression levels of PRAME and NY-ESO-1 (CTAG1B) than the other liposarcomas. In conclusion, PRAME and NY-ESO-1 (CTAG1B) were expressed in the vast majority of myxoid liposarcomas, and their high-level expression correlated with tumour grade and poor prognosis. Our results support the potential use of PRAME and NY

  8. Myxoid Plexiform Fibrohistiocytic Tumor Masquerading as Ganglion Cyst: A Case Report and Literature Review

    PubMed Central

    Lan, Jui; Huang, Hsuan-Ying

    2017-01-01

    Background. Plexiform fibrohistiocytic tumor is a distinctive mesenchymal neoplasm of low-grade malignancy, with the capacity for biphasic differentiation toward a fibroblastic or histiocyte-like morphology. Clinically, these lesions affect different areas of the body and appear as painless, slowly growing, dermal or subcutaneous masses. To date, only three cases of myxoid variant have been reported in the English literature. Case Presentation. A 45-year-old female patient presented with a subcutaneous nodule in the right popliteal fossa. The initial impression was a benign ganglion cyst. The soft tissue tumor has been treated by local excision. The histopathological and the immunohistochemical findings supported the diagnosis of myxoid plexiform fibrohistiocytic tumor. The postoperative course was uneventful, and the patient received regular follow-up examination. She is alive without any recurrence. Conclusions. This case demonstrates how to distinguish this distinctive plexiform fibrohistiocytic tumor from other problematic soft tissue tumors. It is also remarkable for its rarely reported extensive myxoid change. Currently, there is no clear-cut correlation between the clinicopathologic findings and the behavior of this unusual variant. PMID:28255491

  9. Role of Reactive Stroma in Prostate Cancer Progression

    DTIC Science & Technology

    2008-02-01

    AD_________________ Award Number: W81XWH-04-1-0189 TITLE: Role of Reactive Stroma in Prostate Cancer Progression PRINCIPAL INVESTIGATOR: David R...REPORT TYPE Final 3. DATES COVERED 12 JAN 2004 - 11 JAN 2008 4. TITLE AND SUBTITLE Role of Reactive Stroma in Prostate Cancer Progression 5a. CONTRACT...the reactive stroma of experimental prostate cancer . Using a modified approach, we are placing an inducible Cre recombinase behind the FAP gene

  10. Stroma Targeting Nuclear Imaging and Radiopharmaceuticals

    PubMed Central

    Shetty, Dinesh; Jeong, Jae-Min; Shim, Hyunsuk

    2012-01-01

    Malignant transformation of tumor accompanies profound changes in the normal neighboring tissue, called tumor stroma. The tumor stroma provides an environment favoring local tumor growth, invasion, and metastatic spreading. Nuclear imaging (PET/SPECT) measures biochemical and physiologic functions in the human body. In oncology, PET/SPECT is particularly useful for differentiating tumors from postsurgical changes or radiation necrosis, distinguishing benign from malignant lesions, identifying the optimal site for biopsy, staging cancers, and monitoring the response to therapy. Indeed, PET/SPECT is a powerful, proven diagnostic imaging modality that displays information unobtainable through other anatomical imaging, such as CT or MRI. When combined with coregistered CT data, [18F]fluorodeoxyglucose ([18F]FDG)-PET is particularly useful. However, [18F]FDG is not a target-specific PET tracer. This paper will review the tumor microenvironment targeting oncologic imaging such as angiogenesis, invasion, hypoxia, growth, and homing, and also therapeutic radiopharmaceuticals to provide a roadmap for additional applications of tumor imaging and therapy. PMID:22685650

  11. Ectopic micronodular thymoma with lymphoid stroma in the cervical region: a rare case associated with Langerhans cells proliferation

    PubMed Central

    Yu, Min; Meng, Yuan; Xu, Bin; Zhao, Lin; Zhang, Qingfu

    2016-01-01

    Micronodular thymoma (MNT) with lymphoid stroma is a rare thymic epithelial neoplasm with the characteristics of multiple nodules separated by abundant lymphoid stroma. MNTs mainly arise in the anterior mediastinum and thymus, while ectopic MNTs are extremely rarely seen. Here, we report an ectopic MNT that occurred in the neck of a 62-year-old woman. There were also scattered eosinophilic granulocytes and S100+/CD1a+ Langerhans cells within the tumor. This case provides a better understanding of such rare, poorly understood cases. PMID:27486334

  12. Vascular Hyperpermeability, Angiogenesis, and Stroma Generation

    PubMed Central

    Nagy, Janice A.; Dvorak, Ann M.; Dvorak, Harold F.

    2012-01-01

    It has been known for more than half a century that the tumor microvasculature is hyperpermeable to plasma proteins. However, the identity of the leaky vessels and the consequences of vascular hyperpermeability have received little attention. This article places tumor vascular hyperpermeability in a broader context, relating it to (1) the low-level “basal” permeability of the normal vasculature; (2) the “acute,” short-term hyperpermeability induced by vascular permeability factor/vascular endothelial growth factor (VPF/VEGF-A) and other vascular permeabilizing agents; and (3) the “chronic” hyperpermeability associated with longer-term exposure to agents such as VPF/VEGF-A that accompanies many types of pathological angiogenesis. Leakage of plasma protein-rich fluids is important because it activates the clotting system, depositing an extravascular fibrin gel provisional matrix that serves as the first step in stroma generation. PMID:22355795

  13. Myxoid chondrosarcoma of the mandible in a 22-year-old man: A case report

    PubMed Central

    Chen, Ying; Zhang, Ying

    2016-01-01

    This study describes a case of myxoid chondrosarcoma of the mandible in a 22-year-old male patient. A tumour in the buccal gingiva of the lower left premolar region had been identified 2 years earlier. Whole-jaw panoramic radiographs showed a hypodense shadow in the mesiodistal area near the roots of teeth 34 and 35. A maxillofacial computed tomography scan revealed a mass in the lower left premolar soft tissue, with a shadow indicating bone destruction, a clear boundary and uniform density. The preliminary diagnosis at the outpatient department was 34–35 epulis. The patient underwent surgery for 34–35 gingival tumour resection, 34 and 35 extraction, and 34 and 35 immediate implantation. The postoperative pathological examination revealed a cellular type extraskeletal myxoid chondrosarcoma of the lower left mandible. Under general anaesthesia, the patient underwent lower left mandibular block and segmental resection, submandibular triangle dissection and vessel disassociation, and musculocutaneous flap repair in the oral and maxillofacial defect area. After 9 months of follow-up, the patient had no complaints of discomfort, and tumour recurrence was not observed on imaging examinations. PMID:27602220

  14. Extraskeletal myxoid chondrosarcoma arising in the femoral vein: a case report.

    PubMed

    Oike, Naoki; Ogose, Akira; Kawashima, Hiroyuki; Umezu, Hajime; Inagawa, Shoichi

    2014-10-01

    Soft tissue tumors arising in deep veins of the extremities are uncommon, although a few cases of synovial sarcoma or leiomyosarcoma arising in the femoral vein have been documented. However, to the best of our knowledge, an extraskeletal myxoid chondrosarcoma (EMC) arising in the femoral vein has not been reported in the English literature. We report a case of EMC arising in the femoral vein of a 70-year-old man who presented with right leg edema and was diagnosed with a deep venous thrombosis (DVT) by computed tomography (CT). Magnetic resonance imaging (MRI) revealed a mass in the right proximal thigh that was diagnosed as myxomatous sarcoma by aspiration cytology, and anticoagulant therapy was initiated. The mass was surgically resected en bloc, including the femoral vein and surrounding soft tissue, and the femoral artery was preserved. The femoral vein was not reconstructed. The histologic diagnosis was an extraskeletal myxoid chondrosarcoma. The patient received postoperative local radiation treatment, with a total dose of 60 Gy, and is currently doing well with no evidence of local recurrence or metastasis at 8 months after surgery. In summary, this case report shows that EMC can arise in the femoral vein, and that reconstruction of the femoral vein is not always necessary during surgery for soft tissue tumors.

  15. Tumor reactive stroma in cholangiocarcinoma: The fuel behind cancer aggressiveness

    PubMed Central

    Brivio, Simone; Cadamuro, Massimiliano; Strazzabosco, Mario; Fabris, Luca

    2017-01-01

    Cholangiocarcinoma (CCA) is a highly aggressive epithelial malignancy still carrying a dismal prognosis, owing to early lymph node metastatic dissemination and striking resistance to conventional chemotherapy. Although mechanisms underpinning CCA progression are still a conundrum, it is now increasingly recognized that the desmoplastic microenvironment developing in conjunction with biliary carcinogenesis, recently renamed tumor reactive stroma (TRS), behaves as a paramount tumor-promoting driver. Indeed, once being recruited, activated and dangerously co-opted by neoplastic cells, the cellular components of the TRS (myofibroblasts, macrophages, endothelial cells and mesenchymal stem cells) continuously rekindle malignancy by secreting a huge variety of soluble factors (cyto/chemokines, growth factors, morphogens and proteinases). Furthermore, these factors are long-term stored within an abnormally remodeled extracellular matrix (ECM), which in turn can deleteriously mold cancer cell behavior. In this review, we will highlight evidence for the active role played by reactive stromal cells (as well as by the TRS-associated ECM) in CCA progression, including an overview of the most relevant TRS-derived signals possibly fueling CCA cell aggressiveness. Hopefully, a deeper knowledge of the paracrine communications reciprocally exchanged between cancer and stromal cells will steer the development of innovative, combinatorial therapies, which can finally hinder the progression of CCA, as well as of other cancer types with abundant TRS, such as pancreatic and breast carcinomas.

  16. Excellent Local Control Rates and Distinctive Patterns of Failure in Myxoid Liposarcoma Treated With Conservation Surgery and Radiotherapy

    SciTech Connect

    Guadagnolo, B. Ashleigh Zagars, Gunar K.; Ballo, Matthew T.; Patel, Shreyaskumar R.; Lewis, Valerae O.; Benjamin, Robert S.; Pollock, Raphael E.

    2008-03-01

    Purpose: To evaluate the local control rates and patterns of metastatic relapse in patients with localized myxoid liposarcoma treated with conservation surgery and radiotherapy (RT). Patients and Methods: Between 1960 and 2003, 127 patients with non-metastatic myxoid liposarcoma were treated with conservation surgery and RT at our institution. The median patient age was 39 years (range, 14-79 years). Of the 127 patients, 46% underwent preoperative RT (median dose, 50 Gy) and 54% underwent postoperative RT (median dose, 60 Gy). Also, 28% received doxorubicin-based chemotherapy as a part of their treatment. Results: The median follow-up was 9.1 years. The overall survival rate at 5 and 10 years was 87% and 79%, respectively. The corresponding disease-free survival rates were 81% and 73%. The local control rate at {>=}5 years was 97%. The actuarial rate of distant metastases at 5 and 10 years was 15% and 24%, respectively. Of the 27 patients who developed distant metastases, 48% did so in the retroperitoneum, 22% in other extrapulmonary soft tissues, 22% in the lung, 15% in bone, and 4% in the liver. Conclusion: The results of our study have shown that RT and conservation surgery for localized myxoid liposarcoma provide excellent local control. Distant metastatic relapse tended to occur in the retroperitoneum and other nonpulmonary soft tissues. Therefore, staging and surveillance imaging should include the abdomen and pelvis, as well as the thorax, for patients with localized myxoid liposarcoma.

  17. Establishment and characterization of a new human myxoid liposarcoma cell line (DL-221) with the FUS-DDIT3 translocation

    PubMed Central

    de Graaff, Marieke A.; Yu, Jamie S.E.; Cheung, Hannah C.; Ingram, Davis R.; Nguyen, Theresa; Liu, Jeffrey Juehui; Bolshakov, Svetlana; Szuhai, Károly; Åman, Pierre; Torres, Keila E.; Lev, Dina; Nielsen, Torsten O.; Bovée, Judith V.M.G.; Lazar, Alexander J.; Somaiah, Neeta

    2016-01-01

    Myxoid liposarcoma has the pathognomonic fusion oncogene FUS-DDIT3 encoding a chimeric transcription factor. Metastatic risk is higher with an increased round cell component and has been linked to aberrations involving the IGFR/PI3K/AKT pathway. These molecular insights have yet to translate to targeted therapies and the lack of experimental models is a major hindrance. We describe the initial in-depth characterization of a new cell line (DL-221) and establishment of a mouse xenograft model. The cell line DL-221 was derived from a metastatic pleural lesion showing myxoid and round cell histology. This newly established cell line was characterized for phenotypic properties and molecular cytogenetic profile, using PCR, COBRA-FISH and western blot. Next-generation whole exome sequencing was performed to further characterize the cell line and the parent tumor. NOD-SCID-IL2R gamma knockout mice were xenograft hosts. DL-221 cells grew an adhering monolayer and COBRA-FISH showed an aneuploid karyotype with t(12;16)(q13;p11) and several other rearrangements; RT-PCR demonstrated a FUS-DDIT3 fusion transcript type 1. Both the cell line and the original tumor harbored a TP53 compound heterozygous mutation in exon 4 and 7 and were wild type for PIK3CA. Moreover, among the 1254 variants called by whole exome sequencing, there was 77% concordance between the cell line and parent tumor. The recently described hotspot mutation in the TERT promoter region in myxoid liposarcomas was also found at C228T in DL-221. Xenografts suitable for additional pre-clinical studies were successfully established in mice after subcutaneous injection. The established DL-221 cell line is the only published available myxoid liposarcoma cell line that underwent spontaneous immortalization, without requiring SV40 transformation. The cell line and its xenograft model are unique and helpful tools to study the biology and novel potential targeted treatment approaches for myxoid liposarcoma. PMID:27270875

  18. Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma

    PubMed Central

    Chen, Yulong; Terajima, Masahiko; Yang, Yanan; Sun, Li; Ahn, Young-Ho; Pankova, Daniela; Puperi, Daniel S.; Watanabe, Takeshi; Kim, Min P.; Blackmon, Shanda H.; Rodriguez, Jaime; Liu, Hui; Behrens, Carmen; Wistuba, Ignacio I.; Minelli, Rosalba; Scott, Kenneth L.; Sanchez-Adams, Johannah; Guilak, Farshid; Pati, Debananda; Thilaganathan, Nishan; Burns, Alan R.; Creighton, Chad J.; Martinez, Elisabeth D.; Zal, Tomasz; Grande-Allen, K. Jane; Yamauchi, Mitsuo; Kurie, Jonathan M.

    2015-01-01

    Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. However, the biochemical nature of collagen cross-links in cancer is still unclear. Here, we postulated that epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen cross-links. Utilizing resected human lung cancer tissues and a p21CIP1/WAF1-deficient, K-rasG12D-expressing murine metastatic lung cancer model, we showed that, relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde–derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde–derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Gain- and loss-of-function studies in tumor cells showed that lysyl hydroxylase 2 (LH2), which hydroxylates telopeptidyl lysine residues on collagen, shifted the tumor stroma toward a high-HLCC, low-LCC state, increased tumor stiffness, and enhanced tumor cell invasion and metastasis. Together, our data indicate that LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma. PMID:25664850

  19. Anterior and posterior corneal stroma elasticity assessed using nanoindentation

    PubMed Central

    Dias, Janice; Ziebarth, Noël M.

    2013-01-01

    Corneal biomechanics is an essential parameter for developing diagnostic and treatment methods of corneal-related diseases. It is widely accepted that corneal mechanical strength stems from the stroma's collagenous composition. However, more comprehensive insight into the mechanical properties within the stroma is needed to improve current corneal diagnostic and treatment techniques. The purpose of this study was to perform elasticity characterization of anterior and posterior stromal regions of human corneas using atomic force microscopy (AFM). Nine pairs of human whole globes were placed in 20% Dextran solution, cornea side down, to restore the corneal thickness to physiological levels (400-600μm). The epithelium and Bowman's membrane were removed from all eyes. Anterior stromal AFM elasticity testing was then performed on left (OS) eyes. Additional stroma was removed from right (OD) eyes to allow posterior stromal measurements at a depth of 50% of the original thickness. All experiments were performed with corneas submerged in 15% Dextran to maintain corneal hydration. The results of the study showed that the Young's modulus of elasticity of the anterior stroma (average: 281 ± 214kPa; range: 59-764kPa) was significantly higher than that of the posterior stroma (average: 89.5 ± 46.1kPa; range: 29-179kPa) (p=0.014). In addition, a linear relationship was found between the posterior stromal elasticity and anterior stromal elasticity (p=0.0428). On average, the elasticity of the posterior stroma is 39.3% of the anterior stroma. In summary, there appears to be an elasticity gradient within the corneal stroma, which should be considered in the design and development of corneal diagnostic and treatment methods to enhance efficacy. PMID:23800511

  20. Role of Reactive Stroma in Prostate Cancer Progression

    DTIC Science & Technology

    2007-02-01

    approach, we are placing an inducible Cre recombinase behind the FAP gene promoter to target expression to reactive stroma. We will cross this mouse...using the FAP gene to specifically target the expression of an inducible Cre recombinase to cancer associated reactive stroma. Three Specific Aims and...inducible Cre recombinase (CrePR1) into the fibroblast activation protein (FAP) locus. This Aim is to generate a transgenic mouse that uses the FAP

  1. The autophagic tumor stroma model of cancer

    PubMed Central

    Pavlides, Stephanos; Tsirigos, Aristotelis; Migneco, Gemma; Whitaker-Menezes, Diana; Chiavarina, Barbara; Flomenberg, Neal; Frank, Philippe G; Casimiro, Mathew C; Wang, Chenguang; Pestell, Richard G; Martinez-Outschoorn, Ubaldo E; Howell, Anthony

    2010-01-01

    A loss of stromal caveolin-1 (Cav-1) in the tumor fibroblast compartment is associated with early tumor recurrence, lymphnode metastasis and tamoxifen-resistance, resulting in poor clinical outcome in breast cancer patients. Here, we have used Cav-1 (−/−) null mice as a pre-clinical model for this “lethal tumor micro-environment”. Metabolic profiling of Cav-1 (−/−) mammary fat pads revealed the upregulation of numerous metabolites (nearly 100), indicative of a major catabolic phenotype. Our results are consistent with the induction of oxidative stress, mitochondrial dysfunction and autophagy/mitophagy. The two most prominent metabolites that emerged from this analysis were ADMA (asymmetric dimethyl arginine) and BHB (beta-hydroxybutyrate; a ketone body), which are markers of oxidative stress and mitochondrial dysfunction, respectively. Transcriptional profiling of Cav-1 (−/−) stromal cells and human tumor stroma from breast cancer patients directly supported an association with oxidative stress, mitochondrial dysfunction and autophagy/mitophagy, as well as ADMA and ketone production. MicroRNA profiling of Cav-1 (−/−) stromal cells revealed the upregulation of two key cancer-related miR's, namely miR-31 and miR-34c. Consistent with our metabolic findings, these miR's are associated with oxidative stress (miR-34c) or activation of the hypoxic response/HIF1α (miR-31), which is sufficient to drive authophagy/mitophagy. Thus, via an unbiased comprehensive analysis of a lethal tumor micro-environment, we have identified a number of candidate biomarkers (ADMA, ketones and miR-31/34c) that could be used to identify high-risk cancer patients at diagnosis, for treatment stratification and/or for evaluating therapeutic efficacy during anti-cancer therapy. We propose that the levels of these key biomarkers (ADMA, ketones/BHB, miR-31 and miR-34c) could be (1) assayed using serum or plasma from cancer patients or (2) performed directly on excised tumor

  2. Clear cell papillary renal cell carcinoma, renal angiomyoadenomatous tumor, and renal cell carcinoma with leiomyomatous stroma relationship of 3 types of renal tumors: a review.

    PubMed

    Hes, Ondrej; Compérat, Eva Maria; Rioux-Leclercq, Nathalie

    2016-04-01

    Renal angiomyoadenomatous tumor has been described in 2000, followed by description of clear cell papillary renal cell carcinoma in 2006. Discussions about possible relationship of both tumors were published since their description. The main differential diagnostic feature was considered presence/absence of fibroleiomyomatous stroma-relationship of renal angiomyoadenomatous tumor in stroma-rich tumors. However, it was shown that stroma is reactive and nonneoplastic by its nature and that all other histologic, immunohistochemical, and molecular-genetic features of both entities are identical. In upcoming World Health Organization classification of renal tumors (2016), both lesions are considered as a single entity (clear cell papillary renal cell carcinoma [CCPRCC]). Most published cases followed the benign/indolent clinical course. In addition, most tumors has normal status of VHL gene (methylation, LOH 3p, mutations); however, CCPRCC was referred in patients with VHL syndrome. Another issue covered by this review is possible relationship of CCPRCC and "renal cell carcinoma with leiomyomatous stroma" (RCCLS). Renal cell carcinoma with leiomyomatous stroma shows clear cell cytology and abundant leiomyomatous stroma. Some of RCCLS are positive for cytokeratin 7; some are negative. Similar situation exists for relation of RCCLS and VHL gene abnormalities. It is so far unclear whether any relation between CCPRCC and RCCLS exists. From all published studies, it seems that these tumors are less likely related to each other.

  3. Proteins of the corneal stroma: importance in visual function.

    PubMed

    Xuan, Meng; Wang, Shurong; Liu, Xin; He, Yuxi; Li, Ying; Zhang, Yan

    2016-04-01

    The human cornea, consisting of five layers, is the transparent tissue that refracts and transmits light to the lens and retina, providing about two thirds of the refractive power of the eye. The stroma layer comprises nearly 90 % of the thickness of the cornea and thus plays a pivotal role in normal visual function. The bulk of this layer is constituted by proteins in the extracellular martrix secreted by the corneal epithelial, stroma, and endothelial cells. Clinical research has shown that corneal stroma diseases are common and involve conditions such as infections, injuries, and genetic defects, which cause severe visual disturbances or even blindness. To improve our understanding of the basic molecular mechanisms involved in the physiological and pathological activities of the corneal stroma, its proteins have been brought into the limelight to determine their crucial and irreplaceable roles. The data presented in a previous study have demonstrated the presence of 1679 proteins in the stroma, and this data set has subsequently been perfected by utilizing a highly sensitive isobaric peptide-labeling approach. According to their manifestations, these proteins can be classified as a gel-like organic material composed of proteoglycans, enzymes, and hemocyanin-binding proteins and a network of filaments composed of collagen, elastin, keratin, vimentin, and interconnected filaments comprising fibronectin and laminin. The aim of this review is to describe some corneal stroma proteins by highlighting their major functions and valuable applications in ophthalmologic research toward the better characterization and treatment of eye diseases.

  4. Membrane-to-Nucleus Signals and Epigenetic Mechanisms for Myofibroblastic Activation and Desmoplastic Stroma: Potential Therapeutic Targets for Liver Metastasis?

    PubMed Central

    Kang, Ningling; Shah, Vijay H.; Urrutia, Raul

    2015-01-01

    Cancer associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment (TME), are a key source of extracellular matrix (ECM) that constitutes the desmoplastic stroma. Through remodeling of the reactive tumor stroma and paracrine actions, CAFs regulate cancer initiation, progression, and metastasis, as well as tumor resistance to therapies. The CAFs found in stroma-rich primary hepatocellular carcinomas (HCCs) and liver metastases of primary cancers of other organs predominantly originate from hepatic stellate cells (HSTCs), which are pericytes associated with hepatic sinusoids. During tumor invasion, HSTCs transdifferentiate into myofibroblasts in response to paracrine signals emanating from either tumor cells or a heterogenous cell population within the hepatic tumor microenvironment. Mechanistically, HSTC-to-myofibroblast transdifferentiation, also known as, HSTC activation, requires cell surface receptor activation, intracellular signal transduction, gene transcription and epigenetic signals, which combined ultimately modulate distinct gene expression profiles that give rise to and maintain a new phenotype. The current review, defines a paradigm that explains how HSTCs are activated into CAFs to promote liver metastasis. Furthermore, focus on the most relevant intracellular signaling networks and epigenetic mechanisms that control HSTC activation is provided. Finally, we discuss the feasibility of targeting CAF/activated HSTCs, in isolation or in conjunction with targeting cancer cells, which constitutes a promising and viable therapeutic approach for the treatment of primary stroma-rich liver cancers and liver metastasis. PMID:25548101

  5. FGFR2 is overexpressed in myxoid liposarcoma and inhibition of FGFR signaling impairs tumor growth in vitro

    PubMed Central

    Künstlinger, Helen; Fassunke, Jana; Schildhaus, Hans-Ulrich; Brors, Benedikt; Heydt, Carina; Ihle, Michaela Angelika; Mechtersheimer, Gunhild; Wardelmann, Eva; Büttner, Reinhard; Merkelbach-Bruse, Sabine

    2015-01-01

    Myxoid liposarcomas account for more than one third of liposarcomas and about 10% of all adult soft tissue sarcomas. The tumors are characterized by specific chromosomal translocations leading to the chimeric oncogenes FUS-DDIT3 or EWS1R-DDIT3. The encoded fusion proteins act as aberrant transcription factors. Therefore, we implemented comparative expression analyses using whole-genome microarrays in tumor and fat tissue samples. We aimed at identifying differentially expressed genes which may serve as diagnostic or prognostic biomarkers or as therapeutic targets. Microarray analyses revealed overexpression of FGFR2 and other members of the FGF/FGFR family. Overexpression of FGFR2 was validated by qPCR, immunohistochemistry and western blot analysis in primary tumor samples. Treatment of the myxoid liposarcoma cell lines MLS 402 and MLS 1765 with the FGFR inhibitors PD173074, TKI258 (dovitinib) and BGJ398 as well as specific siRNAs reduced cell proliferation, induced apoptosis and delayed cell migration. Combination of FGFR inhibitors with trabectedin further increased the effect. Our study demonstrates overexpression of FGFR2 and a functional role of FGFR signaling in myxoid liposarcoma. As FGFR inhibition showed effects on proliferation and cell migration and induced apoptosis in vitro, our data indicate the potential use of FGFR inhibitors as a targeted therapy for these tumors. PMID:26036639

  6. FGFR2 is overexpressed in myxoid liposarcoma and inhibition of FGFR signaling impairs tumor growth in vitro.

    PubMed

    Künstlinger, Helen; Fassunke, Jana; Schildhaus, Hans-Ulrich; Brors, Benedikt; Heydt, Carina; Ihle, Michaela Angelika; Mechtersheimer, Gunhild; Wardelmann, Eva; Büttner, Reinhard; Merkelbach-Bruse, Sabine

    2015-08-21

    Myxoid liposarcomas account for more than one third of liposarcomas and about 10% of all adult soft tissue sarcomas. The tumors are characterized by specific chromosomal translocations leading to the chimeric oncogenes FUS-DDIT3 or EWS1R-DDIT3. The encoded fusion proteins act as aberrant transcription factors. Therefore, we implemented comparative expression analyses using whole-genome microarrays in tumor and fat tissue samples. We aimed at identifying differentially expressed genes which may serve as diagnostic or prognostic biomarkers or as therapeutic targets. Microarray analyses revealed overexpression of FGFR2 and other members of the FGF/FGFR family. Overexpression of FGFR2 was validated by qPCR, immunohistochemistry and western blot analysis in primary tumor samples. Treatment of the myxoid liposarcoma cell lines MLS 402 and MLS 1765 with the FGFR inhibitors PD173074, TKI258 (dovitinib) and BGJ398 as well as specific siRNAs reduced cell proliferation, induced apoptosis and delayed cell migration. Combination of FGFR inhibitors with trabectedin further increased the effect. Our study demonstrates overexpression of FGFR2 and a functional role of FGFR signaling in myxoid liposarcoma. As FGFR inhibition showed effects on proliferation and cell migration and induced apoptosis in vitro, our data indicate the potential use of FGFR inhibitors as a targeted therapy for these tumors.

  7. Emerging concepts in pancreatic cancer medicine: targeting the tumor stroma

    PubMed Central

    Neesse, Albrecht; Krug, Sebastian; Gress, Thomas M; Tuveson, David A; Michl, Patrick

    2014-01-01

    Pancreatic ductal adenocarcinoma is a stroma-rich and highly challenging cancer to treat. Over recent years, it has become increasingly evident that the complex network of soluble cytokines, growth factors, proteases, and components of the extracellular matrix collaboratively interact within the tumor microenvironment, sustaining and driving cancer cell proliferation, invasion, and early metastasis. More recently, the tumor microenvironment has also been appreciated to mediate therapeutic resistance in pancreatic ductal adenocarcinoma, thus opening numerous avenues for novel therapeutic explorations. Inert and soluble components of the tumor stroma have been targeted in order to break down the extracellular matrix scaffold, relieve vessel compression, and increase drug delivery to hypovascular tumors. Moreover, targeting of antiapoptotic, immunosuppressive, and pro-proliferative effects of the tumor stroma provides novel vantage points of attack. This review focuses on current and future developments in pancreatic cancer medicine, with a particular emphasis on biophysical and biochemical approaches that target the tumor microenvironment. PMID:24379681

  8. Technique for the selective heating of corneal stroma

    SciTech Connect

    Doss, J.D.; Albillar, J.I.

    1980-01-01

    Conventional thermokeratoplasty, which relies upon thermal conduction from the epithelium into the stroma, does not generate a desirable temperature profile through the cornea. Previous reports show that temperature levels in the epithelium and in Bowman's membrane are excessive, often resulting in damage to these structures. In addition, this study shows that when corneal thickness exceeds approximately 300 microns, the central portion of the stroma probably will not reach critical shrinkage temperature. Shrinkage only in the superficial stroma may result in minimal and transitory alterations of corneal shape. Variation in treatment results may also occur due to the difficulty in precise control of treatment duration. An alternative corneal heating technique is discussed which appears to solve these three basic problems.

  9. The cancer-testis antigen NY-ESO-1 is highly expressed in myxoid and round cell subset of liposarcomas.

    PubMed

    Hemminger, Jessica A; Ewart Toland, Amanda; Scharschmidt, Thomas J; Mayerson, Joel L; Kraybill, William G; Guttridge, Denis C; Iwenofu, O Hans

    2013-02-01

    Liposarcomas are a heterogenous group of fat-derived sarcomas, and surgery with or without chemoradiation therapy remains the main stay of treatment. NY-ESO-1 is a cancer-testis antigen expressed in various cancers where it can induce both cellular and humoral immunity. Immunotherapy has shown promise in clinical trials involving NY-ESO-1-expressing tumors. Gene expression studies have shown upregulation of the gene for NY-ESO-1, CTAG1B, in myxoid and round cell liposarcomas. Herein, we evaluated the expression of NY-ESO-1 among liposarcoma subtypes by quantitative real-time PCR, western blot analysis, and immunohistochemistry. Frozen tissue for quantitative real-time PCR and western blot analysis was obtained for the following liposarcoma subtypes (n=15): myxoid and round cell (n=8); well-differentiated (n=4), and dedifferentiated (n=3). Formalin-fixed paraffin-embedded blocks were obtained for the following liposarcoma subtypes (n=44): myxoid and round cell (n=18); well-differentiated (n=10); dedifferentiated (n=10); and pleomorphic (n=6). Full sections were stained with monoclonal antibody NY-ESO-1, and staining was assessed for intensity (1-3+), percentage of tumor positivity, and location. In all, 7/8 (88%) and 16/18 (89%) myxoid and round cell expressed CTAG1B and NY-ESO-1 by quantitative real-time PCR and immunohistochemistry, respectively. Western blot correlated with mRNA expression levels. By immunohistochemistry, 94% (15/16) of positive cases stained homogenously with 2-3+ intensity. Also, 3/6 (50%) pleomorphic liposarcomas demonstrated a range of staining: 1+ intensity in 50% of cells; 2+ intensity in 5% of cells; and 3+ intensity in 90% of cells. One case of dedifferentiated liposarcoma showed strong, diffuse staining (3+ intensity in 75% of cells). Our study shows that both CTAG1B mRNA and protein are overexpressed with high frequency in myxoid and round cell liposarcoma, enabling the potential use of targeted immunotherapy in the treatment of this

  10. Thymus organogenesis and development of the thymic stroma.

    PubMed

    Nowell, Craig S; Farley, Alison M; Blackburn, C Clare

    2007-01-01

    T-cell development occurs principally in the thymus. Here, immature progenitor cells are guided through the differentiation and selection steps required to generate a complex T-cell repertoire that is both self-tolerant and has propensity to bind self major histocompatibility complex. These processes depend on an array of functionally distinct epithelial cell types within the thymic stroma, which have a common developmental origin in the pharyngeal endoderm. Here, we describe the structural and phenotypic attributes of the thymic stroma, and review current cellular and molecular understanding of thymus organogenesis.

  11. Anthracycline-based chemotherapy in extraskeletal myxoid chondrosarcoma: a retrospective study

    PubMed Central

    2013-01-01

    Background Extraskeletal myxoid chondrosarcoma (EMC) is a rare subgroup within soft tissue sarcomas. Its sensitivity to chemotherapy is reported to be low. Methods We retrospectively reviewed a series of 11 EMC patients treated as from 2001 within the Italian Rare Cancer Network (RCN) with anthracycline-based chemotherapy. Pathologic diagnosis was centrally reviewed in all cases and confirmed by the presence of the specific chromosomal rearrangements, involving the NR4A3 gene locus on chromosome 9. Results Eleven patients treated with anthracycline-based chemotherapy were included (M/F: 9/2 – mean age: 52 years – site of primary: lower limb/other = 9/2 - metastatic = 11 – front line/ further line = 10/1 – anthracycline as single agent/ combined with ifosfamide = 1/10). Ten patients are evaluable for response. Overall, best response according to RECIST was: partial response (PR) = 4 (40 %), stable disease (SD) = 3, progressive disease (PD) = 3 cases. Median PFS was 8 (range 2–10) months. Conclusions By contrast to what reported so far, anthracycline-based chemotherapy is active in a distinct proportion of EMC patients. PMID:24345066

  12. Tumor stroma as targets for cancer therapy

    PubMed Central

    Zhang, Jing; Liu, Jinsong

    2012-01-01

    Cancer is not only composed malignant epithelial component but also stromal components such as fibroblasts, endothelial cells, and inflammatory cells, by which an appropriate tumor microenvironment (TME) is formed to promote tumorigenesis, progression, and metastasis. As the most abundant component in the TME, cancer-associated fibroblasts (CAFs) are involved in multifaceted mechanistic details including remodeling the extracellular matrix, suppressing immune responses, and secreting growth factors and cytokines that mediate signaling pathways to extensively affect tumor cell growth and invasiveness, differentiation, angiogenesis, and chronic inflammatory milieu. Today, more and more therapeutic strategies are purposefully designed to target the TME as well as tumor cells. This review will focus on the role of CAFs in tumor development and the novel strategies to target this component to inhibit the tumor growth. PMID:23064233

  13. Chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance.

    PubMed

    Momose, Takashige; Yoshimura, Yasuo; Harumiya, Satoru; Isobe, Ken'ichi; Kito, Munehisa; Fukushima, Mana; Kato, Hiroyuki; Nakayama, Jun

    2016-04-01

    The glycosyltransferases chondroitin sulfate synthase 1 (CHSY1) and exostoses-like 3 (EXTL3) specifically function in biosynthesis of the glycans chondroitin sulfate and heparan sulfate, respectively. Although these glycans play important roles in pathogenesis of various tumors, their significance in soft tissue sarcoma remains unknown. Here, we asked whether CHSY1 or EXTL3 expression correlates with malignant potential of soft tissue sarcomas with myxoid substance. To do so, we examined 40 samples representing specific types, including 12 cases of myxoid liposarcoma, 14 of myxofibrosarcoma, 12 of malignant peripheral nerve sheath tumor, and 2 of low-grade fibromyxoid sarcoma. We performed immunohistochemistry with anti-CHSY1 and anti-EXTL3 antibodies and compared enzyme expression levels with tumor histologic grade as assessed by the Fédération Nationale des Centres de Lutte Contre le Cancer classification and with patient 5-year survival rate. CHSY1 and EXTL3 were expressed in 72.5% and 32.5% of all tumors, respectively. Notably, CHSY1 was strongly expressed in myxofibrosarcoma and malignant peripheral nerve sheath tumor compared with other tumors and significantly associated with higher- rather than lower-grade tumors (P < .01). High expression of CHSY1 was also significantly associated with poorer patient outcomes (P = .031) and higher stages assessed by American Joint Committee on Cancer staging system (P = .004). By contrast, EXTL3 expression was not correlated with histologic grade or patient prognosis. We conclude that CHSY1 expression is closely associated with malignant potential of soft tissue sarcomas with myxoid substance.

  14. Cancer-stroma evolutionary dynamics in stress-gradient microenvironment

    NASA Astrophysics Data System (ADS)

    Wu, Amy; Lambert, Guillaume; Austin, Robert; Sturm, James; Khin, Zayar; Silva, Ariosto

    2012-02-01

    In order to study the evolution of drug resistance in cancer, it is important to mimic the tumor microenvironment, in which cells are exposed to not uniform concentrations but rather gradients of drugs, nutrients, and other factors Compared to traditional in-vitro methods, microfluidic structure enables better control of the temporal and spatial profile of gradients. Here we demonstrate a microfluidic Doxorubicin gradient environment with heterogeneous landscape, and culture multiple myeloma (8226-S, expressing RFP) and bone marrow stroma (HS-5, expressing GFP) cell lines together. The myeloma cells are not directly motile, but they are able to migrate via the adhesion to motile stroma cells. The indirect motility mechanism of the myeloma cells is crucial for the adaptation to stress environment. Finally, we will report the co-culture dynamics under the stress of doxorubicin gradients, observing for cellular migrations and growth

  15. Evolutionary Dynamics of Tumor-Stroma Interactions in Multiple Myeloma

    PubMed Central

    Sartakhti, Javad Salimi; Manshaei, Mohammad Hossein; Bateni, Soroosh; Archetti, Marco

    2016-01-01

    Cancer cells and stromal cells cooperate by exchanging diffusible factors that sustain tumor growth, a form of frequency-dependent selection that can be studied in the framework of evolutionary game theory. In the case of multiple myeloma, three types of cells (malignant plasma cells, osteoblasts and osteoclasts) exchange growth factors with different effects, and tumor-stroma interactions have been analysed using a model of cooperation with pairwise interactions. Here we show that a model in which growth factors have autocrine and paracrine effects on multiple cells, a more realistic assumption for tumor-stroma interactions, leads to different results, with implications for disease progression and treatment. In particular, the model reveals that reducing the number of malignant plasma cells below a critical threshold can lead to their extinction and thus to restore a healthy balance between osteoclast and osteoblast, a result in line with current therapies against multiple myeloma. PMID:28030607

  16. The Functional Role of Reactive Stroma in Benign Prostatic Hyperplasia

    PubMed Central

    Schauer, Isaiah G.; Rowley, David R.

    2011-01-01

    The human prostate gland is one of the only internal organs that continue to enlarge throughout adulthood. The specific mechanisms that regulate this growth, as well as the pathological changes leading to the phenotype observed in the disease benign prostatic hyperplasia (BPH), are essentially unknown. Recent studies and their associated findings have made clear that many complex alterations occur, involving persistent and chronic inflammation, circulating hormonal level deregulation, and aberrant wound repair processes. BPH has been etiologically characterized as a progressive, albeit discontinuous, hyperplasia of both the glandular epithelial and stromal cell compartments coordinately yielding an expansion of the prostate gland and clinical symptoms. Interestingly, the inflammatory and repair responses observed in BPH are also key components of general wound repair in post-natal tissues. These responses include altered expression of chemokines, cytokines, matrix remodeling factors, chronic inflammatory processes, altered immune surveillance and recognition, as well as the formation of a prototypical ‘reactive’ stroma which is similar to that observed across various fibroplasias and malignancies of a variety of tissue sites. Stromal tissue, both embryonic mesenchyme, and adult reactive stroma myofibroblasts, has been shown to exert potent and functional regulatory control over epithelial proliferation and differentiation as well as immunoresponsive modulation. Thus, the functional biology of a reactive stroma, within the context of an adult disease typified by epithelial and stromal aberrant hyperplasia, is critical to understand within the context of prostate disease and beyond. The mechanisms that regulate reactive stroma biology in BPH represent targets of opportunity for new therapeutic approaches that may extend to other tissue contexts. Accordingly, this review seeks to address the dissection of important factors, signaling pathways, genes, and other

  17. Pancreatic cancer and its stroma: a conspiracy theory.

    PubMed

    Xu, Zhihong; Pothula, Srinivasa P; Wilson, Jeremy S; Apte, Minoti V

    2014-08-28

    Pancreatic cancer is characterised by a prominent desmoplastic/stromal reaction that has received little attention until recent times. Given that treatments focusing on pancreatic cancer cells alone have failed to significantly improve patient outcome over many decades, research efforts have now moved to understanding the pathophysiology of the stromal reaction and its role in cancer progression. In this regard, our Group was the first to identify the cells (pancreatic stellate cells, PSCs) that produced the collagenous stroma of pancreatic cancer and to demonstrate that these cells interacted closely with cancer cells to facilitate local tumour growth and distant metastasis. Evidence is accumulating to indicate that stromal PSCs may also mediate angiogenesis, immune evasion and the well known resistance of pancreatic cancer to chemotherapy and radiotherapy. This review will summarise current knowledge regarding the critical role of pancreatic stellate cells and the stroma in pancreatic cancer biology and the therapeutic approaches being developed to target the stroma in a bid to improve the outcome of this devastating disease.

  18. miR-135b, a key regulator of malignancy, is linked to poor prognosis in human myxoid liposarcoma

    PubMed Central

    Nezu, Y; Hagiwara, K; Yamamoto, Y; Fujiwara, T; Matsuo, K; Yoshida, A; Kawai, A; Saito, T; Ochiya, T

    2016-01-01

    Myxoid/round cell (RC) liposarcomas (MLS) were originally classified into two distinct populations based on histological differences; a myxoid component and a RC component. It is notable that, depending on an increase of the RC component, the prognosis significantly differs. Hence, the RC component is associated with metastasis and poor prognosis. However, the molecular mechanisms that contribute to the malignancy of the RC component still remain largely unknown. Here, we report microRNA-135b (miR-135b), a key regulator of the malignancy, highly expressed in the RC component and promoting MLS cell invasion in vitro and metastasis in vivo through the direct suppression of thrombospondin 2 (THBS2). Decreased THBS2 expression by miR-135b increases the total amount of matrix metalloproteinase 2 (MMP2) and influences cellular density and an extracellular matrix structure, thereby resulting in morphological change in tumor. The expression levels of miR-135b and THBS2 significantly correlated with a poor prognosis in MLS patients. Overall, our study reveals that the miR-135b/THBS2/MMP2 axis is tightly related to MLS pathophysiology and has an important clinical implication. This work provides noteworthy evidence for overcoming metastasis and improving patient outcomes, and sheds light on miR-135b and THBS2 as novel molecular targets for diagnosis and therapy in MLS. PMID:27157622

  19. TERT promoter hotspot mutations are recurrent in myxoid liposarcomas but rare in other soft tissue sarcoma entities

    PubMed Central

    2014-01-01

    Background Recently, recurrent point mutations in the telomerase reverse transcriptase (TERT) promoter region have been found in many human cancers, leading to a new transcription factor binding site, increased induction of TERT and subsequently to telomere maintenance. We determined the prevalence of TERT promoter mutations in soft tissue sarcomas of 341 patients comprising 16 entities and in 16 sarcoma cell lines covering 7 different soft tissue sarcoma types. Methods The sarcoma tissue samples were collected from the archives of the Institute of Pathology, University of Heidelberg and were composed of 39 myxoid liposarcomas (MLS), 61 dedifferentiated liposarcomas, 15 pleomorphic liposarcomas, 27 leiomyosarcomas, 25 synovial sarcomas (SS), 35 malignant peripheral nerve sheath tumors (MPNST), 40 undifferentiated pleomorphic sarcomas, 17 myxofibrosarcomas, 9 low grade fibromyxoid sarcomas, 10 cases of dermatofibrosarcoma protuberans, 31 solitary fibrous tumors (SFT), 8 extraskeletal myxoid chondrosarcomas, 9 angiosarcomas, 6 alveolar soft part sarcomas, 5 clear cell sarcomas and 4 epithelioid sarcomas. Sarcoma cell lines were obtained from the raising laboratories. A 193 bp fragment of the TERT promoter region covering the hot-spot mutations C228T and C250T was amplified, and direct sequencing of the PCR products was performed. Results TERT promoter mutations were detected in 36/341 sarcomas. They were highly recurrent in MLS (29/39; 74%) and were in the present MLS series not associated with the phenotype (myxoid vs. round cell variant), tumor grade, tumor site and patients’ median age or gender. In the remaining cases, TERT promoter mutations were found only in 7/302 sarcoma samples and confined to SFTs (4/31; 13%), MPNSTs (2/35; 6%), and SSs (1/25; 4%). Within the collection of sarcoma cell lines examined, TERT promoter mutations were detected in two MLS and in one of three MPNST cell lines. Conclusions TERT promoter mutations are frequent in MLSs including

  20. STROMAS: A Series of Microgravity Experiments on Bone Forming Cells

    NASA Astrophysics Data System (ADS)

    Yi, Liu; Massimilano, Monticone; Federico, Tortelli; Matalija, Pujic; Alessandra, Ruggiu; Ranieri, Cancedda

    2008-06-01

    We developed a novel 3D in vitro culture system by seeding cells onto porous bioceramics, mimicking the physiological niche of bone turn-over and enhancing cellular differentiation respective to conventional 2D Petri Dish cultures. Having overcome several technological difficulties, in a series of STROMA spaceflight experiments 3D cultures of bone marrow derived mesenchymal stem cells (BMSC) and co-cultures of osteoblasts and osteoclast precursors were maintained and conserved in automated bioreactors on orbit. Genechip analysis revealed an inhibition of cell proliferation in microgravity. Unexpectedly, genes related to various processes of neural development were significantly upregulated in microgravity, raising the question on the lineage restriction in BMSC.

  1. Diagnostic efficacy of bone scintigraphy, magnetic resonance imaging, and positron emission tomography in bone metastases of myxoid liposarcoma.

    PubMed

    Conill, Carlos; Setoain, Xavier; Colomo, Luis; Palacín, Antonio; Combalia-Aleu, Andreu; Pomés, Jaime; Marruecos, Jordi; Vargas, Mauricio; Maurel, Joan

    2008-03-01

    Myxoid liposarcomas (MLS) have a tendency to metastasize to unusual sites. We report an unusual case of bone metastases not detected by bone scan and neither by fluorodeoxyglucose positron emission tomography (PET-FDG) and successfully identified with magnetic resonance imaging (MRI) in a patient with metachronic MLS. Histopathological examination of the primary tumor evidenced a tumor with unfavorable prognostic markers, and the biopsy of an iliac bone lesion confirmed the diagnosis of metastatic disease. On histological grounds, the tumor showed features of a more differentiated neoplasm without foci of round cells or necrosis in the latter. MRI allowed the identification of disseminated disease compared to computed tomography (CT) and PET scans. Thus, because of the heterogeneous histological features of MLS and the biological behavior of the disease, a combined approach of FDGPET-CT and MRI, may allow a more accurate staging of soft tissue sarcomas.

  2. Classification of breast cancer stroma as a tool for prognosis

    NASA Astrophysics Data System (ADS)

    Reis, Sara; Gazinska, Patrycja; Hipwell, John H.; Mertzanidou, Thomy; Naidoo, Kalnisha; Pinder, Sarah; Hawkes, David J.

    2016-03-01

    It has been shown that the tumour microenvironment plays a crucial role in regulating tumour progression by a number of different mechanisms, including the remodeling of collagen fibres in tumour-associated stroma. It is still unclear, however, if these stromal changes are of benefit to the host or the tumour. We hypothesise that stromal maturity is an important reflection of tumour biology, and thus can be used to predict prognosis. The aim of this study is to develop a texture analysis methodology which will automatically classify stromal regions from images of hematoxylin and eosin-stained (H and E) sections into two categories: mature and immature. Subsequently we will investigate whether stromal maturity could be used as a predictor of survival and also as a means to better understand the relationship between the radiological imaging signal and the underlying tissue microstructure. We present initial results for 118 regions-of-interest from a dataset of 39 patients diagnosed with invasive breast cancer.

  3. Prognostic Significance of the Tumor-Stroma Ratio in Epithelial Ovarian Cancer

    PubMed Central

    Chen, Ying; Zhang, Lei; Liu, Wenxin; Liu, Xiangyu

    2015-01-01

    Tumor-stroma ratio (TSR) has recently been identified as a promising prognostic parameter for several solid tumors. This study aimed to evaluate the prognostic role of TSR in epithelial ovarian cancer (EOC) and 838 EOC patients were enrolled in this study. TSR was estimated on hematoxylin-and-eosin-stained tissue sections from the most invasive part of the primary tumor. Patients were classified as stroma-rich or stroma-poor according to the proportion of stroma ≥50% or <50%. Chi-square test analysis revealed that TSR were significantly associated with FIGO stage, LN status, and recurrence or not (all of them P < 0.001). The higher stroma-rich proportions were found in EOC patients with advanced stage (36.13% versus 19.75%), LN metastasis (51.93% versus 27.25%), and recurrence (34.27% versus 6.82%). Stroma-rich EOC patients had obvious shorter median time of progression-free survival (29 versus 39 months) and overall survival (50 versus 58 months), respectively. TSR was an independent prognostic factor for the evaluation of PFS in EOC. Stroma-rich tumors had worse prognosis and higher risk of relapse compared with those in stroma-poor tumors in EOC patients. Considered easy to determine for routine pathological examination, TSR may serve as a new prognostic histological parameter in EOC. PMID:26609529

  4. IL-33 activates tumor stroma to promote intestinal polyposis

    PubMed Central

    Maywald, Rebecca L.; Doerner, Stephanie K.; Pastorelli, Luca; De Salvo, Carlo; Benton, Susan M.; Dawson, Emily P.; Lanza, Denise G.; Berger, Nathan A.; Markowitz, Sanford D.; Lenz, Heinz-Josef; Nadeau, Joseph H.; Pizarro, Theresa T.; Heaney, Jason D.

    2015-01-01

    Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by nonepithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin 33 (IL-33) as a regulator of tumor stromal cell activation and mediator of intestinal polyposis. In human colorectal cancer, IL-33 expression was induced in the tumor epithelium of adenomas and carcinomas, and expression of the IL-33 receptor, IL1RL1 (also referred to as IL1-R4 or ST2), localized predominantly to the stroma of adenoma and both the stroma and epithelium of carcinoma. Genetic and antibody abrogation of responsiveness to IL-33 in the ApcMin/+ mouse model of intestinal tumorigenesis inhibited proliferation, induced apoptosis, and suppressed angiogenesis in adenomatous polyps, which reduced both tumor number and size. Similar to human adenomas, IL-33 expression localized to tumor epithelial cells and expression of IL1RL1 associated with two stromal cell types, subepithelial myofibroblasts and mast cells, in ApcMin/+ polyps. In vitro, IL-33 stimulation of human subepithelial myofibroblasts induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in ApcMin/+ polyps and suppressed the expression of mast cell-derived proteases and cytokines known to promote polyposis. Based on these findings, we propose that IL-33 derived from the tumor epithelium promotes polyposis through the coordinated activation of stromal cells and the formation of a protumorigenic microenvironment. PMID:25918379

  5. IP-10/CXCL10 induction in human pancreatic cancer stroma influences lymphocytes recruitment and correlates with poor survival.

    PubMed

    Lunardi, Serena; Jamieson, Nigel B; Lim, Su Yin; Griffiths, Kristin L; Carvalho-Gaspar, Manuela; Al-Assar, Osama; Yameen, Sabira; Carter, Ross C; McKay, Colin J; Spoletini, Gabriele; D'Ugo, Stefano; Silva, Michael A; Sansom, Owen J; Janssen, Klaus-Peter; Muschel, Ruth J; Brunner, Thomas B

    2014-11-30

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant desmoplastic reaction driven by pancreatic stellate cells (PSCs) that contributes to tumor progression. Here we sought to characterize the interactions between pancreatic cancer cells (PCCs) and PSCs that affect the inflammatory and immune response in pancreatic tumors. Conditioned media from mono- and cocultures of PSCs and PCCs were assayed for expression of cytokines and growth factors. IP-10/CXCL10 was the most highly induced chemokine in coculture of PSCs and PCCs. Its expression was induced in the PSCs by PCCs. IP-10 was elevated in human PDAC specimens, and positively correlated with high stroma content. Furthermore, gene expression of IP-10 and its receptor CXCR3 were significantly associated with the intratumoral presence of regulatory T cells (Tregs). In an independent cohort of 48 patients with resectable pancreatic ductal adenocarcinoma, high IP-10 expression levels correlated with decreased median overall survival. Finally, IP-10 stimulated the ex vivo recruitment of CXCR3+ effector T cells as well as CXCR3+ Tregs derived from patients with PDAC. Our findings suggest that, in pancreatic cancer, CXCR3+ Tregs can be recruited by IP-10 expressed by PSCs in the tumor stroma, leading to immunosuppressive and tumor-promoting effects.

  6. Mapping the Extracellular and Membrane Proteome Associated with the Vasculature and the Stroma in the Embryo*

    PubMed Central

    Soulet, Fabienne; Kilarski, Witold W.; Roux-Dalvai, Florence; Herbert, John M. J.; Sacewicz, Izabela; Mouton-Barbosa, Emmanuelle; Bicknell, Roy; Lalor, Patricia; Monsarrat, Bernard; Bikfalvi, Andreas

    2013-01-01

    In order to map the extracellular or membrane proteome associated with the vasculature and the stroma in an embryonic organism in vivo, we developed a biotinylation technique for chicken embryo and combined it with mass spectrometry and bioinformatic analysis. We also applied this procedure to implanted tumors growing on the chorioallantoic membrane or after the induction of granulation tissue. Membrane and extracellular matrix proteins were the most abundant components identified. Relative quantitative analysis revealed differential protein expression patterns in several tissues. Through a bioinformatic approach, we determined endothelial cell protein expression signatures, which allowed us to identify several proteins not yet reported to be associated with endothelial cells or the vasculature. This is the first study reported so far that applies in vivo biotinylation, in combination with robust label-free quantitative proteomics approaches and bioinformatic analysis, to an embryonic organism. It also provides the first description of the vascular and matrix proteome of the embryo that might constitute the starting point for further developments. PMID:23674615

  7. Papillary carcinoma of thyroid with exuberant nodular fasciitis-like stroma. Report of three cases.

    PubMed

    Chan, J K; Carcangiu, M L; Rosai, J

    1991-03-01

    Three examples of an unusual morphologic variant of papillary thyroid carcinoma (PTC) are reported. The presence of a prominent stromal component resulted in low-power microscopic appearances resembling fibroadenoma, phyllodes tumor, or fibrocystic disease of the breast in two cases. The carcinomatous component grew in the form of anastomosing narrow tubules, clustered glands, solid sheets with or without squamous differentiation, and/or papillae, and exhibited the typical nuclear features of PTC. The abundant stroma had a nodular fasciitis-like quality and was composed of short fascicles of spindle cells separated by varying amounts of mucoid matrix, collagen, and extravasated red blood cells; this was interpreted as an exuberant mesenchymal reaction to the carcinoma. The importance of recognizing this variant of PTC is that, when one encounters a fibroproliferative lesion of the thyroid, a diligent search should be made for papillary carcinoma. This variant also must be distinguished from the vastly more aggressive papillary carcinomas with anaplastic transformation and the so-called carcinosarcomas.

  8. Ultrastructure Organization of Collagen Fibrils and Proteoglycans of Stingray and Shark Corneal Stroma

    PubMed Central

    Alanazi, Saud A.; Almubrad, Turki; AlIbrahim, Ahmad I. A.; Khan, Adnan A.; Akhtar, Saeed

    2015-01-01

    We report here the ultrastructural organization of collagen fibrils (CF) and proteoglycans (PGs) of the corneal stroma of both the stingray and the shark. Three corneas from three stingrays and three corneas from three sharks were processed for electron microscopy. Tissues were embedded in TAAB 031 resin. The corneal stroma of both the stingray and shark consisted of parallel running lamellae of CFs which were decorated with PGs. In the stingray, the mean area of PGs in the posterior stroma was significantly larger than the PGs of the anterior and middle stroma, whereas, in the shark, the mean area of PGs was similar throughout the stroma. The mean area of PGs of the stingray was significantly larger compared to the PGs, mean area of the shark corneal stroma. The CF diameter of the stingray was significantly smaller compared to the CF diameter in the shark. The ultrastructural features of the corneal stroma of both the stingray and the shark were similar to each other except for the CFs and PGs. The PGs in the stingray and shark might be composed of chondroitin sulfate (CS)/dermatan sulfate (DS) PGs and these PGs with sutures might contribute to the nonswelling properties of the cornea of the stingray and shark. PMID:26167294

  9. Ultrastructure Organization of Collagen Fibrils and Proteoglycans of Stingray and Shark Corneal Stroma.

    PubMed

    Alanazi, Saud A; Almubrad, Turki; AlIbrahim, Ahmad I A; Khan, Adnan A; Akhtar, Saeed

    2015-01-01

    We report here the ultrastructural organization of collagen fibrils (CF) and proteoglycans (PGs) of the corneal stroma of both the stingray and the shark. Three corneas from three stingrays and three corneas from three sharks were processed for electron microscopy. Tissues were embedded in TAAB 031 resin. The corneal stroma of both the stingray and shark consisted of parallel running lamellae of CFs which were decorated with PGs. In the stingray, the mean area of PGs in the posterior stroma was significantly larger than the PGs of the anterior and middle stroma, whereas, in the shark, the mean area of PGs was similar throughout the stroma. The mean area of PGs of the stingray was significantly larger compared to the PGs, mean area of the shark corneal stroma. The CF diameter of the stingray was significantly smaller compared to the CF diameter in the shark. The ultrastructural features of the corneal stroma of both the stingray and the shark were similar to each other except for the CFs and PGs. The PGs in the stingray and shark might be composed of chondroitin sulfate (CS)/dermatan sulfate (DS) PGs and these PGs with sutures might contribute to the nonswelling properties of the cornea of the stingray and shark.

  10. PRG4 expression in myxoid liposarcoma maintains tumor cell growth through suppression of an antitumor cytokine IL-24.

    PubMed

    Oikawa, Kosuke; Mizusaki, Anna; Takanashi, Masakatsu; Ozaki, Takashi; Sato, Fuyuki; Kuroda, Masahiko; Muragaki, Yasuteru

    2017-02-10

    PRG4 is one of the downstream molecules of the myxoid liposarcoma (MLS)-specific fusion oncoproteins TLS-CHOP and EWS-CHOP. Exogenous PRG4 expression increases the tumorigenicity of cells injected in nude mice. The molecular functions of PRG4 in tumorigenesis and/or tumor progression of MLS cells, however, still remain unclear. In this report, we demonstrated that siRNA-mediated knockdown of PRG4 suppressed the growth of the MLS-derived cell lines 1955/91 and 2645/94. In addition, PRG4 knockdown promoted adipocytic differentiation in 1955/91 cells. Thus, PRG4 may play essential roles in MLS cell growth and have potential as a therapeutic target. On the other hand, our previous study has revealed that TLS-CHOP suppresses expression of an anti-tumor cytokine IL-24, contributing to tumor cell survival. In this study, we found that double knockdown of PRG4 and IL-24 did not inhibit MLS cell growth, and single knockdown of PRG4 remarkably increased IL-24 expression. These results suggest that the growth inhibitory effect of PRG4 knockdown is caused by induction of IL-24 expression, and PRG4 may contribute to maintain MLS cell growth through repression of IL-24 expression.

  11. Limb-sparing surgery as an alternative for limb amputation in an invasive myxoid liposarcoma--case report.

    PubMed

    Adameșteanu, M O; Enache, V; Zamfirescu, D; Lascăr, I

    2015-01-01

    In medical practice, plastic surgeons confront with patients with sarcomas of the extremities that require a radical surgical approach. Knowing when to attempt limb-sparing surgery and when to give in to limb amputation is one of the most difficult decisions a surgeon can take. The correct approach and management of such cases ensure surgical success and the patient survival. In this paper, the case of a 56-year-old man, admitted in our clinic with a crush injury of the right calf and subsequent haematoma is presented. During haematoma drainage, the surgeon noticed abnormal tissue and performed an incisional biopsy. The patient was diagnosed with myxoid liposarcoma of the external compartment of the right calf. Limb amputation was proposed, but the patient refused. After the clinical examination, blood tests and diagnostic imaging, which allowed the correct evaluation of the case-tumor sizes and neighboring tissue reports, and preoperatory radiotherapy, limb sparing surgery, respectively primary tumor excision was decided to be performed. Negative margins could not be obtained by 3 successive resections or by adjuvant chemotherapy. The presented case supports the idea that limb-sparing surgery is only applicable to carefully selected patients with soft tissue sarcoma. In some cases, radical excision involving even mutilating amputations may provide a better oncologic and functional result.

  12. Neutral Peptidases in the Stroma of Pea Chloroplasts 1

    PubMed Central

    Liu, Xiang-Qin; Jagendorf, André T.

    1986-01-01

    One endopeptidase (EP1) and at least three aminopeptidases (AP1, AP2, and AP3) were discovered in the stroma of chloroplasts isolated from pea seedlings (Pisum sativum L.), and purified over 100-fold. EP1 requires added Mg2+ or Ca2+ for activity, may have an additional tightly bound metal atom, and is inhibited by sulfhydryl reagents but not by serine residue-directed inhibitors. It is reversibly inhibited by dithiothreitol. Its specificity is for the bond between two adjacent Ala or Gly residues. Its molecular mass is 93 kilodaltons, estimated on a gel filtration column. Aminopeptidase activities were detected with the aid of different amino acyl-β-naphthylamides as substrates. They were resolved into at least three individual proteins by gel filtration and DEAE-cellulose chromatography, having apparent molecular masses of 269,000 (AP1), 84,000 (AP2), and 42,000 (AP3) daltons, respectively. Each has a unique specificity for substrates, with AP1 hydrolyzing only the Prolyl-β-naphthylamide. None of the APs require added divalent cations for activity, but the possibility of a tightly bound metal function was suggested in AP2 and AP3 (not AP1) from effects of inhibitors. A probable sulfhydryl residue function was indicated for all three, from inhibition by p-hydroxymercuribenzoate and Zn2+. All these peptidases had pH optima at 7.7. PMID:16664864

  13. Hhip regulates tumor-stroma-mediated upregulation of tumor angiogenesis

    PubMed Central

    Agrawal, Vijayendra; Kim, Dong Young; Kwon, Young-Guen

    2017-01-01

    Tumor growth is governed by the coordinated action of various types of cells that are present in the tumor environment. Fibroblasts, which constitute a major fraction of the stroma, participate actively in various signaling events and regulate tumor development and metastasis. The Hedgehog (Hh) pathway plays an important role in promoting tumor malignancy via fibroblasts; however, the role of hedgehog interacting protein (hhip; inhibitor of Hh pathway) in tumor growth is poorly understood. Here we implanted B16F10 tumors in hhip+/− mice to study the tumor growth characteristics and the vascular phenotype. Furthermore, the mechanism involved in the observed phenomena was explored to reveal the role of hhip in tumor growth. The tumors that were implanted in hhip+/− mice exhibited accelerated growth and increased tumor angiogenesis. Although we observed a decrease in hypoxia, blood vessels still had abnormal phenotype. We found that increased Hh signaling in tumor fibroblasts induced a high expression of vascular endothelial growth factor (VEGF), which subsequently resulted in an increased proliferation of endothelial cells. Thus, the heterozygous knockdown of hhip in mice could affect Hh signaling in tumor fibroblasts, which could cause the increased production of the growth factor VEGF. This signaling, via a paracrine effect on endothelial cells, increased tumor vascular density. PMID:28127049

  14. Overcoming Bone Marrow Stroma-Mediated Chemoresistance in Metastatic Breast Cancer Cells

    DTIC Science & Technology

    2004-08-01

    AD Award Number: DAMD17-03- 1 -0524 .TITLE: Overcoming Bone Marrow Stroma- Mediated Chemoresistance in Metastatic Breast Cancer Cells PRINCIPAL...SUBTITLE 5. FUNDING NUMBERS Overcoming Bone Marrow Stroma- Mediated Chemoresistance in DAMD17-03- 1 -0524 Metastatic Breast Cancer Cells 6. AUTHOR(S) Robert...the compound (Figure 1 ). The inhibitor was slightly more effective in T-47D cells than in MCF-7 cells, but did not eradicate dormant clones much past

  15. Defining the Recruitment of Reactive Stroma Progenitor Cells to the Tumor Microenvironment of Human Prostate Cancer

    DTIC Science & Technology

    2009-02-01

    AD Award Number: W81XWH-08-1-0059 TITLE: Defining the Recruitment of Reactive Stroma Progenitor Cells to the Tumor Microenvironment of Human...2008 - 6 Jan 2009 4. TITLE AND SUBTITLE Defining the Recruitment of Reactive Stroma Progenitor Cells to the Tumor Microenvironment of Human...Symposium on Stem Cells , Cancer, and Aging in Singapore RESEARCH EXPERIENCE 2001 Baylor College of Medicine, Department of Pulmonary and Critical

  16. Prognostic significance of tumour stroma ratio in inflammatory breast cancer.

    PubMed

    Downey, Candice L; Thygesen, Helene H; Sharma, Nisha; Shaaban, Abeer M

    2015-01-01

    Tumour stroma ratio (TSR) is emerging as an important prognostic indicator in cancer. We have previously shown TSR to be prognostic in oestrogen receptor positive breast cancer. Its role in inflammatory breast cancer, a rare but aggressive form of breast cancer, has not been identified. Here we aimed to determine the prognostic significance of TSR in a cohort of patients with inflammatory breast carcinoma. TSR was measured by point counting virtual H&E stained tissue sections in 45 inflammatory breast cancer cases. The whole tumour area was sampled. Optimum cut-offs to distinguish high and low TSR was determined by log-rank test. The relationship of TSR to overall survival and disease-free survival (DFS) was analysed alongside multivariate analysis. The optimal cut-offs between high and low TSR were determined to be 31% for OS and 46% for DFS. There was no significant difference in OS (p = 0.53) nor DFS (p = 0.66) between high and low TSR groups. Multivariate analysis did not demonstrate any new trends, within the limits of a small data sample. A significant correlation was found between pathological response to neoadjuvant chemotherapy and survival (p = 0.008). There is no evidence that TSR has prognostic significance in inflammatory breast cancer. When compared with published data in non-inflammatory breast carcinoma, this supports the view that differences in stromal biology exist between tumour types and highlights the importance of considering this when interpreting the prognostic value of TSR. However, these findings must be interpreted in the light of the small sample size.

  17. Size-Dependent Diffusion of Dextrans in Excised Porcine Corneal Stroma.

    PubMed

    Rajapakshal, Ajith; Fink, Michael; Todd, Brian A

    2015-09-01

    Delivery of therapeutic agents to the eye requires efficient transport through cellular and extracellular barriers. We evaluated the rate of diffusive transport in excised porcine corneal stroma using fluorescently labeled dextran molecules with hydrodynamic radii ranging from 1.3 to 34 nm. Fluorescence correlation spectroscopy (FCS) was used to measure diffusion coefficients of dextran molecules in the excised porcine corneal stroma. The preferential sensitivity of FCS to diffusion along two dimensions was used to differentially probe diffusion along the directions parallel to and perpendicular to the collagen lamellae of the corneal stroma. In order to develop an understanding of how size affects diffusion in cornea, diffusion coefficients in cornea were compared to diffusion coefficients measured in a simple buffer solution. Dextran molecules diffuse more slowly in cornea as compared to buffer solution. The reduction in diffusion coefficient is modest however (67% smaller), and is uniform over the range of sizes that we measured. This indicates that, for dextrans in the 1.3 to 34 nm range, the diffusion landscape of corneal stroma can be represented as a simple liquid with a viscosity approximately 1.5 times that of water. Diffusion coefficients measured parallel vs. perpendicular to the collagen lamellae were indistinguishable. This indicates that diffusion in the corneal stroma is not highly anisotropic. Our results support the notion that the corneal stroma is highly permeable and isotropic to transport of hydrophilic molecules and particles with hydrodynamic radii up to at least 34 nm.

  18. Key players in pancreatic cancer-stroma interaction: Cancer-associated fibroblasts, endothelial and inflammatory cells

    PubMed Central

    Nielsen, Michael Friberg Bruun; Mortensen, Michael Bau; Detlefsen, Sönke

    2016-01-01

    Pancreatic cancer (PC) is the most aggressive type of common cancers, and in 2014, nearly 40000 patients died from the disease in the United States. Pancreatic ductal adenocarcinoma, which accounts for the majority of PC cases, is characterized by an intense stromal desmoplastic reaction surrounding the cancer cells. Cancer-associated fibroblasts (CAFs) are the main effector cells in the desmoplastic reaction, and pancreatic stellate cells are the most important source of CAFs. However, other important components of the PC stroma are inflammatory cells and endothelial cells. The aim of this review is to describe the complex interplay between PC cells and the cellular and non-cellular components of the tumour stroma. Published data have indicated that the desmoplastic stroma protects PC cells against chemotherapy and radiation therapy and that it might promote the proliferation and migration of PC cells. However, in animal studies, experimental depletion of the desmoplastic stroma and CAFs has led to more aggressive cancers. Hence, the precise role of the tumour stroma in PC remains to be elucidated. However, it is likely that a context-dependent therapeutic modification, rather than pure depletion, of the PC stroma holds potential for the development of new treatment strategies for PC patients. PMID:26973408

  19. FGFR1-WNT-TGF-β signaling in prostate cancer mouse models recapitulates human reactive stroma

    PubMed Central

    Carstens, Julienne L.; Shahi, Payam; Van Tsang, Susan; Smith, Billie; Creighton, Chad J.; Zhang, Yiqun; Seamans, Amber; Seethammagari, Mamatha; Vedula, Indira; Levitt, Jonathan M.; Ittmann, Michael M.; Rowley, David R.; Spencer, David M.

    2014-01-01

    The reactive stroma surrounding tumor lesions performs critical roles ranging from supporting tumor cell proliferation to inducing tumorigenesis and metastasis. Therefore, it is critical to understand the cellular components and signaling control mechanisms that underlay the etiology of reactive stroma. Previous studies have individually implicated fibroblast growth factor receptor 1 (FGFR1) and canonical WNT/β-catenin signaling in prostate cancer progression and the initiation and maintenance of a reactive stroma; however, both pathways are frequently found co-activated in cancer tissue. Using autochthonous transgenic mouse models for inducible FGFR1 (JOCK1) and prostate-specific and ubiquitously expressed inducible β-catenin (Pro-Cat and Ubi-Cat, respectively) and bigenic crosses between these lines (Pro-Cat × JOCK1 and Ubi-Cat × JOCK1), we describe WNT-induced synergistic acceleration of FGFR1-driven adenocarcinoma, associated with a pronounced fibroblastic reactive stroma activation surrounding prostatic intraepithelial neoplasia (mPIN) lesions found both in situ and reconstitution assays. Both mouse and human reactive stroma exhibited increased transforming growth factor-beta (TGF-β) signaling adjacent to pathologic lesions likely contributing to invasion. Furthermore, elevated stromal TGF-β signaling was associated with higher Gleason scores in archived human biopsies, mirroring murine patterns. Our findings establish the importance of the FGFR1-WNT-TGF-β signaling axes as driving forces behind reactive stroma in aggressive prostate adenocarcinomas, deepening their relevance as therapeutic targets. PMID:24305876

  20. The EWSR1/NR4A3 fusion protein of extraskeletal myxoid chondrosarcoma activates the PPARG nuclear receptor gene.

    PubMed

    Filion, C; Motoi, T; Olshen, A B; Laé, M; Emnett, R J; Gutmann, D H; Perry, A; Ladanyi, M; Labelle, Y

    2009-01-01

    The NR4A3 nuclear receptor is implicated in the development of extraskeletal myxoid chondrosarcoma (EMC), primitive sarcoma unrelated to conventional chondrosarcomas, through a specific fusion with EWSR1 resulting in an aberrant fusion protein that is thought to disrupt the transcriptional regulation of specific target genes. We performed an expression microarray analysis of EMC tumours expressing the EWSR1/NR4A3 fusion protein, comparing their expression profiles to those of other sarcoma types. We thereby identified a set of genes significantly overexpressed in EMC relative to other sarcomas, including PPARG and NDRG2. Western blot or immunohistochemical analyses confirm that PPARG and NDRG2 are expressed in tumours positive for EWSR1/NR4A3. Bioinformatic analysis identified a DNA response element for EWSR1/NR4A3 in the PPARG promoter, and band-shift experiments and transient transfections indicate that EWSR1/NR4A3 can activate transcription through this element. Western blots further show that an isoform of the native NR4A3 receptor lacking the C-terminal domain is very highly expressed in tumours positive for EWSR1/NR4A3, and co-transfections of this isoform along with EWSR1/NR4A3 indicate that it may negatively regulate the activity of the fusion protein on the PPARG promoter. These results suggest that the overall expression of PPARG in EMC may be regulated in part by the balance between EWSR1/NR4A3 and NR4A3, and that PPARG may play a crucial role in the development of these tumours. The specific up-regulation of PPARG by EWSR1/NR4A3 may also have potential therapeutic implications.

  1. Multiscale Investigation of the Depth-Dependent Mechanical Anisotropy of the Human Corneal Stroma

    PubMed Central

    Labate, Cristina; Lombardo, Marco; De Santo, Maria P.; Dias, Janice; Ziebarth, Noel M.; Lombardo, Giuseppe

    2015-01-01

    Purpose. To investigate the depth-dependent mechanical anisotropy of the human corneal stroma at the tissue (stroma) and molecular (collagen) level by using atomic force microscopy (AFM). Methods. Eleven human donor corneas were dissected at different stromal depths by using a microkeratome. Mechanical measurements were performed in 15% dextran on the surface of the exposed stroma of each sample by using a custom-built AFM in force spectroscopy mode using both microspherical (38-μm diameter) and nanoconical (10-nm radius of curvature) indenters at 2-μm/s and 15-μm/s indentation rates. Young's modulus was determined by fitting force curve data using the Hertz and Hertz-Sneddon models for a spherical and a conical indenter, respectively. The depth-dependent anisotropy of stromal elasticity was correlated with images of the corneal stroma acquired by two-photon microscopy. Results. The force curves were obtained at stromal depths ranging from 59 to 218 μm. At the tissue level, Young's modulus (ES) showed a steep decrease at approximately 140-μm stromal depth (from 0.8 MPa to 0.3 MPa; P = 0.03) and then was stable in the posterior stroma. At the molecular level, Young's modulus (EC) was significantly greater than at the tissue level; EC decreased nonlinearly with increasing stromal depth from 3.9 to 2.6 MPa (P = 0.04). The variation of microstructure through the thickness correlated highly with a nonconstant profile of the mechanical properties in the stroma. Conclusions. The corneal stroma exhibits unique anisotropic elastic behavior at the tissue and molecular levels. This knowledge may benefit modeling of corneal behavior and help in the development of biomimetic materials. PMID:26098472

  2. Integrated Bioinformatics Approach Reveals Crosstalk Between Tumor Stroma and Peripheral Blood Mononuclear Cells in Breast Cancer.

    PubMed

    He, Lang; Wang, Dan; Wei, Na; Guo, Zheng

    2016-01-01

    Breast cancer is now the leading cause of cancer death in women worldwide. Cancer progression is driven not only by cancer cell intrinsic alterations and interactions with tumor microenvironment, but also by systemic effects. Integration of multiple profiling data may provide insights into the underlying molecular mechanisms of complex systemic processes. We performed a bioinformatic analysis of two public available microarray datasets for breast tumor stroma and peripheral blood mononuclear cells, featuring integrated transcriptomics data, protein-protein interactions (PPIs) and protein subcellular localization, to identify genes and biological pathways that contribute to dialogue between tumor stroma and the peripheral circulation. Genes of the integrin family as well as CXCR4 proved to be hub nodes of the crosstalk network and may play an important role in response to stroma-derived chemoattractants. This study pointed to potential for development of therapeutic strategies that target systemic signals travelling through the circulation and interdict tumor cell recruitment.

  3. Quantitative analysis of thermally-induced alterations of corneal stroma by second-harmonic generation imaging

    NASA Astrophysics Data System (ADS)

    Matteini, P.; Rossi, F.; Ratto, F.; Cicchi, R.; Kapsokalyvas, D.; Pavone, F. S.; Pini, R.

    2010-02-01

    Thermal modifications induced in the corneal stroma were investigated by means of second harmonic generation (SHG) imaging. Whole fresh cornea samples were heated in a water bath at temperatures in the 35-80 °C range for a 4-min time. SHG images of the structural modifications induced at each temperature were acquired from different areas of cross-sectioned corneal stroma by using an 880 nm linearly- and circularly-polarized excitation light emitted by a mode-locked Ti:Sapphire laser. The SHG images were then analyzed by means of both an empirical approach and a 2D-theoretical model. The proposed analyses provide a detailed description of the changes occurring in the structural architecture of the cornea during the thermal treatment. Our results allow us to depict a temperature-dependent biochemical model for the progressive destructuration occurring to collagen fibrils and nonfibrillar components of the stroma.

  4. Thylakoid direct photobioelectrocatalysis: utilizing stroma thylakoids to improve bio-solar cell performance.

    PubMed

    Rasmussen, Michelle; Minteer, Shelley D

    2014-08-28

    Thylakoid membranes from spinach were separated into grana and stroma thylakoid fractions which were characterized by several methods (pigment content, protein gel electrophoresis, photosystem activities, and electron microscopy analysis) to confirm that the intact thylakoids were differentiated into the two domains. The results of photoelectrochemical experiments showed that stroma thylakoid electrodes generate photocurrents more than four times larger than grana thylakoids (51 ± 4 nA cm(-2) compared to 11 ± 1 nA cm(-2)). A similar trend was seen in a bio-solar cell configuration with stroma thylakoids giving almost twice the current (19 ± 3 μA cm(-2)) as grana thylakoids (11 ± 2 μA cm(-2)) with no change in open circuit voltage.

  5. Gene expression in local stroma reflects breast tumor states and predicts patient outcome

    PubMed Central

    Bainer, Russell; Frankenberger, Casey; Rabe, Daniel; An, Gary; Gilad, Yoav; Rosner, Marsha Rich

    2016-01-01

    The surrounding microenvironment has been implicated in the progression of breast tumors to metastasis. However, the degree to which metastatic breast tumors locally reprogram stromal cells as they disrupt tissue boundaries is not well understood. We used species-specific RNA sequencing in a mouse xenograft model to determine how the metastasis suppressor RKIP influences transcription in a panel of paired tumor and stroma tissues. We find that gene expression in metastatic breast tumors is pervasively correlated with gene expression in local stroma of both mouse xenografts and human patients. Changes in stromal gene expression elicited by tumors better predicts subtype and patient survival than tumor gene expression, and genes with coordinated expression in both tissues predict metastasis-free survival. These observations support the use of stroma-based strategies for the diagnosis and prognosis of breast cancer. PMID:27982086

  6. Second harmonic generation imaging of corneal stroma after infection by Pseudomonas aeruginosa

    PubMed Central

    Robertson, Danielle M.; Rogers, Nathan A.; Petroll, W. Matthew; Zhu, Meifang

    2017-01-01

    Pseudomonas aeruginosa is a pathogenic gram-negative organism that has the ability to cause blinding corneal infections following trauma and during contact lens wear. In this study, we investigated the directional movement and orientation of an invasive corneal isolate of P. aeruginosa in the corneal stroma during infection of ex vivo and in vivo rabbit corneas using multiphoton fluorescence and second harmonic generation (SHG) imaging. Ex vivo, rabbit corneas were subject to three partial thickness wounds prior to inoculation. In vivo, New Zealand white rabbits were fit with P. aeruginosa laden contact lenses in the absence of a penetrating wound. At all time points tested, infiltration of the corneal stroma by P. aeruginosa revealed a high degree of alignment between the bacteria and collagen lamellae ex vivo (p < 0.001). In vivo, P. aeruginosa traveled throughout the stroma in discrete regions or bands. Within each region, the bacteria showed good alignment with collagen lamellae (P = 0.002). Interestingly, in both the in vitro and in vivo models, P. aeruginosa did not appear to cross the corneal limbus. Taken together, our findings suggest that P. aeruginosa exploits the precise spacing of collagen lamellae in the central cornea to facilitate spread throughout the stroma.

  7. Tic40 is important for reinsertion of proteins from the chloroplast stroma into the inner membrane

    PubMed Central

    Chiu, Chi-Chou; Li, Hsou-min

    2008-01-01

    Chloroplast inner-membrane proteins Tic40 and Tic110 are first imported from the cytosol into the chloroplast stroma, and subsequently reinserted from the stroma into the inner membrane. However, the mechanism of reinsertion remains unclear. Here we show that Tic40 itself is involved in this reinsertion process. When precursors of either Tic40 or a Tic110 C-terminal truncate, tpTic110-Tic110N, were imported into chloroplasts isolated from a tic40-null mutant, soluble Tic40 and Tic110N intermediates accumulated in the stroma of tic40-mutant chloroplasts, due to a slower rate of reinsertion. We further show that a larger quantity of soluble Tic21 intermediates also accumulated in the stroma of tic40-mutant chloroplasts. In contrast, inner-membrane insertion of the triose-phosphate/phosphate translocator was not affected by the tic40 mutation. Our data suggest that multiple pathways exist for the insertion of chloroplast inner-membrane proteins. PMID:18657235

  8. Understanding tumor-stroma interplays for targeted therapies by armed mesenchymal stromal progenitors: the Mesenkillers

    PubMed Central

    Grisendi, Giulia; Bussolari, Rita; Veronesi, Elena; Piccinno, Serena; Burns, Jorge S; De Santis, Giorgio; Loschi, Pietro; Pignatti, Marco; Di Benedetto, Fabrizio; Ballarin, Roberto; Di Gregorio, Carmela; Guarneri, Valentina; Piccinini, Lino; Horwitz, Edwin M; Paolucci, Paolo; Conte, PierFranco; Dominici, Massimo

    2011-01-01

    A tumor represents a complex structure containing malignant cells strictly coupled with a large variety of surrounding cells constituting the tumor stroma (TS). In recent years, the importance of TS for cancer initiation, development, local invasion and metastases has become increasingly clear allowing the identification of TS as one of the possible ways to indirectly target tumors. Inside the heterogeneous stromal cell population, tumor associated fibroblasts (TAF) play a crucial role providing both functional and supportive environments. During both tumor and stroma development, several findings suggest that TAF could be recruited from different sources such as locally derived host fibroblasts, via epithelial/endothelial mesenchymal transitions or from circulating pools of fibroblasts deriving form mesenchymal progenitors, namely mesenchymal stem/stromal cells (MSC). These insights prompted scientists to identify multimodal approaches to target TS by biomolecules, monoclonal antibodies, and more recently via cell based strategies. These latter strategies appear extremely promising, although still associated with debated and unclear findings. This review discusses crosstalk between cancers and their stroma, dissecting specific tumor types, such as sarcoma, pancreatic and breast carcinoma, where stroma plays distinct paradigmatic roles. The recognition of these distinct stromal functions may help in planning effective and safer approaches aimed either to eradicate or to substitute TS by novel compounds and/or MSC having specific killing activities. PMID:22016827

  9. Breast Cancer Cell Invasion into a Three Dimensional Tumor-Stroma Microenvironment

    PubMed Central

    Truong, Danh; Puleo, Julieann; Llave, Alison; Mouneimne, Ghassan; Kamm, Roger D.; Nikkhah, Mehdi

    2016-01-01

    In this study, to model 3D chemotactic tumor-stroma invasion in vitro, we developed an innovative microfluidic chip allowing side-by-side positioning of 3D hydrogel-based matrices. We were able to (1) create a dual matrix architecture that extended in a continuous manner, thus allowing invasion from one 3D matrix to another, and (2) establish distinct regions of tumor and stroma cell/ECM compositions, with a clearly demarcated tumor invasion front, thus allowing us to quantitatively analyze progression of cancer cells into the stroma at a tissue or single-cell level. We showed significantly enhanced cancer cell invasion in response to a transient gradient of epidermal growth factor (EGF). 3D tracking at the single-cell level displayed increased migration speed and persistence. Subsequently, we analyzed changes in expression of EGF receptors, cell aspect ratio, and protrusive activity. These findings show the unique ability of our model to quantitatively analyze 3D chemotactic invasion, both globally by tracking the progression of the invasion front, and at the single-cell level by examining changes in cellular behavior and morphology using high-resolution imaging. Taken together, we have shown a novel model recapitulating 3D tumor-stroma interactions for studies of real-time cell invasion and morphological changes within a single platform. PMID:27678304

  10. Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis

    PubMed Central

    Desterke, Christophe; Martinaud, Christophe; Ruzehaji, Nadira; Le Bousse-Kerdilès, Marie-Caroline

    2015-01-01

    Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm where severity as well as treatment complexity is mainly attributed to a long lasting disease and presence of bone marrow stroma alterations as evidenced by myelofibrosis, neoangiogenesis, and osteosclerosis. While recent understanding of mutations role in hematopoietic cells provides an explanation for pathological myeloproliferation, functional involvement of stromal cells in the disease pathogenesis remains poorly understood. The current dogma is that stromal changes are secondary to the cytokine “storm” produced by the hematopoietic clone cells. However, despite therapies targeting the myeloproliferation-sustaining clones, PMF is still regarded as an incurable disease except for patients, who are successful recipients of allogeneic stem cell transplantation. Although the clinical benefits of these inhibitors have been correlated with a marked reduction in serum proinflammatory cytokines produced by the hematopoietic clones, further demonstrating the importance of inflammation in the pathological process, these treatments do not address the role of the altered bone marrow stroma in the pathological process. In this review, we propose hypotheses suggesting that the stroma is inflammatory-imprinted by clonal hematopoietic cells up to a point where it becomes “independent” of hematopoietic cell stimulation, resulting in an inflammatory vicious circle requiring combined stroma targeted therapies. PMID:26640324

  11. Survival and integration of tissue-engineered corneal stroma in a model of corneal ulcer.

    PubMed

    Zhang, Chao; Nie, Xin; Hu, Dan; Liu, Yuan; Deng, Zhihong; Dong, Rui; Zhang, Yongjie; Jin, Yan

    2007-08-01

    Tissue-engineered replacement of diseased or damaged tissue has become a reality for some types of tissue, such as skin and cartilage. Tissue-engineered corneal stroma represents a promising concept to overcome the limitations of cornea replacement with allograft. In this study, porcine cornea was decellularized by a series of extraction methods, and the in vivo biocompatibility of the scaffold was measured subcutaneously in rabbits (n = 8). These were not acutely rejected and no abscesses were observed by hematoxylin and eosin staining at the 8th week, indicating that the scaffolds had good biocompatibility. To investigate the potential value of clinical applications, rabbit stromal keratocytes were implanted onto decellularized scaffolds to fabricate tissue-engineered corneal stroma. Allograft, tissue-engineered corneal stroma, or scaffolds were implanted into a model of corneal ulcer. The survival and reconstruction of corneal transplantation were morphologically evaluated by light and electron microscopy until the 32nd week after implantation. Experiments involving transplantation indicated that the epithelial and stromal defect healed quickly, with improvement in corneal clarity. The integration of the graft was accompanied by neurite ingrowth from the host tissue. By 16 weeks after transplantation, the cornea had gradually regained an intact state similar to that of normal cornea. Our results demonstrate that the tissue-engineered corneal stroma with allogenetic cells is a promising therapeutic method for corneal injury.

  12. Extensively Myxoid and Hyalinized Sinonasal Capillary Hemangiomas: A Clinicopathologic Study of 16 Cases of a Distinctive and Potentially Confusing Hemangioma Variant.

    PubMed

    Guo, Ruifeng; Folpe, Andrew L

    2015-11-01

    Capillary hemangiomas, the most common vascular tumors of the sinonasal region, are benign endothelial neoplasms, typically growing in an easily recognized lobular pattern. Some sinonasal capillary hemangiomas may show atypical features, such as high cellularity or mitotic activity, and represent more challenging diagnoses. Over the past several years we have seen in consultation a number of examples of sinonasal capillary hemangiomas displaying very striking stromal myxoid change and hyalinization, features that have received scant attention in the past. Available slides from 16 sinonasal capillary hemangiomas previously coded as showing such changes were retrieved from our archives. Submitting diagnoses included "query angiofibroma, rule out malignancy" (N=4), "vascular polyp, rule out malignancy" (N=3), "query malignant vascular tumor" (N=4), "sinonasal hemangiopericytoma" (N=1), and "benign vascular tumor" (N=1). Available radiographic studies often showed worrisome features. Grossly, the tumors ranged from 1.1 to 6.0 cm and appeared as ulcerated, vascular-appearing polyps. Microscopically, the tumors showed striking stromal myxoid change and/or hyalinization, which largely obscured the underlying lobular capillary arrangement. Within this myxohyaline matrix, a florid capillary proliferation was present, frequently with nonatypical mitotic activity. In some instances a branching, "hemangiopericytoma-like" vascular pattern was present in areas. The overall cellularity was low to moderate, and endothelial atypia or hyperchromatism was absent. Ulceration and thrombosis were frequently present. Immunostains to CD31, CD34, and SMA highlighted areas of lobular growth pattern inapparent on the routinely stained slides. Four tested cases were negative for androgen receptors and β-catenin. Follow-up from 12 patients revealed no local recurrences or metastases. Awareness of that sinonasal capillary hemangioma may show these unusual stromal changes, and the use of

  13. Elastic microfibril distribution in the cornea: Differences between normal and keratoconic stroma.

    PubMed

    White, Tomas L; Lewis, Philip N; Young, Robert D; Kitazawa, Koji; Inatomi, Tsutomu; Kinoshita, Shigeru; Meek, Keith M

    2017-03-14

    The optical and biomechanical properties of the cornea are largely governed by the collagen-rich stroma, a layer that represents approximately 90% of the total thickness. Within the stroma, the specific arrangement of superimposed lamellae provides the tissue with tensile strength, whilst the spatial arrangement of individual collagen fibrils within the lamellae confers transparency. In keratoconus, this precise stromal arrangement is lost, resulting in ectasia and visual impairment. In the normal cornea, we previously characterised the three-dimensional arrangement of an elastic fiber network spanning the posterior stroma from limbus-to-limbus. In the peripheral cornea/limbus there are elastin-containing sheets or broad fibers, most of which become microfibril bundles (MBs) with little or no elastin component when reaching the central cornea. The purpose of the current study was to compare this network with the elastic fiber distribution in post-surgical keratoconic corneal buttons, using serial block face scanning electron microscopy and transmission electron microscopy. We have demonstrated that the MB distribution is very different in keratoconus. MBs are absent from a region of stroma anterior to Descemet's membrane, an area that is densely populated in normal cornea, whilst being concentrated below the epithelium, an area in which they are absent in normal cornea. We contend that these latter microfibrils are produced as a biomechanical response to provide additional strength to the anterior stroma in order to prevent tissue rupture at the apex of the cone. A lack of MBs anterior to Descemet's membrane in keratoconus would alter the biomechanical properties of the tissue, potentially contributing to the pathogenesis of the disease.

  14. The autophagic tumor stroma model of cancer or “battery-operated tumor growth”

    PubMed Central

    Martinez-Outschoorn, Ubaldo E; Whitaker-Menezes, Diana; Pavlides, Stephanos; Chiavarina, Barbara; Bonuccelli, Gloria; Trimmer, Casey; Tsirigos, Aristotelis; Migneco, Gemma; Witkiewicz, Agnieszka K; Balliet, Renee; Mercier, Isabelle; Wang, Chengwang; Flomenberg, Neal; Howell, Anthony; Lin, Zhao; Caro, Jaime; Pestell, Richard G

    2010-01-01

    The role of autophagy in tumorigenesis is controversial. Both autophagy inhibitors (chloroquine) and autophagy promoters (rapamycin) block tumorigenesis by unknown mechanism(s). This is called the “Autophagy Paradox.” We have recently reported a simple solution to this paradox. We demonstrated that epithelial cancer cells use oxidative stress to induce autophagy in the tumor microenvironment. As a consequence, the autophagic tumor stroma generates recycled nutrients that can then be used as chemical building blocks by anabolic epithelial cancer cells. This model results in a net energy transfer from the tumor stroma to epithelial cancer cells (an energy imbalance), thereby promoting tumor growth. This net energy transfer is both unilateral and vectorial, from the tumor stroma to the epithelial cancer cells, representing a true host-parasite relationship. We have termed this new paradigm “The Autophagic Tumor Stroma Model of Cancer Cell Metabolism” or “Battery-Operated Tumor Growth.” In this sense, autophagy in the tumor stroma serves as a “battery” to fuel tumor growth, progression and metastasis, independently of angiogenesis. Using this model, the systemic induction of autophagy will prevent epithelial cancer cells from using recycled nutrients, while the systemic inhibiton of autophagy will prevent stromal cells from producing recycled nutrients—both effectively “starving” cancer cells. We discuss the idea that tumor cells could become resistant to the systemic induction of autophagy by the upregulation of natural, endogenous autophagy inhibitors in cancer cells. Alternatively, tumor cells could also become resistant to the systemic induction of autophagy by the genetic silencing/deletion of pro-autophagic molecules, such as Beclin1. If autophagy resistance develops in cancer cells, then the systemic inhibition of autophagy would provide a therapeutic solution to this type of drug resistance, as it would still target autophagy in the tumor

  15. Proteomics of the human endometrial glandular epithelium and stroma from the proliferative and secretory phases of the menstrual cycle.

    PubMed

    Hood, Brian L; Liu, Baoquan; Alkhas, Addie; Shoji, Yutaka; Challa, Rusheeswar; Wang, Guisong; Ferguson, Susan; Oliver, Julie; Mitchell, Dave; Bateman, Nicholas W; Zahn, Christopher M; Hamilton, Chad A; Payson, Mark; Lessey, Bruce; Fazleabas, Asgerally T; Maxwell, G Larry; Conrads, Thomas P; Risinger, John I

    2015-04-01

    Despite its importance in reproductive biology and women's health, a detailed molecular-level understanding of the human endometrium is lacking. Indeed, no comprehensive studies have been undertaken to elucidate the important protein expression differences between the endometrial glandular epithelium and surrounding stroma during the proliferative and midsecretory phases of the menstrual cycle. We utilized laser microdissection to harvest epithelial cells and stromal compartments from proliferative and secretory premenopausal endometrial tissue and performed a global, quantitative mass spectrometry-based proteomics analysis. This analysis identified 1224 total proteins from epithelial cells, among which 318 were differentially abundant between the proliferative and secretory phases (q < 0.05), and 1005 proteins from the stromal compartments, 19 of which were differentially abundant between the phases (q < 0.05). Several proteins were chosen for validation by immunohistochemistry in an independent set of uterine tissues, including carboxypeptidase M, tenascin C, neprilysin, and ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3). ENPP3, which was elevated in epithelial glandular cells in the secretory phase, was confirmed to be elevated in midsecretory-phase baboon uterine lavage samples and also observed to have an N-linked glycosylated form that was not observed in the proliferative phase. This study provides a detailed view into the global proteomic alterations of the epithelial cells and stromal compartments of the cycling premenopausal endometrium. These proteomic alterations during endometrial remodeling provide a basis for numerous follow-up investigations on the function of these differentially regulated proteins and their role in reproductive biology and endometrial pathologies.

  16. Characterization of the Tumor Microenvironment and Tumor–Stroma Interaction by Non-invasive Preclinical Imaging

    PubMed Central

    Ramamonjisoa, Nirilanto; Ackerstaff, Ellen

    2017-01-01

    Tumors are often characterized by hypoxia, vascular abnormalities, low extracellular pH, increased interstitial fluid pressure, altered choline-phospholipid metabolism, and aerobic glycolysis (Warburg effect). The impact of these tumor characteristics has been investigated extensively in the context of tumor development, progression, and treatment response, resulting in a number of non-invasive imaging biomarkers. More recent evidence suggests that cancer cells undergo metabolic reprograming, beyond aerobic glycolysis, in the course of tumor development and progression. The resulting altered metabolic content in tumors has the ability to affect cell signaling and block cellular differentiation. Additional emerging evidence reveals that the interaction between tumor and stroma cells can alter tumor metabolism (leading to metabolic reprograming) as well as tumor growth and vascular features. This review will summarize previous and current preclinical, non-invasive, multimodal imaging efforts to characterize the tumor microenvironment, including its stromal components and understand tumor–stroma interaction in cancer development, progression, and treatment response. PMID:28197395

  17. Steroid hormones and the stroma-vascular cells of the adipose tissue.

    PubMed

    Volat, Fanny; Bouloumié, Anne

    2013-09-01

    The stroma-vascular fraction (SVF) of adipose tissue (AT) is a heterogeneous cell fraction composed of progenitor cells, endothelial cells, and immune cells. SVF plays a key role in AT homeostasis and growth as well as in obesity-associated pathologies. The SVF cell composition and phenotype are distinct according to AT location and adiposity. Such discrepancies influence AT function and are involved in obesity-associated disorders such as chronic inflammation. Investigations performed in recent years in rodents and humans provided evidence that the stroma-vascular cells contribute to the conversion of steroid hormones in AT and are also steroid targets. This review describes the link between steroids and SVF depending on gender, adiposity, and AT location and highlights the potential role of sex and corticosteroid hormones in adipogenesis, angiogenesis, and their contributions in AT inflammation.

  18. Identification of tumor epithelium and stroma in tissue microarrays using texture analysis

    PubMed Central

    2012-01-01

    Background The aim of the study was to assess whether texture analysis is feasible for automated identification of epithelium and stroma in digitized tumor tissue microarrays (TMAs). Texture analysis based on local binary patterns (LBP) has previously been used successfully in applications such as face recognition and industrial machine vision. TMAs with tissue samples from 643 patients with colorectal cancer were digitized using a whole slide scanner and areas representing epithelium and stroma were annotated in the images. Well-defined images of epithelium (n = 41) and stroma (n = 39) were used for training a support vector machine (SVM) classifier with LBP texture features and a contrast measure C (LBP/C) as input. We optimized the classifier on a validation set (n = 576) and then assessed its performance on an independent test set of images (n = 720). Finally, the performance of the LBP/C classifier was evaluated against classifiers based on Haralick texture features and Gabor filtered images. Results The proposed approach using LPB/C texture features was able to correctly differentiate epithelium from stroma according to texture: the agreement between the classifier and the human observer was 97 per cent (kappa value = 0.934, P < 0.0001) and the accuracy (area under the ROC curve) of the LBP/C classifier was 0.995 (CI95% 0.991-0.998). The accuracy of the corresponding classifiers based on Haralick features and Gabor-filter images were 0.976 and 0.981 respectively. Conclusions The method illustrates the capability of automated segmentation of epithelial and stromal tissue in TMAs based on texture features and an SVM classifier. Applications include tissue specific assessment of gene and protein expression, as well as computerized analysis of the tumor microenvironment. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4123422336534537 PMID:22385523

  19. Periostin and tumor-stroma interactions in non-small cell lung cancer

    PubMed Central

    Nitsche, Ulrich; Stangel, Daniela; Pan, Zheng; Schlitter, Anna Melissa; Esposito, Irene; Regel, Ivonne; Raulefs, Susanne; Friess, Helmut; Kleeff, Jörg; Erkan, Mert

    2016-01-01

    Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-associated mortality globally. Interactions of the cancer cells with the tumor microenvironment are essential carcinogenic features for the majority of solid tumors, such as pancreatic cancer. The present study investigated the role of stromal activation in NSCLC and analyzed the surgical specimens of 93 patients by immunohistochemistry with regard to periostin (an extracellular matrix protein), α-smooth muscle actin (α-SMA; a marker of myofibroblasts) and cluster of differentiation 31 (CD31; a marker of endothelial cells), and the activated stroma index. There was a trend towards reduced overall survival for patients with high periostin expression (hazard ratio, 1.80; 95% confidence interval, 0.99–3.27; P=0.050). No significant correlations with overall survival were identified for α-SMA (P=0.930), CD31 (P=0.923), collagen (P=0.441) or the activated stroma index (P=0.706). In a multivariable analysis, the histological tumor subtype, tumor stage, lymph node involvement and resection status were independent prognostic factors in NSCLC, but none of the investigated immunohistochemical markers were prognostic factors. Thus, the tumor microenvironment and stroma activation did not prove to be of prognostic relevance for lung cancer, as it has been previously described for pancreatic cancer. Other markers of the microenvironment of NSCLC may be of higher prognostic value, pointing towards tumor-type specific effects. PMID:27895734

  20. Targeting Enox1 in tumor stroma increases the efficacy of fractionated radiotherapy

    PubMed Central

    Smith, Clayton A.; Mont, Stacey; Traver, Geri; Sekhar, Konjeti R.; Crooks, Peter A.; Freeman, Michael L.

    2016-01-01

    The goal of this investigation was to clarify the question of whether targeting Enox1 in tumor stroma would synergistically enhance the survival of tumor-bearing mice treated with fractionated radiotherapy. Enox1, a NADH oxidase, is expressed in tumor vasculature and stroma. However, it is not expressed in many tumor types, including HT-29 colorectal carcinoma cells. Pharmacological inhibition of Enox1 in endothelial cells inhibited repair of DNA double strand breaks, as measured by γH2AX and 53BP1 foci formation, as well as neutral comet assays. For 4 consecutive days athymic mice bearing HT-29 hindlimb xenografts were injected with a small molecule inhibitor of Enox1 or solvent control. Tumors were then administered 2 Gy of x-rays. On day 5 tumors were administered a single ‘top-up’ fraction of 30 Gy, the purpose of which was to amplify intrinsic differences in the radiation fractionation regimen produced by Enox1 targeting. Pharmacological targeting of Enox1 resulted in 80% of the tumor-bearing mice surviving at 90 days compared to only 40% of tumor-bearing mice treated with solvent control. The increase in survival was not a consequence of reoxygenation, as measured by pimonidazole immunostaining. These results are interpreted to indicate that targeting of Enox1 in tumor stroma significantly enhances the effectiveness of 2 Gy fractionated radiotherapy and identifies Enox1 as a potential therapeutic target. PMID:27788492

  1. Lactoferrin at basal side of mouse mammary epithelium derives in part from stroma cells.

    PubMed

    Pecorini, Chiara; Delpal, Serge; Truchet, Sandrine; Le Provost, Fabienne; Baldi, Antonella; Ollivier-Bousquet, Michèle

    2009-11-01

    Lactoferrin is synthesized by glandular epithelial cells and neutrophils and is also present on both sides of the mammary epithelium. We have studied the origin of lactoferrin detected in the various compartments of mouse mammary tissue. As revealed by immunogold electron microscopy, lactoferrin is present in mammary epithelial cells and in the basal region of the epithelium, associated with connective tissue and stroma cells at all physiological stages studied. A perturbation of protein synthesis or transport after in vitro treatment with cycloheximide or brefeldin A does not abrogate lactoferrin labelling in the basal region of the epithelium. The expression of lactoferrin has also been observed in the fat pads of mammary glands from mice surgically depleted of epithelial cells. The sealing of one teat for 24 h is accompanied by an increase in both the number of stroma cells and the labelling of myoepithelial cells. Thus, the lactoferrin present in the interstitial space of the mouse mammary epithelium originates in part from stroma cells. Possible roles of lactoferrin at the basal side of the mammary epithelium are discussed.

  2. Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription

    PubMed Central

    Kaukonen, Riina; Mai, Anja; Georgiadou, Maria; Saari, Markku; De Franceschi, Nicola; Betz, Timo; Sihto, Harri; Ventelä, Sami; Elo, Laura; Jokitalo, Eija; Westermarck, Jukka; Kellokumpu-Lehtinen, Pirkko-Liisa; Joensuu, Heikki; Grenman, Reidar; Ivaska, Johanna

    2016-01-01

    Tissue homeostasis is dependent on the controlled localization of specific cell types and the correct composition of the extracellular stroma. While the role of the cancer stroma in tumour progression has been well characterized, the specific contribution of the matrix itself is unknown. Furthermore, the mechanisms enabling normal—not cancer—stroma to provide tumour-suppressive signals and act as an antitumorigenic barrier are poorly understood. Here we show that extracellular matrix (ECM) generated by normal fibroblasts (NFs) is softer than the CAF matrix, and its physical and structural features regulate cancer cell proliferation. We find that normal ECM triggers downregulation and nuclear exit of the histone demethylase JMJD1a resulting in the epigenetic growth restriction of carcinoma cells. Interestingly, JMJD1a positively regulates transcription of many target genes, including YAP/TAZ (WWTR1), and therefore gene expression in a stiffness-dependent manner. Thus, normal stromal restricts cancer cell proliferation through JMJD1a-dependent modulation of gene expression. PMID:27488962

  3. Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.

    PubMed

    Sandhu, Rupninder; Chollet-Hinton, Lynn; Kirk, Erin L; Midkiff, Bentley; Troester, Melissa A

    2016-02-01

    Complete age-related regression of mammary epithelium, often termed postmenopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study. High-resolution digital images of normal breast hematoxylin and eosin-stained slides were partitioned into epithelium, adipose tissue, and nonfatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models. Stromal area decreased (P = 0.0002), and adipose tissue area increased (P < 0.0001), with an approximate 0.7% change in area for each component, until age 55 years when these area measures reached a steady state. Although epithelial area did not show linear changes with age, epithelial nuclear density decreased linearly beginning in the third decade of life. No significant age-related trends were observed for stromal or adipose nuclear density. Digital image analysis offers a high-throughput method for quantitatively measuring tissue morphometry and for objectively assessing age-related changes in adipose tissue, stroma, and epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period.

  4. Epithelium-stroma classification via convolutional neural networks and unsupervised domain adaptation in histopathological images.

    PubMed

    Huang, Yue; Zheng, Han; Liu, Chi; Ding, Xinghao; Rohde, Gustavo

    2017-04-06

    Epithelium-stroma classification is a necessary preprocessing step in histopathological image analysis. Current deep learning based recognition methods for histology data require collection of large volumes of labeled data in order to train a new neural network when there are changes to the image acquisition procedure. However, it is extremely expensive for pathologists to manually label sufficient volumes of data for each pathology study in a professional manner, which results in limitations in real-world applications. A very simple but effective deep learning method, that introduces the concept of unsupervised domain adaptation to a simple convolutional neural network (CNN), has been proposed in this paper. Inspired by transfer learning, our work assumes that the training data and testing data follow different distributions, and there is an adaptation operation to more accurately estimate the kernels in CNN in feature extraction, in order to enhance performance by transferring knowledge from labeled data in source domain to unlabeled data in target domain. The model has been evaluated using three independent public epithelium-stroma datasets by cross-dataset validations. The experimental results demonstrate that for epithelium-stroma classification, the proposed framework outperforms the state-of-the-art deep neural network model, and it also achieves better performance than other existing deep domain adaptation methods. The proposed model can be considered to be a better option for real-world applications in histopathological image analysis, since there is no longer a requirement for large-scale labeled data in each specified domain.

  5. Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma

    PubMed Central

    Sandhu, Rupninder; Chollet-Hinton, Lynn; Kirk, Erin L.; Midkiff, Bentley; Troester, Melissa A.

    2015-01-01

    Complete age-related regression of mammary epithelium, often termed post-menopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study (NBS). High-resolution digital images of normal breast Hematoxylin & Eosin stained slides were partitioned into epithelium, adipose tissue, and non-fatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models Stromal area decreased (p=0.0002) and adipose tissue area increased (p<0.0001), with an approximate 0.7% change in area for each component, until age 55 when these area measures reached a steady state. While epithelial area did not show linear changes with age, epithelial nuclear density decreased linearly beginning in the third decade of life. No significant age-related trends were observed for stromal or adipose nuclear density. Digital image analysis offers a high-throughput method for quantitatively measuring tissue morphometry and for objectively assessing age-related changes in adipose tissue, stroma, and epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period. PMID:26772400

  6. Galectin-1 drives pancreatic carcinogenesis through stroma remodeling and Hedgehog signaling activation

    PubMed Central

    Martínez-Bosch, Neus; Fernández-Barrena, Maite G.; Moreno, Mireia; Ortiz-Zapater, Elena; André, Sabine; Gabius, Hans-Joachim; Hwang, Rosa F.; Poirier, Françoise; Munné-Collado, Jessica; Iglesias, Mar; Navas, Carolina; Guerra, Carmen; Fernández-Zapico, Martin E.; Navarro, Pilar

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDA) is the most aggressive tumor, showing incidence and mortality values almost identical. Despite remarkable advances in PDA molecular characterization, this disease is still refractory to current treatments. Desmoplastic stroma, a constant hallmark of PDA, has recently emerged as the major responsible for PDA therapeutic resistance, therefore representing a promising target. Galectin-1 (Gal1), a glycan-binding protein, is highly expressed in PDA stroma but its role remains unknown. Here, we aim to understand in vivo Gal1 functions and the molecular pathways responsible for its oncogenic properties. Genetic ablation of Gal1 in Ela-myc mice dampens tumor progression through inhibition of proliferation, angiogenesis, desmoplasia and stimulation of tumor-associated immune response, resulting in a 20% increase on the animal life span. In vitro and in vivo studies unveil that these effects are mediated by modulation of the tumor microenvironment in a non-cell autonomous manner. Importantly, acinar-to-ductal metaplasia, a crucial step for PDA initiation, is also regulated by Gal1. Finally, high-throughput gene expression studies and molecular analysis aimed at identifying the underlying mechanism revealed that Gal1 promotes Hedgehog pathway both in PDA cells and stromal fibroblasts. In summary, our studies define a novel role of Gal1 in PDA tumor epithelium-stroma crosstalk and suggest this lectin as potential molecular target for therapy of neoplasms overexpressing Gal1. PMID:24812270

  7. A novel method in preparation of acellularporcine corneal stroma tissue for lamellar keratoplasty

    PubMed Central

    Shao, Yi; Tang, Jing; Zhou, Yueping; Qu, Yangluowa; He, Hui; Liu, Qiuping; Tan, Gang; Li, Wei; Liu, Zuguo

    2015-01-01

    Our objective was to develop a novel lamellar cornealbiomaterial for corneal reconstruction.Theporcine acellular corneal stroma discs (ACSDs) were prepared from de-epithelized fresh porcine corneas (DFPCs) by incubation with 100% fresh human serum and additional electrophoresis at 4°C. Such manipulation removed theanterior corneal stromal cells without residual of DNA content and α-Galantigen. Human serum decellularizing activity on porcineanterior corneal stroma cells is through apoptosis, and associated with the presence of α-Gal epitopes in anterior stroma. ACSDs displayed similar optical, biomechanical properties and ultrastructure to DFPCs, and showed good histocompatibility in rabbit corneal stromal pockets and anterior chamber. Rabbit corneallamellar keratoplasty (LKP) using ACSDs showed no rejection and high transparency of cornea at 2 months after surgery. In vivo confocal laser scanning microscopy and immunostaining analysis showed complete re-epithelization and stromal cell in growth of ACSDs without inflammatory cell infiltration, new blood vessel ingrowth and excessive wound healing. In conclusion, this novel decellularization method may be valuable for preparation of xenogenic corneal tissue for clinical application, ACSDs resulted from this method may be served as a matrix equivalent for LKP in corneal xenotransplantation. PMID:26885261

  8. Three-dimensional arrangement of elastic fibers in the human corneal stroma.

    PubMed

    Lewis, Philip N; White, Tomas L; Young, Robert D; Bell, James S; Winlove, C Peter; Meek, Keith M

    2016-05-01

    The cornea is the main refracting lens in the eye. As part of the outer tunic it has to be resilient, a property conferred by the organisation of the constituent collagen. It also has to be sufficiently elastic to regain its exact shape when deformed, in order not to distort the retinal image. The basis of this elasticity is not fully understood. The purpose of this study was to characterise in three dimensions the arrangement and distribution of elastic fibers in the human corneal stroma, using serial block face scanning electron microscopy. We have demonstrated that there exists a complex network of elastic fibers that appear to originate in the sclera or limbus. These appear as elastic sheets in the limbus and peripheral cornea immediately above the trabecular meshwork which itself appears to extend above Descemet's membrane in the peripheral stroma. From these sheets, elastic fibers extend into the cornea; moving centrally they bifurcate and trifurcate into narrower fibers and are concentrated in the posterior stroma immediately above Descemet's membrane. We contend that elastic sheets will play an important role in the biomechanical deformation and recovery of the peripheral cornea. The network may also have practical implications for understanding the structural basis behind a number of corneal surgeries.

  9. Protease-Activated Receptor-1 is Upregulated in Reactive Stroma of Primary Prostate Cancer and Bone Metastasis

    PubMed Central

    Zhang, Xiaotun; Wang, Wenbin; True, Lawrence D.; Vessella, Robert L.; Takayama, Thomas K.

    2009-01-01

    BACKGROUND Prostate cancer progression is partly facilitated by tumor-stroma interactions. We recently reported that protease-activated receptors (PAR-1 and PAR-2) are overexpressed in prostate cancer, and PAR-1 expression in peritumoral stroma is associated with biochemical recurrence. However, the nature of PAR expression in prostate tumor microenvironment is not fully understood. We therefore evaluated PAR-1 and PAR-2 expression in primary prostate cancer and bone metastasis. METHODS PAR-1 and PAR-2 expression in normal, primary prostate cancer and the corresponding bone metastatic tissues were examined by immunohistochemistry, and double-label immunohistochemistry with the use of additional markers. RESULTS PAR-1 was expressed in peritumoral stroma in the majority of primary cancer tissues (83%). Serial sections and double-label immunohistochemistry determined that these PAR-1 expressing stromal cells were predominantly myofibroblasts, the primary cell type in reactive stroma. Analysis of cancer glands revealed that PAR-1 expression was significantly increased in the reactive stroma around higher Gleason grade cancers. PAR-2 was predominantly expressed in the primary cancer cells as well as smooth muscle cells but not in reactive stroma. In bone metastasis, PAR-1 expression in cancer cells was elevated compared to the primary site from the same patient. In the bone reactive stroma, PAR-1 was present in vascular endothelial cells and fibroblasts, while both PAR-1 and PAR-2 were expressed in osteoblasts and osteoclasts. CONCLUSIONS In primary prostate cancer and bone metastasis, PAR-1 is upregulated in reactive stroma and PAR-2 is uniformly overexpressed in carcinoma cells, suggesting these receptors may play potentially different roles in prostate cancer development and metastasis. PMID:19170048

  10. Chlorophyll composition and photochemical activity of photosystems detached from chloroplast grana and stroma lamellae.

    PubMed

    Gasanov, R A; French, C S

    1973-07-01

    A stroma fraction that has photosystem 1 activity and grana lamellae fractions that have activities for both photosystems were isolated by differential centrifugation of a needle valve homogenate. Subsequent fractions, corresponding to photosystems 1 (F-1D) and 2 (F-2D) were isolated by digitonin treatment of the grana lamellae (P-10K) and compared with respect to their chlorophyll composition and electron transport activities.Fraction F-2D from grana lamellae having photosystem 2 activity is primarily active in photosystem 2 and contains only the four major forms of chlorophyll a with a predominance of chlorophyll a 677 nm. This fraction differs from the original grana membranes in the absence of the longwavelength form of chlorophyll a and in the widening of the absorption band of chlorophyll a 682 nm from 10.9 to 15.6 nm.Photosystem 1 particles from grana and stroma both have high photosystem 1 activity but differ from each other in the proportions of the four major forms of chlorophyll a. The short-wavelength forms of chlorophyll a and also chlorophyll b 650 nm in particles from grana lamellae comprise relatively more total area than these same forms in the particles from stroma. In addition, the fraction corresponding to photosystem 1 from grana lamellae is not shifted to the long-wavelength side of the main absorption maximum, as compared to the photosystem 2 particles from grana and the original grana membrane fraction; this is usually observed in fractions that have photosystem 1 activity. Furthermore, the longest wavelength form of chlorophyll a in the photosystem 1 particles from grana is at 700 nm, while in the same fraction from stroma, it is at 706 nm.The half-width of the four main forms of chlorophyll a and both forms of chlorophyll b in the photosystem 1 fraction from grana is narrower than that of the corresponding forms in the same fraction from stroma. This may indicate a different packing of pigment molecules that are aggregated on the surface

  11. The hematopoietic defect in PNH is not due to defective stroma, but is due to defective progenitor cells.

    PubMed

    Nishimura, Jun-ichi; Ware, Russell E; Burnette, Angela; Pendleton, Andrew L; Kitano, Kiyoshi; Hirota, Toshiyuki; Machii, Takashi; Kitani, Teruo; Smith, Clay A; Rosse, Wendell F

    2002-01-01

    Although paroxysmal nocturnal hemoglobinuria (PNH) is often associated with aplastic anemia (AA), the nature of the pathogenetic link between PNH and AA remains unclear. Moreover, the PIG-A mutation appears to be necessary but not sufficient for the development of PNH, suggesting other factors are involved. The ability of PNH marrow cells to form in vitro hematopoietic colonies and the ability of PNH marrow to generate stroma that could support hematopoiesis of normal or PNH marrow in cross culture were investigated. PNH marrow from both post-Ficoll and post-lineage depleted hematopoietic progenitor cells grew similarly significantly fewer colonies than normal marrow. Sorting of CD59(+) and CD59(-) CD34(+) CD38(-) cells from patients with PNH showed similarly impaired clonogenic efficiency, indicating that the hematopoietic defect in PNH does not directly relate to GPI-anchored protein expression. PNH marrow readily grew stroma similar to marrow from normal donors. Cross culture experiments revealed that PNH stroma appears to function normally in vitro; it can support growth of normal marrow cells as well as normal stroma does, but neither PNH nor normal stroma could support the growth of PNH marrow cells. The hematopoietic defect in PNH is not due to defective stroma, but is due to defective progenitor cell growth related to additional unknown factors.

  12. Assessment of oestrogen and progestin effects on epithelium and stroma from pre- and postmenopausal endometria.

    PubMed

    King, R J; Lane, G; Siddle, N; Taylor, R W; Townsend, P T; Whitehead, M I

    1981-12-01

    The efficacy of commercially available progestin preparations were investigated with a view toward determining the optimum type, dose, duration, and route of administration required to protect the endometrium. Biochemical indices of estrogen and progestin action in endometria from postmenopausal women receiving various hormone therapies were monitored. The premenopausal samples obtained during the proliferative and secretory phases of the cycle can be compared with physiologically normal activities. Estrogen effects were monitored by nuclear estradiol receptor (REN) and soluble progesterone receptor (RP) content and DNA synthesis by autoradiography after [3-H]-thymidine labelling. Progestin action was assayed by inhibition of estrogen-induced REN and DNA synthesis by induction of isocritic and estradiol dehydrogenases and by morphological criteria. Postmenopausal patients were attending the menopause clinics at King's College Hospital or the Chelsea Hospital for Women in London for symptoms associated with the climacteric. Premenopausal samples were obtained from women attending the above hospitals as well as St. Thomas Hospital in London. There are no differences in REN or estradiol receptor content (RET) between epithelium and stroma for any of the groups. Progestins, regardless of whether they are derived from exogenous (postmenopausal) or endogenous (premenopausal sources, decrease REN and RET in both fractions. Progestins also decreased DNA synthesis in both cell types and this suppression correlates with the fall in REN. The RP content of epithelium is greater than stroma, but the 2 enzymes are markedly stimulated by progestins in epithelium but not stroma. The lower RP content of the stromal fraction could be because of cellular heterogeneity, differential loss of receptor during processing, or to genuine differences between epithelium and stroma. Estrogen induced DNA synthesis is inhibited by progestins in both epithelium ans stroma but the induction of

  13. Roles of limbal microvascular net and limbal stroma in regulating maintenance of limbal epithelial stem cells.

    PubMed

    Huang, Minghai; Wang, Bowen; Wan, Pengxia; Liang, Xuanwei; Wang, Xiaoran; Liu, Ying; Zhou, Qiang; Wang, Zhichong

    2015-02-01

    Knowledge of the microenvironment (niche) of stem cells is helpful for stem-cell-based regenerative medicine. In the eye, limbal epithelial stem cells (corneal epithelial stem cells) provide the self-renewal capacity of the corneal epithelium and are essential for maintaining corneal transparency and vision. Limbal epithelial stem cell deficiency results in significant visual deterioration. Successful treatment of this type of blinding disease requires studies of the limbal epithelial stem cells and their microenvironment. We investigate the function of the limbal microvascular net and the limbal stroma in the maintenace of the limbal epithelial stem cell niche in vivo and examine the regulation of limbal epithelial stem cell survival, proliferation and differentiation in vivo. We assess the temporal and spatial changes in the expression patterns of the following markers during a six-month follow-up of various rabbit limbal autograft transplantation models: vascular endothelial cell marker CD31, corneal epithelium differentiation marker K3, limbal epithelial stem-cell-associated markers P63 and ABCG2 and proliferating cell nuclear marker Ki67. Our results suggest that limbal epithelial stem cells cannot maintain their stemness or proliferation without the support of the limbal microvascular net microenvironment. Thus, both the limbal microvascular net and the limbal stroma play important roles as components of the limbal epithelial stem cell niche maintaining limbal epithelial stem cell survival and proliferation and the avoidance of differentiation. The limbal stroma constitutes the structural basis of the limbal epithelial stem cell niche and the limbal microvascular net is a requirement for this niche. These new insights should aid the eventual construction of tissue-engineered cornea for corneal blind patients in the future.

  14. Antagonizing the Hedgehog Pathway with Vismodegib Impairs Malignant Pleural Mesothelioma Growth In Vivo by Affecting Stroma.

    PubMed

    Meerang, Mayura; Bérard, Karima; Felley-Bosco, Emanuela; Lauk, Olivia; Vrugt, Bart; Boss, Andreas; Kenkel, David; Broggini-Tenzer, Angela; Stahel, Rolf A; Arni, Stephan; Weder, Walter; Opitz, Isabelle

    2016-05-01

    An autocrine-driven upregulation of the Hedgehog (Hh) signaling pathway has been described in malignant pleural mesothelioma (MPM), in which the ligand, desert Hh (DHH), was produced from tumor cells. However, our investigation revealed that the Hh pathway is activated in both tumor and stroma of MPM tumor specimens and an orthotopic immunocompetent rat MPM model. This was demonstrated by positive immunohistochemical staining of Glioma-associated oncogene 1 (GLI1) and Patched1 (PTCH1) in both tumor and stromal fractions. DHH was predominantly expressed in the tumor fractions. To further investigate the role of the Hh pathway in MPM stroma, we antagonized Hh signaling in the rat model of MPM using a Hh antagonist, vismodegib, (100 mg/kg orally). Daily treatment with vismodegib efficiently downregulated Hh target genes Gli1, Hedgehog Interacting Protein (Hhip), and Ptch1, and caused a significant reduction of tumor volume and tumor growth delay. Immunohistochemical analyses revealed that vismodegib treatment primarily downregulated GLI1 and HHIP in the stromal compartment along with a reduced expression of previously described fibroblast Hh-responsive genes such as Fibronectin (Fn1) and Vegfa Primary cells isolated from the rat model cultured in 3% O2 continued to express Dhh but did not respond to vismodegib in vitro However, culture supernatant from these cells stimulated Gli1, Ptch1, and Fn1 expression in mouse embryonic fibroblasts, which was suppressed by vismodegib. Our study provides new evidence regarding the role of Hh signaling in MPM stroma in the maintenance of tumor growth, emphasizing Hh signaling as a treatment target for MPM. Mol Cancer Ther; 15(5); 1095-105. ©2016 AACR.

  15. Evaluation of Stroma-Free Hemoglobin Solutions as Resuscitative Fluids for the Injured Soldier

    DTIC Science & Technology

    1988-11-01

    sri -~ S. i~ -~I *1*~-. - -~ ti- H -~ S - - +1-i-i ~ .--.- -~ ~ .4 ~’ ~ - -Cl -- - :4 - I; I :4 - :4 .44- :4 I :4 . - ~f1 :4 ti- H - H ...hemoglobin solutions have FWo .𔄁~i if !t 1V& lt-j: di aised the question of non-stroma related n:z i i, L𔃼 !, A i h ,7,, ! \\,ycr 4dm’, toxicity in the...animal, wecre anesthetized andsl_ that peratia all\\ prepared as prex.iou’ dcscrillci by- 1_71(2(_bi solta iW P x th px’ I U, \\kit h the modification th

  16. Altered Proteomic Polymorphisms in the Caterpillar Body and Stroma of Natural Cordyceps sinensis during Maturation

    PubMed Central

    Wu, Zi-Mei; Gao, Ling; Yao, Yi-Sang; Tan, Ning-Zhi; Wu, Jian-Yong; Ni, Luqun; Zhu, Jia-Shi

    2014-01-01

    Objective To examine the maturational changes in proteomic polymorphisms resulting from differential expression by multiple intrinsic fungi in the caterpillar body and stroma of natural Cordyceps sinensis (Cs), an integrated micro-ecosystem. Methods The surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) biochip technique was used to profile the altered protein compositions in the caterpillar body and stroma of Cs during its maturation. The MS chromatograms were analyzed using density-weighted algorithms to examine the similarities and cluster relationships among the proteomic polymorphisms of the Cs compartments and the mycelial products Hirsutella sinensis (Hs) and Paecilomyces hepiali (Ph). Results: SELDI-TOF MS chromatograms displayed dynamic proteomic polymorphism alterations among samples from the different Cs compartments during maturation. More than 1,900 protein bands were analyzed using density-weighted ZUNIX similarity equations and clustering methods, revealing integral polymorphism similarities of 57.4% between the premature and mature stromata and 42.8% between the premature and mature caterpillar bodies. The across-compartment similarity was low, ranging from 10.0% to 18.4%. Consequently, each Cs compartment (i.e., the stroma and caterpillar body) formed a clustering clade, and the 2 clades formed a Cs cluster. The polymorphic similarities ranged from 0.51% to 1.04% between Hs and the Cs compartments and were 2.8- to 4.8-fold higher (1.92%–4.34%) between Ph and the Cs compartments. The Hs and Ph mycelial samples formed isolated clades outside of the Cs cluster. Conclusion Proteomic polymorphisms in the caterpillar body and stroma of Cs change dynamically during maturation. The proteomic polymorphisms in Hs and Ph differ from those in Cs, suggesting the presence of multiple Cs-associated fungi and multiple Ophiocordyceps sinensis genotypes with altered differential protein expression in the Cs compartments

  17. Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin.

    PubMed

    Kobayashi, Hanako; Liu, Qingdu; Binns, Thomas C; Urrutia, Andres A; Davidoff, Olena; Kapitsinou, Pinelopi P; Pfaff, Andrew S; Olauson, Hannes; Wernerson, Annika; Fogo, Agnes B; Fong, Guo-Hua; Gross, Kenneth W; Haase, Volker H

    2016-05-02

    Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2-/- renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2-/- mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation.

  18. Regulation of dendritic-cell differentiation by bone marrow stroma via different Notch ligands

    PubMed Central

    Cheng, Pingyan; Nefedova, Yulia; Corzo, Cesar A.; Gabrilovich, Dmitry I.

    2007-01-01

    Notch is a major factor mediating interaction between hematopoietic progenitor cells (HPCs) and bone marrow stroma (BMS). However its contribution to dendritic cell (DC) differentiation is controversial. We found that main Notch ligands Delta-1 and Jagged-1 had the opposite effect on DC differentiation. Delta-1 promoted generation of fully differentiated DCs, whereas Jagged-1 stimulated accumulation of DC precursors but prevented their transition to terminally differentiated DCs. BMS expressed a substantially higher level of Jagged-1 than Delta-1. Just the opposite expression pattern was observed in spleen stroma (SS). The BMS effect on DC differentiation was similar to that of Jagged-1, whereas the effect of SS was similar to the effect of Delta-1. Down-regulation of Jagged-1 in BMS substantially increased DC differentiation. Experiments in vivo with adoptive transfer of DC precursors further supported the different roles of BMS and SS in DC development. Jagged-1 and Delta-1 equally activated CBF-1/RBPJκ transcription factor, which is a major Notch target. However, they produced a different pattern of activation of Notch target gene Hes1. Overexpression of Hes1 resulted in increased DC differentiation from HPCs. Thus, this study not only revealed the different role of Notch ligands in DC differentiation but also may provide a new insight into regulation of DC differentiation by BMS. PMID:16973960

  19. FGFR4 promotes stroma-induced epithelial-to-mesenchymal transition in colorectal cancer.

    PubMed

    Liu, Rui; Li, Jingyi; Xie, Ke; Zhang, Tao; Lei, Yunlong; Chen, Yi; Zhang, Lu; Huang, Kai; Wang, Kui; Wu, Hong; Wu, Min; Nice, Edouard C; Huang, Canhua; Wei, Yuquan

    2013-10-01

    Tumor cells evolve by interacting with the local microenvironment; however, the tumor-stroma interactions that govern tumor metastasis are poorly understood. In this study, proteomic analyses reveal that coculture with tumor-associated fibroblasts (TAF) induces significant overexpression of FGFR4, but not other FGFRs, in colorectal cancer cell lines. Mechanistic study shows that FGFR4 plays crucial roles in TAF-induced epithelial-to-mesenchymal transition (EMT) in colorectal cancer cell lines. Accumulated FGFR4 in cell membrane phosphorylates β-catenin, leading to translocation of β-catenin into the nucleus. Further, TAF-derived CCL2 and its downstream transcription factor, Ets-1, are prerequisites for TAF-induced FGFR4 upregulation. Furthermore, FGFR4-associated pathways are shown to be preferentially activated in colorectal tumor samples, and direct tumor metastasis in a mouse metastasis model. Our study shows a pivotal role of FGFR4 in tumor-stroma interactions during colorectal cancer metastasis, and suggests novel therapeutic opportunities for the treatment of colorectal cancer.

  20. Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin

    PubMed Central

    Liu, Qingdu; Binns, Thomas C.; Davidoff, Olena; Kapitsinou, Pinelopi P.; Pfaff, Andrew S.; Olauson, Hannes; Fogo, Agnes B.; Fong, Guo-Hua; Gross, Kenneth W.

    2016-01-01

    Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2–/– renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2–/– mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation. PMID:27088801

  1. In vitro 3D corneal tissue model with epithelium, stroma, and innervation.

    PubMed

    Wang, Siran; Ghezzi, Chiara E; Gomes, Rachel; Pollard, Rachel E; Funderburgh, James L; Kaplan, David L

    2017-01-01

    The interactions between corneal nerve, epithelium, and stroma are essential for maintaining a healthy cornea. Thus, corneal tissue models that more fully mimic the anatomy, mechanical properties and cellular components of corneal tissue would provide useful systems to study cellular interactions, corneal diseases and provide options for improved drug screening. Here a corneal tissue model was constructed to include the stroma, epithelium, and innervation. Thin silk protein film stacks served as the scaffolding to support the corneal epithelial and stromal layers, while a surrounding silk porous sponge supported neuronal growth. The neurons innervated the stromal and epithelial layers and improved function and viability of the tissues. An air-liquid interface environment of the corneal tissue was also mimicked in vitro, resulting in a positive impact on epithelial maturity. The inclusion of three cell types in co-culture at an air-liquid interface provides an important advance for the field of in vitro corneal tissue engineering, to permit improvements in the study of innervation and corneal tissue development, corneal disease, and tissue responses to environmental factors.

  2. Microscopic analysis of structural changes in diode-laser-welded corneal stroma

    NASA Astrophysics Data System (ADS)

    Matteini, Paolo; Rossi, Francesca; Menabuoni, Luca; Pini, Roberto

    2007-02-01

    Diode laser welding of the cornea is a technique used to provide immediate sealing of corneal wounds: the cut is stained with a water solution of Indocyanine Green and is then irradiated with an 810 nm laser at low power densities (12-16 W/cm2), which induces a localized heating of the stroma in the range 55-66 °C range. In this study, we present a microscopic analysis aimed at evaluating the structural modifications induced in the stromal collagen of pig eyes during the laser welding of corneal wounds. Cornea samples obtained from twenty freshly-enucleated eyes were cut with a pre-calibrated knife and subjected to the laser welding procedure. Histological slices of the laser-welded stroma were examined by means of optical and transmission electron microscopy. These analyses indicated that bridges of lamellar structures crossed the wound edges with no presence of a coagulation effect. After laser welding, collagen fibrils appeared differently oriented among themselves in comparison with those of the control samples, but with similar mean fibril diameters. The laser-induced effect appeared to be confined to the ICG stained area of the cut walls, and no heat damage was observed at the operative power levels of laser corneal welding.

  3. Using genipin-crosslinked acellular porcine corneal stroma for cosmetic corneal lens implants.

    PubMed

    Liu, Zhao; Zhou, Qiang; Zhu, Jixiang; Xiao, Jianhui; Wan, Pengxia; Zhou, Chenjing; Huang, Zheqian; Qiang, Na; Zhang, Wei; Wu, Zheng; Quan, Daping; Wang, Zhichong

    2012-10-01

    Acellular porcine corneal stroma (APCS) has been proven to maintain the matrix microenvironment and is therefore an ideal biomaterial for the repair and reconstruction of corneal stroma. This study aims to develop a method to prepare cosmetic corneal lens implants for leukoma using genipin-crosslinked APCS (Gc-APCS). The Gc-APCS was prepared from APCS immersed in 1.0% genipin aqueous solution (pH 5.5) for 4 h at 37 °C, followed by lyophilization at -10 °C. The color of the Gc-APCS gradually deepened to dark-blue. The degree of crosslinking was 45.7 ± 4.6%, measured by the decrease of basic and hydroxy amino acids. The porous structure and ultrastructure of collagenous lamellae were maintained, and the porosity and BET SSA were 72.7 ± 4.6% and 23.01 ± 3.45 m(2)/g, respectively. The Gc-APCS rehydrated to the physiological water content within 5 min and was highly resistant to collagenase digestion. There were no significant differences in the areal modulus and curvature variation between Gc-APCS and nature porcine cornea. The dark-blue pigments were stable to pH, light and implantation in vivo. Gc-APCS extracts had no inhibitory effects on the proliferation of keratocytes. Corneal neovascularization, graft degradation and corneal rejection were not observed within 6 months.

  4. Antitumor Effects of Chimeric Receptor Engineered Human T Cells Directed to Tumor Stroma

    PubMed Central

    Kakarla, Sunitha; Chow, Kevin KH; Mata, Melinda; Shaffer, Donald R; Song, Xiao-Tong; Wu, Meng-Fen; Liu, Hao; Wang, Lisa L; Rowley, David R; Pfizenmaier, Klaus; Gottschalk, Stephen

    2013-01-01

    Cancer-associated fibroblasts (CAFs), the principle component of the tumor-associated stroma, form a highly protumorigenic and immunosuppressive microenvironment that mediates therapeutic resistance. Co-targeting CAFs in addition to cancer cells may therefore augment the antitumor response. Fibroblast activation protein-α (FAP), a type 2 dipeptidyl peptidase, is expressed on CAFs in a majority of solid tumors making it an attractive immunotherapeutic target. To target FAP-positive CAFs in the tumor-associated stroma, we genetically modified T cells to express a FAP-specific chimeric antigen receptor (CAR). The resulting FAP-specific T cells recognized and killed FAP-positive target cells as determined by proinflammatory cytokine release and target cell lysis. In an established A549 lung cancer model, adoptive transfer of FAP-specific T cells significantly reduced FAP-positive stromal cells, with a concomitant decrease in tumor growth. Combining these FAP-specific T cells with T cells that targeted the EphA2 antigen on the A549 cancer cells themselves significantly enhanced overall antitumor activity and conferred a survival advantage compared to either alone. Our study underscores the value of co-targeting both CAFs and cancer cells to increase the benefits of T-cell immunotherapy for solid tumors. PMID:23732988

  5. On Orbit Osteobiology Experiments: from "STROMA" to "MDS" -from in vitro to in vivo

    NASA Astrophysics Data System (ADS)

    Liu, Yi; Cancedda, Ranieri

    Spaceflight causes profound changes in the skeleton, in particular, in the weight-loading bones. Uncoupling of bone remodeling equilibrium between bone formation and resorption is con-sidered responsible for the microgravity-induced bone loss. These changes result in weak-ened and brittle bones prone to fracture on re-entry and in accelerated osteoporosis, making bone deterioration a major problem obstructing the prospects of long-duration manned space flight. Osteoblasts (bone forming cells) and osteocytes (bone resorption cells) are known to be mechano-sensors. Short-exposure of osteoblasts to simulated microgravity ensnarled cell adhe-sion and cytoskeleton. Also osteoblast precursors such as bone marrow stroma cells (BMSC) were shown to be sensitive to mechanical loading. We performed a series of STROMA space-flight experiments by culturing BMSC or co-culturing osteoblasts and osteoclast precursors in automated bioreactors on orbit. Genechip analysis revealed an inhibition of cell proliferation and an unexpected activation of nervous system development genes by spaceflight. To unravel effects of microgravity on genes governing bone mass, transgenic mice with a higher bone mass were flown to orbit inside the Mice Drawer System (MDS) payload. The MDS experiment was launched inside Shuttle Discovery in STS-128 on August 28 2009 at 23:58 EST, and returned to earth by Shuttle Atlantis in STS129 on November 27 2009 at 9:47 EST, marking it as the first long duration animal experiment on the International Space Station (ISS).

  6. The identification of trans-associations between prostate cancer GWAS SNPs and RNA expression differences in tumor-adjacent stroma

    PubMed Central

    Chen, Xin; McClelland, Michael; Jia, Zhenyu; Rahmatpanah, Farah B.; Sawyers, Anne; Trent, Jeffrey; Duggan, David; Mercola, Dan

    2015-01-01

    Here we tested the hypothesis that SNPs associated with prostate cancer risk, might differentially affect RNA expression in prostate cancer stroma. The most significant 35 SNP loci were selected from Genome Wide Association (GWA) studies of ~40,000 patients. We also selected 4030 transcripts previously associated with prostate cancer diagnosis and prognosis. eQTL analysis was carried out by a modified BAYES method to analyze the associations between the risk variants and expressed transcripts jointly in a single model. We observed 47 significant associations between eight risk variants and the expression patterns of 46 genes. This is the first study to identify associations between multiple SNPs and multiple in trans gene expression differences in cancer stroma. Potentially, a combination of SNPs and associated expression differences in prostate stroma may increase the power of risk assessment for individuals, and for cancer progression. PMID:25638161

  7. Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers

    PubMed Central

    Allaoui, Roni; Bergenfelz, Caroline; Mohlin, Sofie; Hagerling, Catharina; Salari, Kiarash; Werb, Zena; Anderson, Robin L.; Ethier, Stephen P.; Jirström, Karin; Påhlman, Sven; Bexell, Daniel; Tahin, Balázs; Johansson, Martin E.; Larsson, Christer; Leandersson, Karin

    2016-01-01

    Triple-negative (TN) breast cancers (ER−PR−HER2−) are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment. This results in activation of cancer-associated fibroblasts and expression of CXCL16, which we show to be a monocyte chemoattractant. We propose that this migratory feedback loop amplifies the formation of a reactive stroma, contributing to the aggressive phenotype of TN breast tumours. These insights could help select more suitable therapies targeting the stromal component of these tumours, and could aid prediction of drug resistance. PMID:27725631

  8. Whole-body magnetic resonance imaging in myxoid liposarcoma: A useful adjunct for the detection of extra-pulmonary metastatic disease.

    PubMed

    Stevenson, J D; Watson, J J; Cool, P; Cribb, G L; Jenkins, J P R; Leahy, M; Gregory, J J

    2016-04-01

    Myxoid liposarcomas (MLS) are a subgroup of soft-tissue sarcomas which have a propensity for extra-pulmonary metastases. Conventional radiological staging of soft-tissue sarcomas consists of chest radiographs (CXR) and thoracic computed tomography (CT) for possible chest metastases, supplemented by magnetic resonance imaging (MRI) for local disease. The optimal radiological modality to detect extra-pulmonary metastases for systemic staging has not been proven. We reviewed the efficacy of Whole-Body MRI (WBMRI) for this purpose. 33 WBMRI and simultaneous CT scans were performed in 28 patients suffering from MLS between 2007 and 2015. 38 metastases were identified in seven patients via WBMRI. Osseous lesions predominated (spine, pelvis, chest-wall and long bones), followed by soft-tissue and abdominal lesions. Of the 29 soft-tissue or osseous metastases that were within the field-of-view of the simultaneous CT scans, five soft-tissue and zero osseous metastases were identified using CT. Metastatic disease was detected in three patients solely using WBMRI, which directly influenced their management. WBMRI is a useful adjunct in the detection of extra-pulmonary metastatic disease, which directly alters patient management. WBMRI has demonstrated an ability to identify more sites of metastatic disease compared to CT. WBMRI should be used in two situations. Firstly, at diagnosis where ablative treatment will be required e.g. amputation, when the diagnosis of occult metastasis would change treatment planning. Secondly, at diagnosis of relapse to confirm if it is a solitary site of relapse prior to consideration of metastectomy.

  9. Systems Analysis of a Mouse Xenograft Model Reveals Annexin A1 as a Regulator of Gene Expression in Tumor Stroma

    PubMed Central

    Yi, Ming

    2012-01-01

    Annexin A1 is a multi functional molecule which is involved in inflammation, innate and adaptive immune systems, tumor progression and metastasis. We have previously showed the impaired tumor growth, metastasis, angiogenesis and wound healing in annexin A1 knockout mice. While tumor is a piece of heterogeneous mass including not only malignant tumor cells but also the stroma, the importance of the tumor stroma for tumor progression and metastasis is becoming increasingly clear. The tumor stroma is comprised by various components including extracellular matrix and non-malignant cells in the tumor, such as endothelial cells, fibroblasts, immune cells, inflammatory cells. Based on our previous finding of pro-angiogenic functions for annexin A1 in vascular endothelial cell sprouting, wound healing, tumor growth and metastasis, and the previously known properties for annexin A1 in immune cells and inflammation, this study hypothesized that annexin A1 is a key functional player in tumor development, linking the various components in tumor stroma by its actions in endothelial cells and immune cells. Using systems analysis programs commercially available, this paper further compared the gene expression between tumors from annexin A1 wild type mice and annexin A1 knockout mice and found a list of genes that significantly changed in the tumor stroma that lacked annexin A1. This revealed annexin A1 to be an effective regulator in tumor stroma and suggested a mechanism that annexin A1 affects tumor development and metastasis through interaction with the various components in the microenvironment surrounding the tumor cells. PMID:23077482

  10. Fibromyxoma of the axis.

    PubMed

    Mavrogenis, Andreas F; Casadei, Roberto; Gambarotti, Marco; Ruggieri, Pietro

    2012-07-01

    Fibromyxoma of bone is a rare benign tumor of fibrous tissue origin. The typical location is the jaws. Sporadic extragnathic cases have been reported, but fibromyxoma of the spine has not been reported. The histological appearance of fibromyxoma is benign and includes abundant extracellular fibrous and myxoid stroma with varying amounts of calcification and ossification. Myxoid changes are usually extensive. Extragnathic fibromyxoma of bone should be distinguished from benign cartilage-forming bone tumors, such as chondromyxoid and myxoid chondrosarcoma and myxoma of bone. It has also been suggested that fibromyxoma is a variant of myxoid fibrous dysplasia, whereas other authors reported extragnathic fibromyxoma resulting from myxoid degeneration of bone tumors, such as chondrosarcoma or fibrosarcoma. The overtreatment of patients with fibromyxoma of bone due to an aggressive imaging appearance should be avoided; the prognosis is excellent compared with the jaw variant and depends on the location and extent of the tumor. This article describes a case of a 21-year-old woman with fibromyxoma of bone originating from the spinous process of the axis. Clinical examination showed a tender mass in the midline of the posterior aspect the neck and slight limitation of neck range of motion; neurologic examination was normal. Diagnosis was obtained with a preoperative biopsy. Marginal excision of the lesion with posterior laminectomy of the axis was performed. The facets were preserved, and no fusion was performed. At last follow-up 2 years after diagnosis and treatment, the patient was asymptomatic with no evidence of local recurrence.

  11. Abundances in Przybylski's star

    NASA Astrophysics Data System (ADS)

    Cowley, C. R.; Ryabchikova, T.; Kupka, F.; Bord, D. J.; Mathys, G.; Bidelman, W. P.

    2000-09-01

    We have derived abundances for 54 elements in the extreme roAp star HD101065. ESO spectra with a resolution of about 80000, and S/N of 200 or more were employed. The adopted model has Teff=6600K, and log(g)=4.2. Because of the increased line opacity and consequent low gas pressure, convection plays no significant role in the temperature structure. Lighter elemental abundances through the iron group scatter about standard abundance distribution (SAD) (solar) values. Iron and nickel are about one order of magnitude deficient while cobalt is enhanced by 1.5dex. Heavier elements, including the lanthanides, generally follow the solar pattern but enhanced by 3 to 4dex. Odd-Z elements are generally less abundant than their even-Z neighbours. With a few exceptions (e.g. Yb), the abundance pattern among the heavy elements is remarkably coherent, and resembles a displaced solar distribution.

  12. Preparation of High-Density Fibrillar Collagen Matrices that Mimic Desmoplastic Tumor Stroma

    PubMed Central

    Artym, Vira V.

    2016-01-01

    The stroma of invasive tumors becomes enriched in dense fibrillar collagen as a result of the desmoplastic reaction. This desmoplastic collagen exerts profound effects on tumor and normal cells. In view of these findings, it is important to develop novel in vitro cell systems that mimic this desmoplastic extracellular matrix in order to permit cell studies under in vivo-like conditions. This Unit provides a protocol and troubleshooting guide for the preparation of high density fibrillar collagen (HDFC) matrices that closely model the desmoplastic collagenous matrix of malignant tumors. It then describes the use of this HDFC matrix for in vitro cell studies of invadopodia formation and function in extracellular matrix invasion. In addition, this Unit also provides a detailed protocol for immuno-labeling of invadopodial proteins and detection of HDFC matrix degradation associated with invadopodia to permit invadopodia visualization using fluorescence microscopy. PMID:26930554

  13. [The radioprotective effect of hypoxia on clonogenic cells of rat bone marrow stroma (KOE-F)].

    PubMed

    Konopliannikov, A G; Waĭnson, A A; Kolesnikova, A I; Zaĭtsev, A V; Kal'sina, S Sh; Lepekhina, L A

    1992-01-01

    A comparative study was made on the survival rate of cell-precursors of haemopoietic stroma, that form, in a rat bone marrow culture, colonies (clones) of fibroblasts (CFU-F) after gamma-irradiation of animals in the air or in a gas hypoxic mixture, containing 8% of O2 (GHM-8). Irradiation in GHM-8 was shown to increase the survival rate of CFU-F by 1.7 times (as compared to exposure in the air) as estimated by the total number of colonies that are formed in a culture; the radioprotective effect of GHM-8 was more pronounced for CFU-F which form dense colonies: DMF for dense and loose clones was 2.4 and 1.6 respectively.

  14. Squamous cell carcinoma with sarcomatous stroma in the nasal cavity of a dog.

    PubMed

    Bosward, K L; Kessell, A E; Lucy, R J

    2004-09-01

    This is a report of an unusual squamous cell carcinoma in the nasal cavity of a dog. A 13-year-old Golden Retriever was presented with a unilateral nasal and ocular discharge. Although a nasal tumour was suspected, initial diagnostic investigations were unrewarding, and, with worsening clinical signs, the dog was euthanatized. Necropsy examination confirmed the presence of a nasal tumour that was composed histologically of both a well-differentiated squamous cell carcinoma component blending with a predominant spindle cell component. Immunohistochemical staining with anti-human keratin/cytokeratin (AE1/AE3, CAM 5.2 and broad spectrum cytokeratin), Vimentin, Desmin, smooth muscle actin and S-100 protein supported a diagnosis of a squamous cell carcinoma with (pseudo) sarcomatous stroma.

  15. Sclerotic fibroma (storiform collagenoma)-like stroma in a fibroadenoma of axillary accessory breast tissue.

    PubMed

    Val-Bernal, José Fernando; González-Vela, María Carmen; De Grado, Mauricio; Garijo, María Francisca

    2012-08-01

    Accessory breast tissue is a subcutaneous remnant persisting after normal embryological development of the breast. It occurs most frequently in the axilla. Fibroadenomas in axillary breast tissue are rare. We report the case of a 29-year-old female patient who presented a fibroadenoma arising in the accessory breast tissue of the right axillary fossa. The neoplasm showed foci of sclerotic fibroma-like stroma. The patient had no signs of Cowden's syndrome. To the best of our knowledge, a lesion of this kind has not been previously reported. This stromal change suggests an uncommon involutional phase of the fibroadenoma with production of sclerotic and hypocellular collagen. The lesion should be differentiated from extraneural perineuroma, from the changes in fibroadenomas in Cowden's syndrome, from sclerosing lobular hyperplasia (fibroadenomatoid mastopathy) and from pseudoangiomatous stromal hyperplasia.

  16. Antigen archiving by lymph node stroma: a novel function for the lymphatic endothelium

    PubMed Central

    Kedl, Ross M.; Tamburini, Beth A.

    2015-01-01

    Secondary lymphoid stroma performs far more functions than simple structural support for lymphoid tissues, providing a host of soluble and membrane-bound cues to trafficking leukocytes during inflammation and homeostasis. More recently it has become clear that stromal cells can manipulate T cell responses, either through direct antigen-mediated stimulation of T cells or more indirectly through the retention and management of antigen after viral infection or vaccination. In light of recent data, this review provides an overview of stromal cell subsets and functions during the progression of an adaptive immune response with particular emphasis on antigen capture and retention by follicular dendritic cells (FDC) as well as the recently described “antigen archiving” function of lymphatic endothelial cells (LEC). Given its impact on the maintenance of protective immune memory, we conclude by discussing the most pressing questions pertaining to LEC antigen capture, archiving and exchange with hematopoetically derived antigen-presenting cells. PMID:26278423

  17. Multifocal epithelial tumors and field cancerization: stroma as a primary determinant

    PubMed Central

    Dotto, G. Paolo

    2014-01-01

    It is increasingly evident that cancer results from altered organ homeostasis rather than from deregulated control of single cells or groups of cells. This applies especially to epithelial cancer, the most common form of human solid tumors and a major cause of cancer lethality. In the vast majority of cases, in situ epithelial cancer lesions do not progress into malignancy, even if they harbor many of the genetic changes found in invasive and metastatic tumors. While changes in tumor stroma are frequently viewed as secondary to changes in the epithelium, recent evidence indicates that they can play a primary role in both cancer progression and initiation. These processes may explain the phenomenon of field cancerization, i.e., the occurrence of multifocal and recurrent epithelial tumors that are preceded by and associated with widespread changes of surrounding tissue or organ “fields.” PMID:24691479

  18. Immunosuppressive therapy in bone marrow aplasia: the stroma functions normally to support hematopoiesis.

    PubMed

    Novitzky, N; Jacobs, P

    1995-12-01

    In aplastic anemia (AA) patients responsive to antilymphocyte globulin (ALG) therapy, abnormalities in both stroma and progenitor cell (PC) pool have been described. The relevance of each pathophysiologic defect was characterized in 16 individuals, and data were compared to results from seven normal volunteers. Bone marrow mononuclear cells were split into two fractions. Stromal layers (SL) were prepared from the first, and a CD34+ enriched population was obtained by immunomagnetic selection from the second. In cross-culture experiments, 1 x 10(4) of the latter from patients or controls were seeded on preformed SL, and adhesive PC were scored for the formation of blast colonies (CFU-Bl) on day 5 of culture. Nonadherent progenitors were recovered and quantitated in a standard clonogenic assay (CFU-GM). There were significantly fewer CD34+ cells in the AA group (median 0.65%, SD 0.39%, vs. 1.62%, SD 1.4%; p = 0.002). No morphological or cytologic differences between normal and aplastic SL were detected. Both equally supported the growth of CFU-Bl from normal progenitors (mean 117, SD 20.4, and 103.1, SD 30.4), while this value was reduced for the aplastic PC (mean 41.06, SD 42.9; p = 0.0002, exact two-tailed test). Similarly, the AA nonadherent PC had a decreased CFU-GM growth (mean 142.6, SD 104.8, vs. mean 361.7; SD 91.3), with a lower total clonogenic output (p = 0.0009). We conclude that aplastic stroma appropriately supports the growth of normal progenitors, whereas the depressed clonogenicity of the corresponsing population derived from AA is unrelated to their attachment to SL but intrinsic to the CD34+ cells, whether adherent or not.

  19. Characterization of cooperative bicarbonate uptake into chloroplast stroma in the green alga Chlamydomonas reinhardtii

    PubMed Central

    Yamano, Takashi; Sato, Emi; Iguchi, Hiro; Fukuda, Yuri; Fukuzawa, Hideya

    2015-01-01

    The supply of inorganic carbon (Ci; CO2 and HCO3–) is an environmental rate-limiting factor in aquatic photosynthetic organisms. To overcome the difficulty in acquiring Ci in limiting-CO2 conditions, an active Ci uptake system called the CO2-concentrating mechanism (CCM) is induced to increase CO2 concentrations in the chloroplast stroma. An ATP-binding cassette transporter, HLA3, and a formate/nitrite transporter homolog, LCIA, are reported to be associated with HCO3– uptake [Wang and Spalding (2014) Plant Physiol 166(4):2040–2050]. However, direct evidence of the route of HCO3– uptake from the outside of cells to the chloroplast stroma remains elusive owing to a lack of information on HLA3 localization and comparative analyses of the contribution of HLA3 and LCIA to the CCM. In this study, we revealed that HLA3 and LCIA are localized to the plasma membrane and chloroplast envelope, respectively. Insertion mutants of HLA3 and/or LCIA showed decreased Ci affinities/accumulation, especially in alkaline conditions where HCO3– is the predominant form of Ci. HLA3 and LCIA formed protein complexes independently, and the absence of LCIA decreased HLA3 mRNA accumulation, suggesting the presence of unidentified retrograde signals from the chloroplast to the nucleus to maintain HLA3 mRNA expression. Furthermore, although single overexpression of HLA3 or LCIA in high CO2 conditions did not affect Ci affinity, simultaneous overexpression of HLA3 with LCIA significantly increased Ci affinity/accumulation. These results highlight the HLA3/LCIA-driven cooperative uptake of HCO3– and a key role of LCIA in the maintenance of HLA3 stability as well as Ci affinity/accumulation in the CCM. PMID:26015566

  20. Tumor stroma with senescence-associated secretory phenotype in steatohepatitic hepatocellular carcinoma

    PubMed Central

    Lee, Jee San; Yoo, Jeong Eun; Kim, Haeryoung; Rhee, Hyungjin; Koh, Myoung Ju; Nahm, Ji Hae; Choi, Jin Sub; Lee, Kee-Ho; Park, Young Nyun

    2017-01-01

    Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC), a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SH-HCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP) were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs). The expression of α-smooth muscle actin (α-SMA), p21Waf1/Cif1, γ-H2AX, and IL-6 was investigated by immunohistochemistry or immunofluorescence. SH-HCCs were associated with older age, higher body mass index, and a higher incidence of metabolic syndrome, compared to C-HCC (P <0.05, all). The numbers of α-SMA-positive cancer-associated fibroblasts (CAFs) (P = 0.049) and α-SMA-positive CAFs co-expressing p21Waf1/Cif1 (P = 0.038), γ-H2AX (P = 0.065), and IL-6 (P = 0.048) were greater for SH-HCCs than C-HCCs. Additionally, non-tumoral liver from SH-HCCs showed a higher incidence of non-alcoholic fatty liver disease and a higher number of α-SMA-positive stellate cells expressing γ-H2AX and p21Waf1/Cif1 than that from C-HCCs (P <0.05, all). In conclusion, SH-HCCs are considered to occur more frequently in metabolic syndrome patients. Therein, senescent and damaged CAFs, as well as non-tumoral stellate cells, expressing SASP including IL-6 may contribute to the development of SH-HCC. PMID:28273155

  1. Simple test to confirm cleavage with air between Descemet's membrane and stroma during big-bubble deep anterior lamellar keratoplasty.

    PubMed

    Fontana, Luigi; Parente, Gabriella; Tassinari, Giorgio

    2007-04-01

    We describe a simple test to confirm big-bubble formation in deep anterior lamellar keratoplasty by observing the position and movements of small air bubbles injected into the anterior chamber through a limbal paracentesis. The test also allows evaluation of the extension of Descemet's membrane cleavage from the posterior stroma relative to the margins of the corneal trephination.

  2. Bidirectional Signaling of Mammary Epithelium and Stroma: Implications for Breast Cancer—Preventive Actions of Dietary Factors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mammary gland is composed of two major cellular compartments: a highly dynamic epithelium that undergoes cycles of proliferation, differentiation, and apoptosis in response to local and endocrine signals and the underlying stroma comprised of fibroblasts, endothelial cells, and adipocytes that c...

  3. Characterization of reactive stroma in prostate cancer: involvement of growth factors, metalloproteinase matrix, sexual hormones receptors and prostatic stem cells

    PubMed Central

    da Silva, Maurício Moreira; Matheus, Wagner Eduardo; Garcia, Patrick Vianna; Stopiglia, Rafael Mamprim; Billis, Athanase; Ferreira, Ubirajara; Fávaro, Wagner José

    2015-01-01

    ABSTRACT Introduction and Objectives: Reactive Stroma (RStr) is observed in many human cancers and is related to carcinogenesis. The objectives of the present study were to stablish a relationship of the RStr microenvironment with prostate cancer (Pca) through a morphological and molecular characterization, and to identify a possible relationship between RStr with worse prognosis factors and occurrence of malignant prostatic stem cells. Materials and Methods: Forty prostatic samples were selected from men with Pca diagnosis submitted to radical prostatectomy; they were divided in two groups: Group-1 (n=20): samples without reactive stroma; Group-2 (n=20): samples of PCa with intense stroma reaction. Prostatic samples were evaluated for RStr intensity by Masson Trichromic stain and posteriorly submitted to histopathological and immunohistochemistry analysis for antigens: α-actin, vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA, AR, Erα and ERβ. Results: Reactive stroma with intense desmoplastic reactivity was significantly more frequent in intermediate (Gleason 7, 3+4) and high grade tumors (Gleason 7, 4+3). The group with intense stromal reactivity showed significant higher levels of Vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA and ERα. Conclusions: It can be concluded that RStr may be a predictive marker of Pca progression, since it was associated with increase of growth factors, imbalance of androgen and estrogen receptors and presence of malign prostatic stem cells. PMID:26689510

  4. A new species of Trichoderma hypoxylon harbours abundant secondary metabolites

    PubMed Central

    Sun, Jingzu; Pei, Yunfei; Li, Erwei; Li, Wei; Hyde, Kevin D.; Yin, Wen-Bing; Liu, Xingzhong

    2016-01-01

    Some species of Trichoderma are fungicolous on fungi and have been extensively studied and commercialized as biocontrol agents. Multigene analyses coupled with morphology, resulted in the discovery of T. hypoxylon sp. nov., which was isolated from surface of the stroma of Hypoxylon anthochroum. The new taxon produces Trichoderma- to Verticillium-like conidiophores and hyaline conidia. Phylogenetic analyses based on combined ITS, TEF1-α and RPB2 sequence data indicated that T. hypoxylon is a well-distinguished species with strong bootstrap support in the polysporum group. Chemical assessment of this species reveals a richness of secondary metabolites with trichothecenes and epipolythiodiketopiperazines as the major compounds. The fungicolous life style of T. hypoxylon and the production of abundant metabolites are indicative of the important ecological roles of this species in nature. PMID:27869187

  5. Mechanoregulatory tumor-stroma crosstalk in pancreatic cancer: Measurements of the effects of extracellular matrix mechanics on tumor growth behavior, and vice-versa, to inform therapeutics

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan; Jones, Dustin; El-Hamidi, Hamid; Cramer, Gwendolyn; Hanna, William; Caide, Andrew; Jafari, Seyedehrojin

    The rheological properties of the extracellular matrix (ECM) have been shown to play key roles in regulating tumor growth behavior through mechanotranduction pathways. The role of the mechanical microenvironment may be particularly important tumors of the pancreas, noted for an abundance of rigid fibrotic stroma, implicated in therapeutic resistance. At the same time, cancer cells and their stromal partners (e.g. tumor associated fibroblasts) continually alter the mechanical microenvironment in response to extracellular physical and biochemical cues as part of a two-way mechanoregulatory dialog. Here, we describe experimental studies using 3D pancreatic cell cultures with customized mechanical properties, combined with optical microrheology to provide insight into tumor-driven matrix remodeling. Quantitative microscopy provides measurements of phenotypic changes accompanying systematic variation of ECM composition in collagen and laminin-rich basement membrane admixtures, while analysis of the trajectories of passive tracer particles embedded in ECM report dynamic changes in heterogeneity, microstructure and local shear modulus accompanying both ECM stiffening (fibrosis) processes, and ECM degradation near invading cells. We gratefully acknowledge funding from the National Cancer Institute, R00CA155045 (PI: Celli).

  6. OXYGEN ABUNDANCES IN CEPHEIDS

    SciTech Connect

    Luck, R. E.; Andrievsky, S. M.; Korotin, S. N.; Kovtyukh, V. V. E-mail: serkor@skyline.od.ua E-mail: scan@deneb1.odessa.ua

    2013-07-01

    Oxygen abundances in later-type stars, and intermediate-mass stars in particular, are usually determined from the [O I] line at 630.0 nm, and to a lesser extent, from the O I triplet at 615.7 nm. The near-IR triplets at 777.4 nm and 844.6 nm are strong in these stars and generally do not suffer from severe blending with other species. However, these latter two triplets suffer from strong non-local thermodynamic equilibrium (NLTE) effects and thus see limited use in abundance analyses. In this paper, we derive oxygen abundances in a large sample of Cepheids using the near-IR triplets from an NLTE analysis, and compare those abundances to values derived from a local thermodynamic equilibrium (LTE) analysis of the [O I] 630.0 nm line and the O I 615.7 nm triplet as well as LTE abundances for the 777.4 nm triplet. All of these lines suffer from line strength problems making them sensitive to either measurement complications (weak lines) or to line saturation difficulties (strong lines). Upon this realization, the LTE results for the [O I] lines and the O I 615.7 nm triplet are in adequate agreement with the abundance from the NLTE analysis of the near-IR triplets.

  7. The autophagic tumor stroma model of cancer or "battery-operated tumor growth": A simple solution to the autophagy paradox.

    PubMed

    Martinez-Outschoorn, Ubaldo E; Whitaker-Menezes, Diana; Pavlides, Stephanos; Chiavarina, Barbara; Bonuccelli, Gloria; Casey, Trimmer; Tsirigos, Aristotelis; Migneco, Gemma; Witkiewicz, Agnieszka; Balliet, Renee; Mercier, Isabelle; Wang, Chengwang; Flomenberg, Neal; Howell, Anthony; Lin, Zhao; Caro, Jaime; Pestell, Richard G; Sotgia, Federica; Lisanti, Michael P

    2010-11-01

    The role of autophagy in tumorigenesis is controversial. Both autophagy inhibitors (chloroquine) and autophagy promoters (rapamycin) block tumorigenesis by unknown mechanism(s). This is called the "Autophagy Paradox". We have recently reported a simple solution to this paradox. We demonstrated that epithelial cancer cells use oxidative stress to induce autophagy in the tumor microenvironment. As a consequence, the autophagic tumor stroma generates recycled nutrients that can then be used as chemical building blocks by anabolic epithelial cancer cells. This model results in a net energy transfer from the tumor stroma to epithelial cancer cells (an energy imbalance), thereby promoting tumor growth. This net energy transfer is both unilateral and vectorial, from the tumor stroma to the epithelial cancer cells, representing a true host-parasite relationship. We have termed this new paradigm "The Autophagic Tumor Stroma Model of Cancer Cell Metabolism" or "Battery-Operated Tumor Growth". In this sense, autophagy in the tumor stroma serves as a "battery" to fuel tumor growth, progression and metastasis, independently of angiogenesis. Using this model, the systemic induction of autophagy will prevent epithelial cancer cells from using recycled nutrients, while the systemic inhibiton of autophagy will prevent stromal cells from producing recycled nutrients-both effectively "starving" cancer cells. We discuss the idea that tumor cells could become resistant to the systemic induction of autophagy, by the upregulation of natural endogenous autophagy inhibitors in cancer cells. Alternatively, tumor cells could also become resistant to the systemic induction of autophagy, by the genetic silencing/deletion of pro-autophagic molecules, such as Beclin1. If autophagy resistance develops in cancer cells, then the systemic inhibition of autophagy would provide a therapeutic solution to this type of drug resistance, as it would still target autophagy in the tumor stroma. As such, an

  8. SU-E-J-248: Contributions of Tumor and Stroma Phenotyping in Computer-Aided Diagnosis

    SciTech Connect

    Li, H; Lan, L; Sennett, C; Giger, M

    2015-06-15

    Purpose: To gain insight into the role of parenchyma stroma in the characterization of breast tumors by incorporating computerized mammographic parenchyma assessment into breast CADx in the task of distinguishing between malignant and benign lesions. Methods: This study was performed on 182 biopsy-proven breast mass lesions, including 76 benign and 106 malignant lesions. For each full-field digital mammogram (FFDM) case, our quantitative imaging analysis was performed on both the tumor and a region-of-interest (ROI) from the normal contralateral breast. The lesion characterization includes automatic lesion segmentation and feature extraction. Radiographic texture analysis (RTA) was applied on the normal ROIs to assess the mammographic parenchymal patterns of these contralateral normal breasts. Classification performance of both individual computer extracted features and the output from a Bayesian artificial neural network (BANN) were evaluated with a leave-one-lesion-out method using receiver operating characteristic (ROC) analysis with area under the curve (AUC) as the figure of merit. Results: Lesion characterization included computer-extracted phenotypes of spiculation, size, shape, and margin. For parenchymal pattern characterization, five texture features were selected, including power law beta, contrast, and edge gradient. Merging of these computer-selected features using BANN classifiers yielded AUC values of 0.79 (SE=0.03) and 0.67 (SE=0.04) in the task of distinguishing between malignant and benign lesions using only tumor phenotypes and texture features from the contralateral breasts, respectively. Incorporation of tumor phenotypes with parenchyma texture features into the BANN yielded improved classification performance with an AUC value of 0.83 (SE=0.03) in the task of differentiating malignant from benign lesions. Conclusion: Combining computerized tumor and parenchyma phenotyping was found to significantly improve breast cancer diagnostic accuracy

  9. Fabrication and characterization of biodegradable polymeric films as a corneal stroma substitute

    PubMed Central

    Salehi, Sahar; Fathi, Mohammadhossein; Javanmard, Shaghayegh Haghjooy; Barneh, Farnaz; Moshayedi, Mona

    2015-01-01

    Background: Biodegradable elastomeric materials such as poly glycerol sebacate (PGS) have gained much current attention in the field of soft tissue engineering. The present study reports the synthesis of PGS with molar ratios of 1:1, 2:3, and 3:2 of glycerol and sebacic acid via polycondensation reaction and tests the effect of PGS on human corneal epithelial (HCE) cells viability in vitro. Materials and Methods: PGS films were prepared by the casting method. We tried to fabricate PGS with different compositions and various properties as being a viable alternative to the corneal stroma in cornea tissue engineering. The chemical properties of the prepared polymer were investigated by means of attenuated total reflectance – Fourier transform infrared spectroscopy (ATR-FTIR) analysis and the in vitro cytotoxicity was investigated by the Alamarblue method. Results: The functional groups observed in the PGS FTIR spectrums of PGS with various molar ratios were the same. However, the main difference was the time of completing the cross-linking reaction. The PGS prepared by 2:3 ratio as a molar ratio had the fastest and the 3:2 ratio had the lowest cross-linking rate because of the higher amount of sebacic acid. Results of the Alamarblue cytotoxicity test assay showed no deleterious effect on HCE cell viability and proliferation. Conclusions: PGS is a potentially good candidate material for corneal tissue engineering because of its lack of in vitro HCE cell toxicity. PMID:25625115

  10. Pulsed cavity ringdown spectroscopy of thin films and ultrafast thermalization in corneal stroma

    NASA Astrophysics Data System (ADS)

    Marcus, George Alexander

    2005-07-01

    The mid-IR spectral region is of great spectroscopic interest as it corresponds to the energy scales associated with vibrational absorption resonances in molecules. Using the ultrafast mid-IR laser sources at the Stanford Picosecond Free Electron Laser Center, we have pursued two distinct research projects. In one project, we have extended the techniques of cavity ringdown spectroscopy (CRDS), an ultrasensitive linear absorption spectroscopy technique, to the study of condensed matter systems, in the form of thin films. We have compared two different approaches to thin-film CRDS: normal incidence coupled-cavity CRDS and Brewster's angle CRDS. Additionally, we demonstrated the viability of thin film CRDS as a calibrated ultrasensitve absorption measurement technique. In order to overcome the absorption sensitivity limitations imposed by poor optical throughput in CRDS, we have developed and demonstrated two throughput enhancement techniques, cavity-enhancement and pulse-stacking. In the second project, we have developed a two-color mid-IR pump mid-IR probe technique for studying ultrafast temperature changes in the components of biological tissue. We have made measurements that establish the use of transient absorption as an ultrafast thermometer in both water and protein. We have used this method to measure the thermalization between the constituents of corneal stroma in order to examine the assumptions underlying the differential heating model of pulsed mid-IR ablation of soft tissue.

  11. Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma

    PubMed Central

    Hua, Yuanyuan; Choi, Pui-Wah; Trachtenberg, Alexander J.; Ng, Allen C.; Kuo, Winston P.; Ng, Shu-Kay; Dinulescu, Daniela M.; Matzuk, Martin M.; Berkowitz, Ross S.; Ng, Shu-Wing

    2016-01-01

    Epithelial ovarian carcinoma accounts for 90% of all ovarian cancer and is the most deadly gynecologic malignancy. Recent studies have suggested that fallopian tube fimbriae can be the origin of cells for high-grade serous subtype of epithelial ovarian carcinoma (HGSOC). A mouse HGSOC model with conditional Dicer-Pten double knockout (Dicer-Pten DKO) developed primary tumors, intriguingly, from the fallopian tube stroma. We examined the growth and epithelial phenotypes of the Dicer-Pten DKO mouse tumor cells contributable by each gene knockout. Unlike human ovarian epithelial cancer cells that expressed full-length E-cadherin, the Dicer-Pten DKO stromal tumor cells expressed cleaved E-cadherin fragments and metalloproteinase 2, a mixture of epithelial and mesenchymal markers. Although the Dicer-Pten DKO tumor cells lost the expression of mature microRNAs as expected, they showed high levels of tRNA fragment expression and enhanced AKT activation due to the loss of PTEN function. Introduction of a Dicer1-expressing construct into the DKO mouse tumor cells significantly reduced DNA synthesis and the cell growth rate, with concurrent diminished adhesion and ZO1 epithelial staining. Hence, it is likely that the loss of Dicer promoted mesenchymal-epithelial transition in fallopian tube stromal cells, and in conjunction with Pten loss, further promoted cell proliferation and epithelial-like tumorigenesis. PMID:27602775

  12. Irreversible optical clearing of rabbit dermis for autogenic corneal stroma transplantation.

    PubMed

    Tanaka, Yuji; Shi, Dong; Kubota, Akira; Takano, Yoshimasa; Fuse, Nobuo; Yamato, Masayuki; Okano, Teruo; Nishida, Kohji

    2011-10-01

    Tissue engineering and transplantation of autogenic grafts have been widely investigated for solving problems on current allograft treatments (i.g., donor shortage and rejection). However, it is difficult to obtain an autogenic corneal stromal replacement that is composed of transparent, tough, and thick collagen constructs by current cell culture-based tissue engineering. Aim of this study is to develop transparent dermis for an autogenic corneal stroma transplantation. This study examined dehydration at 4-8°C and carbodiimide cross-linking on cloudy rabbit dermis (approx. 1.8%-3.8% light transmittance at 550 nm) for dermis optical clearing. Transparency of dehydrated rabbit dermis was founded to be approx. 37.9%-41.4% at 550 nm. Additional cross-linking treatment on dehydrated dermis prevented from swelling and clouding in saline, and improved its transparency to be 56.9% at 550 nm. Rabbit corneal epithelium was found to regenerate on optically cleared dermis in vitro. Furthermore, no abnormal biological response (i.e., inflammation, vascularization, and the barrier defect of epithelia) or no optical functional change on optically cleared dermis was observed during its 4-week autogenic transplantation into rabbit corneal stromal pocket.

  13. Hyaluronan in Peritumoral Stroma and Malignant Cells Associates with Breast Cancer Spreading and Predicts Survival

    PubMed Central

    Auvinen, Päivi; Tammi, Raija; Parkkinen, Jyrki; Tammi, Markku; Ågren, Ulla; Johansson, Risto; Hirvikoski, Pasi; Eskelinen, Matti; Kosma, Veli-Matti

    2000-01-01

    Hyaluronan (HA) is an extracellular matrix polysaccharide that promotes cell migration through its cell surface receptors and by effecting changes in the physical environment. HA expression is frequently increased in malignant tumors, whereas its association with the invasive potential and patient outcome in breast cancer has not been reported. The localization and signal intensity of HA was analyzed in 143 paraffin-embedded tumor samples of human breast carcinoma using a biotinylated HA-specific probe. In the immediate peritumoral stroma, HA signal was moderately or strongly increased in 39% and 56% of the cases, respectively. Normal ductal epithelium showed no HA, whereas in 57% of the tumors at least some of the carcinoma cells were HA positive. The intensity of the stromal HA signal and the presence of cell-associated HA were both significantly related to poor differentiation of the tumors, axillary lymph node positivity, and short overall survival of the patients. In Cox’s multivariate analysis, both the intensity of stromal HA signal alone and that combined with the HA positivity in tumor cells were independent prognostic factors for overall survival. These results suggest that HA is directly involved in the spreading of breast cancer and may offer a potential target for new therapies. PMID:10666382

  14. Radiation-enhanced therapeutic targeting of galectin-1 enriched malignant stroma in triple negative breast cancer

    PubMed Central

    Upreti, Meenakshi; Jyoti, Amar; Johnson, Sara E.; Swindell, Elden P.; Napier, Dana; Sethi, Pallavi; Chan, Ryan; Feddock, Jonathan M.; Weiss, Heidi L.; O'Halloran, Thomas V.; Mark Evers, B.

    2016-01-01

    Currently there are no FDA approved targeted therapies for Triple Negative Breast Cancer (TNBC). Ongoing clinical trials for TNBC have focused primarily on targeting the epithelial cancer cells. However, targeted delivery of cytotoxic payloads to the non-transformed tumor associated-endothelium can prove to be an alternate approach that is currently unexplored. The present study is supported by recent findings on elevated expression of stromal galectin-1 in clinical samples of TNBC and our ongoing findings on stromal targeting of radiation induced galectin-1 by the anginex-conjugated arsenic-cisplatin loaded liposomes using a novel murine tumor model. We demonstrate inhibition of tumor growth and metastasis in response to the multimodal nanotherapeutic strategy using a TNBC model with orthotopic tumors originating from 3D tumor tissue analogs (TTA) comprised of tumor cells, endothelial cells and fibroblasts. The ‘rigorous’ combined treatment regimen of radiation and targeted liposomes is also shown to be well tolerated. More importantly, the results presented provide a means to exploit clinically relevant radiation dose for concurrent receptor mediated enhanced delivery of chemotherapy while limiting overall toxicity. The proposed study is significant as it falls in line with developing combinatorial therapeutic approaches for stroma-directed tumor targeting using tumor models that have an appropriate representation of the TNBC microenvironment. PMID:27223428

  15. Amount of stroma is associated with mammographic density and stromal expression of oestrogen receptor in normal breast tissues.

    PubMed

    Gabrielson, Marike; Chiesa, Flaminia; Paulsson, Janna; Strell, Carina; Behmer, Catharina; Rönnow, Katarina; Czene, Kamila; Östman, Arne; Hall, Per

    2016-07-01

    Following female sex and age, mammographic density is considered one of the strongest risk factors for breast cancer. Despite the association between mammographic density and breast cancer risk, little is known about the underlying histology and biological basis of breast density. To better understand the mechanisms behind mammographic density we assessed morphology, proliferation and hormone receptor status in relation to mammographic density in breast tissues from healthy women. Tissues were obtained from 2012-2013 by ultrasound-guided core needle biopsy from 160 women as part of the Karma (Karolinska mammography project for risk prediction for breast cancer) project. Mammograms were collected through routine mammography screening and mammographic density was calculated using STRATUS. The histological composition, epithelial and stromal proliferation status and hormone receptor status were assessed through immunohistochemical staining. Higher mammographic density was significantly associated with a greater proportion of stromal and epithelial tissue and a lower proportion of adipose tissue. Epithelial expression levels of Ki-67, oestrogen receptor (ER) and progesterone receptor (PR) were not associated with mammographic density. Epithelial Ki-67 was associated with a greater proportion of epithelial tissue, and epithelial PR was associated with a greater proportion of stromal and a lower proportion of adipose tissue. Epithelial ER was not associated with any tissues. In contrast, expression of ER in the stroma was significantly associated with a greater proportion of stroma, and negatively associated with the amount of adipose tissue. High mammographic density is associated with higher amount of stroma and epithelium and less amount of fat, but is not associated with a change in epithelial proliferation or receptor status. Increased expressions of both epithelial PR and stromal ER are associated with a greater proportion of stroma, suggesting hormonal involvement

  16. Regulation of Leukocyte Infiltration into Ovarian Cancer by Tumour-Stroma Interactions: A Microarray View of Cancer Microenvironment

    DTIC Science & Technology

    2006-03-01

    HEPPES, supplemented with Insulin, Transferin, Albumin, and Selenium from SIGMA®). After 48 hours, epithelial cells from 80% confluence are...microarray data from hundreds of tumor specimens ( Lamb et al., 2003). For this analysis we used the co-culture responsive gene list described in supplement...exclusive in the stroma of breast carcinomas. Nat Genet 32, 355-357. Lamb , J., Ramaswamy, S., Ford, H. L., Contreras, B., Martinez, R. V., Kittrell

  17. PD-L1/PD-1 check-point in gastric carcinoma with lymphoid stroma case report with immunochemical study

    PubMed Central

    Crescenzi, Anna; Taffon, Chiara; Donati, Michele; Guarino, Michele Pier Luca; Valeri, Sergio; Coppola, Roberto

    2017-01-01

    Abstract Introduction: Gastric carcinoma with lymphoid stroma is an unusual type of gastric tumor associated with a better prognosis than typical gastric carcinomas. The hallmark of this cancer is a prominent lymphoid infiltration of the stroma that represents an intense host lymphocytic response. The programmed death 1–programmed death-ligand 1 (PD-1/PD-L1) axis has recently emerged as a master immune checkpoint that controls antitumor immune responses against many neoplasms. Patient's concerns case study and outcome: We report the case of a male patient with gastric carcinoma with lymphoid stroma with a large mass infiltrating the gastric wall without nodal metastasis. He is alive without disease 10 months after surgery. We focused the study on factors that potentially modulate the prognosis. In this setting we demonstrate, for the first time in this type of tumor, by immunohistochemistry a strong PD-L1 expression in neoplastic cell and the presence of PD-1 positive infiltrating lymphocytes. Conclusion: The applied approach may contribute to the knowledge about host reaction in such tumor and it may also be used for tumor precise identification on the endoscopic biopsy time before excision surgery. PMID:28207501

  18. Functional units in rainbow trout (Salmo gairdneri, Richardson) liver: III. Morphometric analysis of parenchyma, stroma, and component cell types.

    PubMed

    Hampton, J A; Lantz, R C; Hinton, D E

    1989-05-01

    Hepatic stroma and parenchyma with its component cell types were quantitatively described in adult male and female actively-spawning 5-year-old rainbow trout (Salmo gairdneri, Richardson). Point-count morphometry of glycol methacrylate sections estimated volume compartments for stroma and parenchyma. Veins composed 85% of the stroma while arteries and bile ducts occupied approximately 6-7% each. Parenchyma accounted for 95% of hepatic volume. Point-count morphometry of transmission electron micrographs estimated volume compartments as well as numerical and surface density measurements for parenchymal components. Within the hepatic parenchymal compartment, hepatocytes occupied 85% and showed significant sex differences. Female hepatocytes were significantly more numerous but were smaller, only 60% of the volume of male hepatocytes. Since hepatocyte nuclear volume was equal in both sexes, differences were due to reduced cytoplasmic volume in females. Perisinusoidal macrophages of females occupied larger volumes of their respective parenchymal compartments, and their larger mean cytoplasmic volumes suggested activation. Biliary epithelial cells of preductules and ductules were numerous. Ratios of numerical density of hepatocytes to biliary epithelial cells were consistent with a tubular arrangement of hepatocytes. Factors possibly mediating the sexual dimorphism are discussed.

  19. Micro-RNA-21 regulates TGF-β-induced myofibroblast differentiation by targeting PDCD4 in tumor-stroma interaction.

    PubMed

    Yao, Qin; Cao, Siyu; Li, Chun; Mengesha, Asferd; Kong, Beihua; Wei, Mingqian

    2011-04-15

    Transforming growth factor-β1 (TGF-β1) induces stromal fibroblast-to-myofibroblast transdifferentiation in the tumor-stroma interactive microenvironment via modulation of multiple phenotypic and functional genes, which plays a critical role in tumor progression. Up to now, the involvement of micro-RNAs (miRNAs) and their roles in TGF-β1-induced myofibroblast differentiation in tumor-stroma interaction are unclear. Using quantitative real-time RT-PCR, we demonstrated that the expression of micro-RNA-21 (miR-21) was upregulated in activated fibroblasts after treatment with TGF-β1 or conditioned medium from cancer cells. To determine the potential roles of miR-21 in TGF-β1-mediated gene regulation during myofibroblast conversion, we showed that miR-21 expression was downregulated by miR-21 inhibitor and upregulated by miR-21 mimic. Interestingly, downregulation of miR-21 with the inhibitor effectively inhibited TGF-β1-induced myofibroblast differentiation while upregulation of miR-21 with a mimic significantly promoted myofibroblast differentiation. We further demonstrated that MiR-21 directly targeted and downregulated programmed cell death 4 (PDCD4) gene, which in turn acted as a negative regulator of several phenotypic and functional genes of myofibroblasts. Taken together, these results suggested that miR-21 participated in TGF-β1-induced myofibroblast transdifferentiation in cancer stroma by targeting PDCD4.

  20. Ammonia abundances in comets

    NASA Astrophysics Data System (ADS)

    Wyckoff, S.; Tegler, S.; Engel, L.

    The emission band strengths of the NH2 bands of Comets Halley, Hartley-Good, Thiele, and Borrelly were measured to determine the NH2 column densities for the comets. Production rates obtained using the Haser and vectorial models are in agreement within the observational errors, suggesting that a simple two-step decay model may be used to approximate the NH2 distribution in a comet's coma. Ammonia-to-water abundance ratios from 0.01 to 0.4 percent were found for the four comets. The ratio in Comet Halley is found to be Q(NH3)/Q(H2O) = 0.002 + or - 0.001. No significant difference in the ammonia abundance was found before or after perihelion in Comet Halley.

  1. Colon cancer molecular subtypes identified by expression profiling and associated to stroma, mucinous type and different clinical behavior

    PubMed Central

    2012-01-01

    Background Colon cancer patients with the same stage show diverse clinical behavior due to tumor heterogeneity. We aimed to discover distinct classes of tumors based on microarray expression patterns, to analyze whether the molecular classification correlated with the histopathological stages or other clinical parameters and to study differences in the survival. Methods Hierarchical clustering was performed for class discovery in 88 colon tumors (stages I to IV). Pathways analysis and correlations between clinical parameters and our classification were analyzed. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the main subtype was generated using the 3-Nearest-Neighbor method. Coincidences with other prognostic predictors were assesed. Results Hierarchical clustering identified four robust tumor subtypes with biologically and clinically distinct behavior. Stromal components (p < 0.001), nuclear β-catenin (p = 0.021), mucinous histology (p = 0.001), microsatellite-instability (p = 0.039) and BRAF mutations (p < 0.001) were associated to this classification but it was independent of Dukes stages (p = 0.646). Molecular subtypes were established from stage I. High-stroma-subtype showed increased levels of genes and altered pathways distinctive of tumour-associated-stroma and components of the extracellular matrix in contrast to Low-stroma-subtype. Mucinous-subtype was reflected by the increased expression of trefoil factors and mucins as well as by a higher proportion of MSI and BRAF mutations. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the Low-stroma-subtype distinguished low risk patients from high risk patients in the external cohort (Dukes B and C:HR = 8.56(2.53-29.01); Dukes B,C and D:HR = 1.87(1.07-3.25)). Eight different reported survival gene signatures segregated our tumors into two groups the Low-stroma-subtype and

  2. Stroma-conditioned media improve expansion of human primitive hematopoietic stem cells and progenitor cells.

    PubMed

    Breems, D A; Blokland, E A; Ploemacher, R E

    1997-01-01

    It has been reported that stroma-dependent cultures support proliferation of hematopoietic stem cells (HSC). In order to investigate the effect of soluble stromal factors, we developed short-term serum-low liquid cultures in which the effect of stroma-conditioned media (SCM) from the murine FBMD-1, and human L87/4 and L88/5 cell lines was studied on the maintenance and expansion of various human HSC subsets in CD34-positive selected mobilized peripheral blood stem cells (PBSC) from autologous transplants of lymphoma and multiple myeloma patients. The human cobblestone area forming cell (CAFC) assay was employed to determine the frequencies of both the CAFC weeks 2 to 4 as tentative indicators of progenitor and transiently repopulating HSC, and the more primitive CAFC weeks 6 to 8 as indicators of long-term repopulating HSC. In 7-day liquid cultures containing interleukin-3 (IL-3), stem cell factor (SCF) and IL-6, we recovered 3.0-fold more colony-forming cells (CFC) and 1.7- to 1.9-fold more CAFC weeks 2 and 4. The absolute number of primitive CAFC weeks 6 and 8 were only maintained (1.1- to 1.4-fold) in these liquid cultures. This modest expansion was significantly improved by the addition of SCM from the FBMD-1, L87/4 or L88/5 cell lines. Output CFC numbers were 6.8-, 5.8- and 9.9-fold higher, respectively, than the input values, while absolute CAFC week 2 to 4 numbers were 4.5-, 10.2- and 10.2-fold expanded, respectively. The addition of SCM also improved expansion of the more primitive CAFC week 6 to 8 stem cell subsets by 2.2-, 4.5- and 4.9-fold, respectively. The addition of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), IL-1beta, IL-11 or macrophage inflammatory protein-1alpha to cultures containing IL-3, SCF and IL-6 could not explain the SCM effect and in all these combinations SCM addition further increased the recovery of HSC subsets. Similarly, addition of anti-cytokine antibodies (ie alpha-G-CSF, alpha-GM-CSF, alpha

  3. Detecting thermal phase transitions in corneal stroma by fluorescence micro-imaging analysis

    NASA Astrophysics Data System (ADS)

    Matteini, P.; Rossi, F.; Ratto, F.; Bruno, I.; Nesi, P.; Pini, R.

    2008-02-01

    Thermal modifications induced in corneal stroma were investigated by the use of fluorescence microscopy. Freshly extracted porcine corneas were immersed for 5 minutes in a water bath at temperatures in the 35-90°C range and stored in formalin. The samples were then sliced in 200-μm-thick transversal sections and analyzed under a stereomicroscope to assess corneal shrinkage. Fluorescence images of the thermally treated corneal samples were acquired using a slow-scan cooled CCD camera, after staining the slices with Indocyanine Green (ICG) fluorescent dye which allowed to detect fluorescence signal from the whole tissue. All measurements were performed using an inverted epifluorescence microscope equipped with a mercury lamp. The thermally-induced modifications to the corneal specimens were evaluated by studying the grey level distribution in the fluorescence images. For each acquired image, Discrete Fourier Transform (DFT) and entropy analyses were performed. The spatial distribution of DFT absolute value indicated the spatial orientation of the lamellar planes, while entropy was used to study the image texture, correlated to the stromal structural transitions. As a result, it was possible to indicate a temperature threshold value (62°C) for high thermal damage, resulting in a disorganization of the lamellar planes and in full agreement with the measured temperature for corneal shrinkage onset. Analysis of the image entropy evidenced five strong modifications in stromal architecture at temperatures of ~45°C, 53°C, 57°C, 66°C, 75°C. The proposed procedure proved to be an effective micro-imaging method capable of detecting subtle changes in corneal tissue subjected to thermal treatment.

  4. Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent.

    PubMed

    Chen, Jane Q; Mori, Hidetoshi; Cardiff, Robert D; Trott, Josephine F; Hovey, Russell C; Hubbard, Neil E; Engelberg, Jesse A; Tepper, Clifford G; Willis, Brandon J; Khan, Imran H; Ravindran, Resmi K; Chan, Szeman R; Schreiber, Robert D; Borowsky, Alexander D

    2015-01-01

    Female 129:Stat1-null mice (129S6/SvEvTac-Stat1(tm1Rds) homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment.

  5. Unique metabolic features of pancreatic cancer stroma: relevance to the tumor compartment, prognosis, and invasive potential

    PubMed Central

    Knudsen, Erik S.; Balaji, Uthra; Freinkman, Elizaveta; McCue, Peter; Witkiewicz, Agnieszka K.

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The aggressiveness and therapeutic recalcitrance of this malignancy has been attributed to multiple factors including the influence of an active desmoplastic stroma. How the stromal microenvironment of PDAC contributes to the fatal nature of this disease is not well defined. In the analysis of clinical specimens, we observed diverse expression of the hypoxic marker carbonic anhydrase IX and the lactate transporter MCT4 in the stromal compartment. These stromal features were associated with the epithelial to mesenchymal phenotype in PDAC tumor cells, and with shorter patient survival. Cultured cancer-associated fibroblasts (CAFs) derived from primary PDAC exhibited a high basal level of hypoxia inducible factor 1a (HIF1α) that was both required and sufficient to modulate the expression of MCT4. This event was associated with increased transcription and protein synthesis of HIF1α in CAFs relative to PDAC cell lines, while surprisingly the protein turnover rate was equivalent. CAFs utilized glucose predominantly for glycolytic intermediates, whereas glutamine was the preferred metabolite for the TCA cycle. Unlike PDAC cell lines, CAFs were resistant to glucose withdrawal but sensitive to glutamine depletion. Consistent with the lack of reliance on glucose, CAFs could survive the acute depletion of MCT4. In co-culture and xenograft studies CAFs stimulated the invasive potential and metastatic spread of PDAC cell lines through a mechanism dependent on HIF1α and MCT4. Together, these data indicate that stromal metabolic features influence PDAC tumor cells to promote invasiveness and metastatic potential and associate with poor outcome in patients with PDAC. PMID:27623078

  6. Proteomic analysis of patient tissue reveals PSA protein in the stroma of benign prostatic hyperplasia

    PubMed Central

    O’Malley, Katherine J.; Eisermann, Kurtis; Pascal, Laura E.; Parwani, Anil V.; Majima, Tsuyoshi; Graham, Lara; Hrebinko, Katherine; Acquafondata, Marie; Stewart, Nicolas A.; Nelson, Joel B.; Yoshimura, Naoki; Wang, Zhou

    2014-01-01

    BACKGROUND Benign prostatic hyperplasia (BPH) is an age-related disease frequently associated with lower urinary tract symptoms (LUTS) that involves hyperplasia of both epithelial and stromal cells. Stromal fibrosis is a distinctive feature of BPH, but the exact mechanisms underlying this phenomenon are poorly understood. METHODS In the current study, proteomics analyses were utilized to identify proteins altered in the BPH stromal compartment from patients with symptomatic BPH. Stromal cells were isolated from histological nodules of BPH by laser capture microdissection (LCM) and subjected to liquid chromatography/mass spectrometry. RESULTS Proteins identified included several stromal-specific proteins involved in extracellular matrix remodeling, focal adhesion and cellular junctions. Additionally, the proteomics array identified the presence of luminal epithelial secretory protein PSA. Immunostaining, ELISA, and in situ hybridization analyses of BPH tissues verified the presence of PSA protein but absence of PSA mRNA in the stromal compartment. E-cadherin was down-regulated in BPH epithelial cells compared to normal adjacent tissues, suggesting that alteration of cellular junctions could contribute to the presence of luminal epithelial secreted proteins PSA and KLK2 in the stromal compartment. CONCLUSIONS The above findings suggest that the presence of secreted proteins PSA and KLK2 from prostate luminal epithelial cells in BPH stroma is a hallmark of BPH nodules which could in part be due to alterations in cellular junction proteins and/or increased epithelial barrier permeability. Elucidating the cause and consequence of these secreted proteins in the stromal compartment of BPH may lead to new understanding of BPH pathogenesis as well as approaches to prevent and/or treat this common disease. PMID:24711254

  7. Porphyromonas gingivalis within Placental Villous Mesenchyme and Umbilical Cord Stroma Is Associated with Adverse Pregnancy Outcome

    PubMed Central

    Vanterpool, Sizzle F.; Been, Jasper V.; Houben, Michiel L.; Nikkels, Peter G. J.; De Krijger, Ronald R.; Zimmermann, Luc J. I.; Kramer, Boris W.; Progulske-Fox, Ann; Reyes, Leticia

    2016-01-01

    Intrauterine presence of Porphyromonas gingivalis (Pg), a common oral pathobiont, is implicated in preterm birth. Our aim was to determine if the location of Pg within placental and/or umbilical cord sections was associated with a specific delivery diagnosis at preterm delivery (histologic chorioamnionitis, chorioamnionitis with funisitis, preeclampsia, and preeclampsia with HELLP-syndrome, small for gestational age). The prevalence and location of Pg within archived placental and umbilical cord specimens from preterm (25 to 32 weeks gestation) and term control cohorts were evaluated by immunofluorescent histology. Detection of Pg was performed blinded to pregnancy characteristics. Multivariate analyses were performed to evaluate independent effects of gestational age, being small for gestational age, specific preterm delivery diagnosis, antenatal steroids, and delivery mode, on the odds of having Pg in the preterm tissue. Within the preterm cohort, 49 of 97 (51%) placentas and 40 of 97 (41%) umbilical cord specimens were positive for Pg. Pg within the placenta was significantly associated with shorter gestation lengths (OR 0.63 (95%CI: 0.48–0.85; p = 0.002) per week) and delivery via caesarean section (OR 4.02 (95%CI: 1.15–14.04; p = 0.03), but not with histological chorioamnionitis or preeclampsia. However, the presence of Pg in the umbilical cord was significantly associated with preeclampsia: OR 6.73 (95%CI: 1.31–36.67; p = 0.02). In the term cohort, 2 of 35 (6%) placentas and no umbilical cord term specimens were positive for Pg. The location of Pg within the placenta was different between preterm and term groups in that Pg within the villous mesenchyme was only detected in the preterm cohort, whereas Pg associated with syncytiotrophoblasts was found in both preterm and term placentas. Taken together, our results suggest that the presence of Pg within the villous stroma or umbilical cord may be an important determinant in Pg-associated adverse pregnancy

  8. Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent

    PubMed Central

    Cardiff, Robert D.; Trott, Josephine F.; Hovey, Russell C.; Hubbard, Neil E.; Engelberg, Jesse A.; Tepper, Clifford G.; Willis, Brandon J.; Khan, Imran H.; Ravindran, Resmi K.; Chan, Szeman R.; Schreiber, Robert D.; Borowsky, Alexander D.

    2015-01-01

    Female 129:Stat1-null mice (129S6/SvEvTac-Stat1tm1Rds homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment. PMID:26075897

  9. Flare Plasma Iron Abundance

    NASA Technical Reports Server (NTRS)

    Dennis, Brian R.; Dan, Chau; Jain, Rajmal; Schwartz, Richard A.; Tolbert, Anne K.

    2008-01-01

    The equivalent width of the iron-line complex at 6.7 keV seen in flare X-ray spectra suggests that the iron abundance of the hottest plasma at temperatures >approx.10 MK may sometimes be significantly lower than the nominal coronal abundance of four times the photospheric value that is commonly assumed. This conclusion is based on X-ray spectral observations of several flares seen in common with the Ramaty High Energy Solar Spectroscopic Imager (RHESSI) and the Solar X-ray Spectrometer (SOXS) on the second Indian geostationary satellite, GSAT-2. The implications of this will be discussed as it relates to the origin of the hot flare plasma - either plasma already in the corona that is directly heated during the flare energy release process or chromospheric plasma that is heated by flare-accelerated particles and driven up into the corona. Other possible explanations of lower-than-expected equivalent widths of the iron-line complex will also be discussed.

  10. Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution

    PubMed Central

    Martinez-Outschoorn, Ubaldo E; Balliet, Renee M; Rivadeneira, Dayana B; Chiavarina, Barbara; Pavlides, Stephanos; Wang, Chenguang; Whitaker-Menezes, Diana; Daumer, Kristin M; Lin, Zhao; Witkiewicz, Agnieszka K; Flomenberg, Neal; Howell, Anthony; Pestell, Richard G; Knudsen, Erik S; Lisanti, Michael P

    2010-01-01

    Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent predictor of poor prognosis in human breast cancer patients, and is associated with early tumor recurrence, lymph node metastasis and tamoxifen-resistance. We developed a novel co-culture system to understand the mechanism(s) by which a loss of stromal fibroblast Cav-1 induces a “lethal tumor microenvironment.” Here, we propose a new paradigm to explain the powerful prognostic value of stromal Cav-1. In this model, cancer cells induce oxidative stress in cancer-associated fibroblasts, which then acts as a “metabolic” and “mutagenic” motor to drive tumor-stroma co-evolution, DNA damage and aneuploidy in cancer cells. More specifically, we show that an acute loss of Cav-1 expression leads to mitochondrial dysfunction, oxidative stress and aerobic glycolysis in cancer associated fibroblasts. Also, we propose that defective mitochondria are removed from cancer-associated fibroblasts by autophagy/mitophagy that is induced by oxidative stress. As a consequence, cancer associated fibroblasts provide nutrients (such as lactate) to stimulate mitochondrial biogenesis and oxidative metabolism in adjacent cancer cells (the “Reverse Warburg effect”). We provide evidence that oxidative stress in cancer-associated fibroblasts is sufficient to induce genomic instability in adjacent cancer cells, via a bystander effect, potentially increasing their aggressive behavior. Finally, we directly demonstrate that nitric oxide (NO) over-production, secondary to Cav-1 loss, is the root cause for mitochondrial dysfunction in cancer associated fibroblasts. In support of this notion, treatment with anti-oxidants (such as N-acetyl-cysteine, metformin and quercetin) or NO inhibitors (L-NAME) was sufficient to reverse many of the cancer-associated fibroblast phenotypes that we describe. Thus, cancer cells use “oxidative stress” in adjacent fibroblasts (1) as an “engine” to fuel their own

  11. Development of a Reactive Stroma Associated with Prostatic Intraepithelial Neoplasia in EAF2 Deficient Mice

    PubMed Central

    Pascal, Laura E.; Ai, Junkui; Masoodi, Khalid Z.; Wang, Yujuan; Wang, Dan; Eisermann, Kurtis; Rigatti, Lora H.; O’Malley, Katherine J.; Ma, Hei M.; Wang, Xinhui; Dar, Javid A.; Parwani, Anil V.; Simons, Brian W.; Ittman, Michael M.; Li, Luyuan; Davies, Benjamin J.; Wang, Zhou

    2013-01-01

    ELL-associated factor 2 (EAF2) is an androgen-responsive tumor suppressor frequently deleted in advanced prostate cancer that functions as a transcription elongation factor of RNA Pol II through interaction with the ELL family proteins. EAF2 knockout mice on a 129P2/OLA-C57BL/6J background developed late-onset lung adenocarcinoma, hepatocellular carcinoma, B-cell lymphoma and high-grade prostatic intraepithelial neoplasia. In order to further characterize the role of EAF2 in the development of prostatic defects, the effects of EAF2 loss were compared in different murine strains. In the current study, aged EAF2−/− mice on both the C57BL/6J and FVB/NJ backgrounds exhibited mPIN lesions as previously reported on a 129P2/OLA-C57BL/6J background. In contrast to the 129P2/OLA-C57BL/6J mixed genetic background, the mPIN lesions in C57BL/6J and FVB/NJ EAF2−/− mice were associated with stromal defects characteristic of a reactive stroma and a statistically significant increase in prostate microvessel density. Stromal inflammation and increased microvessel density was evident in EAF2-deficient mice on a pure C57BL/6J background at an early age and preceded the development of the histologic epithelial hyperplasia and neoplasia found in the prostates of older EAF2−/− animals. Mice deficient in EAF2 had an increased recovery rate and a decreased overall response to the effects of androgen deprivation. EAF2 expression in human cancer was significantly down-regulated and microvessel density was significantly increased compared to matched normal prostate tissue; furthermore EAF2 expression was negatively correlated with microvessel density. These results suggest that the EAF2 knockout mouse on the C57BL/6J and FVB/NJ genetic backgrounds provides a model of PIN lesions associated with an altered prostate microvasculature and reactive stromal compartment corresponding to that reported in human prostate tumors. PMID:24260246

  12. Stromal Response to Prostate Cancer: Nanotechnology-Based Detection of Thioredoxin-Interacting Protein Partners Distinguishes Prostate Cancer Associated Stroma from That of Benign Prostatic Hyperplasia

    PubMed Central

    Singer, Elizabeth; Linehan, Jennifer; Babilonia, Gail; Imam, S. Ashraf; Smith, David; Loera, Sofia; Wilson, Timothy; Smith, Steven

    2013-01-01

    Histological staining of reactive stroma has been shown to be a predictor of biochemical recurrence in prostate cancer, however, molecular markers of the stromal response to prostate cancer have not yet been fully delineated. The objective of this study was to determine whether or not the stromal biomarkers detected with a thioredoxin-targeted nanodevice could be used to distinguish the stroma associated with benign prostatic hyperplasia from that associated with PCA. In this regard, we recently demonstrated that a thioredoxin-targeted nanodevice selectively binds to reactive stroma in frozen prostate tumor tissue sections. To accomplish this, random frozen prostate tissue sections from each of 35 patients who underwent resection were incubated with the nanodevice and graded for fluorescent intensity. An adjacent section from each case was stained with Hematoxylin & Eosin to confirm the diagnosis. Select cases were stained with Masson's Trichrome or immunohistochemically using antibodies to thioredoxin reductase 1, thioredoxin reductase 2 or peroxiredoxin 1. Our results demonstrate that the graded intensity of nanodevice binding to the stroma associated with PCA was significantly higher (p = 0.0127) than that of benign prostatic hyperplasia using the t-test. Immunohistochemical staining of adjacent sections in representative cases showed that none of the two commonly studied thioredoxin interacting protein partners mirrored the fluorescence pattern seen with the nanodevice. However, thioredoxin reductase 2 protein was clearly shown to be a biomarker of prostate cancer-associated reactive stroma whose presence distinguishes the stroma associated with benign prostatic hyperplasia from that associated with prostate cancer. We conclude that the signal detected by the nanodevice, in contrast to individual targets detected with antibodies used in this study, originates from multiple thioredoxin interacting protein partners that distinguish the M2 neutrophil and

  13. Stromal response to prostate cancer: nanotechnology-based detection of thioredoxin-interacting protein partners distinguishes prostate cancer associated stroma from that of benign prostatic hyperplasia.

    PubMed

    Singer, Elizabeth; Linehan, Jennifer; Babilonia, Gail; Imam, S Ashraf; Smith, David; Loera, Sofia; Wilson, Timothy; Smith, Steven

    2013-01-01

    Histological staining of reactive stroma has been shown to be a predictor of biochemical recurrence in prostate cancer, however, molecular markers of the stromal response to prostate cancer have not yet been fully delineated. The objective of this study was to determine whether or not the stromal biomarkers detected with a thioredoxin-targeted nanodevice could be used to distinguish the stroma associated with benign prostatic hyperplasia from that associated with PCA. In this regard, we recently demonstrated that a thioredoxin-targeted nanodevice selectively binds to reactive stroma in frozen prostate tumor tissue sections. To accomplish this, random frozen prostate tissue sections from each of 35 patients who underwent resection were incubated with the nanodevice and graded for fluorescent intensity. An adjacent section from each case was stained with Hematoxylin & Eosin to confirm the diagnosis. Select cases were stained with Masson's Trichrome or immunohistochemically using antibodies to thioredoxin reductase 1, thioredoxin reductase 2 or peroxiredoxin 1. Our results demonstrate that the graded intensity of nanodevice binding to the stroma associated with PCA was significantly higher (p = 0.0127) than that of benign prostatic hyperplasia using the t-test. Immunohistochemical staining of adjacent sections in representative cases showed that none of the two commonly studied thioredoxin interacting protein partners mirrored the fluorescence pattern seen with the nanodevice. However, thioredoxin reductase 2 protein was clearly shown to be a biomarker of prostate cancer-associated reactive stroma whose presence distinguishes the stroma associated with benign prostatic hyperplasia from that associated with prostate cancer. We conclude that the signal detected by the nanodevice, in contrast to individual targets detected with antibodies used in this study, originates from multiple thioredoxin interacting protein partners that distinguish the M2 neutrophil and

  14. SPARC independent delivery of nab-paclitaxel without depleting tumor stroma in patient-derived pancreatic cancer xenografts

    PubMed Central

    Kim, Harrison; Samuel, Sharon L.; Lopez-Casas, Pedro P.; Grizzle, William E.; Hidalgo, Manuel; Kovar, Joy; Oelschlager, Denise K.; Zinn, Kurt R.; Warram, Jason M.; Buchsbaum, Donald J.

    2016-01-01

    The study goal was to examine the relationship between nab-paclitaxel delivery and SPARC (secreted protein acidic and rich in cysteine) expression in pancreatic tumor xenografts and to determine the anti-stromal effect of nab-paclitaxel, which may affect tumor vascular perfusion. SPARC positive and negative mice bearing Panc02 tumor xenografts (n=5–6/group) were injected with IRDye 800CW (IR800)-labeled nab-paclitaxel. After 24 hours, tumors were collected and stained with DL650-labeled anti-SPARC antibody, and the correlation between nab-paclitaxel and SPARC distributions was examined. Eight groups of mice bearing either Panc039 or Panc198 patient-derived xenografts (PDXs) (4 groups/model, 5 animals/group) were untreated (served as control) or treated with gemcitabine (100 mg/kg BW, i.p., twice per week), nab-paclitaxel (30 mg/kg BW, i.v., for 5 consecutive days), and these agents in combination, respectively, for 3 weeks, and tumor volume and perfusion changes were assessed using T2-weighted magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE) MRI, respectively. All tumors were collected and stained with Masson’s Trichrome Stain, followed by a blinded comparative analysis of tumor stroma density. IR800-nab-paclitaxel was mainly distributed in tumor stromal tissue, but nab-paclitaxel and SPARC distributions were minimally correlated in either SPARC positive or negative animals. Nab-paclitaxel treatment did not decrease tumor stroma nor increase tumor vascular perfusion in either PDX model when compared to control groups. These data suggest that the specific tumor delivery of nab-paclitaxel is not directly related to SPARC expression, and nab-paclitaxel does not deplete tumor stroma in general. PMID:26832793

  15. Biochemical characterization of nuclear receptors for vitamin D{sub 3} and glucocorticoids in prostate stroma cell microenvironment

    SciTech Connect

    Hidalgo, Alejandro A.; Montecinos, Viviana P.; Paredes, Roberto; Godoy, Alejandro S.; McNerney, Eileen M.; Tovar, Heribelt; Pantoja, Diego; Johnson, Candace; Trump, Donald; Onate, Sergio A.

    2011-08-19

    Highlights: {yields} Fibroblasts from benign and carcinoma-associated stroma were biochemically characterized for VDR and GR function as transcription factors in prostate stroma cell microenvironment. {yields} Decreased SRC-1/CBP coactivators recruitment to VDR and GR may result in hormone resistance to 1,25D{sub 3} in stromal cell microenvironment prostate cancer. {yields} 1a,25-Dyhidroxyvitamin D{sub 3} (1,25D{sub 3}) and glucocorticoids, either alone or in combination, may not be an alternative for 'some' advanced prostate cancers that fails androgen therapies. -- Abstract: The disruption of stromal cell signals in prostate tissue microenvironment influences the development of prostate cancer to androgen independence. 1{alpha},25-Dihydroxyvitamin D{sub 3} (1,25D{sub 3}) and glucocorticoids, either alone or in combination, have been investigated as alternatives for the treatment of advanced prostate cancers that fails androgen therapies. The effects of glucocorticoids are mediated by the intracellular glucocorticoid receptor (GR). Similarly, the effect of 1,25D{sub 3} is mediated by the 1,25D{sub 3} nuclear receptor (VDR). In this study, fibroblasts from benign- (BAS) and carcinoma-associated stroma (CAS) were isolated from human prostates to characterize VDR and GR function as transcription factors in prostate stroma. The VDR-mediated transcriptional activity assessed using the CYP24-luciferase reporter was limited to 3-fold induction by 1,25D{sub 3} in 9 out of 13 CAS (70%), as compared to >10-fold induction in the BAS clinical sample pair. Expression of His-tagged VDR (Ad-his-VDR) failed to recover the low transcriptional activity of the luciferase reporter in 7 out of 9 CAS. Interestingly, expression of Ad-his-VDR successfully recovered receptor-mediated induction in 2 out of the 9 CAS analyzed, suggesting that changes in the receptor protein itself was responsible for decreased response and resistance to 1,25D{sub 3} action. Conversely, VDR

  16. Oxygen abundance and convection

    NASA Astrophysics Data System (ADS)

    Van't Veer, C.; Cayrel, R.

    The triplet IR lines of O I near 777 nm are computed with the Kurucz's code, modified to accept several convection models. The program has been run with the MLT algorithm, with l/H = 1.25 and 0.5, and with the Canuto-Mazzitelli and Canuto-Goldman-Mazzitelli approaches, on a metal-poor turnoff-star model atmosphere with Teff=6200 K, log g = 4.3, [Fe/H]= -1.5. The results show that the differences in equivalent widths for the 4 cases do not exceed 2 per cent (0.3 mA). The convection treatment is therefore not an issue for the oxygen abundance derived from the permitted lines.

  17. Capella: Structure and Abundances

    NASA Technical Reports Server (NTRS)

    Brickhouse, Nancy S.

    1999-01-01

    This grant covers the analysis of EUVE spectra of the cool star binary system Capella. This project has also required the analysis of simultaneous Advanced Satellite for Cosmology and Astrophysics (ASCA) data. The ASCA spectrum of Capella could not be fit with standard models; by imposing models based on strong lines observed with EUVE, a problem wavelength region was identified. Correcting the problem required calculations of atomic collision strengths of higher principal quantum number than had ever been calculated. With these new models applied to the ASCA spectrum, better fits were obtained. Findings are that: (1) ASCA and EUVE spectra are both dominated by a region at 6 x 10(exp 6) K. (2) The high energy cut-off of the ASCA spectrum is consistent with emission from the highest ionization stages of EUVE, namely Fe XXIV. (3) EUVE requires a continuous emission measure distribution with more than two temperatures. (4) The ASCA spectra are of such high statistical significance that systematic uncertainties dominate, including atomic physics issues and calibration issues. (5) While the ASCA spectral fits achieve lower Chi(exp 2 with two-temperature fits, the EUVE-derived emission measure distribution models are also consistent with the spectra. (6) The Fe/H ratio obtained from the ASCA fit is within 20 % of the Fe/H abundance obtained from the summed spectra of Capella over 5 EUVE pointings, as well as the 1996 EUVE data. This result confirms our claims that quasi-continua composed of weak emission lines in the short wavelength spectrometer of EUVE are not major contributors to the measured Capella continuum. Other abundance ratios are also determined from the ASCA data, using models derived with EUVE. Si, Si, and Mg appear to be close to solar photospheric values, while the ratio of Ne/Fe is three to four times lower than solar photospheric values. Whether there is a general First Ionization Potential (FIP) effect or a specific neon anomaly cannot be determined

  18. Actinide abundances in ordinary chondrites

    NASA Technical Reports Server (NTRS)

    Hagee, B.; Bernatowicz, T. J.; Podosek, F. A.; Johnson, M. L.; Burnett, D. S.

    1990-01-01

    Measurements of actinide and light REE (LREE) abundances and of phosphate abundances in equilibrated ordinary chondrites were obtained and were used to define the Pu abundance in the solar system and to determine the degree of variation of actinide and LREE abundances. The results were also used to compare directly the Pu/U ratio with the earlier obtained ratio determined indirectly, as (Pu/Nd)x(Nd/U), assuming that Pu behaves chemically as a LREE. The data, combined with high-accuracy isotope-dilution data from the literature, show that the degree of gram-scale variability of the Th, U, and LREE abundances for equilibrated ordinary chondrites is a factor of 2-3 for absolute abundances and up to 50 percent for relative abundances. The observed variations are interpreted as reflecting the differences in the compositions and/or proportions of solar nebula components accreted to ordinary chondrite parent bodies.

  19. Osterix-cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma.

    PubMed

    Liu, Yaling; Strecker, Sara; Wang, Liping; Kronenberg, Mark S; Wang, Wen; Rowe, David W; Maye, Peter

    2013-01-01

    We have carried out fate mapping studies using Osterix-EGFPCre and Osterix-CreERt animal models and found Cre reporter expression in many different cell types that make up the bone marrow stroma. Constitutive fate mapping resulted in the labeling of different cellular components located throughout the bone marrow, whereas temporal fate mapping at E14.5 resulted in the labeling of cells within a region of the bone marrow. The identity of cell types marked by constitutive and temporal fate mapping included osteoblasts, adipocytes, vascular smooth muscle, perineural, and stromal cells. Prolonged tracing of embryonic precursors labeled at E14.5dpc revealed the continued existence of their progeny up to 10 months of age, suggesting that fate mapped, labeled embryonic precursors gave rise to long lived bone marrow progenitor cells. To provide further evidence for the marking of bone marrow progenitors, bone marrow cultures derived from Osterix-EGFPCre/Ai9 mice showed that stromal cells retained Cre reporter expression and yielded a FACS sorted population that was able to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and into osteoblasts, adipocytes, and perivascular stromal cells after transplantation. Collectively, our studies reveal the developmental process by which Osterix-Cre labeled embryonic progenitors give rise to adult bone marrow progenitors which establish and maintain the bone marrow stroma.

  20. High expression of PDGFR-β in prostate cancer stroma is independently associated with clinical and biochemical prostate cancer recurrence

    PubMed Central

    Nordby, Yngve; Richardsen, Elin; Rakaee, Mehrdad; Ness, Nora; Donnem, Tom; Patel, Hiten R. H.; Busund, Lill-Tove; Bremnes, Roy M.; Andersen, Sigve

    2017-01-01

    Due to a lack of sufficient diagnostic tools to predict aggressive disease, there is a significant overtreatment of patients with prostate cancer. Platelet derived growth factors (PDGFs) and their receptors (PDGFRs) are key regulators of mesenchymal cells in the tumor microenvironment, and has been associated with unfavorable outcome in several other cancers. Herein, we aimed to investigate the prognostic impact of PDGFR-β and its ligands (PDGF-B and PDGF-D) in a multicenter prostatectomy cohort of 535 Norwegian patients. Using tissue microarrays and immunohistochemistry, the expression of ligands PDGF-B and PDGF-D and their corresponding receptor, PDGFR-β, was assessed in neoplastic tissue and tumor-associated stroma. PDGFR-β was expressed in benign and tumor associated stroma, but not in epithelium. High stromal expression of PDGFR-β was independently associated with clinical relapse (HR = 2.17, p = 0.010) and biochemical failure (HR = 1.58, p = 0.002). This large study highlights the prognostic importance of PDGFR-β expression, implicating its involvement in prostate cancer progression even in early stage disease. Hence, analyses of PDGFR-β may help distinguish which patients will benefit from radical treatment, and since PDGFR-β is associated with relapse and shorter survival, it mandates a focus as a therapeutic target. PMID:28233816

  1. Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis

    SciTech Connect

    Santamaria-Martinez, Albert; Barquinero, Jordi; Barbosa-Desongles, Anna; Hurtado, Antoni; Pinos, Tomas; Seoane, Joan; Poupon, Marie-France; Morote, Joan; Reventos, Jaume; Munell, Francina

    2009-10-15

    Cancer stem cells are a distinct cellular population that is believed to be responsible for tumor initiation and maintenance. Recent data suggest that solid tumors also contain another type of stem cells, the mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs), which contribute to the formation of tumor-associated stroma. The Hoechst 33342 efflux assay has proved useful to identify a rare cellular fraction, named Side Population (SP), enriched in cells with stem-like properties. Using this assay, we identified SP cells in a prostate cancer xenograft containing human prostate cancer cells and mouse stromal cells. The SP isolation, subculture and sequential sorting allowed the generation of single-cell-derived clones of murine origin that were recognized as MSC by their morphology, plastic adherence, proliferative potential, adipogenic and osteogenic differentiation ability and immunophenotype (CD45{sup -}, CD81{sup +} and Sca-1{sup +}). We also demonstrated that SP clonal cells secrete transforming growth factor {beta}1 (TGF-{beta}1) and that their inhibition reduces proliferation and accelerates differentiation. These results reveal the existence of SP cells in the stroma of a cancer xenograft, and provide evidence supporting their MSC nature and the role of TGF-{beta}1 in maintaining their proliferation and undifferentiated status. Our data also reveal the usefulness of the SP assay to identify and isolate MSC cells from carcinomas.

  2. Human Cornea Proteome: Identification and Quantitation of the Proteins of the Three Main Layers Including Epithelium, Stroma, and Endothelium

    PubMed Central

    2012-01-01

    Diseases of the cornea are common and refer to conditions like infections, injuries and genetic defects. Morphologically, many corneal diseases affect only certain layers of the cornea and separate analysis of the individual layers is therefore of interest to explore the basic molecular mechanisms involved in corneal health and disease. In this study, the three main layers including, the epithelium, stroma and endothelium of healthy human corneas were isolated. Prior to analysis by LC–MS/MS the proteins from the different layers were either (i) separated by SDS-PAGE followed by in-gel trypsinization, (ii) in-solution digested without prior protein separation or, (iii) in-solution digested followed by cation exchange chromatography. A total of 3250 unique Swiss-Prot annotated proteins were identified in human corneas, 2737 in the epithelium, 1679 in the stroma, and 880 in the endothelial layer. Of these, 1787 proteins have not previously been identified in the human cornea by mass spectrometry. In total, 771 proteins were quantified, 157 based on in-solution digestion and 770 based on SDS-PAGE separation followed by in-gel digestion of excised gel pieces. Protein analysis showed that many of the identified proteins are plasma proteins involved in defense responses. PMID:22698189

  3. Targeted Disruption of Orchestration between Stroma and Tumor Cells in Pancreatic Cancer: Molecular Basis and Therapeutic Implications

    PubMed Central

    Kong, Xiangyu; Li, Lei; Li, Zhaoshen; Xie, Keping

    2012-01-01

    Pancreatic cancer is one of the most lethal malignancies, with a prominent desmoplastic reaction as the defining hallmark of the disease. The past several decades have seen dramatic progress in understanding of pancreatic cancer pathogenesis, including the identification of precursor lesions, sequential transformation from normal pancreas to invasive pancreatic cancer and corresponding signature genetic events, and the biological impact of those alterations on malignant behaviors. However, the current therapeutic strategies for epithelial tumor cells, which have exhibited potent antitumor activity in cell culture and animal models, have failed to have significant effects in the clinic. The desmoplastic stroma surrounding pancreatic cancer cells, which accounts for about 90% of a tumor’s mass, clearly is not a passive scaffold for cancer cells but an active contributor to carcinogenesis. Improved understanding of the dynamic interaction between cancer cells and their stroma will be important to designing new, effective therapeutic strategies for pancreatic cancer. This review focuses on the origination of stromal molecular and cellular components in pancreatic tumors, their biological effects on pancreatic cancer cells, and the orchestration between these two components. PMID:22749856

  4. Biocompatibility and Biomechanical Effect of Single Wall Carbon Nanotubes Implanted in the Corneal Stroma: A Proof of Concept Investigation

    PubMed Central

    Rodriguez, Alejandra E.; Rodriguez-Reinoso, Francisco; Gomez-Tejedor, Jose A.; Antolinos-Turpin, Carmen M.; Bataille, Laurent; Alio, Jorge L.

    2016-01-01

    Corneal ectatic disorders are characterized by a progressive weakening of the tissue due to biomechanical alterations of the corneal collagen fibers. Carbon nanostructures, mainly carbon nanotubes (CNTs) and graphene, are nanomaterials that offer extraordinary mechanical properties and are used to increase the rigidity of different materials and biomolecules such as collagen fibers. We conducted an experimental investigation where New Zealand rabbits were treated with a composition of CNTs suspended in balanced saline solution which was applied in the corneal tissue. Biocompatibility of the composition was assessed by means of histopathology analysis and mechanical properties by stress-strain measurements. Histopathology samples stained with blue Alcian showed that there were no fibrous scaring and no alterations in the mucopolysaccharides of the stroma. It also showed that there were no signs of active inflammation. These were confirmed when Masson trichrome staining was performed. Biomechanical evaluation assessed by means of tensile test showed that there is a trend to obtain higher levels of rigidity in those corneas implanted with CNTs, although these changes are not statistically significant (p > 0.05). Implanting CNTs is biocompatible and safe procedure for the corneal stroma which can lead to an increase in the rigidity of the collagen fibers. PMID:28116139

  5. Expression of Autoactivated Stromelysin-1 in Mammary Glands of Transgenic Mice Leads to a Reactive Stroma During Early Development

    SciTech Connect

    Thomasset, N.; Lochter, A.; Sympson, C.J.; Lund, L.R.; Williams, D.R.; Behrendtsen, O.; Werb, Z.; Bissell, M.J.

    1998-04-24

    Extracellular matrix and extracellular matrix-degrading matrix metalloproteinases play a key role in interactions between the epithelium and the mesenchyme during mammary gland development and disease. In patients with breast cancer, the mammary mesenchyme undergoes a stromal reaction, the etiology of which is unknown. We previously showed that targeting of an autoactivating mutant of the matrix metalloproteinase stromelysin-1 to mammary epithelia of transgenic mice resulted in reduced mammary function during pregnancy and development of preneoplastic and neoplastic lesions. Here we examine the cascade of alterations before breast tumor formation in the mammary gland stroma once the expression of the stromelysin-1 transgene commences. Beginning in postpubertal virgin animals, low levels of transgene expression in mammary epithelia led to increased expression of endogenous stromelysin-1 in stromal fibroblasts and up-regulation of other matrix metalloproteinases, without basement membrane disruption. These changes were accompanied by the progressive development of a compensatory reactive stroma, characterized by increased collagen content and vascularization in glands from virgin mice. This remodeling of the gland affected epithelial-mesenchymal communication as indicated by inappropriate expression of tenascin-C starting by day 6 of pregnancy. This, together with increased transgene expression, led to basement membrane disruption starting by day 15 of pregnancy. We propose that the highly reactive stroma provides a prelude to breast epithelial tumors observed in these animals. Epithelial development depends on an exquisite series of inductive and instructive interactions between the differentiating epithelium and the mesenchymal (stromal) compartment. The epithelium, which consists of luminal and myoepithelial cells, is separated from the stroma by a basement membrane (BM), which plays a central role in mammary gland homeostasis and gene expression. In vivo, stromal

  6. Capella: Structure and Abundances

    NASA Technical Reports Server (NTRS)

    Brickhouse, Nancy S.

    1999-01-01

    This grant covers the analysis of ASCA spectra of the cool star binary system Capella. This project has also required the analysis of simultaneous EUVE data. The ASCA spectrum of Capella could not be fit with standard models; by imposing models based on strong lines observed with EUVE, a problem wavelength region was identified. Correcting the problem required calculations of atomic collision strengths of higher principal quantum number than had ever been calculated, resulting in a paper in process by Liedahl and Brickhouse. With these new models applied to the ASCA spectrum, better fits were obtained. While solar abundance ratios are generally consistent with the ASCA data, the ratio of Ne/Fe is three to four times lower than solar photospheric values. Whether there is a general First Ionization Potential (FIP) effect or a specific neon anomaly cannot be determined from these data. Detailed discussion has been provided to NASA in the most recent annual report (1997). Two poster presentations have been made regarding modeling requirements. A substantial paper is in the final revision form, following review by six co-authors. The results of this work have wide implications, since the newly calculated emission lines almost certainly contribute to other problems in fitting not only other stellar spectra, but also composite supernova remnants, galaxies, and cooling flow clusters of galaxies. Furthermore, Liedahl and Brickhouse have identified other species for which lines of a similar nature (high principal quantum number) will contribute significant flux. For moderate resolution X-ray spectra, lines left out of the models in relatively isolated bands, will be attributed to continuum flux by spectral fitting engines, causing errors in line-to-continuum ratios. Thus addressing the general theoretical problem is of crucial importance.

  7. Measuring Solar Abundances with Seismology

    NASA Astrophysics Data System (ADS)

    Mussack, K.; Gough, D.

    2009-12-01

    The revision of the photospheric abundances proferred by Asplund et al. (2005) has rendered opacity theory inconsistent with the seismologically determined opacity through the Sun. This highlights the need for a direct seismological measurement of solar abundances. Here we describe the technique used to measure abundances with seismology, examine our ability to detect differences between solar models using this technique, and discuss its application in the Sun.

  8. Efficient Generation of Multipotent Mesenchymal Stem Cells from Umbilical Cord Blood in Stroma-Free Liquid Culture

    PubMed Central

    van den Broek, Maries; Nuvolone, Mario; Dannenmann, Stefanie; Stieger, Bruno; Rapold, Reto; Konrad, Daniel; Rubin, Arnold; Bertino, Joseph R.; Aguzzi, Adriano; Heikenwalder, Mathias; Knuth, Alexander K.

    2010-01-01

    Background Haematopoiesis is sustained by haematopoietic (HSC) and mesenchymal stem cells (MSC). HSC are the precursors for blood cells, whereas marrow, stroma, bone, cartilage, muscle and connective tissues derive from MSC. The generation of MSC from umbilical cord blood (UCB) is possible, but with low and unpredictable success. Here we describe a novel, robust stroma-free dual cell culture system for long-term expansion of primitive UCB-derived MSC. Methods and Findings UCB-derived mononuclear cells (MNC) or selected CD34+ cells were grown in liquid culture in the presence of serum and cytokines. Out of 32 different culture conditions that have been tested for the efficient expansion of HSC, we identified one condition (DMEM, pooled human AB serum, Flt-3 ligand, SCF, MGDF and IL-6; further denoted as D7) which, besides supporting HSC expansion, successfully enabled long-term expansion of stromal/MSC from 8 out of 8 UCB units (5 MNC-derived and 3 CD34+ selected cells). Expanded MSC displayed a fibroblast-like morphology, expressed several stromal/MSC-related antigens (CD105, CD73, CD29, CD44, CD133 and Nestin) but were negative for haematopoietic cell markers (CD45, CD34 and CD14). MSC stemness phenotype and their differentiation capacity in vitro before and after high dilution were preserved throughout long-term culture. Even at passage 24 cells remained Nestin+, CD133+ and >95% were positive for CD105, CD73, CD29 and CD44 with the capacity to differentiate into mesodermal lineages. Similarly we show that UCB derived MSC express pluripotency stem cell markers despite differences in cell confluency and culture passages. Further, we generated MSC from peripheral blood (PB) MNC of 8 healthy volunteers. In all cases, the resulting MSC expressed MSC-related antigens and showed the capacity to form CFU-F colonies. Conclusions This novel stroma-free liquid culture overcomes the existing limitation in obtaining MSC from UCB and PB enabling so far unmet therapeutic

  9. Self-renewal and differentiation of a novel bipotent myeloid progenitor clone in the stroma-dependent culture.

    PubMed

    Okubo, T; Yanai, N; Obinata, M

    2000-06-01

    To understand regulation of myeloid development, it is necessary to obtain the myeloid progenitor cell lines with self-renewal and differentiation capacities. Because prolonged hematopoiesis occurs with the production of myeloid cells at all stages of differentiation in the Dexter-type long-term bone marrow cultures, we tried to obtain stroma-dependent myeloid progenitor cells starting from the long-term bone marrow culture. Murine cobblestone areas generated in long-term bone marrow cultures were serially passaged every 10 days. After 4 months, the resultant hematopoietic cells, designated as DFC, were passaged on a monolayer of established spleen stromal cell line, MSS62. After 10-12 passages of DFC cells on MSS62, several clones were obtained by colony formation on MSS62 cell layer. Among these clones, DFC-a cells could be maintained for a long period by coculturing with the established stromal cell line, MSS62.DFC-a cells proliferated by forming cobblestones and contained blast cells, granulocytes, and macrophages. Cell sorting and coculture experiments indicated that the blast type cells exhibiting c-Kit(+) Gr-1(-) Mac-1(-), stroma-dependently self-renewed, and spontaneously differentiated toward granulocytes (c-Kit(+) Gr-1(+) Mac-1(+)) and macrophages (c-Kit(low/+) Gr-1(-) Mac-1(high)). Although most of DFC-a cells expressed c-Kit, SCF-c-Kit interaction was not always necessary for their growth. In the presence of stromal cells, growth and differentiation of DFC-a cells were stimulated by GM-CSF or IL-3. Without stromal cells, DFC-a was transiently expanded by GM-CSF or IL-3 but could not be maintained constantly by these cytokines. The present study demonstrated that DFC-a is a novel bipotent myeloid progenitor cell clone as a simple model system of stroma-dependent myeloid development. It may reflect distinct properties for the earliest myeloid progenitor cells in vivo. It is of interest to know what signals are provided by MSS62 stromal cells to maintain

  10. Periostin in the Cancer Stroma of Mycosis Fungoides Palmaris et Plantaris: A Case Report and Immunohistochemical Study

    PubMed Central

    Tanita, Kayo; Fujimura, Taku; Kakizaki, Aya; Furudate, Sadanori; Mizuashi, Masato; Watabe, Akiko; Aiba, Setsuya

    2016-01-01

    Mycosis fungoides palmaris et plantaris (MFPP) is a rare variant of mycosis fungoides limited to the palms and soles. Although little is known about the pathogenesis of MFPP, this variant of mycosis fungoides presents a relatively good prognosis. In this report, we describe an 85-year-old Japanese man with MFPP. Immunohistochemical staining revealed the dense deposition of periostin in the cancer stroma, as well as infiltration of CD163+CD206− tumor-associated macrophages (TAMs), which suggested the phenotypes of TAMs were not polarized to the M2 phenotype in the lesional skin of MFPP. Our present case might suggest one of the possible reasons for the good prognosis of MFPP. PMID:27293391

  11. Changing concepts about the distribution of Photosystems I and II between grana-appressed and stroma-exposed thylakoid membranes.

    PubMed

    Anderson, Jan M

    2002-01-01

    Thylakoid membranes of higher plants and some green algae, which house the light-harvesting and energy transducing functions of the chloroplast, are structurally unique. The concept of the photosynthetic unit of the 1930s (Robert Emerson, William Arnold and Hans Gaffron), needing one reaction center per hundreds of antenna molecules, was modified by the discovery of the Enhancement effect in oxygen evolution in two different wavelengths of light (Robert Emerson and his coworkers) in the late 1950s, followed by the 1960 Z scheme of Robin Hill and Fay Bendall. It was realized that two light reactions and two pigment systems were needed for oxygenic photosynthesis. Changing ideas about the distribution of Photosystem II (PS II) and PS I between the green-appressed and stroma-exposed thylakoid membrane domains, which led to the concept of lateral heterogeneity, are discussed.

  12. Fine structure of the developing avian corneal stroma as revealed by quick-freeze, deep-etch electron microscopy.

    PubMed

    Hirsch, M; Noske, W; Prenant, G; Renard, G

    1999-09-01

    Corneal transparency depends on the precise organization of the stromal extracellular matrix. The morphology of the extracellular matrix of the embryonic and adult avian secondary posterior cornea was studied in glutaraldehyde-fixed, quick-frozen, deep-etched replicas with the electron microscope. Although the collagen fibrils changed from a loose network to a more ordered parallel lamellar arrangement during development, their mean diameter remained constant between 30.3 and 31.2 nm. Besides collagen fibrils, other extracellular matrix components were observed: (i) straight or Y-shaped cross-bridging interfibrillar 8-10 nm filaments with 18-22 nm globules; (ii) relatively loose networks of 10-20 nm beaded filaments, with a mean periodicity of 107 nm, often running perpendicular to the collagen fibrils and adhering to the plasma membrane of stromal cells at early developmental stages; (iii) straight or curved 6-12 nm strands forming sheets within the stromal matrix that progressively disappeared, whereas similar structures persisted at the Descemet's membrane-stroma interface; (iv) dense networks of filaments with 6-8 nm filaments, sometimes polygonally arranged, and a substructure of 2-3 nm filaments with globular domains, which progressively disappeared with maturation but remained at the Descemet's membrane-stroma interface; (v) polygonal networks of 9-10 nm filaments with globular domains adherent to the surface of cell plasma membranes at early developmental stages. The temporal expression of deep-etched supramolecular structural assemblies is compatible with that of the so-called 'interstitial basement membrane components' previously described. The quick-freeze and deep-etching method can reveal important aspects of the in situ organization of the corneal extracellular matrix.

  13. Resistance of leukemia cells to cytarabine chemotherapy is mediated by bone marrow stroma, involves cell-surface equilibrative nucleoside transporter-1 removal and correlates with patient outcome.

    PubMed

    Macanas-Pirard, Patricia; Broekhuizen, Richard; González, Alfonso; Oyanadel, Claudia; Ernst, Daniel; García, Patricia; Montecinos, Viviana P; Court, Felipe; Ocqueteau, Mauricio; Ramirez, Pablo; Nervi, Bruno

    2017-02-01

    The interaction between acute myeloid leukemia cells (AML) with the bone marrow stroma cells (BMSCs) determines a protective environment that favors tumor development and resistance to conventional chemotherapy. We showed that BMSCs secrete soluble factors that protect AML cells from Ara-C induced cytotoxicity. This leukemia chemoresistance is associated with a decrease in the equilibrative nucleoside transporter (ENT1) activity by inducing removal of ENT1 from the cell surface. Reduction of cell proliferation was also observed with activation of AKT and mTOR-dependent cell survival pathways, which may also contribute to the tumor chemoprotection. Analysis of primary BMSC cultures has demonstrated that AML patients with stroma capable to confer Ara-C resistance in vitro compared to AML patients without this stroma capacity were associated with a worse prognosis. The two year overall survival rate was 0% versus 80% respectively (p=0.0001). This is the first report of a chemoprotection mechanism based on the removal of a drug transporter from the cell surface and most importantly the first time that a stroma phenotype has correlated with prognostic outcome in cancer.

  14. Probing tumor-stroma interactions and response to photodynamic therapy in a 3D pancreatic cancer-fibroblast co-culture model

    NASA Astrophysics Data System (ADS)

    Glidden, Michael D.; Massodi, Iqbal; Rizvi, Imran; Celli, Jonathan P.; Hasan, Tayyaba

    2012-02-01

    Pancreatic ductal adenocarcinoma is a lethal disease that is often unresectable by the time of diagnosis and is typically non-responsive to chemo- and radiotherapy, resulting in a five year survival of only 3%. Tumors of the pancreas are characterized by a dense fibrous stroma rich in extracellular matrix proteins, which is implicated in poor therapeutic response, though its precise roles remain poorly understood. Indeed, while the use of therapeutics that target the stroma is an emerging paradigm in the clinical management of this disease, the primary focus of such efforts is to enhance drug penetration through dense fibrous stroma and it is unclear to what extent the characteristically rigid stroma of pancreatic tumors imparts drug resistance by acting as a complex signaling partner, or merely as a physical barrier for drug delivery. Here we use 3D in vitro co-cultures of pancreatic cancer cells and normal human fibroblasts as a model system to study heterotypic interactions between these populations. Leveraging this in vitro model along with image-based methods for quantification of growth and therapeutic endpoints, we characterize these co-cultures and examine the role of verteporfin-based photodynamic therapy (PDT) for targeting tumor-fibroblast interactions in pancreatic tumors.

  15. Targeting of metastasis-promoting tumor-associated fibroblasts and modulation of pancreatic tumor-associated stroma with a carboxymethylcellulose-docetaxel nanoparticle.

    PubMed

    Ernsting, Mark J; Hoang, Bryan; Lohse, Ines; Undzys, Elijus; Cao, Pinjiang; Do, Trevor; Gill, Bethany; Pintilie, Melania; Hedley, David; Li, Shyh-Dar

    2015-05-28

    Pancreatic ductal adenocarcinomas are characterized by the desmoplastic reaction, a dense fibrous stroma that has been shown to be supportive of tumor cell growth, invasion, and metastasis, and has been associated with resistance to chemotherapy and reduced patient survival. Here, we investigated targeted depletion of stroma for pancreatic cancer therapy via taxane nanoparticles. Cellax-DTX polymer is a conjugate of docetaxel (DTX), polyethylene glycol (PEG), and acetylated carboxymethylcellulose, a construct which condenses into well-defined 120nm particles in an aqueous solution, and is suitable for intravenous injection. We examined Cellax-DTX treatment effects in highly stromal primary patient-derived pancreatic cancer xenografts and in a metastatic PAN02 mouse model of pancreatic cancer, focusing on specific cellular interactions in the stroma, pancreatic tumor growth and metastasis. Greater than 90% of Cellax-DTX particles accumulate in smooth muscle actin (SMA) positive cancer-associated fibroblasts which results in long-term depletion of this stromal cell population, an effect not observed with Nab-paclitaxel (Nab-PTX). The reduction in stromal density leads to a >10-fold increase in tumor perfusion, reduced tumor weight and a reduction in metastasis. Consentingly, Cellax-DTX treatment increased survival when compared to treatment with gemcitabine or Nab-PTX in a metastatic PAN02 mouse model. Cellax-DTX nanoparticles interact with the tumor-associated stroma, selectively interacting with and depleting SMA positive cells and macrophage, effects of which are associated with significant changes in tumor progression and metastasis.

  16. Transcriptional evidence for the "Reverse Warburg Effect" in human breast cancer tumor stroma and metastasis: similarities with oxidative stress, inflammation, Alzheimer's disease, and "Neuron-Glia Metabolic Coupling".

    PubMed

    Pavlides, Stephanos; Tsirigos, Aristotelis; Vera, Iset; Flomenberg, Neal; Frank, Philippe G; Casimiro, Mathew C; Wang, Chenguang; Pestell, Richard G; Martinez-Outschoorn, Ubaldo E; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P

    2010-04-01

    Caveolin-1 (-/-) null stromal cells are a novel genetic model for cancer-associated fibroblasts and myofibroblasts. Here, we used an unbiased informatics analysis of transcriptional gene profiling to show that Cav-1 (-/-) bone-marrow derived stromal cells bear a striking resemblance to the activated tumor stroma of human breast cancers. More specifically, the transcriptional profiles of Cav-1 (-/-) stromal cells were most closely related to the primary tumor stroma of breast cancer patients that had undergone lymph-node (LN) metastasis. This is consistent with previous morphological data demonstrating that a loss of stromal Cav-1 protein (by immuno-histochemical staining in the fibroblast compartment) is significantly associated with increased LN-metastasis. We also provide evidence that the tumor stroma of human breast cancers shows a transcriptional shift towards oxidative stress, DNA damage/repair, inflammation, hypoxia, and aerobic glycolysis, consistent with the "Reverse Warburg Effect". Finally, the tumor stroma of "metastasis-prone" breast cancer patients was most closely related to the transcriptional profiles derived from the brains of patients with Alzheimer's disease. This suggests that certain fundamental biological processes are common to both an activated tumor stroma and neuro-degenerative stress. These processes may include oxidative stress, NO over-production (peroxynitrite formation), inflammation, hypoxia, and mitochondrial dysfunction, which are thought to occur in Alzheimer?s disease pathology. Thus, a loss of Cav-1 expression in cancer-associated myofibroblasts may be a protein biomarker for oxidative stress, aerobic glycolysis, and inflammation, driving the "Reverse Warburg Effect" in the tumor micro-environment and cancer cell metastasis.

  17. TβRIII Expression in Human Breast Cancer Stroma and the Role of Soluble TβRIII in Breast Cancer Associated Fibroblasts

    PubMed Central

    Jovanović, Bojana; Pickup, Michael W.; Chytil, Anna; Gorska, Agnieszka E.; Johnson, Kimberly C.; Moses, Harold L.; Owens, Philip

    2016-01-01

    The TGF-β pathway plays a major role in tumor progression through regulation of epithelial and stromal cell signaling. Dysfunction of the pathway can lead to carcinoma progression and metastasis. To gain insight into the stromal role of the TGF-β pathway in breast cancer, we performed laser capture microdissection (LCM) from breast cancer patients and reduction mammoplasty patients. Microdissected tumor stroma and normal breast stroma were examined for gene expression. Expression of the TGF-β type III receptor (TGFBR3) was greatly decreased in the tumor stroma compared to control healthy breast tissue. These results demonstrated a 44-fold decrease in TGFBR3 mRNA in tumor stroma in comparison to control tissue. We investigated publicly available databases, and have identified that TGFBR3 mRNA levels are decreased in tumor stroma. We next investigated fibroblast cell lines derived from cancerous and normal breast tissue and found that in addition to mRNA levels, TβRIII protein levels were significantly reduced. Having previously identified that cancer-associated fibroblasts secrete greater levels of tumor promoting cytokines, we investigated the consequences of soluble-TβRIII (sTβRIII) on fibroblasts. Fibroblast conditioned medium was analyzed for 102 human secreted cytokines and distinct changes in response to sTβRIII were observed. Next, we used the fibroblast-conditioned medium to stimulate human monocyte cell line THP-1. These results indicate a distinct transcriptional response depending on sTβRIII treatment and whether it was derived from normal or cancerous breast tissue. We conclude that the effect of TβRIII has distinct roles not only in cancer-associated fibroblasts but that sTβRIII has distinct paracrine functions in the tumor microenvironment. PMID:27827906

  18. The boron abundance of Procyon

    NASA Technical Reports Server (NTRS)

    Lemke, Michael; Lambert, David L.; Edvardsson, Bengt

    1993-01-01

    The B I 2496.8 A resonance line and HST/GHRS echelle spectra are used with model atmospheres and synthetic spectra to derive the B abundance of the F dwarfs Procyon (Alpha Canis Minoris), Theta Ursae Majoris, and Iota Pegasi. The B abundance of Theta UMa and Iota Peg is similar to that derived by Boesgaard and Heacox (1978) from the B II resonance line in spectra of A- and B-type stars. These two dwarfs show normal abundances of Li, Be, and B. Procyon, which is highly depleted in Li and Be, is depleted in B by a factor of at least 3. Comparison of the spectra of Procyon and the halo dwarf HD 140283 shows that the B abundance assigned by Duncan et al. (1992) to three halo dwarfs is not greatly overestimated as a result of contamination of the B I line by an unidentified line.

  19. Ammonia abundances in four comets

    NASA Astrophysics Data System (ADS)

    Wyckoff, S.; Tegler, S. C.; Engel, L.

    1991-02-01

    NH2 emission band strengths were measured in four comets and the NH2 column densities were determined in order to measure the ammonia content of the comets. The mean ammonia/water abundance ratio derived for the four comets is found to be 0.13 + or - 0.06 percent, with no significant variation among the comets. The uniformity of this abundance attests to a remarkable degree of chemical homogeneity over large scales in the comet-forming region of the primordial solar nebula, and contrasts with the CO abundance variations found previously in comets. The N2 and NH3 abundances indicate a condensation temperature in the range 20-160 K, consistent with virtually all comet formation hypotheses.

  20. The boron abundance of Procyon

    NASA Astrophysics Data System (ADS)

    Lemke, Michael; Lambert, David L.; Edvardsson, Bengt

    1993-05-01

    The B I 2496.8 A resonance line and HST/GHRS echelle spectra are used with model atmospheres and synthetic spectra to derive the B abundance of the F dwarfs Procyon (Alpha Canis Minoris), Theta Ursae Majoris, and Iota Pegasi. The B abundance of Theta UMa and Iota Peg is similar to that derived by Boesgaard and Heacox (1978) from the B II resonance line in spectra of A- and B-type stars. These two dwarfs show normal abundances of Li, Be, and B. Procyon, which is highly depleted in Li and Be, is depleted in B by a factor of at least 3. Comparison of the spectra of Procyon and the halo dwarf HD 140283 shows that the B abundance assigned by Duncan et al. (1992) to three halo dwarfs is not greatly overestimated as a result of contamination of the B I line by an unidentified line.

  1. Chlorine Abundances in Cool Stars

    NASA Astrophysics Data System (ADS)

    Maas, Z. G.; Pilachowski, C. A.; Hinkle, K.

    2016-12-01

    Chlorine abundances are reported in 15 evolved giants and 1 M dwarf in the solar neighborhood. The Cl abundance was measured using the vibration-rotation 1-0 P8 line of H35Cl at 3.69851 μm. The high-resolution L-band spectra were observed using the Phoenix infrared spectrometer on the Kitt Peak Mayall 4 m telescope. The average [35Cl/Fe] abundance in stars with -0.72 < [Fe/H] < 0.20 is [35Cl/Fe] = (-0.10 ± 0.15) dex. The mean difference between the [35Cl/Fe] ratios measured in our stars and chemical evolution model values is (0.16 ± 0.15) dex. The [35Cl/Ca] ratio has an offset of ˜0.35 dex above model predictions, suggesting that chemical evolution models are underproducing Cl at the high metallicity range. Abundances of C, N, O, Si, and Ca were also measured in our spectral region and are consistent with F and G dwarfs. The Cl versus O abundances from our sample match Cl abundances measured in planetary nebula and H ii regions. In one star where both H35Cl and H37Cl could be measured, a 35Cl/37Cl isotope ratio of 2.2 ± 0.4 was found, consistent with values found in the Galactic ISM and predicted chemical evolution models.

  2. Solar and stellar photospheric abundances

    NASA Astrophysics Data System (ADS)

    Allende Prieto, Carlos

    2016-12-01

    The determination of photospheric abundances in late-type stars from spectroscopic observations is a well-established field, built on solid theoretical foundations. Improving those foundations to refine the accuracy of the inferred abundances has proven challenging, but progress has been made. In parallel, developments on instrumentation, chiefly regarding multi-object spectroscopy, have been spectacular, and a number of projects are collecting large numbers of observations for stars across the Milky Way and nearby galaxies, promising important advances in our understanding of galaxy formation and evolution. After providing a brief description of the basic physics and input data involved in the analysis of stellar spectra, a review is made of the analysis steps, and the available tools to cope with large observational efforts. The paper closes with a quick overview of relevant ongoing and planned spectroscopic surveys, and highlights of recent research on photospheric abundances.

  3. Robust Abundance Estimation in Animal Abundance Surveys with Imperfect Detection

    EPA Science Inventory

    Surveys of animal abundance are central to the conservation and management of living natural resources. However, detection uncertainty complicates the sampling process of many species. One sampling method employed to deal with this problem is depletion (or removal) surveys in whi...

  4. Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors

    SciTech Connect

    Greene, Carol Ann Chang, Chuan-Yuan; Fraser, Cameron J.; Nelidova, Dasha E.; Chen, Jing A.; Lim, Angela; Brebner, Alex; McGhee, Jennifer; Sherwin, Trevor; Green, Colin R.

    2014-03-10

    Cells thought to be stem cells isolated from the cornea of the eye have been shown to exhibit neurogenic potential. We set out to uncover the identity and location of these cells within the cornea and to elucidate their neuronal protein and gene expression profile during the process of switching to a neuron-like cell. Here we report that every cell of the adult human and rat corneal stroma is capable of differentiating into a neuron-like cell when treated with neurogenic differentiation specifying growth factors. Furthermore, the expression of genes regulating neurogenesis and mature neuronal structure and function was increased. The switch from a corneal stromal cell to a neuron-like cell was also shown to occur in vivo in intact corneas of living rats. Our results clearly indicate that lineage specifying growth factors can affect changes in the protein and gene expression profiles of adult cells, suggesting that possibly many adult cell populations can be made to switch into another type of mature cell by simply modifying the growth factor environment. - Highlights: • Adult corneal stromal cells can differentiated into neuron-like cells. • Neuronal specification of the adult stromal cell population is stochastic. • Neuronal specification in an adult cell population can be brought about by growth factors.

  5. Gluteal and abdominal subcutaneous adipose tissue depots as stroma cell source: gluteal cells display increased adipogenic and osteogenic differentiation potentials.

    PubMed

    Iwen, Karl Alexander; Priewe, Anna-Christin; Winnefeld, Marc; Rose, Christian; Siemers, Frank; Rohwedel, Jürgen; Cakiroglu, Figen; Lehnert, Hendrik; Schepky, Andreas; Klein, Johannes; Kramer, Jan

    2014-06-01

    Human adipose-derived stroma cells (ADSCs) have successfully been employed in explorative therapeutic studies. Current evidence suggests that ADSCs are unevenly distributed in subcutaneous adipose tissue; therefore, the anatomical origin of ADSCs may influence clinical outcomes. This study was designed to investigate proliferation and differentiation capacities of ADSCs from the gluteal and abdominal depot of 8 females. All had normal BMI (22.01 ± 0.39 kg/m(2) ) and waist circumference (81.13 ± 2.33 cm). Examination by physicians and analysis of 31 laboratory parameters did not reveal possibly confounding medical disorders. Gluteal and abdominal adipose tissue was sampled by en bloc resection on day 7 (±1) after the last menses. Histological examination did not reveal significant depot-specific differences. As assessed by BrdU assay, proliferation of cells from both depots was similar after 24 h and analysis of 15 cell surface markers by flow cytometry identified the isolated cells as ADSCs, again without depot-specific differences. ADSCs from both depots differentiated poorly to chondroblasts. Gluteal ADSCs displayed significantly higher adipogenic differentiation potential than abdominal cells. Osteogenic differentiation was most pronounced in gluteal cells, whereas differentiation of abdominal ADSCs was severely impaired. Our data demonstrate a depot-specific difference in ADSC differentiation potential with abdominal cells failing to meet the criteria of multipotent ADSCs. This finding should be taken into account in future explorations of ADSC-derived therapeutic strategies.

  6. Abnormalities of Thymic Stroma may Contribute to Immune Dysregulation in Murine Models of Leaky Severe Combined Immunodeficiency

    PubMed Central

    Rucci, Francesca; Poliani, Pietro Luigi; Caraffi, Stefano; Paganini, Tiziana; Fontana, Elena; Giliani, Silvia; Alt, Frederick W.; Notarangelo, Luigi Daniele

    2011-01-01

    Lymphostromal cross-talk in the thymus is essential to allow generation of a diversified repertoire of T lymphocytes and to prevent autoimmunity by self-reactive T cells. Hypomorphic mutations in genes that control T cell development have been associated with immunodeficiency and immune dysregulation both in humans and in mice. We have studied T cell development and thymic stroma architecture and maturation in two mouse models of leaky severe combined immune deficiency, carrying hypomorphic mutations in rag1 and lig4 genes. Defective T cell development was associated with abnormalities of thymic architecture that predominantly affect the thymic medulla, with reduction of the pool of mature medullary thymic epithelial cells (mTECs). While the ability of mTECs to express autoimmune regulator (Aire) is preserved in mutant mice, the frequency of mature mTECs expressing Aire and tissue-specific antigens is severely reduced. Similarly, the ability of CD4+ T cells to differentiate into Foxp3+ natural regulatory T cells is preserved in rag1 and lig4 mutant mice, but their number is greatly reduced. These data indicate that hypomorphic defects in T cell development may cause defective lymphostromal cross-talk and impinge on thymic stromal cells maturation, and thus favor immune dysregulation. PMID:21822418

  7. Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma.

    PubMed

    Chmielewski, Markus; Hombach, Andreas A; Abken, Hinrich

    2014-01-01

    Adoptive T-cell therapy recently achieved impressive efficacy in early phase trials, in particular in hematologic malignancies, strongly supporting the notion that the immune system can control cancer. A current strategy of favor is based on ex vivo-engineered patient T cells, which are redirected by a chimeric antigen receptor (CAR) and recognize a predefined target by an antibody-derived binding domain. Such CAR T cells can substantially reduce the tumor burden as long as the targeted antigen is present on the cancer cells. However, given the tremendous phenotypic diversity in solid tumor lesions, a reasonable number of cancer cells are not recognized by a given CAR, considerably reducing the therapeutic success. This article reviews a recently described strategy for overcoming this shortcoming of the CAR T-cell therapy by modulating the tumor stroma by a CAR T-cell-secreted transgenic cytokine like interleukin-12 (IL-12). The basic process is that CAR T cells, when activated by their CAR, deposit IL-12 in the targeted tumor lesion, which in turn attracts an innate immune cell response toward those cancer cells that are invisible to CAR T cells. Such TRUCKs, T cells redirected for universal cytokine-mediated killing, exhibited remarkable efficacy against solid tumors with diverse cancer cell phenotypes, suggesting their evaluation in clinical trials.

  8. Tumor Stroma Engraftment of Gene-Modified Mesenchymal Stem Cells as Anti-Tumor Therapy against Ovarian Cancer

    PubMed Central

    Dembinski, Jennifer L.; Wilson, Shanna M.; Spaeth, Erika L.; Studeny, Matus; Zompetta, Claudia; Samudio, Ismael; Roby, Katherine; Andreeff, Michael; Marini, Frank C.

    2013-01-01

    Many ovarian cancers originate from ovarian surface epithelium, where they develop from cysts intermixed with stroma. The stromal layer is critical to the progression and survival of the neoplasm and consequently is recruited into the tumor microenvironment. Using both syngenic mouse tumors (ID8-R), and human xenograft (OVCAR3, SKOV3) tumor models, we first confirmed intraperitoneally-circulating MSC could target, preferentially engraft and differentiate into α-SMA+ myofibroblasts, suggesting their role as “reactive stroma” in ovarian carcinoma development and confirming their potential as a targeted delivery vehicle for the intratumoral production of interferon-beta (IFNβ). Then, mice with ovarian carcinomas received weekly IP injections of IFNβ expressing MSC, resulting in complete eradication of tumors in 70% of treated OVCAR3 mice (P = 0.004) and an increased survival of treated SKOV3 mice compared with controls (P = 0.01). Similar tumor growth control was observed using murine IFNβ delivered by murine MSC in ID8-R ovarian carcinoma. As a potential mechanism of tumor killing, MSC produced IFNβ induced caspase-dependent tumor cell apoptosis. Our results demonstrate that ovarian carcinoma engraft MSC to participate in myofibrovascular networks and that IFNβ produced by MSC intratumorally modulates tumor kinetics, resulting in prolonged survival. PMID:23260083

  9. Comparison of in vitro-cultivation of human mesenchymal stroma/stem cells derived from bone marrow and umbilical cord.

    PubMed

    Hoffmann, Andrea; Floerkemeier, Thilo; Melzer, Catharina; Hass, Ralf

    2016-04-28

    Cell-mediated therapy is currently considered as a novel approach for many human diseases. Potential uses range from topic applications with the regeneration of confined tissue areas to systemic applications. Stem cells including mesenchymal stroma/stem cells (MSCs) represent a highly attractive option. Their potential to cure or alleviate human diseases is investigated in a number of clinical trials. A wide variety of methods has been established in the past years for isolation, cultivation and characterization of human MSCs as expansion is presently deemed a prerequisite for clinical application with high numbers of cells carrying reproducible properties. MSCs have been retrieved from various tissues and used in a multitude of settings whereby numerous experimental protocols are available for expansion of MSCs in vitro. Accordingly, different isolation, culture and upscaling techniques contribute to the heterogeneity of MSC characteristics and the, sometimes, controversial results. Therefore, this review discusses and summarizes certain experimental conditions for MSC in vitro culture focusing on adult bone marrow-derived and neonatal umbilical cord-derived MSCs in order to enhance our understanding for MSC tissue sources and to stratify different procedures. Copyright © 2016 John Wiley & Sons, Ltd.

  10. A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFα-TGFα-EGFR.

    PubMed

    Lau, T-S; Chan, L K-Y; Wong, E C-H; Hui, C W-C; Sneddon, K; Cheung, T-H; Yim, S-F; Lee, J H-S; Yeung, C S-Y; Chung, T K-H; Kwong, J

    2017-02-06

    Peritoneum is the most common site for ovarian cancer metastasis. Here we investigate how cancer epigenetics regulates reciprocal tumor-stromal interactions in peritoneal metastasis of ovarian cancer. Firstly, we find that omental stromal fibroblasts enhance colony formation of metastatic ovarian cancer cells, and de novo expression of transforming growth factor-alpha (TGF-α) is induced in stromal fibroblasts co-cultured with ovarian cancer cells. We also observed an over-expression of tumor necrosis factor-alpha (TNF-α) in ovarian cancer cells, which is regulated by promoter DNA hypomethylation as well as chromatin remodeling. Interestingly, this ovarian cancer-derived TNF-α induces TGF-α transcription in stromal fibroblasts through nuclear factor-κB (NF-κB). We further show that TGF-α secreted by stromal fibroblasts in turn promotes peritoneal metastasis of ovarian cancer through epidermal growth factor receptor (EGFR) signaling. Finally, we identify a TNFα-TGFα-EGFR interacting loop between tumor and stromal compartments of human omental metastases. Our results therefore demonstrate cancer epigenetics induces a loop of cancer-stroma-cancer interaction in omental microenvironment that promotes peritoneal metastasis of ovarian cancer cells via TNFα-TGFα-EGFR.Oncogene advance online publication, 6 February 2017; doi:10.1038/onc.2016.509.

  11. IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer

    NASA Astrophysics Data System (ADS)

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M.; Zhou, Zhiyang; Wang, Liya; Wang, Andrew; Mao, Hui; Yang, Lily

    2016-05-01

    Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer.

  12. Concentrative uptake of cyclic ADP-ribose generated by BST-1+ stroma stimulates proliferation of human hematopoietic progenitors.

    PubMed

    Podestà, Marina; Benvenuto, Federica; Pitto, Anna; Figari, Osvaldo; Bacigalupo, Andrea; Bruzzone, Santina; Guida, Lucrezia; Franco, Luisa; Paleari, Laura; Bodrato, Nicoletta; Usai, Cesare; De Flora, Antonio; Zocchi, Elena

    2005-02-18

    Cyclic ADP-ribose (cADPR) is an intracellular calcium mobilizer generated from NAD(+) by the ADP-ribosyl cyclases CD38 and BST-1. cADPR, both exogenously added and paracrinally produced by a CD38(+) feeder layer, has recently been demonstrated to stimulate the in vitro proliferation of human hemopoietic progenitors (HP) and also the in vivo expansion of hemopoietic stem cells. The low density of BST-1 expression on bone marrow (BM) stromal cells and the low specific activity of the enzyme made it unclear whether cADPR generation by a BST-1(+) stroma could stimulate HP proliferation in the BM microenvironment. We developed and characterized two BST-1(+) stromal cell lines, expressing an ectocellular cyclase activity similar to that of BST-1(+) human mesenchymal stem cells, the precursors of BM stromal cells. Long term co-culture of cord blood-derived HP over these BST-1(+) feeders determined their expansion. Influx of paracrinally generated cADPR into clonogenic HP was mediated by a concentrative, nitrobenzylthioinosine- and dipyridamole-inhibitable nucleoside transporter, this providing a possible explanation to the effectiveness of the hormone-like concentrations of the cyclic nucleotide measured in the medium conditioned by BST-1(+) feeders. These results suggest that the BST-1-catalyzed generation of extracellular cADPR, followed by the concentrative uptake of the cyclic nucleotide by HP, may be physiologically relevant in normal hemopoiesis.

  13. IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer

    PubMed Central

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M.; Zhou, Zhiyang; Wang, Liya; Wang, Andrew; Mao, Hui

    2016-01-01

    Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer. PMID:27313332

  14. Proteome Analysis During Chondrocyte Differentiation in a New Chondrogenesis Model Using Human Umbilical Cord Stroma Mesenchymal Stem Cells*

    PubMed Central

    De la Fuente, Alexandre; Mateos, Jesús; Lesende-Rodríguez, Iván; Calamia, Valentina; Fuentes-Boquete, Isaac; de Toro, Francisco J.; Arufe, Maria C.; Blanco, Francisco J.

    2012-01-01

    Umbilical cord stroma mesenchymal stem cells were differentiated toward chondrocyte-like cells using a new in vitro model that consists of the random formation of spheroids in a medium supplemented with fetal bovine serum on a nonadherent surface. The medium was changed after 2 days to one specific for the induction of chondrocyte differentiation. We assessed this model using reverse transcriptase-polymerase chain reaction, flow cytometry, immunohistochemistry, and secretome analyses. The purpose of this study was to determine which proteins were differentially expressed during chondrogenesis. Differential gel electrophoresis analysis was performed, followed by matrix-assisted laser desorption/ionization mass spectrometry protein identification. A total of 97 spots were modulated during the chondrogenesis process, 54 of these spots were identified as 39 different proteins and 15 were isoforms. Of the 39 different proteins identified 15 were down-regulated, 21 were up-regulated, and 3 were up- and down-regulated during the chondrogenesis process. Using Pathway Studio 7.0 software, our results showed that the major cell functions modulated during chondrogenesis were cellular differentiation, proliferation, and migration. Five proteins involved in cartilage extracellular matrix metabolism found during the differential gel electrophoresis study were confirmed using Western blot. The results indicate that our in vitro chondrogenesis model is an efficient and rapid technique for obtaining cells similar to chondrocytes that express proteins characteristic of the cartilage extracellular matrix. These chondrocyte-like cells could prove useful for future cell therapy treatment of cartilage pathologies. PMID:22008206

  15. Proteome analysis during chondrocyte differentiation in a new chondrogenesis model using human umbilical cord stroma mesenchymal stem cells.

    PubMed

    De la Fuente, Alexandre; Mateos, Jesús; Lesende-Rodríguez, Iván; Calamia, Valentina; Fuentes-Boquete, Isaac; de Toro, Francisco J; Arufe, Maria C; Blanco, Francisco J

    2012-02-01

    Umbilical cord stroma mesenchymal stem cells were differentiated toward chondrocyte-like cells using a new in vitro model that consists of the random formation of spheroids in a medium supplemented with fetal bovine serum on a nonadherent surface. The medium was changed after 2 days to one specific for the induction of chondrocyte differentiation. We assessed this model using reverse transcriptase-polymerase chain reaction, flow cytometry, immunohistochemistry, and secretome analyses. The purpose of this study was to determine which proteins were differentially expressed during chondrogenesis. Differential gel electrophoresis analysis was performed, followed by matrix-assisted laser desorption/ionization mass spectrometry protein identification. A total of 97 spots were modulated during the chondrogenesis process, 54 of these spots were identified as 39 different proteins and 15 were isoforms. Of the 39 different proteins identified 15 were down-regulated, 21 were up-regulated, and 3 were up- and down-regulated during the chondrogenesis process. Using Pathway Studio 7.0 software, our results showed that the major cell functions modulated during chondrogenesis were cellular differentiation, proliferation, and migration. Five proteins involved in cartilage extracellular matrix metabolism found during the differential gel electrophoresis study were confirmed using Western blot. The results indicate that our in vitro chondrogenesis model is an efficient and rapid technique for obtaining cells similar to chondrocytes that express proteins characteristic of the cartilage extracellular matrix. These chondrocyte-like cells could prove useful for future cell therapy treatment of cartilage pathologies.

  16. Quantitation of Murine Stroma and Selective Purification of the Human Tumor Component of Patient-Derived Xenografts for Genomic Analysis.

    PubMed

    Schneeberger, Valentina E; Allaj, Viola; Gardner, Eric E; Poirier, J T; Rudin, Charles M

    2016-01-01

    Patient-derived xenograft (PDX) mouse models are increasingly used for preclinical therapeutic testing of human cancer. A limitation in molecular and genetic characterization of PDX tumors is the presence of integral murine stroma. This is particularly problematic for genomic sequencing of PDX models. Rapid and dependable approaches for quantitating stromal content and purifying the malignant human component of these tumors are needed. We used a recently developed technique exploiting species-specific polymerase chain reaction (PCR) amplicon length (ssPAL) differences to define the fractional composition of murine and human DNA, which was proportional to the fractional composition of cells in a series of lung cancer PDX lines. We compared four methods of human cancer cell isolation: fluorescence-activated cell sorting (FACS), an immunomagnetic mouse cell depletion (MCD) approach, and two distinct EpCAM-based immunomagnetic positive selection methods. We further analyzed DNA extracted from the resulting enriched human cancer cells by targeted sequencing using a clinically validated multi-gene panel. Stromal content varied widely among tumors of similar histology, but appeared stable over multiple serial tumor passages of an individual model. FACS and MCD were superior to either positive selection approach, especially in cases of high stromal content, and consistently allowed high quality human-specific genomic profiling. ssPAL is a dependable approach to quantitation of murine stromal content, and MCD is a simple, efficient, and high yield approach to human cancer cell isolation for genomic analysis of PDX tumors.

  17. Quantitation of Murine Stroma and Selective Purification of the Human Tumor Component of Patient-Derived Xenografts for Genomic Analysis

    PubMed Central

    Schneeberger, Valentina E.; Allaj, Viola; Gardner, Eric E.; Rudin, Charles M.

    2016-01-01

    Patient-derived xenograft (PDX) mouse models are increasingly used for preclinical therapeutic testing of human cancer. A limitation in molecular and genetic characterization of PDX tumors is the presence of integral murine stroma. This is particularly problematic for genomic sequencing of PDX models. Rapid and dependable approaches for quantitating stromal content and purifying the malignant human component of these tumors are needed. We used a recently developed technique exploiting species-specific polymerase chain reaction (PCR) amplicon length (ssPAL) differences to define the fractional composition of murine and human DNA, which was proportional to the fractional composition of cells in a series of lung cancer PDX lines. We compared four methods of human cancer cell isolation: fluorescence-activated cell sorting (FACS), an immunomagnetic mouse cell depletion (MCD) approach, and two distinct EpCAM-based immunomagnetic positive selection methods. We further analyzed DNA extracted from the resulting enriched human cancer cells by targeted sequencing using a clinically validated multi-gene panel. Stromal content varied widely among tumors of similar histology, but appeared stable over multiple serial tumor passages of an individual model. FACS and MCD were superior to either positive selection approach, especially in cases of high stromal content, and consistently allowed high quality human-specific genomic profiling. ssPAL is a dependable approach to quantitation of murine stromal content, and MCD is a simple, efficient, and high yield approach to human cancer cell isolation for genomic analysis of PDX tumors. PMID:27611664

  18. Role of Human Corneal Stroma-Derived Mesenchymal-Like Stem Cells in Corneal Immunity and Wound Healing

    PubMed Central

    Veréb, Zoltán; Póliska, Szilárd; Albert, Réka; Olstad, Ole Kristoffer; Boratkó, Anita; Csortos, Csilla; Moe, Morten C.; Facskó, Andrea; Petrovski, Goran

    2016-01-01

    Corneal tissue regeneration is of crucial importance for maintaining normal vision. We aimed to isolate and cultivate human corneal stroma-derived mesenchymal stem-like cells (CSMSCs) from the central part of cadaver corneas and study their phenotype, multipotency, role in immunity and wound healing. The isolated cells grew as monolayers in vitro, expressed mesenchymal- and stemness-related surface markers (CD73, CD90, CD105, CD140b), and were negative for hematopoietic markers as determined by flow cytometry. CSMSCs were able to differentiate in vitro into fat, bone and cartilage. Their gene expression profile was closer to bone marrow-derived MSCs (BMMSCs) than to limbal epithelial stem cells (LESC) as determined by high-throughput screening. The immunosuppressive properties of CSMSCs were confirmed by a mixed lymphocyte reaction (MLR), while they could inhibit proliferation of activated immune cells. Treatment of CSMSCs by pro-inflammatory cytokines and toll-like receptor ligands significantly increased the secreted interleukin-6 (IL-6), interleukin-8 (IL-8) and C-X-C motif chemokine 10 (CXCL-10) levels, as well as the cell surface adhesion molecules. CSMSCs were capable of closing a wound in vitro under different stimuli. These cells thus contribute to corneal tissue homeostasis and play an immunomodulatory and regenerative role with possible implications in future cell therapies for treating sight-threatening corneal diseases. PMID:27195722

  19. Stroma derived COL6A3 is a potential prognosis marker of colorectal carcinoma revealed by quantitative proteomics

    PubMed Central

    Chen, Sun-Xia; Wang, Xiao-Qing; Cui, Shu-Jian; Liu, Xiao-Hui; Jiang, Ying-Hua; Wang, Jie; Zhang, Yang; Yang, Peng-Yuan; Liu, Feng

    2015-01-01

    Colorectal cancer (CRC) represents the third most common cancer in males and second in females worldwide. Here, we performed a quantitative 8-plex iTRAQ proteomics analysis of the secreted proteins from five colonic fibroblast cultures and three colon cancer epithelial cell lines. We identified 1114 proteins at 0% FDR, including 587 potential secreted proteins. We further recognized 116 fibroblast-enriched proteins which were significantly associated with cell movement, angiogenesis, proliferation and wound healing, and 44 epithelial cell-enriched proteins. By interrogation of Oncomine database, we found that 20 and 8 fibroblast-enriched proteins were up- and downregulated in CRC, respectively. Western blots confirmed the fibroblast-specific secretion of filamin C, COL6A3, COL4A1 and spondin-2. Upregulated mRNA and stroma expression of COL6A3 in CRC, which were revealed by Oncomine analyses and tissue-microarray-immunohistochemistry, indicated poor prognosis. COL6A3 expression was significantly associated with Dukes stage, T stage, stage, recurrence and smoking status. Circulating plasma COL6A3 in CRC patients was upregulated significantly comparing with healthy peoples. Receiver operating characteristic curve analysis revealed that COL6A3 has better predictive performance for CRC with an area under the curve of 0.885 and the best sensitivity/specificity of 92.9%/81.3%. Thus we demonstrated that COL6A3 was a potential diagnosis and prognosis marker of CRC. PMID:26338966

  20. The solar abundance of beryllium

    NASA Technical Reports Server (NTRS)

    Ross, J. E.; Aller, L. H.

    1974-01-01

    The solar abundance of beryllium is deduced from high-resolution Kitt Peak observations of the 3130.43- and 3131.08-A lines of Be II interpreted by the method of spectrum synthesis. The results are in good agreement with those previously obtained by Grevesse (1968) and by Hauge and Engvold (1968) and indicate that in the photospheric layers, beryllium is depleted below the chondritic value by a factor of about two. It is found that the beryllium abundance is equal to logN(Be)/N(H) + 12 = 1.08 plus or minus 0.05.

  1. Toward automatic segmentation and quantification of tumor and stroma in whole-slide images of H and E stained rectal carcinomas

    NASA Astrophysics Data System (ADS)

    Geessink, Oscar G. F.; Baidoshvili, Alexi; Freling, Gerard; Klaase, Joost M.; Slump, Cornelis H.; van der Heijden, Ferdinand

    2015-03-01

    Visual estimation of tumor and stroma proportions in microscopy images yields a strong, Tumor-(lymph)Node- Metastasis (TNM) classification-independent predictor for patient survival in colorectal cancer. Therefore, it is also a potent (contra)indicator for adjuvant chemotherapy. However, quantification of tumor and stroma through visual estimation is highly subject to intra- and inter-observer variability. The aim of this study is to develop and clinically validate a method for objective quantification of tumor and stroma in standard hematoxylin and eosin (H and E) stained microscopy slides of rectal carcinomas. A tissue segmentation algorithm, based on supervised machine learning and pixel classification, was developed, trained and validated using histological slides that were prepared from surgically excised rectal carcinomas in patients who had not received neoadjuvant chemotherapy and/or radiotherapy. Whole-slide scanning was performed at 20× magnification. A total of 40 images (4 million pixels each) were extracted from 20 whole-slide images at sites showing various relative proportions of tumor and stroma. Experienced pathologists provided detailed annotations for every extracted image. The performance of the algorithm was evaluated using cross-validation by testing on 1 image at a time while using the other 39 images for training. The total classification error of the algorithm was 9.4% (SD = 3.2%). Compared to visual estimation by pathologists, the algorithm was 7.3 times (P = 0.033) more accurate in quantifying tissues, also showing 60% less variability. Automatic tissue quantification was shown to be both reliable and practicable. We ultimately intend to facilitate refined prognostic stratification of (colo)rectal cancer patients and enable better personalized treatment.

  2. Loss of caveolin-1 in prostate cancer stroma correlates with reduced relapse-free survival and is functionally relevant to tumour progression.

    PubMed

    Ayala, Gustavo; Morello, Matteo; Frolov, Anna; You, Sungyong; Li, Rile; Rosati, Fabiana; Bartolucci, Gianluca; Danza, Giovanna; Adam, Rosalyn M; Thompson, Timothy C; Lisanti, Michael P; Freeman, Michael R; Di Vizio, Dolores

    2013-09-01

    Levels of caveolin-1 (Cav-1) in tumour epithelial cells increase during prostate cancer progression. Conversely, Cav-1 expression in the stroma can decline in advanced and metastatic prostate cancer. In a large cohort of 724 prostate cancers, we observed significantly decreased levels of stromal Cav-1 in concordance with increased Gleason score (p = 0.012). Importantly, reduced expression of Cav-1 in the stroma correlated with reduced relapse-free survival (p = 0.009), suggesting a role for stromal Cav-1 in inhibiting advanced disease. Silencing of Cav-1 by shRNA in WPMY-1 prostate fibroblasts resulted in up-regulation of Akt phosphorylation, and significantly altered expression of genes involved in angiogenesis, invasion, and metastasis, including a > 2.5-fold increase in TGF-β1 and γ-synuclein (SNCG) gene expression. Moreover, silencing of Cav-1 induced migration of prostate cancer cells when stromal cells were used as attractants. Pharmacological inhibition of Akt caused down-regulation of TGF-β1 and SNCG, suggesting that loss of Cav-1 in the stroma can influence Akt-mediated signalling in the tumour microenvironment. Cav-1-depleted stromal cells exhibited increased levels of intracellular cholesterol, a precursor for androgen biosynthesis, steroidogenic enzymes, and testosterone. These findings suggest that loss of Cav-1 in the tumour microenvironment contributes to the metastatic behaviour of tumour cells by a mechanism that involves up-regulation of TGF-β1 and SNCG through Akt activation. They also suggest that intracrine production of androgens, a process relevant to castration resistance, may occur in the stroma.

  3. Loss of caveolin-1 in prostate cancer stroma correlates with reduced relapse-free survival and is functionally relevant to tumour progression

    PubMed Central

    Frolov, Anna; You, Sungyong; Li, Rile; Rosati, Fabiana; Bartolucci, Gianluca; Danza, Giovanna; Adam, Rosalyn M; Thompson, Timothy C; Lisanti, Michael P; Freeman, Michael R; Vizio, Dolores Di

    2014-01-01

    Levels of caveolin-1 (Cav-1) in tumour epithelial cells increase during prostate cancer progression. Conversely, Cav-1 expression in the stroma can decline in advanced and metastatic prostate cancer. In a large cohort of 724 prostate cancers, we observed significantly decreased levels of stromal Cav-1 in concordance with increased Gleason score (p = 0.012). Importantly, reduced expression of Cav-1 in the stroma correlated with reduced relapse-free survival (p = 0.009), suggesting a role for stromal Cav-1 in inhibiting advanced disease. Silencing of Cav-1 by shRNA in WPMY-1 prostate fibroblasts resulted in up-regulation of Akt phosphorylation, and significantly altered expression of genes involved in angiogenesis, invasion, and metastasis, including a > 2.5-fold increase in TGF-β1 and γ-synuclein (SNCG) gene expression. Moreover, silencing of Cav-1 induced migration of prostate cancer cells when stromal cells were used as attractants. Pharmacological inhibition of Akt caused down-regulation of TGF-β1 and SNCG, suggesting that loss of Cav-1 in the stroma can influence Akt-mediated signalling in the tumour microenvironment. Cav-1-depleted stromal cells exhibited increased levels of intracellular cholesterol, a precursor for androgen biosynthesis, steroidogenic enzymes, and testosterone. These findings suggest that loss of Cav-1 in the tumour microenvironment contributes to the metastatic behaviour of tumour cells by a mechanism that involves up-regulation of TGF-β1 and SNCG through Akt activation. They also suggest that intracrine production of androgens, a process relevant to castration resistance, may occur in the stroma. PMID:23729330

  4. Prognostic value, localization and correlation of PD-1/PD-L1, CD8 and FOXP3 with the desmoplastic stroma in pancreatic ductal adenocarcinoma

    PubMed Central

    Diana, Angela; Wang, Lai Mun; D'Costa, Zenobia; Allen, Paul; Azad, Abul; Silva, Michael A.; Soonawalla, Zahir; Liu, Stanley; McKenna, W. Gillies; Muschel, Ruth J.; Fokas, Emmanouil

    2016-01-01

    We examined the prognostic value of programmed cell death-1 (PD-1) and its ligand (PD-L1) together with CD8+ tumor-infiltrating lymphocytes (TILs) and FOXP3+ Tregs in resectable pancreatic ductal adenocarcinoma (PDAC) samples treated with adjuvant chemotherapy. Whole-mount FFPE tissue sections from 145 pancreatectomies were immunohistochemically stained for PD-1, PD-L1, CD8 and FOXP3. Their expression was correlated with clinicopathological characteristics, and overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), in the context of stroma density (haematoxylin-eosin) and activity (alpha-smooth muscle actin) and in regard to intratumoral lymphoid aggregates. The median OS was 21 months after a mean follow-up of 20 months (range, 2-69 months). In multivariate analysis, high PD-1+ TILs expression was associated with better OS (p = 0.049), LPFS (p = 0.017) and DMFS (p = 0.021). Similar findings were observed for CD8+ TILs, whereas FOXP3 and PD-L1 lacked prognostic significance. Although TIL distribution was heterogeneous, tumors of high stroma density had higher infiltration of CD8+ TILs than loose density stroma and vice versa (p < 0.001), whereas no correlation was found with stromal activity. Sixty (41.4%) tumors contained lymphoid aggregates and the presence of PD-1+ TILs was associated with better OS (p = 0.030), LPFS (p = 0.025) and DMFS (p = 0.033), whereas CD8+ TILs only correlated with superior LPFS (p = 0.039). PD-1+ and CD8+ TILs constitute independent prognostic markers in patients with PDAC treated with adjuvant chemotherapy. Our study provides important insight on the role of PD-1/PD-L1 in the context of desmoplastic stroma and could help guide future immunotherapies in PDAC. PMID:27329602

  5. THE SOLAR FLARE IRON ABUNDANCE

    SciTech Connect

    Phillips, K. J. H.; Dennis, B. R. E-mail: Brian.R.Dennis@nasa.gov

    2012-03-20

    The abundance of iron is measured from emission line complexes at 6.65 keV (Fe line) and 8 keV (Fe/Ni line) in RHESSI X-ray spectra during solar flares. Spectra during long-duration flares with steady declines were selected, with an isothermal assumption and improved data analysis methods over previous work. Two spectral fitting models give comparable results, viz., an iron abundance that is lower than previous coronal values but higher than photospheric values. In the preferred method, the estimated Fe abundance is A(Fe) = 7.91 {+-} 0.10 (on a logarithmic scale, with A(H) = 12) or 2.6 {+-} 0.6 times the photospheric Fe abundance. Our estimate is based on a detailed analysis of 1898 spectra taken during 20 flares. No variation from flare to flare is indicated. This argues for a fractionation mechanism similar to quiet-Sun plasma. The new value of A(Fe) has important implications for radiation loss curves, which are estimated.

  6. Multipotent nestin-positive stem cells reside in the stroma of human eccrine and apocrine sweat glands and can be propagated robustly in vitro.

    PubMed

    Nagel, Sabine; Rohr, Franziska; Weber, Caroline; Kier, Janina; Siemers, Frank; Kruse, Charli; Danner, Sandra; Brandenburger, Matthias; Matthiessen, Anna Emilia

    2013-01-01

    Human skin harbours multiple different stem cell populations. In contrast to the relatively well-characterized niches of epidermal and hair follicle stem cells, the localization and niches of stem cells in other human skin compartments are as yet insufficiently investigated. Previously, we had shown in a pilot study that human sweat gland stroma contains Nestin-positive stem cells. Isolated sweat gland stroma-derived stem cells (SGSCs) proliferated in vitro and expressed Nestin in 80% of the cells. In this study, we were able to determine the precise localization of Nestin-positive cells in both eccrine and apocrine sweat glands of human axillary skin. We established a reproducible isolation procedure and characterized the spontaneous, long-lasting multipotent differentiation capacity of SGSCs. Thereby, a pronounced ectodermal differentiation was observed. Moreover, the secretion of prominent cytokines demonstrated the immunological potential of SGSCs. The comparison to human adult epidermal stem cells (EpiSCs) and bone marrow stem cells (BMSCs) revealed differences in protein expression and differentiation capacity. Furthermore, we found a coexpression of the stem cell markers Nestin and Iα6 within SGSCs and human sweat gland stroma. In conclusion the initial results of the pilot study were confirmed, indicating that human sweat glands are a new source of unique stem cells with multilineage differentiation potential, high proliferation capacity and remarkable self renewal. With regard to the easy accessibility of skin tissue biopsies, an autologous application of SGSCs in clinical therapies appears promising.

  7. The effects of stroma-free and dextran-conjugated hemoglobin on hemodynamics and carotid blood flow in hemorrhaged guinea pigs.

    PubMed

    Caron, A; Menu, P; Faivre-Fiorina, B; Labrude, P; Vigneron, C

    1999-01-01

    Hemoglobin solutions are potential resuscitative fluids with volume expanding and oxygen delivery abilities developed to reduce the use of blood transfusion. Most hemoglobin solutions in clinical trials increase transiently arterial pressure by inhibiting nitric oxide-dependent vasodilation. Our objective was to compare the effects on central hemodynamics and carotid blood flow of two hemoglobin solutions after resuscitation from hemorrhage in anesthetized guinea pigs. After anesthesia and instrumentation, severe hemorrhage was induced by withdrawing 50% of the blood volume. Resuscitation was performed after 15 min of hypovolemia with 5% albumin, stroma-free hemoglobin, or hemoglobin conjugated to dextran-benzenetetracarboxylate (Dex-BTC-Hb). The mean arterial pressure (MAP), carotid blood flow (CBF), vascular resistance index and heart rate (HR) were monitored for 3 hours after resuscitation. After hemorrhage, MAP and CBF dropped to 57.6 +/- 4.4% and 58.9 +/- 3.7% of control values respectively. Albumin failed to maintain hemodynamics in the decompensatory phase of shock. Both hemoglobin solutions gave rise to a transient increase in MAP (35%); stroma-free hemoglobin increased the CBF (150%) and resistance index (24%) whereas Dex-BTC-Hb had no effect on CBF and vascular resistances. None of the solutions affected the HR. Modified hemoglobin has attenuated effects on CBF and resistance index compared to stroma-free hemoglobin. This may be due to a balance between the stimulation of nitric oxide synthesis by shear-stress and the inhibition of vasodilation by nitric oxide trapping.

  8. Prognostic value and clinicopathological features of PD-1/PD-L1 expression with mismatch repair status and desmoplastic stroma in Chinese patients with pancreatic cancer.

    PubMed

    Wang, Yu; Lin, Jiacheng; Cui, Jiujie; Han, Ting; Jiao, Feng; Meng, Zhuo; Wang, Liwei

    2017-02-07

    Pancreatic cancer (PC) is a highly lethal cancer. Thus, the immune molecular markers which help to select PC patients are especially important. In this study, we aimed at systematically analyzing the expression of MLH1, MSH2, PD-L1 and PD-1, investigate their clinical significance and prognostic value. We found that high expression of PD-L1 on cancer cell membranes correlated with lymph node metastasis (P = 0.033) and strongly correlated with poor-differentiation (P = 0.008); high expression of PD-1 on cell membranes of T-cells correlated with well-differentiation (P = 0.018) and strongly correlated with advanced T stage (P = 0.004); high PD-1 expression was associated with a significantly superior OS and was an independent prognostic factor (P = 0.031). Then we found an inverse correlation between MSH2 expression and PD-L1 expression (Spearman correlation coefficient r = -0.295, P = 0.004). In subgroup analyses, we observed that PD-1 expression level was associated with OS only at low PD-L1 expression subgroup (P = 0.021). Finally, when we stratified the cases into four subgroups based on PD-1 expression and stroma density, we found that patients with high PD-1 expression and dense stroma had a better OS, while patients with low PD-1 expression and moderate stroma showed a worst outcome. Our result may provide more effective molecular markers for immunotherapeutic strategies of PC patients in clinical practice.

  9. Abundance estimation and conservation biology

    USGS Publications Warehouse

    Nichols, J.D.; MacKenzie, D.I.

    2004-01-01

    Abundance is the state variable of interest in most population–level ecological research and in most programs involving management and conservation of animal populations. Abundance is the single parameter of interest in capture–recapture models for closed populations (e.g., Darroch, 1958; Otis et al., 1978; Chao, 2001). The initial capture–recapture models developed for partially (Darroch, 1959) and completely (Jolly, 1965; Seber, 1965) open populations represented efforts to relax the restrictive assumption of population closure for the purpose of estimating abundance. Subsequent emphases in capture–recapture work were on survival rate estimation in the 1970’s and 1980’s (e.g., Burnham et al., 1987; Lebreton et al.,1992), and on movement estimation in the 1990’s (Brownie et al., 1993; Schwarz et al., 1993). However, from the mid–1990’s until the present time, capture–recapture investigators have expressed a renewed interest in abundance and related parameters (Pradel, 1996; Schwarz & Arnason, 1996; Schwarz, 2001). The focus of this session was abundance, and presentations covered topics ranging from estimation of abundance and rate of change in abundance, to inferences about the demographic processes underlying changes in abundance, to occupancy as a surrogate of abundance. The plenary paper by Link & Barker (2004) is provocative and very interesting, and it contains a number of important messages and suggestions. Link & Barker (2004) emphasize that the increasing complexity of capture–recapture models has resulted in large numbers of parameters and that a challenge to ecologists is to extract ecological signals from this complexity. They offer hierarchical models as a natural approach to inference in which traditional parameters are viewed as realizations of stochastic processes. These processes are governed by hyperparameters, and the inferential approach focuses on these hyperparameters. Link & Barker (2004) also suggest that our attention

  10. Actinide abundances in ordinary chondrites

    USGS Publications Warehouse

    Hagee, B.; Bernatowicz, T.J.; Podosek, F.A.; Johnson, M.L.; Burnett, D.S.; Tatsumoto, M.

    1990-01-01

    Measurements of 244Pu fission Xe, U, Th, and light REE (LREE) abundances, along with modal petrographic determinations of phosphate abundances, were carried out on equilibrated ordinary chondrites in order to define better the solar system Pu abundance and to determine the degree of variation of actinide and LREE abundances. Our data permit comparison of the directly measured Pu/ U ratio with that determined indirectly as (Pu/Nd) ?? (Nd/U) assuming that Pu behaves chemically as a LREE. Except for Guaren??a, and perhaps H chondrites in general, Pu concentrations are similar to that determined previously for St. Se??verin, although less precise because of higher trapped Xe contents. Trapped 130Xe 136Xe ratios appear to vary from meteorite to meteorite, but, relative to AVCC, all are similar in the sense of having less of the interstellar heavy Xe found in carbonaceous chondrite acid residues. The Pu/U and Pu/Nd ratios are consistent with previous data for St. Se??verin, but both tend to be slightly higher than those inferred from previous data on Angra dos Reis. Although significant variations exist, the distribution of our Th/U ratios, along with other precise isotope dilution data for ordinary chondrites, is rather symmetric about the CI chondrite value; however, actinide/(LREE) ratios are systematically lower than the CI value. Variations in actinide or LREE absolute and relative abundances are interpreted as reflecting differences in the proportions and/or compositions of more primitive components (chondrules and CAI materials?) incorporated into different regions of the ordinary chondrite parent bodies. The observed variations of Th/U, Nd/U, or Ce/U suggest that measurements of Pu/U on any single equilibrated ordinary chondrite specimen, such as St. Se??verin, should statistically be within ??20-30% of the average solar system value, although it is also clear that anomalous samples exist. ?? 1990.

  11. The Molecular Signature of the Stroma Response in Prostate Cancer-Induced Osteoblastic Bone Metastasis Highlights Expansion of Hematopoietic and Prostate Epithelial Stem Cell Niches

    PubMed Central

    Secondini, Chiara; Wetterwald, Antoinette; Schwaninger, Ruth; Fleischmann, Achim; Raffelsberger, Wolfgang; Poch, Olivier; Delorenzi, Mauro; Temanni, Ramzi; Mills, Ian G.; van der Pluijm, Gabri; Thalmann, George N.; Cecchini, Marco G.

    2014-01-01

    The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature (“Core” OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this

  12. A clinically suitable ex vivo expansion culture system for LTC-IC and CFC using stroma-conditioned medium.

    PubMed

    Bhatia, R; McGlave, P B; Miller, J S; Wissink, S; Lin, W N; Verfaillie, C M

    1997-08-01

    FACS-selected CD34+ HLA-DR- cells (DR- cells) may provide a source of benign stem cells suitable for autografting in chronic myelogenous leukemia (CML) and other hematological malignancies. However, DR- cell selection depletes the majority of committed hematopoietic progenitors, which may be important for early engraftment. Furthermore, only a small number of DR- cells may be selectable in certain patients. These impediments to the use of DR- cells for autografting may be overcome through the development of ex vivo culture systems that support expansion and initial differentiation of primitive progenitors. Because 2-week culture of DR- cells in a stroma "noncontact" system supplemented with interleukin-3 (IL-3) and macrophage inflammatory protein 1-alpha (MIP-1alpha) expands both long-term culture-initiating cells (LTC-ICs) and colony-forming cells (CFCs), we adapted this system to a clinically applicable method for expanding LTC-ICs and CFCs ex vivo. In initial small-scale studies, DR cells were grown in stroma conditioned medium (SCM) supplemented with IL-3 with or without additional growth-promoting cytokines and the chemokines PF-4 and BB10010, all approved for clinical use. An IL-3 dose-dependent expansion of committed progenitors and LTC-ICs was observed when DR- cells were cultured in tissue culture plates in SCM+IL-3 for 2 weeks. Similar CFC expansion along with increased (5-fold) LTC-IC expansion was observed following addition of PF-4 to SCM+IL-3 cultures. The addition of stem cell factor (SCF), but not of IL-6, IL-11, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, IL-1, and IL-7, increased CFC and LTC-IC expansion beyond the levels observed with SCM+IL-3 alone. We next evaluated the suitability of this culture system for scale-up. Culture of 2-6 x 10(5) DR- cells in gas-permeable bags with SCM+IL-3 resulted in similar CFC and LTC-IC expansion as seen in small-scale cultures. In addition, we observed that progenitors

  13. A phenotype from tumor stroma based on the expression of metalloproteases and their inhibitors, associated with prognosis in breast cancer

    PubMed Central

    Eiró, Noemí; Fernandez-Garcia, Belen; Vázquez, Julio; del Casar, José M; González, Luis O; Vizoso, Francisco J

    2015-01-01

    The objective of the present work was to evaluate the impact of the phenotype of both mononuclear inflammatory cells (MICs) and cancer-associated fibroblast (CAFs) in early breast cancer patients, specifically assessed as to their expression of MMP/TIMP relative to their position within the tumor (i.e., localization at the tumor center or invasive front) and the occurrence of distant metastases.. An immunohistochemical study was performed using tissue arrays and specific antibodies against matrix metalloproteinase (MMP)−1, −2, −7, −9, −11, −13 and −14, tissue inhibitors of metalloproteinase (TIMP)−1, −2 and −3, both at tumor center and at invasive front, in 107 patients with primary ductal invasive breast tumors. Data were analyzed by unsupervised hierarchical clustering analysis. Our results indicated that MMP-11 expression by MICs, and TIMP-2 expression by CAFs at either the tumor center or the invasive front, were the most potent independent prognostic factors for predicting the clinical outcome of patients. Using the unsupervised hierarchical clustering analysis, we found well-defined clusters of cases identifying subgroups of tumors showing a high molecular profile of MMPs/TIMPs expression by stromal cells (CAFs and MICs), both at the tumor center and at the invasive front, which were strongly associated with a higher prevalence of distant metastasis. In addition, we found combinations of these clusters defining subpopulations of breast carcinomas differing widely in their clinical outcome. The results presented here identify biologic markers useful to categorize patients into different subgroups based on their tumor stroma, which may contribute to improved understanding of the prognosis of breast cancer patients. PMID:26140253

  14. SCCOHT tumors acquire chemoresistance and protection by interacting mesenchymal stroma/stem cells within the tumor microenvironment.

    PubMed

    Otte, Anna; Yang, Yuanyuan; von der Ohe, Juliane; Melzer, Catharina; Hillemanns, Peter; Feuerhake, Friedrich; Hass, Ralf

    2016-12-01

    Chemotherapeutic drug testing of SCCOHT-1 and BIN-67 tumor cells revealed synergistic growth-inhibition of >95% in vitro with a combination of foretinib and FK228. Application of this drug combination in vivo in NODscid mice-induced SCCOHT-1GFP tumors was associated with ~6-fold reduction in tumor mass within 10 days, whereby synergistic effects of the two compounds remained undetectable compared to previous results with foretinib treatment alone. Histopathologic evaluation revealed a reduced vascularization and a lower amount of proliferating cells in the treated tumors. Surprisingly, a simultaneous significant accumulation of extracellular matrix structures with positive elastin-van Gieson staining was observed following foretinib/FK228 exposure. Expression analysis of treated animal tumors exhibited various changes including increased mouse transcript levels of elastin, laminin, and fibronectin. In parallel, markers for mesenchymal stroma/stem cells (MSC) including CD73 and CD90 were detectable in all mouse tumors suggesting a possible involvement of these cells in extracellular matrix restructure. Indeed, incubation of MSC with FK228 or foretinib/FK228 demonstrated morphologic alterations and enhanced expression of laminin and fibronectin. Moreover, a co-culture of MSC with lentiviral-labeled SCCOHT-1GFP cells contributed to protection of the tumor cells against FK228-mediated cytotoxicity. Furthermore, explant cultures of SCCOHT-1GFP-induced tumors acquired an increased resistance to FK228 and a combination of foretinib/FK228 in contrast to foretinib alone. Together, these data suggested that FK228-mediated extracellular matrix protein expression by MSC contributes to increased protection and enhanced resistance of SCCOHT tumors which could represent a more general mechanism of MSC during drug-induced alterations of a tumor microenvironment.

  15. Human mesenchymal stroma/stem cells exchange membrane proteins and alter functionality during interaction with different tumor cell lines.

    PubMed

    Yang, Yuanyuan; Otte, Anna; Hass, Ralf

    2015-05-15

    To analyze effects of cellular interaction between human mesenchymal stroma/stem cells (MSC) and different cancer cells, direct co-cultures were performed and revealed significant growth stimulation of the tumor populations and a variety of protein exchanges. More than 90% of MCF-7 and primary human HBCEC699 breast cancer cells as well as NIH:OVCAR-3 ovarian adenocarcinoma cells acquired CD90 proteins during MSC co-culture, respectively. Furthermore, SK-OV-3 ovarian cancer cells progressively elevated CD105 and CD90 proteins in co-culture with MSC. Primary small cell hypercalcemic ovarian carcinoma cells (SCCOHT-1) demonstrated undetectable levels of CD73 and CD105; however, both proteins were significantly increased in the presence of MSC. This co-culture-mediated protein induction was also observed at transcriptional levels and changed functionality of SCCOHT-1 cells by an acquired capability to metabolize 5'cAMP. Moreover, exchange between tumor cells and MSC worked bidirectional, as undetectable expression of epithelial cell adhesion molecule (EpCAM) in MSC significantly increased after co-culture with SK-OV-3 or NIH:OVCAR-3 cells. In addition, a small population of chimeric/hybrid cells appeared in each MSC/tumor cell co-culture by spontaneous cell fusion. Immune fluorescence demonstrated nanotube structures and exosomes between MSC and tumor cells, whereas cytochalasin-D partially abolished the intercellular protein transfer. More detailed functional analysis of FACS-separated MSC and NIH:OVCAR-3 cells after co-culture revealed the acquisition of epithelial cell-specific properties by MSC, including increased gene expression for cytokeratins and epithelial-like differentiation factors. Vice versa, a variety of transcriptional regulatory genes were down-modulated in NIH:OVCAR-3 cells after co-culture with MSC. Together, these mutual cellular interactions contributed to functional alterations in MSC and tumor cells.

  16. Analysis of the chondrogenic potential and secretome of mesenchymal stem cells derived from human umbilical cord stroma.

    PubMed

    Arufe, Maria C; De la Fuente, Alexandre; Mateos, Jesus; Fuentes, Isaac; De Toro, Francisco J; Blanco, Francisco J

    2011-07-01

    Mesenchymal stem cells (MSCs) from umbilical cord stroma were isolated by plastic adherence and characterized by flow cytometry, looking for cells positive for OCT3/4 and SSEA-4 as well as the classic MSC markers CD44, CD73, CD90, Ki67, CD105, and CD106 and negative for CD34 and CD45. Quantitative reverse transcriptase-polymerase chain reaction analysis of the genes ALP, MEF2C, MyoD, LPL, FAB4, and AMP, characteristic for the differentiated lineages, were used to evaluate early and late differentiation of 3 germ lines. Direct chondrogenic differentiation was achieved through spheroid formation by MSCs in a chondrogenic medium and the presence of chondrogenic markers at 4, 7, 14, 28, and 46 days of culture was tested. Immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction analyses were utilized to assess the expression of collagen type I, collagen type II, and collagen type X throughout the time studied. We found expression of all the markers as early as 4 days of chondrogenic differentiation culture, with their expression increasing with time, except for collagen type I, which decreased in expression in the formed spheroids after 4 days of differentiation. The signaling role of Wnt during chondrogenic differentiation was studied by western blot. We observed that β-catenin expression decreased during the chondrogenic process. Further, a secretome study to validate our model of differentiation in vitro was performed on spheroids formed during the chondrogenesis process. Our results indicate the multipotential capacity of this source of human cells; their chondrogenic capacity could be useful for future cell therapy in articular diseases.

  17. Two-wave nanotherapy to target the stroma and optimize gemcitabine delivery to a human pancreatic cancer model in mice.

    PubMed

    Meng, Huan; Zhao, Yang; Dong, Juyao; Xue, Min; Lin, Yu-Shen; Ji, Zhaoxia; Mai, Wilson X; Zhang, Haiyuan; Chang, Chong Hyun; Brinker, C Jeffrey; Zink, Jeffrey I; Nel, Andre E

    2013-11-26

    Pancreatic ductal adenocarcinoma (PDAC) elicits a dense stromal response that blocks vascular access because of pericyte coverage of vascular fenestrations. In this way, the PDAC stroma contributes to chemotherapy resistance in addition to causing other problems. In order to improve the delivery of gemcitabine, a first-line chemotherapeutic agent, a PEGylated drug-carrying liposome was developed, using a transmembrane ammonium sulfate gradient to encapsulate the protonated drug up to 20% w/w. However, because the liposome was precluded from entering the xenograft site due to the stromal interference, we developed a first-wave nanocarrier that decreases pericyte coverage of the vasculature through interference in the pericyte recruiting TGF-β signaling pathway. This was accomplished using a polyethyleneimine (PEI)/polyethylene glycol (PEG)-coated mesoporous silica nanoparticle (MSNP) for molecular complexation to a small molecule TGF-β inhibitor, LY364947. LY364947 contains a nitrogen atom that attaches, through H-bonding, to PEI amines with a high rate of efficiency. The copolymer coating also facilitates systemic biodistribution and retention at the tumor site. Because of the high loading capacity and pH-dependent LY364947 release from the MSNPs, we achieved rapid entry of IV-injected liposomes and MSNPs at the PDAC tumor site. This two-wave approach provided effective shrinkage of the tumor xenografts beyond 25 days, compared to the treatment with free drug or gemcitabine-loaded liposomes only. Not only does this approach overcome stromal resistance to drug delivery in PDAC, but it also introduces the concept of using a stepwise engineered approach to address a range of biological impediments that interfere in nanocancer therapy in a spectrum of cancers.

  18. Element abundances at high redshift

    NASA Technical Reports Server (NTRS)

    Meyer, David M.; Welty, D. E.; York, D. G.

    1989-01-01

    Abundances of Si(+), S(+), Cr(+), Mn(+), Fe(_), and Zn(+) are considered for two absorption-line systems in the spectrum of the QSO PKS 0528 - 250. Zinc and sulfur are underabundant, relative to H, by a factor of 10 compared to their solar and Galactic interstellar abundances. The silicon-, chromium-, iron-, and nickel-to-hydrogen ratios are less than the solar values and comparable to the local interstellar ratios. A straightforward interpretation is that nucleosynthesis in these high-redshift systems has led to only about one-tenth as much heavy production as in the gas clouds around the sun, and that the amount of the observed underabundances attributable to grain depletion is small. The dust-to-gas ratio in these clouds is less than 8 percent of the Galactic value.

  19. Coronal abundances and their variation

    NASA Technical Reports Server (NTRS)

    Saba, Julia L. R.

    1994-01-01

    This contract supports the investigation of elemental abundances in the solar corona, principally through analysis of high-resolution software X-ray spectra from the Flat Crystal Spectrometer on NASA's Solar Maximum Mission. The goals of the study are a characterization of the mean values of relative abundances of elements accessible in the FCS data, and information on the extent and circumstances of their variability. This report is a summation of the data analysis and reporting activities which occurred since the last report, submitted two months early, in April 1994, to facilitate evaluation of the first year's progress for contract renewal. Hence this report covers the period 15 April 1994 - 15 December 1994. A list of publications resulting from this research is included.

  20. The CALIFA survey: Oxygen abundances

    NASA Astrophysics Data System (ADS)

    Sánchez, S. F.; Aff001

    We present here the last results we obtained on the spatial resolved analysis of the ionized gas of disk-dominated galaxies based on CALIFA data. CALIFA is an ongoing IFS survey of galaxies in the Local Univese (0.005 < z < 0.03) that has already obtained spectroscopic information up to ~2.5r e with a spatial resolution better than ~1 kpc for a total number of an statiscal sample of galaxies of different morphological types, covering the CM-diagram up to Mr<-18 mag. With nearly 2000 spectra obtained for each galaxy, CALIFA offer one of the best IFU data to study the starformation histories and chemical enrichment of galaxies. In this article we focus on the main results based on the analysis of the oxygen abundances based on the study of ionized gas in H ii regions and individual spaxels, and their relations with the global properties of galaxies. In summary we have found that: (1) the -Z relation does not present a secondary relation with the star-formation rate, when the abundance is measured at the effective radius; (2) the oxygen abundance present a strong correlation with the stellar surface density (Σ-Z relation); (3) the oxygen abundance profiles present three well defined regimes, (a) an overall negative radial gradient, between 0.5-2 r e , with a characteristic slope of α O/H ~-0.1 dex/r e , (b) an universal flatenning beyond >2r e and (c) an inner drop at <0.5r e which presence depends on the mass. All these results indicates that disk-galaxies present an overall inside-out growth, although with clear deviations from this simple scenario.

  1. The solar abundance of thulium

    NASA Technical Reports Server (NTRS)

    Ross, J. E.; Aller, L. H.

    1974-01-01

    Consideration of one relatively unblended line of the solar spectrum, namely, the 3131.258-A line of Tm II, which yields a thulium abundance of 0.80 plus or minus 0.10 with the Corliss and Bozman (1962) f-value. The uncertainty of this figure is discussed in conjunction with the contradictory findings of some other investigators. The need for further detailed study of the lanthanides by the method of spectrum synthesis is pointed out.

  2. Chlorine Abundances in Martian Meteorites

    NASA Technical Reports Server (NTRS)

    Bogard, D.D.; Garrison, D.H.; Park, J.

    2009-01-01

    Chlorine measurements made in martian surface rocks by robotic spacecraft typically give Chlorine (Cl) abundances of approximately 0.1-0.8%. In contrast, Cl abundances in martian meteorites appear lower, although data is limited, and martian nakhlites were also subjected to Cl contamination by Mars surface brines. Chlorine abundances reported by one lab for whole rock (WR) samples of Shergotty, ALH77005, and EET79001 range 108-14 ppm, whereas Cl in nakhlites range 73-1900 ppm. Measurements of Cl in various martian weathering phases of nakhlites varied 0.04-4.7% and reveal significant concentration of Cl by martian brines Martian meteorites contain much lower Chlorine than those measured in martian surface rocks and give further confirmation that Cl in these surface rocks was introduced by brines and weathering. It has been argued that Cl is twice as effective as water in lowering the melting point and promoting melting at shallower martian depths, and that significant Cl in the shergottite source region would negate any need for significant water. However, this conclusion was based on experiments that utilized Cl concentrations more analogous to martian surface rocks than to shergottite meteorites, and may not be applicable to shergottites.

  3. Elemental Abundances from Very Low Abundance HII Regions

    NASA Astrophysics Data System (ADS)

    Skillman, Evan D.; Terlevich, Roberto J.; Terlevich, Elena

    1992-12-01

    In 1987 we initiated a program to mitigate the deficiency of known low metallicity galaxies. Following our discoveries of very low abundance H II regions in nearby dwarf galaxies (Skillman et al. 1988, 1989a,b), we used the IDS on the INT to to collect spectra of dwarf galaxies in the Second Byurakan Survey (SBS) of UV excess galaxies. Our survey of over 40 SBS galaxies was completed in January 1990 and we have identified roughly one dozen very low metallicity H II galaxies. Now, with a significant sample of these galaxies, several observational programs are possible; foremost of these is the measurement of the primordial helium abundance (eg., Pagel et al. 1992). We report here on observations from March 1991 and 1992 using the ISIS spectrograph on the WHT to obtain very high quality spectra of 8 of these newly discovered metal-poor galaxies. The ISIS double spectrograph allows simultaneous observations of the blue (3600 - 5100 Angstroms) and red (6300 - 6800 Angstroms). Thus, He, N, O, Ne and S abundances can be derived with relatively small observational uncertainties. We compare our new observations with those in the literature. Our preliminary analysis indicates a slightly larger scatter in He/H at low O/H than had been seen previously. The small scatter may have been due simply to the paucity of observations at low metallicity. References: Pagel, B.E.J., Simonson, E.A., Terlevich, R.J., & Edmunds, M.G. 1992, MNRAS, 255, 325 Skillman, E.D., Kennicutt, R.C., & Hodge, P.W. 1989a, ApJ, 347, 875 Skillman, E.D., Melnick, J., Terlevich, R., & Moles, M. 1988, A&A, 196, 31 Skillman, E.D., Terlevich, R., & Melnick, J. 1989b, MNRAS, 240, 563

  4. The Abundance of Interstellar Fluorine

    NASA Technical Reports Server (NTRS)

    Lauroesch, James T.

    2005-01-01

    The primary objective of this program was to obtain FUSE observations of the interstellar absorption lines of F I at 951 and 954 Angstroms to derive the abundance of fluorine toward the star HD 164816. The nucleosynthetic source(s) of fluorine are still a matter of debate - the present day abundance of fluorine can potentially constrain models for pulsationally driven dredge-up in asymptotic giant branch stars. An accurate measure for the depletion behavior of fluorine will determine whether it may be detectable in QSO absorption line systems - an unambiguous detection of fluorine at suitably high redshifts would provide the best evidence to date for the neutrino process in massive stars. Furthermore, due to its extreme reactivity, measurement of the gas-phase interstellar fluorine abundance is important for models of grain chemistry. Despite the importance of measuring the interstellar fluorine abundance, at the time of our proposal only one previous detection has been made due to the low relative abundance of fluorine, the lack of lines outside the far-UV, and the blending of the available F I transitions with lines of Hz. The star HD 164816 is associated with the Lagoon nebula (M8), and at a distance of approximately 1.5 kpc probes both distant and local gas. Beginning April 8th, 2004 FUSE FP-Split observations of the star HD 164816 were obtained for this program. This data became available in the FUSE data archive May 21, 2004, and these observations were then downloaded and we began our analysis. Our analysis procedure has involved (1) fitting stellar models to the FUSE spectra, (2) using the multiple lines of Hz and N I at other wavelengths in the FUSE bandpass to derive column densities for the lines of H2 and N I which are blended with the F I features at 951 and 954 angstroms (3) the measurement of the column densities of F I and the species O I and C1 I which are important species for the dis-entangling of dust and nucleosynthetic effects. As discussed in

  5. Abundance measurements in stellar environments

    SciTech Connect

    Leone, F.

    2014-05-09

    Most of what we know about stars, and systems of stars, is derived from the analysis of their electromagnetic radiation. This lesson is an attempt to describe to Physicists, without any Astrophysical background, the framework to understand the present status of abundance determination in stellar environments and its limit. These notes are dedicated to the recently passed, November 21, 2013, Prof. Dimitri Mihalas who spent his life confuting the 19th century positivist philosopher Auguste Comte who stated that we shall not at all be able to determine the chemical composition of stars.

  6. Abundance measurements in stellar environments

    NASA Astrophysics Data System (ADS)

    Leone, F.

    2014-05-01

    Most of what we know about stars, and systems of stars, is derived from the analysis of their electromagnetic radiation. This lesson is an attempt to describe to Physicists, without any Astrophysical background, the framework to understand the present status of abundance determination in stellar environments and its limit. These notes are dedicated to the recently passed, November 21, 2013, Prof. Dimitri Mihalas who spent his life confuting the 19th century positivist philosopher Auguste Comte who stated that we shall not at all be able to determine the chemical composition of stars.

  7. The solar abundance of Oxygen

    NASA Astrophysics Data System (ADS)

    Grevesse, N.

    2009-07-01

    With Martin Asplund (Max Planck Institute of Astrophysics, Garching) and Jacques Sauval (Observatoire Royal de Belgique, Brussels) I recently published detailed reviews on the solar chemical composition ({Asplund et al. 2005}, {Grevesse et al. 2007}). A new one, with Pat Scott (Stockholm University) as additional co-author, will appear in Annual Review of Astronomy and Astrophysics ({Asplund et al. 2009}). Here we briefly analyze recent works on the solar abundance of Oxygen and recommend a value of 8.70 in the usual astronomical scale.

  8. Influence of Coronal Abundance Variations

    NASA Technical Reports Server (NTRS)

    Gurman, Joseph (Technical Monitor); DeLuca, Edward

    2005-01-01

    During the final year of this program we concentrated on understanding the how to constrain the models with the best available observations. Work on developing accurate temperature and density diagnostics fkom TRACE and CDS together with constrained fits of non-potential force free fields will be extremely useful in the guiding the next generation of coronal models. The program has produced three fully operation numerical codes that model multi-species of ions in coronal loops: Static models and constant flow models. The time dependent numerical models have not been completed. We have extended the steady flow investigations to study the effect these flows have on coronal structure as observed with TRACE. Coronal observations derive from heavy-ion emission; thus, we focus on the extent to which flow may modify coronal abundances by examining the heavy-ion abundance stratification within long-lived loops. We discuss the magnitudes of the physical effects modeled and compare simulated results with TRACE observations. These results can have a profound effect on the interpretation of TRACE observations.

  9. Abundances in Hot Evolved Stars

    NASA Astrophysics Data System (ADS)

    Werner, Klaus; Rauch, Thomas; Kruk, Jeffrey W.

    2009-05-01

    The hydrogen-deficiency in extremely hot post-AGB stars of spectral class PG1159 is probably caused by a (very) late helium-shell flash or a AGB final thermal pulse that consumes the hydrogen envelope, exposing the usually-hidden intershell region. Thus, the photospheric element abundances of these stars allow us to draw conclusions about details of nuclear burning and mixing processes in the precursor AGB stars. We compare predicted element abundances to those determined by quantitative spectral analyses performed with advanced non-LTE model atmospheres. A good qualitative and quantitative agreement is found for many species (He, C, N, O, Ne, F, Si, Ar) but discrepancies for others (P, S, Fe) point at shortcomings in stellar evolution models for AGB stars. Almost all of the chemical trace elements in these hot stars can only be identified in the UV spectral range. The Far Ultraviolet Spectroscopic Explorer and the Hubble Space Telescope played a crucial role for this research.

  10. A role for stroma-derived annexin A1 as mediator in the control of genetic susceptibility to T-cell lymphoblastic malignancies through prostaglandin E2 secretion.

    PubMed

    Santos, Javier; González-Sánchez, Laura; Matabuena-Deyzaguirre, María; Villa-Morales, María; Cozar, Patricia; López-Nieva, Pilar; Fernández-Navarro, Pablo; Fresno, Manuel; Díaz-Muñoz, Manuel D; Guenet, Jean-Louis; Montagutelli, Xavier; Fernández-Piqueras, José

    2009-03-15

    Cancer susceptibility is essentially attributable to multiple low-penetrance genes. Using interspecific consomic and congenic mice between the tumor-resistant SEG/Pas and the tumor-sensitive C57BL/6J strains, a region on chromosome 19 involved in the genetic resistance to gamma-irradiation-induced T-cell lymphomas (Tlyr1) has been identified. Through the development of nonoverlapping subcongenic strains, it has been further shown that Anxa1 may be a candidate resistance gene on the basis of its differential expression in thymus stroma cells after gamma-radiation exposure. In addition, thymus stroma cells of thymic lymphomas exhibited a significant reduction in the expression levels of Anxa1. Interestingly, the activity of Anxa1 relies on prostaglandin E(2) (PGE(2)) induction that brings about apoptosis in thymocytes. In fact, in vitro transfection experiments revealed that PGE(2) production was enhanced when HEK 293 cells were transfected with full-length cDNAs of Anxa1, with PGE(2) production in the cells transfected with the allele of the resistant strain (Anxa1(Tyr)) being higher than that in cells transfected with the allele of the susceptible strain (Anxa1(Phe)). Furthermore, the presence of this compound in the medium induced apoptosis of immature CD4(+)CD8(+)CD3(low) cells in a dose-dependent manner. These results improve our knowledge of the molecular mechanisms triggering T-cell lymphoblastic lymphoma development while highlighting the relevance of the stroma in controlling genetic susceptibility and the use of PGE(2) as a new therapeutic approach in T-cell hematologic malignancies.

  11. Prognostic role and correlation of CA9, CD31, CD68 and CD20 with the desmoplastic stroma in pancreatic ductal adenocarcinoma

    PubMed Central

    D'Costa, Zenobia; Azad, Abul; Silva, Michael A.; Soonawalla, Zahir; Allen, Paul; Liu, Stanley; McKenna, W. Gillies; Muschel, Ruth J.; Fokas, Emmanouil

    2016-01-01

    We assessed the prognostic value of hypoxia (carbonic anhydrase 9; CA9), vessel density (CD31), with macrophages (CD68) and B cells (CD20) that can interact and lead to immune suppression and disease progression using scanning and histological mapping of whole-mount FFPE pancreatectomy tissue sections from 141 primarily resectable pancreatic ductal adenocarcinoma (PDAC) samples treated with surgery and adjuvant chemotherapy. Their expression was correlated with clinicopathological characteristics, and overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of stroma density (haematoxylin-eosin) and activity (alpha-smooth muscle actin). The median OS was 21 months after a mean follow-up of 20 months (range, 2–69 months). The median tumor surface area positive for CA9 and CD31 was 7.8% and 8.1%, respectively. Although total expression of these markers lacked prognostic value in the entire cohort, nevertheless, high tumor compartment CD68 expression correlated with worse PFS (p = 0.033) and DMFS (p = 0.047). Also, high CD31 expression predicted for worse OS (p = 0.004), PFS (p = 0.008), LPFS (p = 0.014) and DMFS (p = 0.004) in patients with moderate density stroma. High stromal and peripheral compartment CD68 expression predicted for significantly worse outcome in patients with loose and moderate stroma density, respectively. Altogether, in contrast to the current notion, hypoxia levels in PDAC appear to be comparable to other malignancies. CD31 and CD68 constitute prognostic markers in patient subgroups that vary according to tumor compartment and stromal density. Our study provides important insight on the pathophysiology of PDAC and should be exploited for future treatments. PMID:27637082

  12. Expression of pim-1 in tumors, tumor stroma and tumor-adjacent mucosa co-determines the prognosis of colon cancer patients.

    PubMed

    Peng, Yong-hai; Li, Jian-jun; Xie, Fang-wei; Chen, Jian-fang; Yu, Ying-hao; Ouyang, Xue-nong; Liang, Hou-jie

    2013-01-01

    Provirus integration site for Moloney murine leukemia virus (pim-1) is a proto-oncogene that is linked to the development and progression of several cancers. In this study, we evaluated pim-1 expression in tumors, tumor stroma and tumor-adjacent mucosa together as an independent prognostic factor for colon cancer patients. The study included 343 colon cancer patients. Immunohistochemical staining was used to detect pim-1. Multivariate cox regression for disease-free survival (DFS) were used to identify independent prognostic factors. Analytic hierarchy process (AHP) was used to calculate the weight of pim-1 in tumors, tumor stroma and tumor-adjacent mucosa in order to obtain a Pim-1 total score (PTS) for recurrence and survival. Kaplan-Meier DFS curves and OS curves for patients with different pim-1 expression levels were compared using the log-rank test. In this study, four independent prognostic factors were identified for colon cancer patients: pim-1 expression in tumors, tumor stroma, tumor-adjacent mucosa, as well as tumor stage. It has been established that clinical stage is an important prognostic factor for colon cancer patients. However, PTS can identify the patients who are likely to recur not only in the whole radical excision group but also within each stage of this group. Based on the results of this study we can conclude that the PTS combined with clinical staging system may be a better predictor of colon cancer patients' prognosis than using the clinical stage system alone. ClinicalTrials.gov Number: ChiCTR-PRCH-12002842.

  13. Supra-organization and optical anisotropies of the extracellular matrix in the amniotic membrane and limbal stroma before and after explant culture

    PubMed Central

    Valdetaro, Gisele P.; Aldrovani, Marcela; Padua, Ivan R. M.; Cristovam, Priscila C.; Gomes, José A. P.; Laus, José L.

    2016-01-01

    In this research we evaluated the supramolecular organizations and the optical anisotropical properties of the de-epithelialized human amniotic membrane and rabbit limbal stroma, before and after explant culture. Birefringence, monochromatic light spectral absorption and linear dichroism of the main extracellular matrix biopolymers, that is, the fibrillar collagens and proteoglycans, were investigated by polarized light microscopy combined with image analysis. Our results demonstrated that the culture procedure–induced stimuli altered the supra-organizational characteristics (in terms of collagens/proteoglycans spatial orientation and ordered-aggregational state) of the amniotic and limbal extracellular matrix, which led to changes in optical anisotropical properties. PMID:28018719

  14. Solar-system abundances of the elements

    NASA Technical Reports Server (NTRS)

    Anders, E.; Ebihara, M.

    1982-01-01

    Elemental analyses of the Ogueil Cl meteorite and all previous Cl chondrite analyses were employed to develop a new solar system abundance table, including the standard deviation and number of analyses for each element. The table also comprises the abundances of radioactive and radiogenic nuclides at the present and 4.55 AE ago, as well as abundances by weight in a typical Cl chondrite. The new abundances were within 20% of those determined by Cameron (1982), except for 14 cases in the range 20-50%, and 5 over 50%. The solar abundances were compared with the Cl abundances, showing a total of only 7 disagreements. No significant discrepancies were detected in the major cosmochemical groups, and a smooth trend was found in the abundances of odd-A nuclides. The new set is interpreted as accurate to 10%, with the Cl chondrites matching the primordial solar system abundances to at most 10% deviation.

  15. Hematite Abundance Map at Echo

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This image shows the hematite abundance map for a portion of the Meridiani Planum rock outcrop near where the Mars Exploration Rover Opportunity landed. It was acquired by the rover's miniature thermal emission spectrometer instrument from a spot called 'Echo.' Portions of the inner crater wall in this region appear rich in hematite (red). The sharp boundary from hematite-rich to hematite-poor (yellow and green) surfaces corresponds to a change in the surface texture and color. The hematite-rich surfaces have ripple-like forms suggesting wind transported hematite to these surfaces. The bounce marks produced during landing at the base of the slope on the left are low in hematite (blue). The hematite grains that originally covered the surface were pushed below the surface by the lander, exposing a soil that has less hematite.

  16. A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice.

    PubMed

    Lopez, M Veronica; Rivera, Angel A; Viale, Diego L; Benedetti, Lorena; Cuneo, Nicasio; Kimball, Kristopher J; Wang, Minghui; Douglas, Joanne T; Zhu, Zeng B; Bravo, Alicia I; Gidekel, Manuel; Alvarez, Ronald D; Curiel, David T; Podhajcer, Osvaldo L

    2012-12-01

    Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 10(10) v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15-40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression.

  17. Functional and molecular mapping of uncoupling between vascular permeability and loss of vascular maturation in ovarian carcinoma xenografts: the role of stroma cells in tumor angiogenesis.

    PubMed

    Gilad, Assaf A; Israely, Tomer; Dafni, Hagit; Meir, Gila; Cohen, Batya; Neeman, Michal

    2005-11-01

    Maintaining homogeneous perfusion in tissues undergoing remodeling and vascular expansion requires tight orchestration of the signals leading to endothelial sprouting and subsequent recruitment of perivascular contractile cells and vascular maturation. This regulation, however, is frequently disrupted in tumors. We previously demonstrated the role of tumor-associated myofibroblasts in vascularization and exit from dormancy of human ovarian carcinoma xenografts in nude mice. The aim of this work was to determine the contribution of stroma- and tumor cell-derived angiogenic growth factors to the heterogeneity of vascular permeability and maturation in MLS human ovarian carcinoma tumors. We show by RT-PCR and by in situ hybridization that VEGF was expressed by the tumor cells, while angiopoietin-1 and -2 were expressed only by the infiltrating host stroma cells. Vascular maturation was detected in vivo by vasoreactivity to hypercapnia, measured by BOLD contrast MRI and validated by immunostaining of histologic sections to alpha-smooth muscle actin. Vascular permeability was measured in vivo by dynamic contrast-enhanced MRI using albumin-based contrast material and validated in histologic sections by fluorescent staining of the biotinylated contrast material. MRI as well as histologic correlation maps between vascular maturation and vascular permeability revealed a wide range of vascular phenotypes, in which the distribution of vascular maturation and vasoreactivity did not overlap spatially with reduced permeability. The large heterogeneity in the degree of vascular maturation and permeability is consistent with the differential expression pattern of VEGF and angiopoietins during tumor angiogenesis.

  18. Photosynthesis under osmotic stress : Effect of high solute concentrations on the permeability properties of the chloroplast envelope and on activity of stroma enzymes.

    PubMed

    Kaiser, W M; Heber, U

    1981-12-01

    1. Increasing the sorbitol concentration in a suspension of intact chloroplasts induced a fast, transient and not very specific efflux of metabolites from chloroplasts to the medium. Stroma proteins were retained by the chloroplasts. 2. Within the first 30 s following hypertonic stress, the chloroplast volume decreased according to the Boyle-Mariotte relation. A subsequent and transient increase suggested some influx of external solute. 3. Dark reactions of intact chloroplasts such as starch degradation and formation of labelled 3-phosphoglycerate from dihydroxyacetone phosphate or ribose-5-phosphate and (14)CO2 were inhibited at low water potentials. After chloroplast rupture, the activity of stromal enzymes was decreased by high solute concentrations. Ribulose bisphosphate carboxylase exhibited a decrease of Vmax, while KmCO 2 remained unaltered. With sorbitol, sucrose, glycerol or glycinebetaine, 50% inhibition of enzymes was observed at osmotic potentials between 40 and 50 bar, with ethyleneglycol at about 70 bar. With salts such as KCl, 50% inhibition was found at 15 to 20 bar. 4. A comparison between inhibition of photosynthesis in intact chloroplasts and inhibition of enzymes in stroma extracts by solutes supports the notion that inhibition of photosynthesis at high osmotic potentials is mainly a solute effect. Another factor contributing to inhibition of photosynthesis in isolated chloroplasts is the loss of intermediates and cofactors which occurs during rapid osmotic dehydration.

  19. A Tumor-stroma Targeted Oncolytic Adenovirus Replicated in Human Ovary Cancer Samples and Inhibited Growth of Disseminated Solid Tumors in Mice

    PubMed Central

    Lopez, M Veronica; Rivera, Angel A; Viale, Diego L; Benedetti, Lorena; Cuneo, Nicasio; Kimball, Kristopher J; Wang, Minghui; Douglas, Joanne T; Zhu, Zeng B; Bravo, Alicia I; Gidekel, Manuel; Alvarez, Ronald D; Curiel, David T; Podhajcer, Osvaldo L

    2012-01-01

    Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 1010 v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15–40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression. PMID:22948673

  20. Ovarian steroids, mitogen-activated protein kinases, and/or aspartic proteinases cooperate to control endometrial remodeling by regulating gene expression in the stroma and glands.

    PubMed

    Gaide Chevronnay, Héloïse P; Lemoine, Pascale; Courtoy, Pierre J; Marbaix, Etienne; Henriet, Patrick

    2010-09-01

    Explants from nonmenstrual endometria cultured in the absence of ovarian hormones undergo tissue breakdown. Addition of estradiol and progesterone (EP) prevents proteolysis. Explants include stromal and epithelial compartments which play different but complementary roles in endometrial physiology, including tissue remodeling and hormonal response. In order to characterize the cell type-specific contribution to regulation of tissue breakdown, we characterized the transcriptomes of microdissected stromal and glandular areas from endometrial explants cultured with or without EP. The datasets were also compared to other published endometrial transcriptomes. Finally, the contribution of proteolysis, hypoxia, and MAPKs to the regulation of selected genes was further investigated in explant culture. This analysis identified distinct gene expression profiles in stroma and glands, with differential response to EP, but functional clustering underlined convergence in biological processes, further indicating that endometrial remodeling requires cooperation between the two compartments through expression of cell type-specific genes. Only partial overlaps were observed between lists of genes involved in different occurrences of endometrial breakdown, pointing to a limited number of potentially crucial regulators but also to the requirement for additional mechanisms controlling tissue remodeling. We identified a group of genes differentially regulated by EP in stroma and glands among which some were sensitive to MAPKs and/or aspartic proteinases and were not induced by hypoxia. In conclusion, MAPKs and/or aspartic proteinases likely act in concert with EP to locally and specifically control differential expression of genes between degrading and preserved areas of the human endometrium.

  1. Surface abundances of ON stars

    NASA Astrophysics Data System (ADS)

    Martins, F.; Simón-Díaz, S.; Palacios, A.; Howarth, I.; Georgy, C.; Walborn, N. R.; Bouret, J.-C.; Barbá, R.

    2015-06-01

    Context. Massive stars burn hydrogen through the CNO cycle during most of their evolution. When mixing is efficient or when mass transfer in binary systems occurs, chemically processed material is observed at the surface of O and B stars. Aims: ON stars show stronger lines of nitrogen than morphologically normal counterparts. Whether this corresponds to the presence of material processed through the CNO cycle is not known. Our goal is to answer this question. Methods: We performed a spectroscopic analysis of a sample of ON stars with atmosphere models. We determined the fundamental parameters as well as the He, C, N, and O surface abundances. We also measured the projected rotational velocities. We compared the properties of the ON stars to those of normal O stars. Results: We show that ON stars are usually rich in helium. Their CNO surface abundances are fully consistent with predictions of nucleosynthesis. ON stars are more chemically evolved and rotate - on average - faster than normal O stars. Evolutionary models including rotation cannot account for the extreme enrichment observed among ON main sequence stars. Some ON stars are members of binary systems, but others are single stars as indicated by stable radial velocities. Mass transfer is therefore not a simple explanation for the observed chemical properties. Conclusions: We conclude that ON stars show extreme chemical enrichment at their surface, consistent with nucleosynthesis through the CNO cycle. Its origin is not clear at present. Based on observations obtained 1) at the Anglo-Australian Telescope; 2) at the Canada-France-Hawaii Telescope (CFHT), which is operated by the National Research Council (NRC) of Canada, the Institut National des Science de l'Univers of the Centre National de la Recherche Scientifique (CNRS) of France, and the University of Hawaii; 3) at the ESO/La Silla Observatory under programs 081.D-2008, 083.D-0589, 086.D-0997; 4) the Nordic Optical Telescope, operated on the island of La

  2. Observing chemical abundances in comets

    NASA Technical Reports Server (NTRS)

    Delsemme, A. H.

    1981-01-01

    The atomic resonance lines of the major elements were observed in the atmospheres of a few comets, by using vacuum ultraviolet spectrographs on board rockets or orbiting observatories. Dust-to-gas ratios were also deduced for two comets through a Finson-Probstein's analysis of their dust-tail isophotes. The geometric albedo of the dust for the phase angle alpha of the observations is not accurately known but, the dust-to-gas ratio is not overly sensitive to the actual value of this albedo. Infrared observations of the dust head of some comets show that the bulk of cometary dust must be silicates, although a minor component (5-10 percent) of carbon compounds is rather likely, because of poor dielectric properties of the grains. This interpretation is confirmed by the fact that interplanetary dust probably of cometary origin, that was collected in the stratosphere by NASA-U2 Spacecraft, is chondritic in nature. Metal abundances in the head of a sungrazing comet support the chondritic hypothesis.

  3. Increased Expression of CCN2, Epithelial Membrane Antigen, and Fibroblast Activation Protein in Hepatocellular Carcinoma with Fibrous Stroma Showing Aggressive Behavior

    PubMed Central

    Yoo, Jeong Eun; Ko, Jung Eun; Lee, Jee San; Kim, Hyunki; Choi, Jin Sub; Park, Young Nyun

    2014-01-01

    Tumor behavior is affected by the tumor microenvironment, composed of cancer-associated fibroblasts (CAFs). Meanwhile, hepatocellular carcinomas (HCC) with fibrous stroma reportedly exhibit aggressive behavior suggestive of tumor-stroma interaction. However, evidence of the crosstalk remains unclear. In this study, CCN2, epithelial membrane antigen (EMA), fibroblast activation protein (FAP), and keratin 19 (K19) expression was studied in 314 HCCs (cohort 1), 42 scirrhous HCCs (cohort 2), and 36 chronic hepatitis/cirrhosis specimens by immunohistochemistry. Clinicopathological parameters were analyzed according to the expressions of these markers. In tumor epithelial cells from cohort 1, CCN2 and EMA were expressed in 15.3% and 17.2%, respectively, and their expressions were more frequent in HCCs with fibrous stroma (≥5% of tumor area) than those without (P<0.05 for all); CCN2 expression was well correlated with K19 and EMA expression. In tumor stromal cells, FAP expression was found in 6.7%. In cohort 2, CCN2, EMA, and FAP expression was noted in 40.5%, 40.5%, and 66.7%, respectively, which was more frequent than that in cohort 1 (P<0.05 for all). Additionally, EMA expression was associated with the expression of K19, CCN2, and FAP (P<0.05 for all); EMA expressing tumor epithelial cells showed a topographic closeness to FAP-expressing CAFs. Analysis of disease-free survival revealed CCN2 expression to be a worse prognostic factor in both cohort 1 (P = 0.005) and cohort 2 (P = 0.023), as well as EMA as a worse prognostic factor in cohort 2 (P = 0.048). In conclusion, expression of CCN2, EMA, and FAP may be involved in the activation of CAFs in HCC, giving rise to aggressive behavior. Significant correlation between EMA-expressing tumor cells and FAP-expressing CAFs and their topographic closeness suggests possible cross-talk between tumor epithelial cells and stromal cells in the tumor microenvironment of HCC. PMID:25126747

  4. Primordial abundance of 40Ar

    NASA Astrophysics Data System (ADS)

    Sripada, V. S. Murty

    Primordial abundance of the isotope (40) Ar is still not known accurately. Recent results from Genesis could also not provide (40) Ar/ (36) Ar value of solar wind, due mainly to the overwhelming (40) Ar blank. A major part of (40) Ar is contributed by the radioactive decay of (40) K (half life = 1.25 Ga), even in the nebula, as the nebula grew old. Any attempt to determine this quantity needs a sample that satisfies the following criteria: A primitive mineral/phase that formed very early in the nebula, that can trap a large amount of noble gas (Ar); and a phase that acquires minimum amount (or total absence) of in situ produced components (cosmogenic and radiogenic) of Ar. Carbon phases in the ureilite meteorites and Phase Q from chondrites best fit this criteria. The minimum (40) Ar/ (36) Ar value so far observed in Phase Q is 0.2. Also, the relatively lower value of 1.035±±0.002 for trapped (129) Xe/ (132) Xe in ureilites, as compared to 1.042±±0.002 in Phase Q suggests that trapping of gases in ureilites might have predated that of Phase Q. If this interpretation is valid, ureilites are a better host of most primitive nebular Ar. Earlier attempts on ureilite studies in 1970s have yielded the lowest (40) Ar/ (36) Ar ratio in the meteorite Dayalpur, the major uncertainty for this value mostly coming from blank correction for (40) Ar/ (36) Ar. Recent developments in low blank extraction systems and more sensitive multi-collector noble gas mass spectrometers, as compared to 1970s have prompted us to make a fresh attempt in measuring this important quantity. We have analysed a number of ureilite acid residues by stepwise temperature extraction, using both pyrolysis and combustion techniques, for Ar to ascertain the trapped (40) Ar/ (36) Ar ratio in the solar nebula. These acid residues are mostly made of C rich phases, with only trace amounts of K (radiogenic parent of (40) Ar) and target elements for the production of cosmogenic Ar component. They mostly contain

  5. Cold-Regulated Cereal Chloroplast Late Embryogenesis Abundant-Like Proteins. Molecular Characterization and Functional Analyses

    PubMed Central

    NDong, Christian; Danyluk, Jean; Wilson, Kenneth E.; Pocock, Tessa; Huner, Norman P.A.; Sarhan, Fathey

    2002-01-01

    Cold acclimation and freezing tolerance are the result of complex interaction between low temperature, light, and photosystem II (PSII) excitation pressure. Previous results have shown that expression of the Wcs19 gene is correlated with PSII excitation pressure measured in vivo as the relative reduction state of PSII. Using cDNA library screening and data mining, we have identified three different groups of proteins, late embryogenesis abundant (LEA) 3-L1, LEA3-L2, and LEA3-L3, sharing identities with WCS19. These groups represent a new class of proteins in cereals related to group 3 LEA proteins. They share important characteristics such as a sorting signal that is predicted to target them to either the chloroplast or mitochondria and a C-terminal sequence that may be involved in oligomerization. The results of subcellular fractionation, immunolocalization by electron microscopy and the analyses of target sequences within the Wcs19 gene are consistent with the localization of WCS19 within the chloroplast stroma of wheat (Triticum aestivum) and rye (Secale cereale). Western analysis showed that the accumulation of chloroplastic LEA3-L2 proteins is correlated with the capacity of different wheat and rye cultivars to develop freezing tolerance. Arabidopsis was transformed with the Wcs19 gene and the transgenic plants showed a significant increase in their freezing tolerance. This increase was only evident in cold-acclimated plants. The putative function of this protein in the enhancement of freezing tolerance is discussed. PMID:12114590

  6. T cell abundance in blood predicts acute organ toxicity in chemoradiotherapy for head and neck cancer

    PubMed Central

    Reichardt, Sybille D.; Rave-Fränk, Margret; Schirmer, Markus A.; Stadelmann, Christine; Canis, Martin; Wolff, Hendrik A.

    2016-01-01

    Treatment of head and neck squamous cell carcinoma (HNSCC) by chemoradiotherapy (CRT) often results in high-grade acute organ toxicity (HGAOT). As these adverse effects impair the patients' quality of life and the feasibility of the planned therapy, we sought to analyze immunological parameters in tumor material and blood samples obtained from 48 HNSCC patients in order to assess the potential to predict the individual acute organ toxicity. T cells in the tumor stroma were enriched in patients developing HGAOT whereas levels of soluble factors in the plasma and gene expression in whole blood did not coincide with the occurrence of acute organ toxicity. In contrast, the frequency and absolute numbers of selected leukocyte subpopulations measured in samples of peripheral blood mononuclear cells (PBMCs) directly before the beginning of CRT were significantly different in patients with HGAOT as compared to those without. When we validated several potential markers including the abundance of T cells in a small prospective study with 16 HNSCC patients, we were able to correctly predict acute organ toxicity in up to 81% of the patients. We conclude that analysis of PBMCs by fluorescence-activated cell sorting (FACS) might be a convenient strategy to identify patients at risk of developing HGAOT caused by CRT, which might allow to adapt the treatment regimen and possibly improve disease outcome. PMID:27589568

  7. Abundance of introduced species at home predicts abundance away in herbaceous communities

    USGS Publications Warehouse

    Firn, Jennifer; Moore, Joslin L.; MacDougall, Andrew S.; Borer, Elizabeth T.; Seabloom, Eric W.; HilleRisLambers, Janneke; Harpole, W. Stanley; Cleland, Elsa E.; Brown, Cynthia S.; Knops, Johannes M.H.; Prober, Suzanne M.; Pyke, David A.; Farrell, Kelly A.; Bakker, John D.; O'Halloran, Lydia R.; Adler, Peter B.; Collins, Scott L.; D'Antonio, Carla M.; Crawley, Michael J.; Wolkovich, Elizabeth M.; La Pierre, Kimberly J.; Melbourne, Brett A.; Hautier, Yann; Morgan, John W.; Leakey, Andrew D.B.; Kay, Adam; McCulley, Rebecca; Davies, Kendi F.; Stevens, Carly J.; Chu, Cheng-Jin; Holl, Karen D.; Klein, Julia A.; Fay, Phillip A.; Hagenah, Nicole; Kirkman, Kevin P.; Buckley, Yvonne M.

    2011-01-01

    Many ecosystems worldwide are dominated by introduced plant species, leading to loss of biodiversity and ecosystem function. A common but rarely tested assumption is that these plants are more abundant in introduced vs. native communities, because ecological or evolutionary-based shifts in populations underlie invasion success. Here, data for 26 herbaceous species at 39 sites, within eight countries, revealed that species abundances were similar at native (home) and introduced (away) sites - grass species were generally abundant home and away, while forbs were low in abundance, but more abundant at home. Sites with six or more of these species had similar community abundance hierarchies, suggesting that suites of introduced species are assembling similarly on different continents. Overall, we found that substantial changes to populations are not necessarily a pre-condition for invasion success and that increases in species abundance are unusual. Instead, abundance at home predicts abundance away, a potentially useful additional criterion for biosecurity programmes.

  8. Abundance of introduced species at home predicts abundance away in herbaceous communities.

    PubMed

    Firn, Jennifer; Moore, Joslin L; MacDougall, Andrew S; Borer, Elizabeth T; Seabloom, Eric W; HilleRisLambers, Janneke; Harpole, W Stanley; Cleland, Elsa E; Brown, Cynthia S; Knops, Johannes M H; Prober, Suzanne M; Pyke, David A; Farrell, Kelly A; Bakker, John D; O'Halloran, Lydia R; Adler, Peter B; Collins, Scott L; D'Antonio, Carla M; Crawley, Michael J; Wolkovich, Elizabeth M; La Pierre, Kimberly J; Melbourne, Brett A; Hautier, Yann; Morgan, John W; Leakey, Andrew D B; Kay, Adam; McCulley, Rebecca; Davies, Kendi F; Stevens, Carly J; Chu, Cheng-Jin; Holl, Karen D; Klein, Julia A; Fay, Philip A; Hagenah, Nicole; Kirkman, Kevin P; Buckley, Yvonne M

    2011-03-01

    Many ecosystems worldwide are dominated by introduced plant species, leading to loss of biodiversity and ecosystem function. A common but rarely tested assumption is that these plants are more abundant in introduced vs. native communities, because ecological or evolutionary-based shifts in populations underlie invasion success. Here, data for 26 herbaceous species at 39 sites, within eight countries, revealed that species abundances were similar at native (home) and introduced (away) sites - grass species were generally abundant home and away, while forbs were low in abundance, but more abundant at home. Sites with six or more of these species had similar community abundance hierarchies, suggesting that suites of introduced species are assembling similarly on different continents. Overall, we found that substantial changes to populations are not necessarily a pre-condition for invasion success and that increases in species abundance are unusual. Instead, abundance at home predicts abundance away, a potentially useful additional criterion for biosecurity programmes.

  9. Reflectance spectroscopy for diagnosis of epithelial precancer: model-based analysis of fiber-optic probe designs to resolve spectral information from epithelium and stroma

    PubMed Central

    Arifler, Dizem; Schwarz, Richard A.; Chang, Sung K.; Richards-Kortum, Rebecca

    2009-01-01

    Reflectance spectroscopy is a promising technology for detection of epithelial precancer. Fiber-optic probes that selectively collect scattered light from both the epithelium and the underlying stroma are likely to improve diagnostic performance of in vivo reflectance spectroscopy by revealing diagnostic features unique to each layer. We present Monte Carlo models with which to evaluate fiber-optic probe geometries with respect to sampling depth and depth resolution. We propose a probe design that utilizes half-ball lens coupled source and detector fibers to isolate epithelial scattering from stromal scattering and hence to resolve spectral information from the two layers. The probe is extremely compact and can provide easy access to different organ sites. PMID:16045217

  10. Membrane-bound ICAM-1 contributes to the onset of proinvasive tumor stroma by controlling acto-myosin contractility in carcinoma-associated fibroblasts

    PubMed Central

    Bonan, Stephanie; Albrengues, Jean; Grasset, Eloise; Kuzet, Sanya-Eduarda; Nottet, Nicolas; Bourget, Isabelle; Bertero, Thomas; Mari, Bernard; Meneguzzi, Guerrino; Gaggioli, Cedric

    2017-01-01

    Acto-myosin contractility in carcinoma-associated fibroblasts leads to assembly of the tumor extracellular matrix. The pro-inflammatory cytokine LIF governs fibroblast activation in cancer by regulating the myosin light chain 2 activity. So far, however, how LIF mediates cytoskeleton contractility remains unknown. Using phenotypic screening assays based on knock-down of LIF-dependent genes in fibroblasts, we identified the glycoprotein ICAM-1 as a crucial regulator of stroma fibroblast proinvasive matrix remodeling. We demonstrate that the membrane-bound ICAM-1 isoform is necessary and sufficient to promote inflammation-dependent extracellular matrix contraction, which favors cancer cell invasion. Indeed, ICAM-1 mediates generation of acto-myosin contractility downstream of the Src kinases in stromal fibroblasts. Moreover, acto-myosin contractility regulates ICAM-1 expression by establishing a positive feedback signaling. Thus, targeting stromal ICAM-1 might constitute a possible therapeutic mean to counteract tumor cell invasion and dissemination. PMID:27901489

  11. Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma.

    PubMed

    Hurt, Elaine M; Wiestner, Adrian; Rosenwald, Andreas; Shaffer, A L; Campo, Elias; Grogan, Tom; Bergsagel, P Leif; Kuehl, W Michael; Staudt, Louis M

    2004-02-01

    The oncogene c-maf is translocated in approximately 5%-10% of multiple myelomas. Unexpectedly, we observed c-maf expression in myeloma cell lines lacking c-maf translocations and in 50% of multiple myeloma bone marrow samples. By gene expression profiling, we identified three c-maf target genes: cyclin D2, integrin beta7, and CCR1. c-maf transactivated the cyclin D2 promoter and enhanced myeloma proliferation, whereas dominant inhibition of c-maf blocked tumor formation in immunodeficient mice. c-maf-driven expression of integrin beta7 enhanced myeloma adhesion to bone marrow stroma and increased production of VEGF. We propose that c-maf transforms plasma cells by stimulating cell cycle progression and by altering bone marrow stromal interactions. The frequent overexpression of c-maf in myeloma makes it an attractive target for therapeutic intervention.

  12. Analysis of Stroma Labeling During Multiple Passage of a Sarcoma Imageable Patient-derived Orthotopic Xenograft (iPDOX) in Red Fluorescent Protein Transgenic Nude Mice.

    PubMed

    Kiyuna, Tasuku; Murakami, Takashi; Tome, Yasunori; Kawaguchi, Kei; Igarashi, Kentaro; Miyake, Kentaro; Kanaya, Fuminori; Singh, Arun; Eilber, Fritz C; Hoffman, Robert M

    2017-03-16

    A patient-derived orthotopic xenograft (PDOX) model of undifferentiated pleomorphic sarcoma (UPS) was previously established that acquired red fluorescent protein (RFP)-expressing stroma by growth in an RFP transgenic nude mouse. In the present study, an imageable PDOX model (iPDOX) of UPS was established by orthotopic implantation in the biceps femoris of transgenic RFP nude mice. After the tumors grew to a diameter of 10 mm, they were harvested and the brightest portion of the tumors were subsequently orthotopically transplanted to both RFP and non-colored nude mice. The UPS PDOX tumor was again transplanted to RFP transgenic and non-colored nude mice and finally a 3(rd) passage was made in the same manner. Five UPS tumors from each passage in both RFP and non-colored mouse models were harvested. The FV1000 confocal microscope was used to visualize and quantitate the RFP area of the resected tumors. The average percent fluorescent area in the first passage of RFP mice was 34 ± 22%; in the second passage, 34 ± 20%; and 36 ± 11% in the third passage of RFP transgenic nude mice. The average tumor RFP area in the first passage from RFP mice to non-colored mice was 20 ± 7%; in the second passage, 28 ± 11%; in the third passage was 27 ± 13%. The present results demonstrate the extensive and stable acquisition of stroma by the UPS-tumor growing orthotopically in transgenic RFP nude mice (iPDOX). This model can be used for screening for effective drugs for individual patients and drug discovery. This article is protected by copyright. All rights reserved.

  13. Improved adipogenic in vitro differentiation: comparison of different adipogenic cell culture media on human fat and bone stroma cells for fat tissue engineering.

    PubMed

    Ghoniem, Amir-Alexander; Açil, Yahya; Wiltfang, Jörg; Gierloff, Matthias

    2015-06-01

    To date there is no sufficient in vitro fat tissue engineering and a protocol has not been well established for this purpose. Therefore, we evaluated the in vitro influence of two different adipogenic growth media for their stimulation potential on different cell lineages to clearly define the most potent adipogenic growth media for future in vitro tissue engineering approaches. The samples for differentiation were composed of human adipogenic-derived stroma cells (hADSCs) and human bone marrow mesenchymal stroma cells (hMSCs). A normal adipogenic medium (NAM) and a specific adipogenic medium (SAM) were tested for their adipogenic stimulation potential. After 10 days and 21 days the relative gene expression was measured for the adipogenic marker genes PPARγ2, C/EBPα, FABP4, LPL, and GLUT4 detected through real time reverse transcriptase polymease chain reaction (RT-PCR). Other study variables were the comparison between NAM and SAM and between the used cells hADSCs and hMSCs. Additionally an Oil-Red staining was performed after 21 days. Our results revealed that only SAM was significantly (P<0.05) superior in the differentiation process in contrast to NAM for 10 days and 21 days. As well was SAM superior to differentiate the used cell lineages. This was evaluated by the detected marker genes PPARγ2, C/EBPα, FABP4, LPL, and GLUT4 through real time RT-PCR and by Oil-Red staining. In addition, the hMSCs proofed to be equal donor cells for adipogenic differentiation especially when stimulated by SAM. The results suggest that the SAM should be established as a new standard medium for a more promising in vitro adipogenic differentiation.

  14. 3, 3', 5-triiodo-L-thyronine Increases In Vitro Chondrogenesis of Mesenchymal Stem Cells From Human Umbilical Cord Stroma Through SRC2.

    PubMed

    Fernández-Pernas, Pablo; Fafián-Labora, Juan; Lesende-Rodriguez, Iván; Mateos, Jesús; De la Fuente, Alexandre; Fuentes, Isaac; De Toro Santos, Javier; Blanco García, Fco; Arufe, María C

    2016-09-01

    Our group focuses on the study of mesenchymal stem cells (MSCs) from human umbilical cord stroma or Warthońs jelly and their directed differentiation toward chondrocyte-like cells capable of regenerating damaged cartilage when transplanted into an injured joint. This study aimed to determine whether lactogenic hormone prolactin (PRL) or 3, 3', 5-triiodo-L-thyronine (T3), the active thyroid hormone, modulates chondrogenesis in our in vitro model of directed chondrogenic differentiation, and whether Wnt signalling is involved in this modulation. MSCs from human umbilical cord stroma underwent directed differentiation toward chondrocyte-like cells by spheroid formation. The addition of T3 to the chondrogenic medium increased the expression of genes linked to chondrogenesis like collagen type 2, integrin alpha 10 beta 1, and Sox9 measured by quantitative real time polymerase chain reaction (qRT-PCR) analysis. Levels of collagen type 2 and aggrecane analyzed by immunohistochemistry, and staining by Safranin O were increased after 14 days in spheroid culture with T3 compared to those without T3 or only with PRL. B-catenin, Frizzled, and GSK-3β gene expressions were significantly higher in spheroids cultured with chondrogenic medium (CM) plus T3 compared to CM alone after 14 days in culture. The increase of chondrogenic differentiation was inhibited when the cells were treated with T3 plus ML151, an inhibitor of the T3 steroid receptor. This work demonstrates, for first time, that T3 promotes differentiation towards chondrocytes-like cells in our in vitro model, that this differentiation is mediated by steroid receptor co-activator 2 (SRC2) and does not induce hypertrophy. J. Cell. Biochem. 117: 2097-2108, 2016. © 2016 Wiley Periodicals, Inc.

  15. Understanding of the Viscoelastic Response of the Human Corneal Stroma Induced by Riboflavin/UV-A Cross-Linking at the Nano Level

    PubMed Central

    Labate, Cristina; De Santo, Maria Penelope; Lombardo, Giuseppe; Lombardo, Marco

    2015-01-01

    Purpose To investigate the viscoelastic changes of the human cornea induced by riboflavin/UV-A cross-linking using Atomic Force Microscopy (AFM) at the nano level. Methods Seven eye bank donor corneas were investigated, after gently removing the epithelium, using a commercial AFM in the force spectroscopy mode. Silicon cantilevers with tip radius of 10 nm and spring elastic constants between 26- and 86-N/m were used to probe the viscoelastic properties of the anterior stroma up to 3 µm indentation depth. Five specimens were tested before and after riboflavin/UV-A cross-linking; the other two specimens were chemically cross-linked using glutaraldehyde 2.5% solution and used as controls. The Young’s modulus (E) and the hysteresis (H) of the corneal stroma were quantified as a function of the application load and scan rate. Results The Young’s modulus increased by a mean of 1.1-1.5 times after riboflavin/UV-A cross-linking (P<0.05). A higher increase of E, by a mean of 1.5-2.6 times, was found in chemically cross-linked specimens using glutaraldehyde 2.5% (P<0.05). The hysteresis decreased, by a mean of 0.9-1.5 times, in all specimens after riboflavin/UV-A cross-linking (P<0.05). A substantial decrease of H, ranging between 2.6 and 3.5 times with respect to baseline values, was observed in glutaraldehyde-treated corneas (P<0.05). Conclusions The present study provides the first evidence that riboflavin/UV-A cross-linking induces changes of the viscoelastic properties of the cornea at the scale of stromal molecular interactions. PMID:25830534

  16. Evaluation of T, B and natural killer lymphocyte in the cervical stroma of HIV-positive and negative patients with cervical intraepithelial neoplasia.

    PubMed

    Lucena, Adriana A S; Guimarães, Mírian Viviane M B; Michelin, Márcia A; Lodi, Cláudia T C; Lima, Maria Inês M; Murta, Eddie Fernando Candido; Melo, Victor Hugo

    2016-01-01

    Cervical intraepithelial neoplasias (CIN) are closely associated with oncogenic subtypes of the human papillomavirus (HPV). In the presence of this virus, it is known that the activation or suppression of immune system is the key to the development, progression and/or regression of cervical lesions. Therefore, the objective of this study is to compare the local immune response among HIV-seropositive and seronegative patients with cervical intraepithelial neoplasia regarding the expression of T lymphocytes (CD3+, CD4+ and CD8+), B lymphocytes (CD20+) and natural killers cells (CD56+) in the cervical stroma. A cross-sectional study of paraffin blocks containing cervical tissue after conization by the Loop Electrosurgical Excision Procedure (LEEP) from 47 HIV-seropositive and 38 seronegative patients with CIN. Cervical stroma immunohistochemistry was performed in the CIN area. The Fisher's exact test was used for the statistical analysis. When HIV-seropositive and seronegative women were compared, the seropositive women had a higher count of CD8+ T lymphocytes (52.1% versus 28.9%, P<0.04). Considering CIN degree (CIN 1 and CIN 2/3), the HIV-seronegative patients with CIN 1 had a low count of CD20+B-lymphocytes (7.1%) in comparison with CIN 1 HIV seropositive and with CIN 2/3 HIV-seronegative patients, respectively 50% (P<0.018) and 54.5% (P<0.0048). The HIV infection and degree of CIN influenced the cytotoxic lymphocytes inducing an increase in the number of cells high count of CD20+ lymphocytes with CIN 1.

  17. Gray level entropy matrix is a superior predictor than multiplex ELISA in the detection of reactive stroma and metastatic potential of high-grade prostatic adenocarcinoma.

    PubMed

    Jia, Xiaopeng; Sun, Yanan; Wang, Baozhi

    2014-12-01

    Recent reports have indicated that not only the primary glandular tissue but also the surrounding stromal tissue plays an active role in the progression of carcinoma. Such is true for cancer tissues arising in the prostate. However, the precise role of stromal tissue in benign prostatic hyperplasia (BPH) and prostate adenocarcinoma is not well described. We undertook this current investigation to examine the changes in orientation of the extracellular matrix and correlate with prostatic cancer progression. We used a novel form of image analysis called gray level entropy matrix (GLEM) texture analysis to evaluate morphometric changes in stromal tissues. We used normal prostatic tissue obtained from cadaveric specimen and compared with BPH, prostatic intraepithelium neoplastic, hormone responsive prostatic adenocarcinoma and castration-resistant prostatic adenocarcinoma tissues. GLEM showed higher entropy in disease-resistant prostatic tissues, compared with benign forms of all spectra of pathologically diagnosed prostatic tissues (P < 0.05, ANOVA, between groups). Higher entropy is reflective of the disorganized morphological organization of the stroma, possibly reflecting the reactive matrix. In contrast, ELISA revealed that although individually correlated with the progressive stages of benign and carcinomatous prostatic tissues and trend correlation between groups, intergroup comparisons failed to arrive at statistical significance of comparisons between markers of neovasculogenesis, vascular endothelial growth factor, epithelial-mesenchymal transition (beta1-integrin, E-cadherin, MMP3) and osteogenic metastasis (RANKL and osteoprotegerin). The results of our study demonstrate the potential of GLEM entropy of gray level pixel in providing quasiquantitative estimate of a reactive stroma in advance stages of prostatic adenocarcinoma and thus can be routinely used in clinical decision making.

  18. Stroma-directed imatinib therapy impairs the tumor-promoting effect of bone marrow-derived mesenchymal stem cells in an orthotopic transplantation model of colon cancer.

    PubMed

    Shinagawa, Kei; Kitadai, Yasuhiko; Tanaka, Miwako; Sumida, Tomonori; Onoyama, Mieko; Ohnishi, Mayu; Ohara, Eiji; Higashi, Yukihito; Tanaka, Shinji; Yasui, Wataru; Chayama, Kazuaki

    2013-02-15

    Bone marrow-derived mesenchymal stem cells (MSCs) are reported to contribute to formation of tumor-promoting stromal cells. We reported recently that, in an orthotopic nude mice model of colon cancer, MSCs traveled to tumor stroma, where they differentiated into carcinoma-associated fibroblast (CAF)-like cells. We also found that CAFs express platelet-derived growth factor receptor (PDGFR) at a high level and that imatinib therapy targeting PDGFR in CAFs inhibits growth and metastasis of human colon cancer. These findings led us to examine whether the tumor-promoting effect of MSCs is impaired by blockade of PDGFR signaling achieved with imatinib. Orthotopic transplantation and splenic injection of human MSCs along with KM12SM human colon cancer cells, in comparison with transplantation of KM12SM cells alone, resulted in significantly greater promotion of tumor growth and liver metastasis. The KM12SM + MSC xenograft enhanced cell proliferation and angiogenesis and inhibited tumor cell apoptosis. When tumor-bearing animals were treated with imatinib, there was no significant increase in primary tumor volume or total volume of liver metastases, despite the KM12SM+MSC xenograft, and survival in the mixed-cell group was prolonged by imatinib treatment. Moreover, the ability of MSCs to migrate to tumor stroma was impaired, and the number of MSCs surviving in the tumor microenvironment was significantly decreased. In in vitro experiments, treatment with imatinib inhibited migration of MSCs. Our data suggest that blockade of PDGF signaling pathways influences the interaction between bone marrow-derived MSCs and tumor cells in the tumor microenvironment and, hence, inhibits the progressive growth of colon cancer.

  19. Climate and local abundance in freshwater fishes

    PubMed Central

    Knouft, Jason H.; Anthony, Melissa M.

    2016-01-01

    Identifying factors regulating variation in numbers of individuals among populations across a species' distribution is a fundamental goal in ecology. A common prediction, often referred to as the abundant-centre hypothesis, suggests that abundance is highest near the centre of a species' range. However, because of the primary focus on the geographical position of a population, this framework provides little insight into the environmental factors regulating local abundance. While range-wide variation in population abundance associated with environmental conditions has been investigated in terrestrial species, the relationship between climate and local abundance in freshwater taxa across species' distributions is not well understood. We used GIS-based temperature and precipitation data to determine the relationships between climatic conditions and range-wide variation in local abundance for 19 species of North American freshwater fishes. Climate predicted a portion of the variation in local abundance among populations for 18 species. In addition, the relationship between climatic conditions and local abundance varied among species, which is expected as lineages partition the environment across geographical space. The influence of local habitat quality on species persistence is well documented; however, our results also indicate the importance of climate in regulating population sizes across a species geographical range, even in aquatic taxa. PMID:27429769

  20. Climate and local abundance in freshwater fishes.

    PubMed

    Knouft, Jason H; Anthony, Melissa M

    2016-06-01

    Identifying factors regulating variation in numbers of individuals among populations across a species' distribution is a fundamental goal in ecology. A common prediction, often referred to as the abundant-centre hypothesis, suggests that abundance is highest near the centre of a species' range. However, because of the primary focus on the geographical position of a population, this framework provides little insight into the environmental factors regulating local abundance. While range-wide variation in population abundance associated with environmental conditions has been investigated in terrestrial species, the relationship between climate and local abundance in freshwater taxa across species' distributions is not well understood. We used GIS-based temperature and precipitation data to determine the relationships between climatic conditions and range-wide variation in local abundance for 19 species of North American freshwater fishes. Climate predicted a portion of the variation in local abundance among populations for 18 species. In addition, the relationship between climatic conditions and local abundance varied among species, which is expected as lineages partition the environment across geographical space. The influence of local habitat quality on species persistence is well documented; however, our results also indicate the importance of climate in regulating population sizes across a species geographical range, even in aquatic taxa.

  1. Abundances of the elements - Meteoritic and solar

    NASA Technical Reports Server (NTRS)

    Anders, Edward; Grevesse, Nicolas

    1989-01-01

    New abundance tables have been compiled for C1 chondrites and the solar photosphere and corona, based on a critical review of the literature to mid-1988. The meteorite data are generally accurate to + or - 5-10 percent. Significant discrepancies between the sun and meteorites occur only for Fe, Mn, Ge, Pb, and W; other well-determined elements agree to + or - 9 percent on the average. There is no evidence for group fractionations in C1 chondrites of cosmochemically similar elements (refractories, siderophiles, volatiles, etc.), but a selective fractionation of Fe cannot be ruled out. Abundances of odd-A nuclides between A = 65 and 209 show a generally smooth trend, with elemental abundances conforming to the slope defined by isotopic abundances. Significant irregularities occur in the Nd-Sm-Eu region, however, suggesting that the abundance curve is dependably smooth only down to about 20 percent level.

  2. Influence of Coronal Abundance Variations

    NASA Technical Reports Server (NTRS)

    Scargle, Jeffrey D. (Technical Monitor); Kashyap, Vinay

    2005-01-01

    The PI of this project was Jeff Scargle of NASA/Ames. Co-I's were Alma Connors of Eureka Scientific/Wellesley, and myself. Part of the work was subcontracted to Eureka Scientific via SAO, with Vinay Kashyap as PI. This project was originally assigned grant number NCC2-1206, and was later changed to NCC2-1350 for administrative reasons. The goal of the project was to obtain, derive, and develop statistical and data analysis tools that would be of use in the analyses of high-resolution, high-sensitivity data that are becoming available with new instruments. This is envisioned as a cross-disciplinary effort with a number of "collaborators" including some at SA0 (Aneta Siemiginowska, Peter Freeman) and at the Harvard Statistics department (David van Dyk, Rostislav Protassov, Xiao-li Meng, Epaminondas Sourlas, et al). We have developed a new tool to reliably measure the metallicities of thermal plasma. It is unfeasible to obtain high-resolution grating spectra for most stars, and one must make the best possible determination based on lower-resolution, CCD-type spectra. It has been noticed that most analyses of such spectra have resulted in measured metallicities that were significantly lower than when compared with analyses of high- resolution grating data where available (see, e.g., Brickhouse et al., 2000, ApJ 530,387). Such results have led to the proposal of the existence of so-called Metal Abundance Deficient, or "MAD" stars (e.g., Drake, J.J., 1996, Cool Stars 9, ASP Conf.Ser. 109, 203). We however find that much of these analyses may be systematically underestimating the metallicities, and using a newly developed method to correctly treat the low-counts regime at the high-energy tail of the stellar spectra (van Dyk et al. 2001, ApJ 548,224), have found that the metallicities of these stars are generally comparable to their photospheric values. The results were reported at the AAS (Sourlas, Yu, van Dyk, Kashyap, and Drake, 2000, BAAS 196, v32, #54.02), and at the

  3. Immunohistochemical analysis of steroidogenic enzymes in ovarian-type stroma of pancreatic mucinous cystic neoplasms: Comparative study of subepithelial stromal cells in intraductal papillary mucinous neoplasms of the pancreas.

    PubMed

    Ishida, Kazuyuki; Sasano, Hironobu; Moriya, Takuya; Takahashi, Yayoi; Sugimoto, Ryo; Mue, Yoshiharu; Murakami, Keigo; Fujishima, Fumiyoshi; Nakamura, Yasuhiro; Morikawa, Takanori; Motoi, Fuyuhiko; Suzuki, Takashi; Unno, Michiaki; Sugai, Tamotsu

    2016-05-01

    Mucinous cystic neoplasms (MCNs) are generally defined as cyst-forming epithelial neoplasms that arise in the pancreas and harbor characteristic ovarian-type stroma beneath the epithelium. In this study, we compared the immunoreactivity of steroid-related factors in these subepithelial stromal cells in MCNs to those in intraductal papillary mucinous neoplasms (IPMNs) to further characterize this unique MCN ovarian-type stroma through evaluation of sex steroid biosynthesis. Twenty MCNs and twenty IPMNs were examined. Immunoreactivity of steroid hormone receptors, including estrogen receptor (ERα and ERβ), progesterone receptor (PR, PR-A, and PR-B), and androgen receptor (AR), was more frequently detected in MCN ovarian-type stromal cells than in IPMN stromal cells (P < 0.01). The H-scores (mean ± SD) of steroidogenic factor (SF)-1 were also significantly higher in MCNs (112.3 ± 33.1) than in IPMNs (0.9 ± 1.2) (P < 0.01). The steroidogenic enzymes cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), cytochrome P450 17 alpha-hydroxylase (P450c17) and 3β-hydroxysteroid dehydrogenase (3β-HSD) showed immunoreactivity in 9/20 (45.0 %), 15/20 (75.0 %) and 13/20 (65.0 %), respectively, of ovarian-type stroma from MCN cases. These results demonstrate that the ovarian-type stroma of MCNs can express steroidogenic enzymes. Thus, the ovarian-type stroma of MCNs can produce sex steroids that may also act on these cells.

  4. Modeling void abundance in modified gravity

    NASA Astrophysics Data System (ADS)

    Voivodic, Rodrigo; Lima, Marcos; Llinares, Claudio; Mota, David F.

    2017-01-01

    We use a spherical model and an extended excursion set formalism with drifting diffusive barriers to predict the abundance of cosmic voids in the context of general relativity as well as f (R ) and symmetron models of modified gravity. We detect spherical voids from a suite of N-body simulations of these gravity theories and compare the measured void abundance to theory predictions. We find that our model correctly describes the abundance of both dark matter and galaxy voids, providing a better fit than previous proposals in the literature based on static barriers. We use the simulation abundance results to fit for the abundance model free parameters as a function of modified gravity parameters, and show that counts of dark matter voids can provide interesting constraints on modified gravity. For galaxy voids, more closely related to optical observations, we find that constraining modified gravity from void abundance alone may be significantly more challenging. In the context of current and upcoming galaxy surveys, the combination of void and halo statistics including their abundances, profiles and correlations should be effective in distinguishing modified gravity models that display different screening mechanisms.

  5. Oxygen abundance maps of CALIFA galaxies

    NASA Astrophysics Data System (ADS)

    Zinchenko, I. A.; Pilyugin, L. S.; Grebel, E. K.; Sánchez, S. F.; Vílchez, J. M.

    2016-11-01

    We construct maps of the oxygen abundance distribution across the discs of 88 galaxies using Calar Alto Legacy Integral Field Area survey (CALIFA) Data Release 2 (DR2) spectra. The position of the centre of a galaxy (coordinates on the plate) was also taken from the CALIFA DR2. The galaxy inclination, the position angle of the major axis, and the optical radius were determined from the analysis of the surface brightnesses in the Sloan Digital Sky Survey (SDSS) g and r bands of the photometric maps of SDSS Data Release 9. We explore the global azimuthal abundance asymmetry in the discs of the CALIFA galaxies and the presence of a break in the radial oxygen abundance distribution. We found that there is no significant global azimuthal asymmetry for our sample of galaxies, i.e. the asymmetry is small, usually lower than 0.05 dex. The scatter in oxygen abundances around the abundance gradient has a comparable value, ≲0.05 dex. A significant (possibly dominant) fraction of the asymmetry can be attributed to the uncertainties in the geometrical parameters of these galaxies. There is evidence for a flattening of the radial abundance gradient in the central part of 18 galaxies. We also estimated the geometric parameters (coordinates of the centre, the galaxy inclination and the position angle of the major axis) of our galaxies from the analysis of the abundance map. The photometry-map-based and the abundance-map-based geometrical parameters are relatively close to each other for the majority of the galaxies but the discrepancy is large for a few galaxies with a flat radial abundance gradient.

  6. Abundance fluctuations in the interstellar medium

    NASA Technical Reports Server (NTRS)

    Jura, M.

    1982-01-01

    The determination of abundances within the interstellar medium is reviewed. It appears that interstellar abundances within 1 kpc of the Sun are uniform to within a factor of two or three, but it is not yet possible to determine whether there are real fluctuations at this level except for deuterium for which the factor of two variations appear to be real. Establishing the level of local fluctuations in the abundances is of considerable importance for understanding the history of nucleosynthesis in the solar neighborhood, the evolution of the interstellar medium and the formation of stars.

  7. Interstellar Abundances Toward X Per, Revisited

    NASA Technical Reports Server (NTRS)

    Valencic, Lynne A.; Smith, Randall K.

    2012-01-01

    The nearby X-ray binary X Per (HD 24534) provides a useful beacon with which to measure elemental abundances in the local ISM. We examine absorption features of O, Mg, and Si along this line of sight using spectra from the Chandra Observatory's LETG/ACIS-S and XMM-Newton's RGS instruments. In general, we find that the abundances and their ratios are similar to those of young F and G stars and the most recent solar values. We compare our results with abundances required by dust grain models.

  8. Interstellar Abundances Toward X Per, Revisited

    NASA Technical Reports Server (NTRS)

    Valencic, Lynne A.; Smith, Randall K.

    2014-01-01

    The nearby X-ray binary X Per (HD 24534) provides a useful beacon with which to measure elemental abundances in the local ISM. We examine absorption features of 0, Mg, and Si along this line of sight using spectra from the Chandra Observatory's LETG/ ACIS-S and XMM-Newton's RGS instruments. In general, we find that the abundances and their ratios are similar to those of young F and G stars and the most recent solar values. We compare our results with abundances required by dust grain models.

  9. Abundances of Elements in Stellar Coronae

    NASA Technical Reports Server (NTRS)

    Drake, Jeremy

    1998-01-01

    Interest in stellar coronal abundances was piqued several years ago by the launch of satellites that were able to study the compositions of coronae on stars other than the sun. Motivated by the possibility that other stellar coronae might share the First Ionization Potential (FIP) Effect solar abundance anomaly, we have in recent years been attempting to determine coronal element abundances in other stars. I will review these results, together with similar results reported in the literature, from a critical perspective of understanding the true uncertainties involved in the measurements. The importance of element abundances for coronal physics will be highlighted, and it will be shown that the differences in the chemical compositions of active stars allow us to draw new conclusions regarding the nature of stellar coronae and coronal heating.

  10. The lithium abundance in extreme halo stars

    SciTech Connect

    Hobbs, L.M.; Thorburn, J.A. )

    1991-07-01

    New observations are reported of atmospheric Li abundances for six extremely metal-poor dwarfs with Fe-H ratios not higher than {minus}2.59 and T(e) not lower than 5950 K. The spectra were obtained in 1990 at Kitt Peak National Observatory, using the echelle spectrograph with the UV Fast camera. The resulting Li abundances for these stars range between N(Li) values of 1.99 and 2.24, where N(Li) = 12 + log (Li/H). These results agree with the abundances reported previously for five other metal-poor dwarfs with the Fe/H ratios not above {minus}2.60. The invariance of Li abundance in these 11 stars indicates a primordial origin for most of the Li observed in these Galactic stars. 23 refs.

  11. Coronae of Stars with Supersolar Elemental Abundances

    NASA Technical Reports Server (NTRS)

    Peretz, Uria; Behar, Ehud; Drake, Stephen A.

    2015-01-01

    Coronal elemental abundances are known to deviate from the photospheric values of their parent star, with the degree of deviation depending on the first ionization potential (FIP). This study focuses on the coronal composition of stars with supersolar photospheric abundances. We present the coronal abundances of six such stars: 11 LMi, iota Hor, HR 7291, tau Boo, and alpha Cen A and B. These stars all have high-statistics X-ray spectra, three of which are presented for the first time. The abundances we measured were obtained using the line-resolved spectra of the Reflection Grating Spectrometer (RGS) in conjunction with the higher throughput EPIC-pn camera spectra onboard the XMM-Newton observatory. A collisionally ionized plasma model with two or three temperature components is found to represent the spectra well. All elements are found to be consistently depleted in the coronae compared to their respective photospheres. For 11 LMi and tau Boo no FIP effect is present, while iota Hor, HR 7291, and alpha Cen A and B show a clear FIP trend. These conclusions hold whether the comparison is made with solar abundances or the individual stellar abundances. Unlike the solar corona, where low-FIP elements are enriched, in these stars the FIP effect is consistently due to a depletion of high-FIP elements with respect to actual photospheric abundances. A comparison with solar (instead of stellar) abundances yields the same fractionation trend as on the Sun. In both cases, a similar FIP bias is inferred, but different fractionation mechanisms need to be invoked.

  12. Hymenoscyphus fraxineus vs. Hymenoscyphus albidus – A comparative light microscopic study on the causal agent of European ash dieback and related foliicolous, stroma-forming species

    PubMed Central

    Baral, Hans-Otto; Bemmann, Martin

    2014-01-01

    Five species of Hymenoscyphus that fruit on black stromatized parts of dead leaves of deciduous trees are presented, giving details on their morphological and ecological characteristics. Several of these species have previously been misplaced in rutstroemiaceous genera because of the presence of a substratal stroma. However, the heteropolar, scutuloid ascospores with an often hook-like lateral protrusion at the rounded apex and the ascus apical ring of the Hymenoscyphus-type represent two reliable morphological characteristics that, together with molecular data, provide clear evidence for their placement in the genus Hymenoscyphus (Helotiaceae). Among the species treated is Hymenoscyphus fraxineus (=Hymenoscyphus pseudoalbidus), the causal agent of the European ash dieback disease. Since 1992 this species started within Europe to replace the rather uncommon Hymenoscyphus albidus, which is likewise confined to leaves of Fraxinus. Hy. fraxineus has been recorded already since 1990 in Eastern Asia (Japan, Korea, northeast of China), where it had been initially misidentified as Lambertella albida (≡Hy. albidus). In these regions, it occurs as a harmless saprotroph on Fraxinus mandshurica and Fraxinus rhynchophylla, suggesting that those populations are native while the European ash dieback disease has a recent Eastern Asiatic origin. The distinctly higher genetic diversity found in Japanese Hy. fraxineus in contrast to European Hy. fraxineus supports this view. Genetic similarities between Japanese Hy. fraxineus and European Hy. albidus suggest that also Hy. albidus might be a descendant of Asian Hy. fraxineus, though having invaded Europe much earlier. However, consistent genetic deviation between European and Asian Hy. fraxineus at two nucleotide positions of the ITS region indicates that the European ash disease originates from a region different from the presently known areas in Eastern Asia. Our results underline the importance of detailed morphological studies

  13. Hymenoscyphus fraxineus vs. Hymenoscyphus albidus - A comparative light microscopic study on the causal agent of European ash dieback and related foliicolous, stroma-forming species.

    PubMed

    Baral, Hans-Otto; Bemmann, Martin

    2014-10-02

    Five species of Hymenoscyphus that fruit on black stromatized parts of dead leaves of deciduous trees are presented, giving details on their morphological and ecological characteristics. Several of these species have previously been misplaced in rutstroemiaceous genera because of the presence of a substratal stroma. However, the heteropolar, scutuloid ascospores with an often hook-like lateral protrusion at the rounded apex and the ascus apical ring of the Hymenoscyphus-type represent two reliable morphological characteristics that, together with molecular data, provide clear evidence for their placement in the genus Hymenoscyphus (Helotiaceae). Among the species treated is Hymenoscyphus fraxineus (=Hymenoscyphus pseudoalbidus), the causal agent of the European ash dieback disease. Since 1992 this species started within Europe to replace the rather uncommon Hymenoscyphus albidus, which is likewise confined to leaves of Fraxinus. Hy. fraxineus has been recorded already since 1990 in Eastern Asia (Japan, Korea, northeast of China), where it had been initially misidentified as Lambertella albida (≡Hy. albidus). In these regions, it occurs as a harmless saprotroph on Fraxinus mandshurica and Fraxinus rhynchophylla, suggesting that those populations are native while the European ash dieback disease has a recent Eastern Asiatic origin. The distinctly higher genetic diversity found in Japanese Hy. fraxineus in contrast to European Hy. fraxineus supports this view. Genetic similarities between Japanese Hy. fraxineus and European Hy. albidus suggest that also Hy. albidus might be a descendant of Asian Hy. fraxineus, though having invaded Europe much earlier. However, consistent genetic deviation between European and Asian Hy. fraxineus at two nucleotide positions of the ITS region indicates that the European ash disease originates from a region different from the presently known areas in Eastern Asia. Our results underline the importance of detailed morphological studies

  14. Modeling abundance effects in distance sampling

    USGS Publications Warehouse

    Royle, J. Andrew; Dawson, D.K.; Bates, S.

    2004-01-01

    Distance-sampling methods are commonly used in studies of animal populations to estimate population density. A common objective of such studies is to evaluate the relationship between abundance or density and covariates that describe animal habitat or other environmental influences. However, little attention has been focused on methods of modeling abundance covariate effects in conventional distance-sampling models. In this paper we propose a distance-sampling model that accommodates covariate effects on abundance. The model is based on specification of the distance-sampling likelihood at the level of the sample unit in terms of local abundance (for each sampling unit). This model is augmented with a Poisson regression model for local abundance that is parameterized in terms of available covariates. Maximum-likelihood estimation of detection and density parameters is based on the integrated likelihood, wherein local abundance is removed from the likelihood by integration. We provide an example using avian point-transect data of Ovenbirds (Seiurus aurocapillus) collected using a distance-sampling protocol and two measures of habitat structure (understory cover and basal area of overstory trees). The model yields a sensible description (positive effect of understory cover, negative effect on basal area) of the relationship between habitat and Ovenbird density that can be used to evaluate the effects of habitat management on Ovenbird populations.

  15. TEA: A Code Calculating Thermochemical Equilibrium Abundances

    NASA Astrophysics Data System (ADS)

    Blecic, Jasmina; Harrington, Joseph; Bowman, M. Oliver

    2016-07-01

    We present an open-source Thermochemical Equilibrium Abundances (TEA) code that calculates the abundances of gaseous molecular species. The code is based on the methodology of White et al. and Eriksson. It applies Gibbs free-energy minimization using an iterative, Lagrangian optimization scheme. Given elemental abundances, TEA calculates molecular abundances for a particular temperature and pressure or a list of temperature-pressure pairs. We tested the code against the method of Burrows & Sharp, the free thermochemical equilibrium code Chemical Equilibrium with Applications (CEA), and the example given by Burrows & Sharp. Using their thermodynamic data, TEA reproduces their final abundances, but with higher precision. We also applied the TEA abundance calculations to models of several hot-Jupiter exoplanets, producing expected results. TEA is written in Python in a modular format. There is a start guide, a user manual, and a code document in addition to this theory paper. TEA is available under a reproducible-research, open-source license via https://github.com/dzesmin/TEA.

  16. Report on carbon and nitrogen abundance studies

    NASA Technical Reports Server (NTRS)

    Boehm-Vitense, Erika

    1991-01-01

    The aim of the proposal was to determine the nitrogen to carbon abundance ratios from transition layer lines in stars with different T(sub eff) and luminosities. The equations which give the surface emission line fluxes and the measured ratio of the NV to CIV emission line fluxes are presented and explained. The abundance results are compared with those of photospheric abundance studies for stars in common with the photospheric investigations. The results show that the analyses are at least as accurate as the photospheric determinations. These studies can be extended to F and early G stars for which photospheric abundance determinations for giants are hard to do because molecular bands become too weak. The abundance determination in the context of stellar evolution is addressed. The N/C abundance ratio increases steeply at the point of evolution for which the convection zone reaches deepest. Looking at the evolution of the rotation velocities v sin i, a steep decrease in v sin i is related to the increasing depth of the convection zone. It is concluded that the decrease in v sin i for T(sub eff) less than or approximately = 5800 K is most probably due to the rearrangement of the angular momentum in the stars due to deep convective mixing. It appears that the convection zone is rotating with nearly depth independent angular momentum. Other research results and ongoing projects are discussed.

  17. Solar Models with New Low Metal Abundances

    NASA Astrophysics Data System (ADS)

    Yang, Wuming

    2016-04-01

    In the past decade, the photospheric abundances of the Sun had been revised several times by many observers. The standard solar models constructed with the new low-metal abundances disagree with helioseismic results and detected neutrino fluxes. The solar model problem has puzzled some stellar physicists for more than 10 years. Rotation, enhanced diffusion, convection overshoot, and magnetic fields are used to reconcile the new abundances with helioseismology. The too low helium subsurface abundance in enhanced diffusion models can be improved by the mixing caused by rotation and magnetic fields. The problem of the depth of the convective zone in rotating models can be resolved by convection overshoot. Consequently, the Asplund-Grevesse-Sauval rotation model including overshooting (AGSR) reproduces the seismically inferred sound-speed and density profiles and the convection zone depth as well as the Grevesse & Sauval model computed before. But this model fails to reproduce the surface helium abundance, which is 0.2393 (2.6σ away from the seismic value), and neutrino fluxes. The magnetic model called AGSM keeps the agreement of the AGSR and improves the prediction of the surface helium abundance. The observed separation ratios r02 and r13 are reasonably reproduced by AGSM. Moreover, neutrino fluxes calculated by this model are not far from the detected neutrino fluxes and the predictions of previous works.

  18. Infrared microspectroscopy identifies biomolecular changes associated with chronic oxidative stress in mammary epithelium and stroma of breast tissues from healthy young women

    PubMed Central

    Patel, Imran I; Shearer, Debra A; Fogarty, Simon W; Fullwood, Nigel J; Quaroni, Luca; Martin, Francis L; Weisz, Judith

    2014-01-01

    Studies of the decades-long latent stages of breast carcinogenesis have been limited to when hyperplastic lesions are already present. Investigations of earlier stages of breast cancer (BC) latency have been stymied by the lack of fiducial biomarkers needed to identify where in histologically normal tissues progression toward a BC might be taking place. Recent evidence suggests that a marker of chronic oxidative stress (OxS), protein adducts of 4-hydroxy-2-nonenal (4HNE), can meet this need. Specifically: (1) 4HNE immunopositive (4HNE+) mammary epithelial (ME) cells were found to be prevalent in normal (reduction mammoplasty) tissues of most women (including many teenagers) studied, representative of those living in the United States’ high risk-posing environment and: (2) marked (>1.5-fold) differences were identified between tissues of healthy young women with many vs. few 4HNE+ ME cells in the relative levels of transcripts for 42 of the 84 OxS-associated genes represented in SABioscience Oxidative-Stress/Oxidative-Defense PCR array. Herein we used synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to identify molecular changes associated with 4HNE adducts in basal and luminal ME cells in terminal ductal units (TDLU), which are the cells of origin of BC, and associated intralobular and interlobular stroma, known contributors to carcinogenesis. Multivariate analysis-derived wavenumbers differentiated 4HNE+ and 4HNE− cells in each of the anatomical compartments. Specifically, principal component and linear discriminant analyses of mid-infrared spectra obtained from these cells revealed unambiguous, statistically highly significant differences in the “biochemical fingerprint” of 4HNE+ vs. 4HNE− luminal and basal ME cells, as well as between associated intralobular and interlobular stroma. These findings demonstrate further SR-FTIR microspectroscopy’s ability to identify molecular changes associated with altered

  19. Capacity of lung stroma to educate dendritic cells inhibiting mycobacteria-specific T-cell response depends upon genetic susceptibility to tuberculosis.

    PubMed

    Kapina, Marina A; Rubakova, Elvira I; Majorov, Konstantin B; Logunova, Nadezhda N; Apt, Alexander S

    2013-01-01

    The balance between activation and inhibition of local immune responses in affected tissues during prolonged chronic infections is important for host protection. There is ample evidence that regulatory, tolerogenic dendritic cells (DC) are developed and present in tissues and inhibit overwhelming inflammatory reactions. Also, it was firmly established that stromal microenvironment of many organs is able to induce development of immature regulatory DC (DCreg), an essential element of a general immune regulatory network. However, direct experimental data demonstrating inhibition of immune responses by stroma-instructed immature DCreg in infectious models are scarce, and virtually nothing is known about functioning of this axis of immunity during tuberculosis (TB) infection. In this study, we demonstrate that lung stromal cells are capable of supporting the development in culture of immature CD11b(+)CD11c(low)CD103(-) DCreg from lineage-negative (lin(-)) bone marrow precursors. DCreg developed on lung stroma isolated from mice of genetically TB-hyper-susceptible I/St and relatively resistant B6 inbred strains inhibited proliferative response of mycobacteria-specific CD4(+) T-cell lines a dose-dependent manner. Importantly, the inhibitory activity of B6 DCreg was substantially higher than that of I/St Dcreg. Moreover, when the donors of stromal cells were chronically infected with virulent mycobacteria, the capacity to instruct inhibitory DCreg was retained in B6, but further diminished in I/St stromal cells. DCreg-provided suppression was mediated by a few soluble mediators, including PGE2, NO and IL-10. The content of CD4(+)Foxp3(+) Treg cells in the mediastinal, lung-draining lymph nodes at the advanced stages of chronic infection did not change in I/St, but increased 2-fold in B6 mice, and lung pathology was much more pronounced in the former mice. Taken together, these data provide genetic evidence that the capacity to maintain populations of regulatory cells

  20. The elemental abundances in interplanetary dust particles

    NASA Astrophysics Data System (ADS)

    Arndt, Peter; Bohsung, Jörg; Maetz, Mischa; Jessberger, Elmar K.

    1996-11-01

    We compiled a table of all major, minor, and trace-element abundances in 89 interplanetary dust particles (IDPs) that includes data obtained with proton-induced x-ray emission (PIXE), synchroton x-ray fluorescence (SXRF), and secondary ion mass spectrometry (SIMS). For the first time, the reliability of the trace-element abundances in IDPs is tested by various crosschecks. We also report on the results of cluster analyses that we performed on IDP compositions. Because of the incompleteness of the data set, we included only the elements Cr, Mn, Ni, Cu, and Zn, normalized to Fe and CI chondrite abundances, that are determined in 73 IDPs. The data arrange themselves in four rather poorly defined groups that we discuss in relation to CI chondrites following the assumption that on the average CI abundances are most probable. The largest group (chondritic), with 44 members, has close to CI abundances for many refractory and moderately refractory elements (Na, Al, Si, P, K, Sc, Ti, V, Cr, Co, Ge, Sr). It is slightly depleted in Fe and more in Ca and S, while the volatile elements (Cl, Cu, Zn, Ga, Se, Rb) are enriched by =1.7 × CI and Br by 21 × CI. The low-Zn group, with 12 members, is very similar to the chondritic group except for its Zn-depletion, stronger Ca-depletion and Fe-enrichment. The low-Ni group, with 11 members, has Ni/Fe = 0.03 × CI and almost CI-like Ca, but its extraterrestrial origin is not established. The last group (6 members) contains non-systematic particles of unknown origin. We found that Fe is inhomogeneously distributed on a micron scale. Furthermore, the abundances of elements that are measured near their limits of detection are easily overestimated. These biases involved, the incomplete data set and possible contaminating processes prevent us from obtaining information on the specific origin(s) of IDPs from elemental abundances.

  1. Clonal growth and plant species abundance

    PubMed Central

    Herben, Tomáš; Nováková, Zuzana; Klimešová, Jitka

    2014-01-01

    Background and Aims Both regional and local plant abundances are driven by species' dispersal capacities and their abilities to exploit new habitats and persist there. These processes are affected by clonal growth, which is difficult to evaluate and compare across large numbers of species. This study assessed the influence of clonal reproduction on local and regional abundances of a large set of species and compared the predictive power of morphologically defined traits of clonal growth with data on actual clonal growth from a botanical garden. The role of clonal growth was compared with the effects of seed reproduction, habitat requirements and growth, proxied both by LHS (leaf–height–seed) traits and by actual performance in the botanical garden. Methods Morphological parameters of clonal growth, actual clonal reproduction in the garden and LHS traits (leaf-specific area – height – seed mass) were used as predictors of species abundance, both regional (number of species records in the Czech Republic) and local (mean species cover in vegetation records) for 836 perennial herbaceous species. Species differences in habitat requirements were accounted for by classifying the dataset by habitat type and also by using Ellenberg indicator values as covariates. Key Results After habitat differences were accounted for, clonal growth parameters explained an important part of variation in species abundance, both at regional and at local levels. At both levels, both greater vegetative growth in cultivation and greater lateral expansion trait values were correlated with higher abundance. Seed reproduction had weaker effects, being positive at the regional level and negative at the local level. Conclusions Morphologically defined traits are predictive of species abundance, and it is concluded that simultaneous investigation of several such traits can help develop hypotheses on specific processes (e.g. avoidance of self-competition, support of offspring) potentially

  2. Tumor stroma-derived Wnt5a induces differentiation of basal cell carcinoma of Ptch-mutant mice via CaMKII.

    PubMed

    Nitzki, Frauke; Zibat, Arne; König, Simone; Wijgerde, Mark; Rosenberger, Albert; Brembeck, Felix H; Carstens, Per-Ole; Frommhold, Anke; Uhmann, Anja; Klingler, Stefan; Reifenberger, Julia; Pukrop, Tobias; Aberger, Fritz; Schulz-Schaeffer, Walter; Hahn, Heidi

    2010-04-01

    Basal cell carcinoma (BCC) is the most common skin tumor in humans. Although BCCs rarely metastasize, they can cause significant morbidity due to local aggressiveness. Approximately 20% of BCCs show signs of spontaneous regression. The understanding of molecular events mediating spontaneous regression has the potential to reduce morbidity of BCC and, potentially, other tumors, if translated into tumor therapies. We show that BCCs induced in conditional Ptch(flox/flox)ERT2(+/-) knockout mice regress with time and show a more differentiated phenotype. Differentiation is accompanied by Wnt5a expression in the tumor stroma, which is first detectable at the fully developed tumor stage. Coculture experiments revealed that Wnt5a is upregulated in tumor-adjacent macrophages by soluble signals derived from BCC cells. In turn, Wnt5a induces the expression of the differentiation marker K10 in tumor cells, which is mediated by Wnt/Ca(2+) signaling in a CaMKII-dependent manner. These data support a role of stromal Wnt5a in BCC differentiation and regression, which may have important implications for development of new treatment strategies for this tumor. Taken together, our results establish BCC as an easily accessible model of tumor regression. The regression of BCC despite sustained Hedgehog signaling activity seems to be mediated by tumor-stromal interactions via Wnt5a signaling.

  3. Hepatoid carcinoma of the pancreas with lymphoid stroma: first description of the clinical, morphological, immunohistochemical, and molecular characteristics of an unusual pancreatic carcinoma.

    PubMed

    Vanoli, Alessandro; Argenti, Francesca; Vinci, Alessio; La Rosa, Stefano; Viglio, Alessandra; Riboni, Roberta; Necchi, Vittorio; Pugliese, Luigi; Sessa, Fausto; Pietrabissa, Andrea; Paulli, Marco

    2015-08-01

    We report a case of tumour in the head of the pancreas observed in a 57-year-old man with a history of worsening jaundice and elevated alpha-fetoprotein (AFP) serum level, who underwent Whipple pancreatoduodenectomy. Histologically, the tumour was predominantly composed of solid sheets of large eosinophilic cells with a prominent lymphoid infiltration without association neither with DNA microsatellite instability nor Epstein-Barr virus infection. The tumour was diffusely and strongly positive for hepatocyte paraffin-1 (Hep Par-1) and glypican-3 leading to the diagnosis of hepatoid carcinoma. Strong cytoplasmic staining for AFP was focally observed. Moreover, tumour cells showed countless cytoplasmic eosinophilic globules immunoreactive for the stress protein p62. A primary hepatocellular carcinoma of the liver was ruled out by careful clinical analysis. Hepatoid carcinoma is an extremely rare pancreatic neoplasm, and here, we describe the first case of such variant associated with lymphoid stroma. The characteristic histologic features and the immunophenotypic profile help in distinguishing this carcinoma from other pancreatic tumours, notably from medullary carcinoma.

  4. Role of beta 1 and beta 2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma.

    PubMed Central

    Teixidó, J; Hemler, M E; Greenberger, J S; Anklesaria, P

    1992-01-01

    Hematopoietic stem cell interaction with elements of the underlying stroma is essential for sustained normal hematopoiesis. Here we have determined that adhesion receptors in the integrin family play a role in promoting adhesion of human hematopoietic stem cells to cultured human marrow stromal cells. Enriched CD34hi progenitor cells expressed VLA-4, VLA-5, and at least one or more beta 2 integrins. Homogeneous marrow stromal cell monolayers capable of supporting proliferation of cocultivated CD34hi cells expressed VCAM-1 and fibronectin (ligands for VLA-4 and VLA-5) as well as ICAM-1 (ligand for LFA-1 and Mac-1). Adhesion-blocking experiments indicated that VLA-4/VCAM-1, VLA-5/fibronectin, and beta 2-integrin/ICAM-1 pathways all are important for CD34hi cell attachment to stromal cells. Consistent with this suggestion, IL-1 stimulation of stromal cells caused both increased VCAM-1 and ICAM-1 expression and increased attachment by CD34hi bone marrow cells. In addition, CD34hi cells utilized VLA-4 to adhere to purified VCAM-1 and employed VLA-5 (and to a lesser extent VLA-4) to adhere to purified fibronectin. Together these results suggest that CD34hi stem cells may utilize multiple integrin-mediated adhesion pathways to localize within specialized microenvironmental niches created by marrow stromal cells. Images PMID:1379610

  5. The hollow fiber bioreactor as a stroma-supported, serum-free ex vivo expansion platform for human umbilical cord blood cells.

    PubMed

    Xue, Cao; Kwek, Kenneth Y C; Chan, Jerry K Y; Chen, Qingfeng; Lim, Mayasari

    2014-07-01

    The bone marrow microenvironment plays an integral role in the regulation of hematopoiesis. Residing stromal cells and the extracellular matrix in the bone marrow microenvironment provide biological signals that control hematopoietic stem cell (HSC) function. In this study, we developed a bio-mimetic co-culture platform using the hollow fiber bioreactor (HFBR) for ex vivo expansion of HSCs. We evaluated the efficacy of such a platform in comparison to standard cultures performed on tissue culture polystyrene (TCP), using a human stromal cell line (HS-5) as stromal support, co-cultured with lineage-depleted human cord blood cells in serum-free medium supplemented with a cytokine cocktail. Our results showed that the performance of the HFBR in supporting total cell and CD34(+) progenitor cell expansion was comparable to that of cultures on TCP. Cells harvested from the HFBR had a higher clonogenic ability. The performance of ex vivo-expanded cells from the HFBR in hematopoietic reconstitution in humanized mice was comparable to that of the TCP control. Scanning electron microscopy revealed that stroma cell growth inside the HFBR created a three-dimensional cell matrix architecture. These findings demonstrate the feasibility of utilizing the HFBR for creating a complex cell matrix architecture, which may provide good in vitro mimicry of the bone marrow, supporting large-scale expansion of HSCs.

  6. Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial.

    PubMed

    Thomas, Sushma S; Makar, Karen W; Li, Lin; Zheng, Yingye; Yang, Peiying; Levy, Lisa; Rudolph, Rebecca Y; Lampe, Paul D; Yan, Min; Markowitz, Sanford D; Bigler, Jeannette; Lampe, Johanna W; Potter, John D

    2015-12-01

    Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133 + 2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d) on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2) levels. We conducted a comprehensive study of differential gene expression between normal human colonic epithelium and stroma from healthy individuals. Although no statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, we have identified the genes uniquely and reproducibly expressed in each tissue type and have analyzed the biologic processes they represent. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) - accession number GSE71571 - was generated including the basic analysis as contained in the manuscript published in BMC Medical Genetics with the PMID 25927723 (Thomas et al., 2015 [9]).

  7. Abundances in Eight M31 Planetary Nebulae

    NASA Astrophysics Data System (ADS)

    Hensley, Kerry G.; Kwitter, Karen B.; Corradi, Romano; Galera-Rosillo, R.; Balick, Bruce; Henry, Richard B. C.

    2014-06-01

    As part of a continuing project using planetary nebulae (PNe) to study the chemical evolution and formation history of M31 (see accompanying poster by Balick et al.), we obtained spectra of eight PNe in the fall of 2013 with the OSIRIS spectrograph on the GTC. All of these PNe are located outside M31’s inner disk and bulge. Spectral coverage extended from 3700-7800Å with a resolution of ~6 Å. Especially important in abundance determinations is the detection of the weak, temperature-sensitive auroral line of [O III], at 4363Å, which is often contaminated by Hg I 4358Å from streetlights; the remoteness of the GTC eliminated this difficulty. We reduced and measured the spectra using IRAF, and derived nebular diagnostics and abundances with ELSA, our in-house five-level-atom program. Here we report the chemical abundances determined from these spectra. The bottom line is that the oxygen abundances in these PNe are all within a factor of 2-3 of the solar value, (as are all the other M31 PNe our team has previously measured) despite the significant range of galactocentric distance. Future work will use these abundances to constrain models of the central star to estimate progenitor masses and ages. In particular we will use the results to investigate the hypothesis that these PNe might represent a population related to the encounter between M31 and M33 ~3 Gy ago. We gratefully acknowledge support from Williams College.

  8. Why is Trichodesmium abundant in the Kuroshio?

    NASA Astrophysics Data System (ADS)

    Shiozaki, T.; Takeda, S.; Itoh, S.; Kodama, T.; Liu, X.; Hashihama, F.; Furuya, K.

    2015-12-01

    The genus Trichodesmium is recognized as an abundant and major diazotroph in the Kuroshio, but the reason for this remains unclear. The present study investigated the abundance of Trichodesmium spp. and nitrogen fixation together with concentrations of dissolved iron and phosphate in the Kuroshio and its marginal seas. We performed the observations near the Miyako Islands, which form part of the Ryukyu Islands, situated along the Kuroshio, since our satellite analysis suggested that material transport could occur from the islands to the Kuroshio. Trichodesmium spp. bloomed (> 20 000 filaments L-1) near the Miyako Islands, abundance was high in the Kuroshio and the Kuroshio bifurcation region of the East China Sea, but was low in the Philippine Sea. The abundance of Trichodesmium spp. was significantly correlated with the total nitrogen fixation activity. The surface concentrations of dissolved iron (0.19-0.89 nM) and phosphate (< 3-36 nM) were similar for all of the study areas, indicating that the nutrient distribution could not explain the spatial differences in Trichodesmium spp. abundance and nitrogen fixation. Numerical particle-tracking experiments simulated the transportation of water around the Ryukyu Islands to the Kuroshio. Our results indicate that Trichodesmium growing around the Ryukyu Islands could be advected into the Kuroshio.

  9. REVIEW: Can habitat selection predict abundance?

    PubMed

    Boyce, Mark S; Johnson, Chris J; Merrill, Evelyn H; Nielsen, Scott E; Solberg, Erling J; van Moorter, Bram

    2016-01-01

    Habitats have substantial influence on the distribution and abundance of animals. Animals' selective movement yields their habitat use. Animals generally are more abundant in habitats that are selected most strongly. Models of habitat selection can be used to distribute animals on the landscape or their distribution can be modelled based on data of habitat use, occupancy, intensity of use or counts of animals. When the population is at carrying capacity or in an ideal-free distribution, habitat selection and related metrics of habitat use can be used to estimate abundance. If the population is not at equilibrium, models have the flexibility to incorporate density into models of habitat selection; but abundance might be influenced by factors influencing fitness that are not directly related to habitat thereby compromising the use of habitat-based models for predicting population size. Scale and domain of the sampling frame, both in time and space, are crucial considerations limiting application of these models. Ultimately, identifying reliable models for predicting abundance from habitat data requires an understanding of the mechanisms underlying population regulation and limitation.

  10. Hierarchical models of animal abundance and occurrence

    USGS Publications Warehouse

    Royle, J. Andrew; Dorazio, R.M.

    2006-01-01

    Much of animal ecology is devoted to studies of abundance and occurrence of species, based on surveys of spatially referenced sample units. These surveys frequently yield sparse counts that are contaminated by imperfect detection, making direct inference about abundance or occurrence based on observational data infeasible. This article describes a flexible hierarchical modeling framework for estimation and inference about animal abundance and occurrence from survey data that are subject to imperfect detection. Within this framework, we specify models of abundance and detectability of animals at the level of the local populations defined by the sample units. Information at the level of the local population is aggregated by specifying models that describe variation in abundance and detection among sites. We describe likelihood-based and Bayesian methods for estimation and inference under the resulting hierarchical model. We provide two examples of the application of hierarchical models to animal survey data, the first based on removal counts of stream fish and the second based on avian quadrat counts. For both examples, we provide a Bayesian analysis of the models using the software WinBUGS.

  11. Abundance of sea kraits correlates with precipitation.

    PubMed

    Lillywhite, Harvey B; Tu, Ming-Chung

    2011-01-01

    Recent studies have shown that sea kraits (Laticauda spp.)--amphibious sea snakes--dehydrate without a source of fresh water, drink only fresh water or very dilute brackish water, and have a spatial distribution of abundance that correlates with freshwater sites in Taiwan. The spatial distribution correlates with sites where there is a source of fresh water in addition to local precipitation. Here we report six years of longitudinal data on the abundance of sea kraits related to precipitation at sites where these snakes are normally abundant in the coastal waters of Lanyu (Orchid Island), Taiwan. The number of observed sea kraits varies from year-to-year and correlates positively with previous 6-mo cumulative rainfall, which serves as an inverse index of drought. Grouped data for snake counts indicate that mean abundance in wet years is nearly 3-fold greater than in dry years, and this difference is significant. These data corroborate previous findings and suggest that freshwater dependence influences the abundance or activity of sea kraits on both spatial and temporal scales. The increasing evidence for freshwater dependence in these and other marine species have important implications for the possible impact of climate change on sea snake distributions.

  12. RELATIVE ABUNDANCE MEASUREMENTS IN PLUMES AND INTERPLUMES

    SciTech Connect

    Guennou, C.; Hahn, M.; Savin, D. W.

    2015-07-10

    We present measurements of relative elemental abundances in plumes and interplumes. Plumes are bright, narrow structures in coronal holes that extend along open magnetic field lines far out into the corona. Previous work has found that in some coronal structures the abundances of elements with a low first ionization potential (FIP) <10 eV are enhanced relative to their photospheric abundances. This coronal-to-photospheric abundance ratio, commonly called the FIP bias, is typically 1 for elements with a high-FIP (>10 eV). We have used Extreme Ultraviolet Imaging Spectrometer observations made on 2007 March 13 and 14 over a ≈24 hr period to characterize abundance variations in plumes and interplumes. To assess their elemental composition, we used a differential emission measure analysis, which accounts for the thermal structure of the observed plasma. We used lines from ions of iron, silicon, and sulfur. From these we estimated the ratio of the iron and silicon FIP bias relative to that for sulfur. From the results, we have created FIP-bias-ratio maps. We find that the FIP-bias ratio is sometimes higher in plumes than in interplumes and that this enhancement can be time dependent. These results may help to identify whether plumes or interplumes contribute to the fast solar wind observed in situ and may also provide constraints on the formation and heating mechanisms of plumes.

  13. Measuring Abundance Ratios from Integrated Light

    NASA Astrophysics Data System (ADS)

    Worthey, G.

    2010-06-01

    Age, overall abundance, and detailed, element-by-element abundances can be extracted from the integrated light of distant galaxies. The method, at its most basic, is merely the comparison of observed spectra with appropriate models. The relative ratios of elements C, N, O, Na, Mg, Ca, Sc, Ti, Cr, Mn, Fe, Co, Ni, Sr, and Ba can be determined to scientifically useful precision. Cases of interest that are borderline because they suffer internal degeneracies (although plenty of signal is present) are Al and the trio C, N, and O. The elements S, K, Cu, Eu, and the noble gases are too difficult to measure, and V is borderline. Changing the relative abundance ratios, even at fixed heavy-element content, changes the temperatures, luminosities, and number densities of the underlying stellar evolution, as well as more direct changes in the spectra of the stars present. The latter effects dominate the spectral shape, while the former effects render age estimation quite difficult.

  14. Chemical Abundances of Compact Planetary Nebulae

    NASA Astrophysics Data System (ADS)

    Lee, Ting-Hui; Shaw, Richard A.; Stanghellini, letizia; Riley, Ben

    2015-08-01

    We present preliminary results from an optical spectroscopic survey of compact planetary nebulae (PNe) in the Galactic disk. This is an ongoing optical+infrared spectral survey of 150 compact PNe to build a deep sample of PN chemical abundances. We obtained optical spectra of PNe with the Southern Astrophysical Research (SOAR) Telescope and Goodman High-Throughput Spectrograph between 2012 and 2015. These data were used to calculate the nebulae diagnostics such as electron temperature and density for each PN, and to derive the elemental abundances of He, N, O Ne, S and Ar. These abundances are vital to understanding the nature of the PNe, and their low- to intermediate-mass progenitor stars.

  15. Rare-earth abundances in chondritic meteorites

    NASA Technical Reports Server (NTRS)

    Evensen, N. M.; Hamilton, P. J.; Onions, R. K.

    1978-01-01

    Fifteen chondrites, including eight carbonaceous chondrites, were analyzed for rare earth element abundances by isotope dilution. Examination of REE for a large number of individual chondrites shows that only a small proportion of the analyses have flat unfractionated REE patterns within experimental error. While some of the remaining analyses are consistent with magmatic fractionation, many patterns, in particular those with positive Ce anomalies, can not be explained by known magmatic processes. Elemental abundance anomalies are found in all major chondrite classes. The persistence of anomalies in chondritic materials relatively removed from direct condensational processes implies that anomalous components are resistant to equilibrium or were introduced at a late stage of chondrite formation. Large-scale segregation of gas and condensate is implied, and bulk variations in REE abundances between planetary bodies is possible.

  16. On the abundance enigma in Ionized Regions

    NASA Astrophysics Data System (ADS)

    Bohigas, J.

    2009-04-01

    In ionized regions with temperature gradients and fluctuations, the ratio of the ion abundance obtained from a recombination line to that found from a collisionally excited line (CEL), or ADF, is smaller than observed (ADF ≥ 2). Larger ADFs are found when there is an additional component that is ≥ 30% colder. The temperature in the cold component must be ≈ 500, 200 and 100 K if the ADF found from an IR CEL is ≃2, 5 and 10. Most of the mass is in the hot region. The total H+ mass has been underestimated if it was found from the intensity of a Balmer line. [O IIII]5007/Hβ images can also render the relative distribution of cold and hot matter. The determination of accurate abundances is forestalled by the fact that observations cannot discriminate light from these components, the existence of distinct abundance sets and insufficient spectral information for the hot region.

  17. Abundance and chemistry of interstellar HOCO(+)

    NASA Technical Reports Server (NTRS)

    Minh, Y. C.; Brewer, M. K.; Irvine, W. M.; Friberg, P.; Johansson, L. E. B.

    1991-01-01

    Column densities of 10 to the 15th/sq cm toward the Galactic center and not more than 10 to the 12th/sq cm for cold dark clouds are derived from observations using an LVG model, and the chemical implications are discussed. The HOCO(+) 4(04)-3(03) line toward Sgr A is mapped. The fractional abundance of HOCO(+) in the Galactic center region was found to be three orders of magnitude larger than predicted by quiescent ion-molecule chemistry and an order of magnitude larger than predicted by an MHD shock model. It is suggested that the possibly high CO2 abundance, and consequently the observed HOCO(+) abundance in the Galactic center, may result from UV photolysis of grain mantles.

  18. INTERSTELLAR ABUNDANCES TOWARD X Per, REVISITED

    SciTech Connect

    Valencic, Lynne A.; Smith, Randall K.

    2013-06-10

    The nearby X-ray binary X Per (HD 24534) provides a useful beacon with which to examine dust grain types and measure elemental abundances in the local interstellar medium (ISM). The absorption features of O, Fe, Mg, and Si along this line of sight were measured using spectra from the Chandra X-Ray Observatory's LETG/ACIS-S and XMM-Newton's RGS instruments, and the Spex software package. The spectra were fit with dust analogs measured in the laboratory. The O, Mg, and Si abundances were compared to those from standard references, and the O abundance was compared to that along lines of sight toward other X-ray binaries. The results are as follows. First, it was found that a combination of MgSiO{sub 3} (enstatite) and Mg{sub 1.6}Fe{sub 0.4}SiO{sub 4} (olivine) provided the best fit to the O K edge, with N(MgSiO{sub 3})/N(Mg{sub 1.6}Fe{sub 0.4}SiO{sub 4}) = 3.4. Second, the Fe L edge could be fit with models that included metallic iron, but it was not well described by the laboratory spectra currently available. Third, the total abundances of O, Mg, and Si were in very good agreement with that of recently re-analyzed B stars, suggesting that they are good indicators of abundances in the local ISM, and the depletions were also in agreement with expected values for the diffuse ISM. Finally, the O abundances found from X-ray binary absorption spectra show a similar correlation with Galactocentric distances as seen in other objects.

  19. Understanding the "lethal" drivers of tumor-stroma co-evolution: emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment.

    PubMed

    Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E; Chiavarina, Barbara; Pavlides, Stephanos; Whitaker-Menezes, Diana; Tsirigos, Aristotelis; Witkiewicz, Agnieszka; Lin, Zhao; Balliet, Renee; Howell, Anthony; Sotgia, Federica

    2010-09-15

    We have recently proposed a new model for understanding how tumors evolve. To achieve successful "Tumor-Stroma Co-Evolution", cancer cells induce oxidative stress in adjacent fibroblasts and possibly other stromal cells. Oxidative stress in the tumor stroma mimics the effects of hypoxia, under aerobic conditions, resulting in an excess production of reactive oxygen species (ROS). Excess stromal production of ROS drives the onset of an anti-oxidant defense in adjacent cancer cells, protecting them from apoptosis. Moreover, excess stromal ROS production has a "Bystander-Effect", leading to DNA damage and aneuploidy in adjacent cancer cells, both hallmarks of genomic instability. Finally, ROS-driven oxidative stress induces autophagy and mitophagy in the tumor micro-environment, leading to the stromal over-production of recycled nutrients (including energy-rich metabolites, such as ketones and L-lactate). These recycled nutrients or chemical building blocks then help drive mitochondrial biogenesis in cancer cells, thereby promoting the anabolic growth of cancer cells (via an energy imbalance). We also show that ketones and lactate help "fuel" tumor growth and cancer cell metastasis and can act as chemo-attractants for cancer cells. We have termed this new paradigm for accelerating tumor-stroma co-evolution, "The Autophagic Tumor Stroma Model of Cancer Cell Metabolism". Heterotypic signaling in cancer-associated fibroblasts activates the transcription factors HIF1alpha and NFκB, potentiating the onset of hypoxic and inflammatory response(s), which further upregulates the autophagic program in the stromal compartment. Via stromal autophagy, this hypoxic/inflammatory response may provide a new escape mechanism for cancer cells during anti-angiogenic therapy, further exacerbating tumor recurrence and metastasis.

  20. OH vertical column abundance - Tropical measurements

    NASA Astrophysics Data System (ADS)

    Burnett, Clyde R.; Minschwaner, Kenneth R.; Burnett, Elizabeth B.

    1990-09-01

    Measurements of the vertical column abundance of atmospheric hydroxyl (OH) have been made during the period 1987-1989 at the National Weather Service (NWS) station at Moen, Truk, Federated States of Micronesia (7 deg N, 152 deg E). A total of 384 independent data sets was obtained. Tropical OH abundance levels average about 22 percent above corresponding mid-latitude values, with OH levels during late winter and early spring up to 50 percent above those observed at 40 deg N. Stratospheric wind and temperature data obtained from the daily NWS radiosonde data are examined for correlations with the OH results.

  1. OH vertical column abundance - Tropical measurements

    NASA Technical Reports Server (NTRS)

    Burnett, Clyde R.; Minschwaner, Kenneth R.; Burnett, Elizabeth B.

    1990-01-01

    Measurements of the vertical column abundance of atmospheric hydroxyl (OH) have been made during the period 1987-1989 at the National Weather Service (NWS) station at Moen, Truk, Federated States of Micronesia (7 deg N, 152 deg E). A total of 384 independent data sets was obtained. Tropical OH abundance levels average about 22 percent above corresponding mid-latitude values, with OH levels during late winter and early spring up to 50 percent above those observed at 40 deg N. Stratospheric wind and temperature data obtained from the daily NWS radiosonde data are examined for correlations with the OH results.

  2. Dispersion in DLA metallicities and deuterium abundances

    NASA Astrophysics Data System (ADS)

    Dvorkin, Irina; Silk, Joseph; Vangioni, Elisabeth; Petitjean, Patrick; Olive, Keith A.

    2017-03-01

    Recent chemical abundance measurements of damped Lyman-alpha absorbers (DLAs) revealed a large intrinsic scatter in their metallicities. We discuss a semi-analytic model that was specifically designed to study this scatter by tracing the chemical evolution of the interstellar matter in small regions of the Universe with different mean density, from over- to underdense regions. It is shown that different histories of structure formation in these regions are reflected in the chemical properties of the proto-galaxies. We also address deuterium abundance measurements, which constitute a complementary probe of the star formation and infall histories.

  3. ABUNDANT OR RARE? A HYBRID APPROACH FOR DETERMINING SPECIES RELATIVE ABUNDANCE AT AN ECOREGOIONAL SCALE

    EPA Science Inventory

    Everyone knows what abundant and rare species are, but quantifying the concept proves elusive. As part of an EPA/USGS project to assess near-coastal species vulnerability to climate change affects, we designed a hybrid approach to determine species relative abundance at an ecoreg...

  4. ABUNDANT OR RARE? A HYBRID APPROACH FOR DETERMINING SPECIES RELATIVE ABUNDANCE AT AN ECOREGOIONAL SCALE - 2014

    EPA Science Inventory

    Everyone knows what abundant and rare species are, but quantifying the concept proves elusive. As part of an EPA/USGS project to assess near-coastal species vulnerability to climate change affects, we designed a hybrid approach to determine species relative abundance at an ecoreg...

  5. Empirical oxygen abundances and physical conditions for relatively low abundance H II regions

    SciTech Connect

    Skillman, E.D. )

    1989-12-01

    The utility of the emission-line ratio (3727 + 4959 + 5007 A)/H-beta as an estimate of the total oxygen abundance in H II regions of low abundance (less than 10 percent of the solar value) is discussed. Using both observational data where the 4363A line is measured and model H II regions it is concluded that, for low abundance systems, total oxygen abundances can be determined with an accuracy of + or - 0.2 dex in the absence of a 4363A measurement. An attempt is made to study the average behavior of the stellar effective temperature (Teff) and ionization parameter (U) with changing abundance in low abundance systems. It is shown that some diagnostic methods which are viable for high abundance systems are not capable of uniquely determining Teff and U in low abundance systems. The most promising method of determining Teff and U requires measuring emission lines of forbidden O II, O III, S II, and S III. 53 refs.

  6. On a Rare Cutaneous Metastasis from a Sacrococcygeal Chordoma

    PubMed Central

    Brunelli, Matteo; Floccari, Federica; De Caro, Francesco

    2017-01-01

    Chordomas are rare malignant tumors of notochordal origin and are rare locally aggressive ones with a metastatic potential. The skin rarely is seen as metastatic site. We describe a case of an adult woman with cutaneous metastasis of a primary sacral chordoma excised ten years before, which appeared as a painless cutaneous mass located in the dorsal region. Once removed, the surgical specimen was formalin fixed and in paraffin embedded. Sections were stained with haematoxylin-eosin, and histochemical and immunohistochemical investigations were performed. Histologically, the neoplasia was characterized by cords or single tumor cells with an abundant myxoid stroma, conspicuous pale vacuolated cytoplasm (the classic “physaliphorous cells”), and mild nuclear atypia. Mitotic activity was scanty. At immunohistochemistry, the tumor cells were diffusely positive for S-100 protein, pan-keratins, EMA, and vimentin. A diagnosis of cutaneous metastasis of chordoma was performed. This case illustrates a diagnostic challenge because of the unusual presentation of an already rare tumor.

  7. The Abundance of Large Arcs From CLASH

    NASA Astrophysics Data System (ADS)

    Xu, Bingxiao; Postman, Marc; Meneghetti, Massimo; Coe, Dan A.; Clash Team

    2015-01-01

    We have developed an automated arc-finding algorithm to perform a rigorous comparison of the observed and simulated abundance of large lensed background galaxies (a.k.a arcs). We use images from the CLASH program to derive our observed arc abundance. Simulated CLASH images are created by performing ray tracing through mock clusters generated by the N-body simulation calibrated tool -- MOKA, and N-body/hydrodynamic simulations -- MUSIC, over the same mass and redshift range as the CLASH X-ray selected sample. We derive a lensing efficiency of 15 ± 3 arcs per cluster for the X-ray selected CLASH sample and 4 ± 2 arcs per cluster for the simulated sample. The marginally significant difference (3.0 σ) between the results for the observations and the simulations can be explained by the systematically smaller area with magnification larger than 3 (by a factor of ˜4) in both MOKA and MUSIC mass models relative to those derived from the CLASH data. Accounting for this difference brings the observed and simulated arc statistics into full agreement. We find that the source redshift distribution does not have big impact on the arc abundance but the arc abundance is very sensitive to the concentration of the dark matter halos. Our results suggest that the solution to the "arc statistics problem" lies primarily in matching the cluster dark matter distribution.

  8. In Abundance: Networked Participatory Practices as Scholarship

    ERIC Educational Resources Information Center

    Stewart, Bonnie E.

    2015-01-01

    In an era of knowledge abundance, scholars have the capacity to distribute and share ideas and artifacts via digital networks, yet networked scholarship often remains unrecognized within institutional spheres of influence. Using ethnographic methods including participant observation, interviews, and document analysis, this study investigates…

  9. Will Abundant Natural Gas Solve Climate Change?

    NASA Astrophysics Data System (ADS)

    McJeon, H. C.; Edmonds, J.; Bauer, N.; Leon, C.; Fisher, B.; Flannery, B.; Hilaire, J.; Krey, V.; Marangoni, G.; Mi, R.; Riahi, K.; Rogner, H.; Tavoni, M.

    2015-12-01

    The rapid deployment of hydraulic fracturing and horizontal drilling technologies enabled the production of previously uneconomic shale gas resources in North America. Global deployment of these advanced gas production technologies could bring large influx of economically competitive unconventional gas resources to the energy system. It has been hoped that abundant natural gas substituting for coal could reduce carbon dioxide (CO2) emissions, which in turn could reduce climate forcing. Other researchers countered that the non-CO2 greenhouse gas (GHG) emissions associated with shale gas production make its lifecycle emissions higher than those of coal. In this study, we employ five state-of-the-art integrated assessment models (IAMs) of energy-economy-climate systems to assess the full impact of abundant gas on climate change. The models show large additional natural gas consumption up to +170% by 2050. The impact on CO2 emissions, however, is found to be much smaller (from -2% to +11%), and a majority of the models reported a small increase in climate forcing (from -0.3% to +7%) associated with the increased use of abundant gas. Our results show that while globally abundant gas may substantially change the future energy market equilibrium, it will not significantly mitigate climate change on its own in the absence of climate policies.

  10. Heavy element abundances and massive star formation

    NASA Technical Reports Server (NTRS)

    Wang, Boqi; Silk, Joseph

    1993-01-01

    The determination of the stellar initial mass function (IMF) remains a great challenge in astronomy. In the solar neighborhood, the IMF is reasonable well determined for stellar masses from about 0.1 to 60 solar mass. However, outside the solar neighborhood, the IMF is poorly known. Among those frequently discussed arguments favoring a different IMF outside the solar neighborhood are the estimated time to consume the remaining gas in spiral galaxies, and the high rate of forming massive stars in starburst galaxies. An interesting question then is whether there may be an independent way of testing possible variations in the IMF. Indeed, the heavy elements in the interstellar medium are mostly synthesized in massive stars, so increasing, or decreasing, the fraction of massive stars naturally leads to a variation in the heavy element yield, and thus, the metallicity. The observed abundance should severely constrain any deviations of the IMF from the locally determined IMF. We focus on element oxygen, which is the most abundant heavy element in the interstellar medium. Oxygen is ejected only by massive stars that can become Type 1 supernovae, and the oxygen abundance is, therefore, a sensitive function of the fraction of massive stars in the IMF. Adopting oxygen enables us to avoid uncertainties in Type 1 supernovae. We use the nucleosynthesis results to calculate the oxygen yield for given IMF. We then calculate the oxygen abundance in the interstellar medium assuming instantaneous recycling of oxygen.

  11. Considerations when quantitating protein abundance by immunoblot.

    PubMed

    McDonough, Alicia A; Veiras, Luciana C; Minas, Jacqueline N; Ralph, Donna Lee

    2015-03-15

    The development of the immunoblot to detect and characterize a protein with an antisera, even in a crude mixture, was a breakthrough with wide-ranging and unpredictable applications across physiology and medicine. Initially, this technique was viewed as a tool for qualitative, not quantitative, analyses of proteins because of the high number of variables between sample preparation and detection with antibodies. Nonetheless, as the immunoblot method was streamlined and improved, investigators pushed it to quantitate protein abundance in unpurified samples as a function of treatment, genotype, or pathology. This short review, geared at investigators, reviewers, and critical readers, presents a set of issues that are of critical importance for quantitative analysis of protein abundance: 1) Consider whether tissue samples are of equivalent integrity and assess how handling between collection and assay influences the apparent relative abundance. 2) Establish the specificity of the antiserum for the protein of interest by providing clear images, molecular weight markers, positive and negative controls, and vendor details. 3) Provide convincing evidence for linearity of the detection system by assessing signal density as a function of sample loaded. 4) Recognize that loading control proteins are rarely in the same linear range of detection as the protein of interest; consider protein staining of the gel or blot. In summary, with careful attention to sample integrity, antibody specificity, linearity of the detection system, and acceptable loading controls, investigators can implement quantitative immunoblots to convincingly assess protein abundance in their samples.

  12. Toward Reliable Estimates of Abundance: Comparing Index Methods to Assess the Abundance of a Mammalian Predator

    PubMed Central

    Güthlin, Denise; Storch, Ilse; Küchenhoff, Helmut

    2014-01-01

    Due to time and financial constraints indices are often used to obtain landscape-scale estimates of relative species abundance. Using two different field methods and comparing the results can help to detect possible bias or a non monotonic relationship between the index and the true abundance, providing more reliable results. We used data obtained from camera traps and feces counts to independently estimate relative abundance of red foxes in the Black Forest, a forested landscape in southern Germany. Applying negative binomial regression models, we identified landscape parameters that influence red fox abundance, which we then used to predict relative red fox abundance. We compared the estimated regression coefficients of the landscape parameters and the predicted abundance of the two methods. Further, we compared the costs and the precision of the two field methods. The predicted relative abundances were similar between the two methods, suggesting that the two indices were closely related to the true abundance of red foxes. For both methods, landscape diversity and edge density best described differences in the indices and had positive estimated effects on the relative fox abundance. In our study the costs of each method were of similar magnitude, but the sample size obtained from the feces counts (262 transects) was larger than the camera trap sample size (88 camera locations). The precision of the camera traps was lower than the precision of the feces counts. The approach we applied can be used as a framework to compare and combine the results of two or more different field methods to estimate abundance and by this enhance the reliability of the result. PMID:24743565

  13. Toward reliable estimates of abundance: comparing index methods to assess the abundance of a Mammalian predator.

    PubMed

    Güthlin, Denise; Storch, Ilse; Küchenhoff, Helmut

    2014-01-01

    Due to time and financial constraints indices are often used to obtain landscape-scale estimates of relative species abundance. Using two different field methods and comparing the results can help to detect possible bias or a non monotonic relationship between the index and the true abundance, providing more reliable results. We used data obtained from camera traps and feces counts to independently estimate relative abundance of red foxes in the Black Forest, a forested landscape in southern Germany. Applying negative binomial regression models, we identified landscape parameters that influence red fox abundance, which we then used to predict relative red fox abundance. We compared the estimated regression coefficients of the landscape parameters and the predicted abundance of the two methods. Further, we compared the costs and the precision of the two field methods. The predicted relative abundances were similar between the two methods, suggesting that the two indices were closely related to the true abundance of red foxes. For both methods, landscape diversity and edge density best described differences in the indices and had positive estimated effects on the relative fox abundance. In our study the costs of each method were of similar magnitude, but the sample size obtained from the feces counts (262 transects) was larger than the camera trap sample size (88 camera locations). The precision of the camera traps was lower than the precision of the feces counts. The approach we applied can be used as a framework to compare and combine the results of two or more different field methods to estimate abundance and by this enhance the reliability of the result.

  14. Thermal relics: Do we know their abundances

    NASA Technical Reports Server (NTRS)

    Kamionkowski, Marc; Turner, Michael S.

    1990-01-01

    The relic abundance of a particle species that was once in thermal equilibrium in the expanding Universe depends upon a competition between the annihilation rate of the species and the expansion rate of the Universe. Assuming that the Universe is radiation dominated at early times the relic abundance is easy to compute and well known. At times earlier than about 1 sec after the bang there is little or no evidence that the Universe had to be radiation dominated, although that is the simplest and standard assumption. Because early-Universe relics are of such importance both to particle physics and to cosmology, three nonstandard possibilities are considered in detail for the Universe at the time a species' abundance froze in: energy density dominated by shear (i.e., anisotropic expansion), energy density dominated by some other nonrelativistic species, and energy density dominated by the kinetic energy of the scalar field that sets the gravitational constant in a Brans-Dicke-Jordan cosmological mode. In the second case the relic abundance is less than the standard value, while in the other two cases it can be enhanced by a significant factor. Two other more exotic possibilities for enhancing the relic abundance of a species are also mentioned--a larger value of Newton's constant at early times (e.g., as might occur in superstring or Kaluza-Klein theories) or a component of the energy density at early times with a very stiff equation of state (p greater than rho/3), e.g., a scalar field phi with potential V(phi) = Beta /phi/ (exp n) with n greater than 4. Results have implications for dark matter searches and searches for particle relics in general.

  15. Chemical abundances and kinematics of barium stars

    NASA Astrophysics Data System (ADS)

    de Castro, D. B.; Pereira, C. B.; Roig, F.; Jilinski, E.; Drake, N. A.; Chavero, C.; Sales Silva, J. V.

    2016-07-01

    In this paper, we present an homogeneous analysis of photospheric abundances based on high-resolution spectroscopy of a sample of 182 barium stars and candidates. We determined atmospheric parameters, spectroscopic distances, stellar masses, ages, luminosities and scaleheight, radial velocities, abundances of the Na, Al, α-elements, iron-peak elements, and s-process elements Y, Zr, La, Ce, and Nd. We employed the local thermodynamic equilibrium model atmospheres of Kurucz and the spectral analysis code MOOG. We found that the metallicities, the temperatures and the surface gravities for barium stars cannot be represented by a single Gaussian distribution. The abundances of α-elements and iron peak elements are similar to those of field giants with the same metallicity. Sodium presents some degree of enrichment in more evolved stars that could be attributed to the NeNa cycle. As expected, the barium stars show overabundance of the elements created by the s-process. By measuring the mean heavy-element abundance pattern as given by the ratio [s/Fe], we found that the barium stars present several degrees of enrichment. We also obtained the [hs/ls] ratio by measuring the photospheric abundances of the Ba-peak and the Zr-peak elements. Our results indicated that the [s/Fe] and the [hs/ls] ratios are strongly anticorrelated with the metallicity. Our kinematical analysis showed that 90 per cent of the barium stars belong to the thin disc population. Based on their luminosities, none of the barium stars are luminous enough to be an asymptotic giant branch star, nor to become self-enriched in the s-process elements. Finally, we determined that the barium stars also follow an age-metallicity relation.

  16. Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells: implications for preventing chemotherapy resistance.

    PubMed

    Ko, Ying-Hui; Lin, Zhao; Flomenberg, Neal; Pestell, Richard G; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E

    2011-12-15

    activity, driving a vicious cycle of catabolism in the tumor stroma and anabolic tumor cell expansion.

  17. Interferon regulatory factor-two restricts expression of interferon-stimulated genes to the endometrial stroma and glandular epithelium of the ovine uterus.

    PubMed

    Choi, Y; Johnson, G A; Burghardt, R C; Berghman, L R; Joyce, M M; Taylor, K M; Stewart, M D; Bazer, F W; Spencer, T E

    2001-10-01

    Interferon tau (IFNtau) is the signal for maternal recognition of pregnancy in ruminants. The positive effects of IFNtau on IFN-stimulated gene (ISG) expression are mediated by ISG factor 3 (ISGF3), which is composed of signal transducer and activator of transcription (Stat) 1, Stat 2, and IFN regulatory factor-9 (IRF-9), and by gamma-activated factor (GAF), which is a Stat 1 homodimer. Induction of ISGs, such as ISG17 and 2',5'-oligoadenylate synthetase, by IFNtau during pregnancy is limited to the endometrial stroma (S) and glandular epithelium (GE) of the ovine uterus. The IRF-2, a potent transcriptional repressor of ISG expression, is expressed in the luminal epithelium (LE). This study determined effects of the estrous cycle, pregnancy, and IFNtau on expression of Stat 1, Stat 2, IRF-9, IRF-1, and IRF-2 genes in the ovine endometrium. In cyclic ewes, Stat 1, Stat 2, IRF-1, and IRF-9 mRNA and protein were detected at low levels in the S and GE. During pregnancy, expression of these genes increased only in the S and GE. Expression of IRF-2 was detected only in the LE and superficial GE (sGE) of both cyclic and pregnant ewes. In cyclic ewes, intrauterine administration of IFNtau stimulated Stat 1, Stat 2, IRF-9, and IRF-1 expression in the endometrium. Ovine IRF-2 repressed transcriptional activity driven by IFN-stimulated response elements that bind ISGF3, but not by gamma-activation sequences that bind GAF. These results suggest that IRF-2 in the LE and sGE restricts IFNtau induction of ISGs to the S and GE. In the S and GE, IFNtau hyperactivation of ISG expression likely involves formation and actions of the transcription factors ISGF3 and, perhaps, IRF-1.

  18. Long-lasting morphofunctional remodelling of liver parenchyma and stroma after a single exposure to low and moderate doses of cadmium in rats

    PubMed Central

    Cupertino, Marli C; Costa, Kyvia L C; Santos, Daiane C M; Novaes, Rômulo D; Condessa, Suellen S; Neves, Ana C; Oliveira, Juraci A; Matta, Sérgio L P

    2013-01-01

    Frequent exposure to cadmium (Cd) in low doses is common; however, the long-lasting effects of this exposure are still poorly understood. Therefore in this study we have evaluated long-lasting hepatic morphofunctional adaptations in rats exposed to low and moderate doses of Cd. Five experimental groups were tested: control (0.9% saline) and other four receiving single intraperitoneal doses of 0.67, 0.74, 0.86 and 1.1 mg of Cd/kg. The animals were killed after eight weeks and the following parameters were analysed: biometrics, oedema, Cd bio-accumulation, collagen, glycogen, lipid droplets, superoxide dismutase (SOD) and catalase (CAT), serum transaminases, liver histopathology and stereology. In all groups exposed to Cd there was significant increase in SOD and CAT activities, ALP levels, proportion of binucleated hepatocytes, nuclei/cytoplasm ratio, macrophages (Kupffer cells) and collagen fibres. In these groups, glycogen accumulation by hepatocytes and the proportion of sinusoidal capillaries were significantly reduced compared with controls. The liver somatic index was increased, and liver oedema was evident in animals exposed to higher dose of Cd. Areas of necrosis were found in animals exposed to the three highest doses. These results indicate that Cd is an extremely toxic bioactive heavy metal, which even at low doses is able to disrupt liver homeostasis. At low and moderate doses, Cd exposure induces morphofunctional pathological remodelling of the hepatic stroma and parenchyma, which remain active after eight weeks. In response to injury, the liver tissue triggers a reactive process by enhancing activation of antioxidant enzymes and collagenogenesis. PMID:24020407

  19. Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter–Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth

    PubMed Central

    Sung, Shian-Ying; Chang, Junn-Liang; Chen, Kuan-Chou; Yeh, Shauh-Der; Liu, Yun-Ru; Su, Yen-Hao; Hsueh, Chia-Yen; Chung, Leland W. K.; Hsieh, Chia-Ling

    2016-01-01

    Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E) containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor–promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc) into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter–driven herpes simplex virus thymidine kinase gene (Ad-522E-TK) was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers. PMID:27054343

  20. The assessment of cryopreservation conditions for human umbilical cord stroma-derived mesenchymal stem cells towards a potential use for stem cell banking.

    PubMed

    Balci, Deniz; Can, Alp

    2013-01-01

    Human umbilical cord stroma-derived mesenchymal stem cells (hUCS-MSCs) are considered as a remarkable and promising stem cell source to be potentially used in cellular therapies. While no graft rejection has been reported in the recipient organism even in xeno-transplantation studies, attenuate tumor cell growth and gene transfers have been experimentally shown. In this study, we have demonstrated a reliable, reproducible and efficient cryopreservation method of hUCS-MSCs resulting in one of the highest cell survival rates reported so far. Conventional, computer-controlled multistep slow freezing (MSSF), and vitrification methods were comparatively tested using cell permeable [dimethylsulfoxide (DMSO), ethylene glycol] and impermeable [trehalose, sucrose, hydroxyethyl starch (HES), human serum albumin] cryoprotectant agents (CPAs). After determining the ice nucleation point for each solution, latent heat evolution was suppressed during freezing, followed by a cooling process to -40°C at 1°C/min or 0.3°C/min. The efficiency of the cryopreservation techniques used was determined by cell viability and proliferation assays, the expression of cell surface markers, cytoskeletal proteins and chromosome alignments. The cell survival rate was found to be highest (87 ± 5%) by MSSF with sucrose (0.1 M) +DMSO (10%) at 1°C/min freezing rate. In this group, no significant difference was noted before and after the cryopreservation in cell morphology, cytokeratin, vimentin, and α-smooth muscle actin profiles and the expressions of CD105, CD90, CD73, CD29 and HLA-DR. Second highest cell survival ratio (85 ± 6%) was obtained in DMSO (10%) alone at 1°C/min freezing rate. Interestingly, poor (18 ± 15%) cell survival rates were obtained after vitrification. Cumulatively, results indicated that MSSF favors the other freezing protocols with an addition of sucrose or DMSO alone depending on the freezing rate used.

  1. Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter-Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth.

    PubMed

    Sung, Shian-Ying; Chang, Junn-Liang; Chen, Kuan-Chou; Yeh, Shauh-Der; Liu, Yun-Ru; Su, Yen-Hao; Hsueh, Chia-Yen; Chung, Leland W K; Hsieh, Chia-Ling

    2016-01-01

    Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E) containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor-promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc) into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter-driven herpes simplex virus thymidine kinase gene (Ad-522E-TK) was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers.

  2. Macrophage migration inhibitory factor produced by the tumour stroma but not by tumour cells regulates angiogenesis in the B16-F10 melanoma model

    PubMed Central

    Girard, E; Strathdee, C; Trueblood, E; Quéva, C

    2012-01-01

    Background: Macrophage migration inhibitory factor (MIF) has been proposed as a link between inflammation and tumorigenesis. Despite its potentially broad influence in tumour biology and prevalent expression, the value of MIF as a therapeutic target in cancer remains unclear. We sought to validate MIF in tumour models by achieving a complete inhibition of its expression in tumour cells and in the tumour stroma. Methods: We used MIF shRNA-transduced B16-F10 melanoma cells implanted in wild-type and MIF−/− C57Bl6 mice to investigate the effect of loss of MIF on tumour growth. Cytokine detection and immunohistochemistry (IHC) were used to evaluate tumours ex vivo. Results: Macrophage migration inhibitory factor shRNA inhibited expression of MIF protein by B16-F10 melanoma cells in vitro and in vivo. In vitro, the loss of MIF in this cell line resulted in a decreased response to hypoxia as indicated by reduced expression of VEGF. In vivo the growth of B16-F10 tumours was inhibited by an average of 47% in the MIF−/− mice compared with wild-type but was unaffected by loss of MIF expression by the tumour cells. Immunohistochemistry analysis revealed that microvessel density was decreased in tumours implanted in the MIF−/− mice. Profiling of serum cytokines showed a decrease in pro-angiogenic cytokines in MIF−/− mice. Conclusion: We report that the absence of MIF in the host resulted in slower tumour growth, which was associated with reduced vascularity. While the major contribution of MIF appeared to be in the regulation of angiogenesis, tumour cell-derived MIF played a negligible role in this process. PMID:22955855

  3. Chemical Cartography in the Milky Way with SDSS/APOGEE: Multi-element abundances and abundance ratio variations

    NASA Astrophysics Data System (ADS)

    Holtzman, Jon A.; Hasselquist, Sten; Johnson, Jennifer; Bird, Jonathan C.; Majewski, Steven R.; SDSS/APOGEE Team

    2017-01-01

    The SDSS/APOGEE project is measuring abundances of multiple elements for several hundred thousand stars across the Milky Way. These allow the mapping of abundances and abundance ratio variations. Results will be presented for multiple abundance ratios across of the Galactic disk. The interpretation of mean abundance maps is complicated by variations in star formation history across the disk and by changing abundance ratios that result from an overall metallicity gradient. Variations in chemical abundance sequences, however, show the potential for using abundance ratios to track the movement of stars through the disk, and provide key information for constraining Galaxy formation and chemical evolution models.

  4. Deuterium Abundance in Consciousness and Current Cosmology

    NASA Astrophysics Data System (ADS)

    Rauscher, Elizabeth A.

    We utilize the deuterium-hydrogen abundances and their role in setting limits on the mass and other conditions of cosmogenesis and cosmological evolution. We calculate the dependence of a set of physical variables such as density, temperature, energy mass, entropy and other physical variable parameters through the evolution of the universe under the Schwarzschild conditions as a function from early to present time. Reconciliation with the 3°K and missing mass is made. We first examine the Schwarzschild condition; second, the geometrical constraints of a multidimensional Cartesian space on closed cosmologies, and third we will consider the cosmogenesis and evolution of the universe in a multidimensional Cartesian space, obeying the Schwarzschild condition. Implications of this model for matter creation are made. We also examine experimental evidence for closed versus open cosmologies; x-ray detection of the "missing mass" density. Also the interstellar deuterium abundance, along with the value of the Hubble constant set a general criterion on the value of the curvature constant, k. Once the value of the Hubble constant, H is determined, the deuterium abundance sets stringent restrictions on the value of the curvature constant k by an detailed discussion is presented. The experimental evidences for the determination of H and the primary set of coupled equations to determine D abundance is given. 'The value of k for an open, closed, or flat universe will be discussed in terms of the D abundance which will affect the interpretation of the Schwarzschild, black hole universe. We determine cosmology solutions to Einstein's field obeying the Schwarzschild solutions condition. With this model, we can form a reconciliation of the black hole, from galactic to cosmological scale. Continuous creation occurs at the dynamic blackhole plasma field. We term this new model the multiple big bang or "little whimper model". We utilize the deuteriumhydrogen abundances and their role in

  5. Lithium Abundance in M3 Red Giant

    NASA Astrophysics Data System (ADS)

    Givens, Rashad; Pilachowski, Catherine A.

    2015-01-01

    We present the abundance of lithium in the red giant star vZ 1050 (SK 291) in the globular cluster M3. A previous survey of giants in the cluster showed that like IV-101, vZ 1050 displays a prominent Li I 6707 Å feature. vZ 1050 lies on the blue side of the red giant branch about 1.3 magnitudes above the level of the horizontal branch, and may be an asymptotic giant branch star. A high resolution spectrum of M3 vZ1050 was obtained with the ARC 3.5m telescope and the ARC Echelle Spectrograph (ARCES). Atmospheric parameters were determined using Fe I and Fe II lines from the spectrum using the MOOG spectral analysis program, and the lithium abundance was determined using spectrum synthesis.

  6. THE OXYGEN ABUNDANCE IN THE SOLAR NEIGHBORHOOD

    SciTech Connect

    RodrIguez, Monica; Delgado-Inglada, Gloria E-mail: gloria@inaoep.mx

    2011-06-01

    We present a homogeneous analysis of the oxygen abundance in five H II regions and eight planetary nebulae (PNe) located at distances lower than 2 kpc and with available spectra of high quality. We find that both the collisionally excited lines (CELs) and recombination lines imply that the PNe are overabundant in oxygen by about 0.2 dex. An explanation that reconciles the oxygen abundances derived with CELs for H II regions and PNe with the values found for B stars, the Sun, and the diffuse interstellar medium (ISM) requires the presence in H II regions of an organic refractory dust component that is not present in PNe. This dust component has already been invoked to explain the depletion of oxygen in molecular clouds and in the diffuse ISM.

  7. Top consumer abundance influences lake methane efflux.

    PubMed

    Devlin, Shawn P; Saarenheimo, Jatta; Syväranta, Jari; Jones, Roger I

    2015-11-04

    Lakes are important habitats for biogeochemical cycling of carbon. The organization and structure of aquatic communities influences the biogeochemical interactions between lakes and the atmosphere. Understanding how trophic structure regulates ecosystem functions and influences greenhouse gas efflux from lakes is critical to understanding global carbon cycling and climate change. With a whole-lake experiment in which a previously fishless lake was divided into two treatment basins where fish abundance was manipulated, we show how a trophic cascade from fish to microbes affects methane efflux to the atmosphere. Here, fish exert high grazing pressure and remove nearly all zooplankton. This reduction in zooplankton density increases the abundance of methanotrophic bacteria, which in turn reduce CH4 efflux rates by roughly 10 times. Given that globally there are millions of lakes emitting methane, an important greenhouse gas, our findings that aquatic trophic interactions significantly influence the biogeochemical cycle of methane has important implications.

  8. Chemical abundances in nearby spiral galaxies

    NASA Astrophysics Data System (ADS)

    Richer, Michael Gerard

    2015-08-01

    The chemical abundances observed in planetary nebulae in the discs of spiral galaxies are revealing a rich variety of information about their progenitor stars as well as the structure and evolution of the galaxies they inhabit. As concerns galaxy structure and evolution, most of the attention has been on whether gradients in chemical abundances have changed with time, but there is also the issue of the formation and origin of the stellar progenitors of planetary nebulae. The gradients in oxygen abundances for planetary nebulae in M81 and NGC 300 are shallower than the corresponding gradients for H II regions in these galaxies. On the other hand, the gradients for H II regions and planetary nebulae are similar in M33. In the case of M31, there is mounting evidence whose simplest explanation may not be related to internal processes, but instead may lay in the gravitational interaction between it and its neighbours, past and present. As concerns the nucleosynthesis of the stellar progenitors of these planetary nebulae, some results for both nitrogen and oxygen may indicate the production of these elements during the previous evolutionary stages of their progenitor stars. Nominally, this may not be surprising for nitrogen, but the results do not agree quantitatively with canonical theory. At this point, though, there are still too few studies to draw very firm conclusions regrading any of these topics. Even so, the surprises among the results found so far make clear that interpreting the chemical abundances in the planetary nebulae in nearby spirals will require considering the processes affecting both stellar and galactic evolution.

  9. Globular Clusters: Chemical Abundance - Integrated Colour calibration

    NASA Astrophysics Data System (ADS)

    Moyano Loyola, G.; Faifer, F. R.; Forte, J. C.

    In this work, we improve the chemical abundance - integrated colour cali- bration presented in Forte, Faifer & Geisler, 2007 (FFG07 hereafter) using a new (g-i) vs. (C-T1) colours calibration obtained from M87. Using this calibration and better values of the reddening for the galactic globulars, we found that a quadratic calibration is still enough to represent the observa- tional data, as in FFG07.

  10. Helium isotopic abundance variation in nature

    SciTech Connect

    Holden, N.E.

    1993-08-01

    The isotopic abundance of helium in nature has been reviewed. This atomic weight value is based on the value of helium in the atmosphere, which is invariant around the world and up to a distance of 100,000 feet. Helium does vary in natural gas, volcanic rocks and gases, ocean floor sediments, waters of various types and in radioactive minerals and ores due to {alpha} particle decay of radioactive nuclides.

  11. The Abundance of Sulfur in Venus Magmas

    NASA Astrophysics Data System (ADS)

    Bullock, M. A.; Grinspoon, D. H.

    1999-09-01

    Outgassing of sulfur gases due to volcanism within the past 100 My on Venus is probably responsible for the planet's globally encircling H2SO4 cloud layers. Dramatic changes in volcanic output on Venus would have altered the atmospheric inventory of sulfur gases, and hence the structure of its clouds (Bullock and Grinspoon, Icarus, submitted 1999). Although Magellan radar images provide some constraints on the magnitude of volcanism in the geologically recent past, little is known of the sulfur content of Venus lavas. In order to assess the effects that Venus' volcanic history may have had on cloud and therefore climate change, it is desirable to place some constraints on the abundance of sulfur in Venus magmas. The sulfur content of terrestrial volcanic lavas varies widely, depending upon the local sedimentary environment and the source and history of upwelling magmas. We estimate the average abundance of sulfur in Venus lavas from an analysis of the production and loss of atmospheric SO2. The volumetric rate of resurfacing on Venus in the recent past is approximately 0.1 to 2 km3/yr (Bullock et al., JGR 20, 1993, Basilevsky and Head, GRL 23, 1996). Outgassed SO2 reacts quickly with crustal carbonate -- residence times in the atmosphere with respect to the reaction SO2 + CaCO3 <=> CaSO4 + CO are about 2-30 My (Fegley and Prinn, Nature 337, 1989, Bullock and Grinspoon, Icarus, submitted 1999). Assuming steady state conditions and an abundance of 25-180 ppm of atmospheric SO2 (Oyama et al., JGR 85, 1980, Bertaux et al., JGR 101, 1996), we will discuss constraints on the abundance of this important greenhouse and cloud-precursor gas in Venus lavas.

  12. Revised Thorium Abundances for Lunar Red Spots

    NASA Technical Reports Server (NTRS)

    Hagerty, J. J.; Lawrence, D. J.; Elphic, R. C.; Feldman, W. C.; Vaniman, D. T.; Hawke, B. R.

    2005-01-01

    Lunar red spots are features on the nearside of the Moon that are characterized by high albedo and by a strong absorption in the ultraviolet. These red spots include the Gruithuisen domes, the Mairan domes, Hansteen Alpha, the southern portion of Montes Riphaeus, Darney Chi and Tau, Helmet, and an area near the Lassell crater. It has been suggested that many of the red spots are extrusive, nonmare, volcanic features that could be composed of an evolved lithlogy enriched in thorium. In fact, Hawke et al. used morphological characteristics to show that Hansteen Alpha is a nonmare volcanic construct. However, because the apparent Th abundances (6 - 7 ppm) were lower than that expected for evolved rock types, Hawke et al. concluded that Hansteen Alpha was composed of an unknown rock type. Subsequent studies by Lawrence et al. used improved knowledge of the Th spatial distribution for small area features on the lunar surface to revisit the interpretation of Th abundances at the Hansteen Alpha red spot. As part of their study, Lawrence et al. used a forward modeling technique to show that the Th abundance at Hansteen Alpha is not 6 ppm, but is more likely closer to 25 ppm, a value consistent with evolved lithologies. This positive correlation between the morphology and composition of Hansteen Alpha provides support for the presence of evolved lithologies on the lunar surface. It is possible, however, that Hansteen Alpha represents an isolated occurrence of non-mare volcanism. That is why we have chosen to use the forward modeling technique of Lawrence et al. to investigate the Th abundances at other lunar red spots, starting with the Gruithuisen domes. Additional information is included in the original extended abstract.

  13. Angel lichen moth abundance and morphology data

    USGS Publications Warehouse

    Metcalfe, Anya; Kennedy, Theodore A.; Muehlbauer, Jeffrey D.

    2016-01-01

    Two unique datasets on the abundance and morphology of the angel lichen moth ( Cisthene angelus) in Grand Canyon, Arizona, USA were compiled to describe the phenology and life history of this common, but poorly known, species. The abundance data were collected from 2012 to 2013 through a collaboration with river runners in Grand Canyon National Park. These citizen scientists deployed light traps from their campsites for one hour each night of their expedition. Insects were preserved in ethanol on site, and returned to the Southwest Biological Science Center in Flagstaff, Arizona for analysis in the laboratory. A total of 2,437 light trap samples were sorted through, 903 of which contained C. angelus. In total, 73,841 C. angelus were identified and enumerated to create the abundance data set. The morphology dataset is based on a subset of 28 light trap samples from sampling year 2012 (14 from spring and 14 from fall.) It includes gender and forewing lengths for 2,674 individual moths and dry weights for 1,102 of those individuals.

  14. Absolute Quantification of Endogenous Ras Isoform Abundance

    PubMed Central

    Mageean, Craig J.; Griffiths, John R.; Smith, Duncan L.; Clague, Michael J.; Prior, Ian A.

    2015-01-01

    Ras proteins are important signalling hubs situated near the top of networks controlling cell proliferation, differentiation and survival. Three almost identical isoforms, HRAS, KRAS and NRAS, are ubiquitously expressed yet have differing biological and oncogenic properties. In order to help understand the relative biological contributions of each isoform we have optimised a quantitative proteomics method for accurately measuring Ras isoform protein copy number per cell. The use of isotopic protein standards together with selected reaction monitoring for diagnostic peptides is sensitive, robust and suitable for application to sub-milligram quantities of lysates. We find that in a panel of isogenic SW48 colorectal cancer cells, endogenous Ras proteins are highly abundant with ≥260,000 total Ras protein copies per cell and the rank order of isoform abundance is KRAS>NRAS≥HRAS. A subset of oncogenic KRAS mutants exhibit increased total cellular Ras abundance and altered the ratio of mutant versus wild type KRAS protein. These data and methodology are significant because Ras protein copy number is required to parameterise models of signalling networks and informs interpretation of isoform-specific Ras functional data. PMID:26560143

  15. The shape of terrestrial abundance distributions.

    PubMed

    Alroy, John

    2015-09-01

    Ecologists widely accept that the distribution of abundances in most communities is fairly flat but heavily dominated by a few species. The reason for this is that species abundances are thought to follow certain theoretical distributions that predict such a pattern. However, previous studies have focused on either a few theoretical distributions or a few empirical distributions. I illustrate abundance patterns in 1055 samples of trees, bats, small terrestrial mammals, birds, lizards, frogs, ants, dung beetles, butterflies, and odonates. Five existing theoretical distributions make inaccurate predictions about the frequencies of the most common species and of the average species, and most of them fit the overall patterns poorly, according to the maximum likelihood-related Kullback-Leibler divergence statistic. Instead, the data support a low-dominance distribution here called the "double geometric." Depending on the value of its two governing parameters, it may resemble either the geometric series distribution or the lognormal series distribution. However, unlike any other model, it assumes both that richness is finite and that species compete unequally for resources in a two-dimensional niche landscape, which implies that niche breadths are variable and that trait distributions are neither arrayed along a single dimension nor randomly associated. The hypothesis that niche space is multidimensional helps to explain how numerous species can coexist despite interacting strongly.

  16. A global database of ant species abundances

    USGS Publications Warehouse

    Gibb, Heloise; Dunn, Rob R.; Sanders, Nathan J.; Grossman, Blair F.; Photakis, Manoli; Abril, Silvia; Agosti, Donat; Andersen, Alan N.; Angulo, Elena; Armbrecht, Ingre; Arnan, Xavier; Baccaro, Fabricio B.; Bishop, Tom R.; Boulay, Raphael; Bruhl, Carsten; Castracani, Cristina; Cerda, Xim; Del Toro, Israel; Delsinne, Thibaut; Diaz, Mireia; Donoso, David A.; Ellison, Aaron M.; Enriquez, Martha L.; Fayle, Tom M.; Feener Jr., Donald H.; Fisher, Brian L.; Fisher, Robert N.; Fitpatrick, Matthew C.; Gomez, Cristanto; Gotelli, Nicholas J.; Gove, Aaron; Grasso, Donato A.; Groc, Sarah; Guenard, Benoit; Gunawardene, Nihara; Heterick, Brian; Hoffmann, Benjamin; Janda, Milan; Jenkins, Clinton; Kaspari, Michael; Klimes, Petr; Lach, Lori; Laeger, Thomas; Lattke, John; Leponce, Maurice; Lessard, Jean-Philippe; Longino, John; Lucky, Andrea; Luke, Sarah H.; Majer, Jonathan; McGlynn, Terrence P.; Menke, Sean; Mezger, Dirk; Mori, Alessandra; Moses, Jimmy; Munyai, Thinandavha Caswell; Pacheco, Renata; Paknia, Omid; Pearce-Duvet, Jessica; Pfeiffer, Martin; Philpott, Stacy M.; Resasco, Julian; Retana, Javier; Silva, Rogerio R.; Sorger, Magdalena D.; Souza, Jorge; Suarez, Andrew V.; Tista, Melanie; Vasconcelos, Heraldo L.; Vonshak, Merav; Weiser, Michael D.; Yates, Michelle; Parr, Catherine L.

    2017-01-01

    What forces structure ecological assemblages? A key limitation to general insights about assemblage structure is the availability of data that are collected at a small spatial grain (local assemblages) and a large spatial extent (global coverage). Here, we present published and unpublished data from 51,388 ant abundance and occurrence records of more than 2693 species and 7953 morphospecies from local assemblages collected at 4212 locations around the world. Ants were selected because they are diverse and abundant globally, comprise a large fraction of animal biomass in most terrestrial communities, and are key contributors to a range of ecosystem functions. Data were collected between 1949 and 2014, and include, for each geo-referenced sampling site, both the identity of the ants collected and details of sampling design, habitat type and degree of disturbance. The aim of compiling this dataset was to provide comprehensive species abundance data in order to test relationships between assemblage structure and environmental and biogeographic factors. Data were collected using a variety of standardised methods, such as pitfall and Winkler traps, and will be valuable for studies investigating large-scale forces structuring local assemblages. Understanding such relationships is particularly critical under current rates of global change. We encourage authors holding additional data on systematically collected ant assemblages, especially those in dry and cold, and remote areas, to contact us and contribute their data to this growing dataset.

  17. Elemental abundances of solar sibling candidates

    SciTech Connect

    Ramírez, I.; Lambert, D. L.; Endl, M.; Cochran, W. D.; MacQueen, P. J.; Bajkova, A. T.; Bobylev, V. V.; Wittenmyer, R. A.

    2014-06-01

    Dynamical information along with survey data on metallicity and in some cases age have been used recently by some authors to search for candidates of stars that were born in the cluster where the Sun formed. We have acquired high-resolution, high signal-to-noise ratio spectra for 30 of these objects to determine, using detailed elemental abundance analysis, if they could be true solar siblings. Only two of the candidates are found to have solar chemical composition. Updated modeling of the stars' past orbits in a realistic Galactic potential reveals that one of them, HD 162826, satisfies both chemical and dynamical conditions for being a sibling of the Sun. Measurements of rare-element abundances for this star further confirm its solar composition, with the only possible exception of Sm. Analysis of long-term high-precision radial velocity data rules out the presence of hot Jupiters and confirms that this star is not in a binary system. We find that chemical tagging does not necessarily benefit from studying as many elements as possible but instead from identifying and carefully measuring the abundances of those elements that show large star-to-star scatter at a given metallicity. Future searches employing data products from ongoing massive astrometric and spectroscopic surveys can be optimized by acknowledging this fact.

  18. Distribution and Abundance of Mars' Atmospheric Argon

    NASA Technical Reports Server (NTRS)

    Sprague, A. L.; Boynton, W. V.; Kerry, K. E.; Nelli, Steven; Murphy, Jim; Reedy, R. C.; Metzger, A. E.; Hunten, D. M.; Janes, K. D.; Crombie, M. K.

    2005-01-01

    One and one half Mars years (MY 26 and 27) of atmospheric Argon measurements are described and studied in the context of understanding how Argon, a minor constituent of Mars atmosphere that does not condense at Mars temperatures, can be used to study martian circulation and dynamics. Argon data are from the 2001 Mars Odyssey Gamma Subsystem (GS) of the suite of three instruments comprising the Gamma Ray Spectrometer (GRS). A comprehensive data analysis including gamma-ray production and attenuation by the atmosphere is included. Of particular interest is the enhanced abundance of Ar over the observed Ar abundance at lower latitudes at south (up to a factor of 10) and north (up to a factor of 4) polar regions during winter. Calibration of the measurements to actual Ar abundance is possible because GS measurements cover the same latitude and season as measurements made by the gas chromatograph mass spectrometer (GCMS) on Viking Landers 1 and 2 (VL1 and VL2). [2].

  19. A global database of ant species abundances.

    PubMed

    Gibb, Heloise; Dunn, Rob R; Sanders, Nathan J; Grossman, Blair F; Photakis, Manoli; Abril, Silvia; Agosti, Donat; Andersen, Alan N; Angulo, Elena; Armbrecht, Inge; Arnan, Xavier; Baccaro, Fabricio B; Bishop, Tom R; Boulay, Raphaël; Brühl, Carsten; Castracani, Cristina; Cerda, Xim; Del Toro, Israel; Delsinne, Thibaut; Diaz, Mireia; Donoso, David A; Ellison, Aaron M; Enriquez, Martha L; Fayle, Tom M; Feener, Donald H; Fisher, Brian L; Fisher, Robert N; Fitzpatrick, Matthew C; Gómez, Crisanto; Gotelli, Nicholas J; Gove, Aaron; Grasso, Donato A; Groc, Sarah; Guenard, Benoit; Gunawardene, Nihara; Heterick, Brian; Hoffmann, Benjamin; Janda, Milan; Jenkins, Clinton; Kaspari, Michael; Klimes, Petr; Lach, Lori; Laeger, Thomas; Lattke, John; Leponce, Maurice; Lessard, Jean-Philippe; Longino, John; Lucky, Andrea; Luke, Sarah H; Majer, Jonathan; McGlynn, Terrence P; Menke, Sean; Mezger, Dirk; Mori, Alessandra; Moses, Jimmy; Munyai, Thinandavha Caswell; Pacheco, Renata; Paknia, Omid; Pearce-Duvet, Jessica; Pfeiffer, Martin; Philpott, Stacy M; Resasco, Julian; Retana, Javier; Silva, Rogerio R; Sorger, Magdalena D; Souza, Jorge; Suarez, Andrew; Tista, Melanie; Vasconcelos, Heraldo L; Vonshak, Merav; Weiser, Michael D; Yates, Michelle; Parr, Catherine L

    2017-03-01

    What forces structure ecological assemblages? A key limitation to general insights about assemblage structure is the availability of data that are collected at a small spatial grain (local assemblages) and a large spatial extent (global coverage). Here, we present published and unpublished data from 51 ,388 ant abundance and occurrence records of more than 2,693 species and 7,953 morphospecies from local assemblages collected at 4,212 locations around the world. Ants were selected because they are diverse and abundant globally, comprise a large fraction of animal biomass in most terrestrial communities, and are key contributors to a range of ecosystem functions. Data were collected between 1949 and 2014, and include, for each geo-referenced sampling site, both the identity of the ants collected and details of sampling design, habitat type, and degree of disturbance. The aim of compiling this data set was to provide comprehensive species abundance data in order to test relationships between assemblage structure and environmental and biogeographic factors. Data were collected using a variety of standardized methods, such as pitfall and Winkler traps, and will be valuable for studies investigating large-scale forces structuring local assemblages. Understanding such relationships is particularly critical under current rates of global change. We encourage authors holding additional data on systematically collected ant assemblages, especially those in dry and cold, and remote areas, to contact us and contribute their data to this growing data set.

  20. The shape of terrestrial abundance distributions

    PubMed Central

    Alroy, John

    2015-01-01

    Ecologists widely accept that the distribution of abundances in most communities is fairly flat but heavily dominated by a few species. The reason for this is that species abundances are thought to follow certain theoretical distributions that predict such a pattern. However, previous studies have focused on either a few theoretical distributions or a few empirical distributions. I illustrate abundance patterns in 1055 samples of trees, bats, small terrestrial mammals, birds, lizards, frogs, ants, dung beetles, butterflies, and odonates. Five existing theoretical distributions make inaccurate predictions about the frequencies of the most common species and of the average species, and most of them fit the overall patterns poorly, according to the maximum likelihood–related Kullback-Leibler divergence statistic. Instead, the data support a low-dominance distribution here called the “double geometric.” Depending on the value of its two governing parameters, it may resemble either the geometric series distribution or the lognormal series distribution. However, unlike any other model, it assumes both that richness is finite and that species compete unequally for resources in a two-dimensional niche landscape, which implies that niche breadths are variable and that trait distributions are neither arrayed along a single dimension nor randomly associated. The hypothesis that niche space is multidimensional helps to explain how numerous species can coexist despite interacting strongly. PMID:26601249

  1. The primordial helium abundance from updated emissivities

    SciTech Connect

    Aver, Erik; Olive, Keith A.; Skillman, Evan D.; Porter, R.L. E-mail: olive@umn.edu E-mail: skillman@astro.umn.edu

    2013-11-01

    Observations of metal-poor extragalactic H II regions allow the determination of the primordial helium abundance, Y{sub p}. The He I emissivities are the foundation of the model of the H II region's emission. Porter, Ferland, Storey, and Detisch (2012) have recently published updated He I emissivities based on improved photoionization cross-sections. We incorporate these new atomic data and update our recent Markov Chain Monte Carlo analysis of the dataset published by Izotov, Thuan, and Stasi'nska (2007). As before, cuts are made to promote quality and reliability, and only solutions which fit the data within 95% confidence level are used to determine the primordial He abundance. The previously qualifying dataset is almost entirely retained and with strong concordance between the physical parameters. Overall, an upward bias from the new emissivities leads to a decrease in Y{sub p}. In addition, we find a general trend to larger uncertainties in individual objects (due to changes in the emissivities) and an increased variance (due to additional objects included). From a regression to zero metallicity, we determine Y{sub p} = 0.2465 ± 0.0097, in good agreement with the BBN result, Y{sub p} = 0.2485 ± 0.0002, based on the Planck determination of the baryon density. In the future, a better understanding of why a large fraction of spectra are not well fit by the model will be crucial to achieving an increase in the precision of the primordial helium abundance determination.

  2. Fluorine Abundances in the Milky Way Bulge

    NASA Astrophysics Data System (ADS)

    Cunha, Katia; Smith, Verne V.; Gibson, Brad K.

    2008-05-01

    Fluorine (19F) abundances are derived in a sample of six bulge red giants in Baade's window. These giants span a factor of 10 in metallicity, and this is the first study to define the behavior of 19F with metallicity in the bulge. The bulge results show an increase in F/O with increasing oxygen. This trend overlaps what is found in the disk at comparable metallicities, with the most oxygen-rich bulge target extending the disk trend. The increase in F/O in the disk arises from 19F synthesis in both asymptotic giant branch (AGB) stars and metal-rich Wolf-Rayet (WR) stars through stellar winds. The lack of an s-process enhancement in the most fluorine-rich bulge giant in this study suggests that WR stars represented a larger contribution than did AGB stars to 19F production in the bulge, when compared to the disk. If this result for fluorine is combined with the previously published overall decline in the O/Mg abundance ratios in metal-rich bulge stars, it suggests that WR winds played a role in shaping chemical evolution in the bulge. One star in this study exhibits a very low value of F/O while having a large O abundance; this chemical mixture can be understood if this star formed from gas that was enriched by metal-poor core-collapse supernovae, and it may indicate that chemical evolution in the bulge was inhomogeneous.

  3. Elemental Abundances of Solar Sibling Candidates

    NASA Astrophysics Data System (ADS)

    Ramírez, I.; Bajkova, A. T.; Bobylev, V. V.; Roederer, I. U.; Lambert, D. L.; Endl, M.; Cochran, W. D.; MacQueen, P. J.; Wittenmyer, R. A.

    2014-06-01

    Dynamical information along with survey data on metallicity and in some cases age have been used recently by some authors to search for candidates of stars that were born in the cluster where the Sun formed. We have acquired high-resolution, high signal-to-noise ratio spectra for 30 of these objects to determine, using detailed elemental abundance analysis, if they could be true solar siblings. Only two of the candidates are found to have solar chemical composition. Updated modeling of the stars' past orbits in a realistic Galactic potential reveals that one of them, HD 162826, satisfies both chemical and dynamical conditions for being a sibling of the Sun. Measurements of rare-element abundances for this star further confirm its solar composition, with the only possible exception of Sm. Analysis of long-term high-precision radial velocity data rules out the presence of hot Jupiters and confirms that this star is not in a binary system. We find that chemical tagging does not necessarily benefit from studying as many elements as possible but instead from identifying and carefully measuring the abundances of those elements that show large star-to-star scatter at a given metallicity. Future searches employing data products from ongoing massive astrometric and spectroscopic surveys can be optimized by acknowledging this fact.

  4. Abundances from solar-flare gamma-ray line spectroscopy

    NASA Technical Reports Server (NTRS)

    Murphy, R. J.; Ramaty, R.; Forrest, D. J.; Kozlovsky, B.

    1985-01-01

    Elemental abundances of the ambient gas at the site of gamma ray line production inthe solar atmosphere are deduced using gamma ray line observations from a solar flare. The resultant abundances are different from local galactic abundances which are thought to be similar to photospheric abundances.

  5. Abundant Solar Nebula Solids in Comets

    NASA Technical Reports Server (NTRS)

    Messenger, S.; Keller, L. P.; Nakamura-Messenger, K.; Nguyen, A. N.; Clemett, S.

    2016-01-01

    Comets have been proposed to consist of unprocessed interstellar materials together with a variable amount of thermally annealed interstellar grains. Recent studies of cometary solids in the laboratory have shown that comets instead consist of a wide range of materials from across the protoplanetary disk, in addition to a minor complement of interstellar materials. These advances were made possible by the return of direct samples of comet 81P/Wild 2 coma dust by the NASA Stardust mission and recent advances in microscale analytical techniques. Isotopic studies of 'cometary' chondritic porous interplanetary dust particles (CP-IDPs) and comet 81P/Wild 2 Stardust samples show that preserved interstellar materials are more abundant in comets than in any class of meteorite. Identified interstellar materials include sub-micron-sized presolar silicates, oxides, and SiC dust grains and some fraction of the organic material that binds the samples together. Presolar grain abundances reach 1 weight percentage in the most stardust-rich CP-IDPs, 50 times greater than in meteorites. Yet, order of magnitude variations in presolar grain abundances among CP-IDPs suggest cometary solids experienced significant variations in the degree of processing in the solar nebula. Comets contain a surprisingly high abundance of nebular solids formed or altered at high temperatures. Comet 81P/Wild 2 samples include 10-40 micron-sized, refractory Ca- Al-rich inclusion (CAI)-, chondrule-, and ameboid olivine aggregate (AOA)-like materials. The O isotopic compositions of these refractory materials are remarkably similar to their meteoritic counterparts, ranging from 5 percent enrichments in (sup 16) O to near-terrestrial values. Comet 81P/Wild 2 and CP-IDPs also contain abundant Mg-Fe crystalline and amorphous silicates whose O isotopic compositions are also consistent with Solar System origins. Unlike meteorites, that are dominated by locally-produced materials, comets appear to be composed of

  6. Abundances in Blue Compact Dwarf Galaxies

    NASA Astrophysics Data System (ADS)

    Dewolfe, O. M.; Salzer, J. J.

    1994-12-01

    The nebular abundances in dwarf galaxies provide valuable clues to their star-formation histories. We have been engaged in an extensive observational study of actively star-forming blue compact dwarf galaxies (BCDs). Our program combines optical and NIR imaging, optical spectroscopy, and HI and CO radio data in an attempt to understand the status of star-formation and chemical evolution in these systems. Luminosities of the BCDs in our sample lie in the range M_B = -13 -- -16. We have obtained high-quality optical spectra of 21 BCDs for the purpose of deriving nebular abundances. We present values for the abundances of He, N, O, S, Ne, and Ar for this sample. In addition, we have estimated O and N abundances for a sample of 7 non-dwarf starburst galaxies of higher luminosity. For the BCD sample, we find that the N/O ratio remains constant at a mean value of 0.032 +/- 0.004 with increasing O/H. This result, which extends over a factor of more than 10 in O/H, is indicative of the N being chiefly of primary origin in these systems. The value of N/O is observed to increase in the sample of larger starburst galaxies for log(O/H) above -3.5, consistent with previous studies. S/O and Ne/O are also both constant with increasing O/H, and have mean values of 0.032 +/- 0.007 and 0.135 +/- 0.013 respectively. The BCD and starburst O/H values were used to calibrate an abundance sequence for a number of key emission-line diagnostic ratios which allow us to estimate metallicities for a large sample of emission-line galaxies (ELGs) to an accuracy of 0.1 -- 0.2 dex. The calibrations were applied to spectral data from two large published samples of ELGs from the Michigan and Case surveys. We use these data, representing nearly 200 individual galaxies, to investigate the existence of a metallicity-luminosity relationship for actively star-forming galaxies. We find the ELGs exhibit a relationship very similar to that found for more quiescent dwarf and Magellanic irregular galaxies by

  7. Chemical abundances in early B-type stars. 5: Metal abundances and LTE/NLTE comparison

    NASA Astrophysics Data System (ADS)

    Kilian, J.

    1994-02-01

    Chemical abundances of neon, magnesium, aluminum, sulfur, and iron are derived for a sample of 21 unevolved B-stars in the local field and nearby associations. While aluminum, sulfur, and iron are underabundant in nearly all stars, near solar abundances are found for magnesium and neon. In agreement with earlier results for carbon, nitrogen, oxygen, and silicon (Kilian 1992), the present results show no correlation with surface gravities or evolutionary states, which indicates that the metal abundances reflect the original composition of the interstellar medium. The results are supplemented by a comparison of local thermodynamic equilibrium (LTE) and non-LTE (NLTE) abundances for C, N, O, Si, Mg, and Al. In most cases the differences amount to +/- (0.1-0.2) dex, which slightly exceeds the estimated accuracy of the NLTE abundance determination. However, a clear temperature gradient is evident for most elements, which indicates systematic LTE abundance errors with a maximum amplitude of 0.4 dex between 21 000 K and 31 000 K.

  8. Beryllium and Boron abundances in population II stars

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The scientific focus of this program was to undertake UV spectroscopic abundance analyses of extremely metal poor stars with attention to determining abundances of light elements such as beryllium and boron. The abundances are likely to reflect primordial abundances within the early galaxy and help to constrain models for early galactic nucleosynthesis. The general metal abundances of these stars are also important for understanding stellar evolution.

  9. Mimicking Metastases Including Tumor Stroma: A New Technique to Generate a Three-Dimensional Colorectal Cancer Model Based on a Biological Decellularized Intestinal Scaffold

    PubMed Central

    Nietzer, Sarah; Baur, Florentin; Sieber, Stefan; Hansmann, Jan; Schwarz, Thomas; Stoffer, Carolin; Häfner, Heide; Gasser, Martin; Waaga-Gasser, Ana Maria; Walles, Heike

    2016-01-01

    generation, a bioreactor was constructed for dynamic culture approaches. This induced a close tissue-like association of cultured tumor cells with fibroblasts reflecting tumor biopsies. Therapy with 5-fluorouracil (5-FU) was effective only in 3D coculture. In conclusion, our 3D tumor model reflects human tissue-related tumor characteristics, including lower tumor cell proliferation. It is now available for drug testing in metastatic context—especially for substances targeting tumor–stroma interactions. PMID:27137941

  10. Bringing abundance into environmental politics: Constructing a Zionist network of water abundance, immigration, and colonization.

    PubMed

    Alatout, Samer

    2009-06-01

    For more than five decades, resource scarcity has been the lead story in debates over environmental politics. More importantly, and whenever environmental politics implies conflict, resource scarcity is constructed as the culprit. Abundance of resources, if at all visited in the literature, holds less importance. Resource abundance is seen, at best, as the other side of scarcity--maybe the successful conclusion of multiple interventions that may turn scarcity into abundance. This paper reinstates abundance as a politico-environmental category in its own right. Rather than relegating abundance to a second-order environmental actor that matters only on occasion, this paper foregrounds it as a crucial element in modern environmental politics. On the substantive level, and using insights from science and technology studies, especially a slightly modified actor-network framework, I describe the emergence and consolidation of a Zionist network of abundance, immigration, and colonization in Palestine between 1918 and 1948. The essential argument here is that water abundance was constructed as fact, and became a political rallying point around which a techno-political network emerged that included a great number of elements. To name just a few, the following were enrolled in the service of such a network: geologists, geophysicists, Zionist settlement experts, Zionist organizations, political and technical categories of all sorts, Palestinians as the negated others, Palestinian revolts in search of political rights, the British Mandate authorities, the hydrological system of Palestine, and the absorptive capacity of Palestine, among others. The point was to successfully articulate these disparate elements into a network that seeks opening Palestine for Jewish immigration, redefining Palestinian geography and history through Judeo-Christian Biblical narratives, and, in the process, de-legitimizing political Palestinian presence in historic Palestine.

  11. Can occupancy-abundance models be used to monitor wolf abundance?

    PubMed

    Latham, M Cecilia; Latham, A David M; Webb, Nathan F; Mccutchen, Nicole A; Boutin, Stan

    2014-01-01

    Estimating the abundance of wild carnivores is of foremost importance for conservation and management. However, given their elusive habits, direct observations of these animals are difficult to obtain, so abundance is more commonly estimated from sign surveys or radio-marked individuals. These methods can be costly and difficult, particularly in large areas with heavy forest cover. As an alternative, recent research has suggested that wolf abundance can be estimated from occupancy-abundance curves derived from "virtual" surveys of simulated wolf track networks. Although potentially more cost-effective, the utility of this approach hinges on its robustness to violations of its assumptions. We assessed the sensitivity of the occupancy-abundance approach to four assumptions: variation in wolf movement rates, changes in pack cohesion, presence of lone wolves, and size of survey units. Our simulations showed that occupancy rates and wolf pack abundances were biased high if track surveys were conducted when wolves made long compared to short movements, wolf packs were moving as multiple hunting units as opposed to a cohesive pack, and lone wolves were moving throughout the surveyed landscape. We also found that larger survey units (400 and 576 km2) were more robust to changes in these factors than smaller survey units (36 and 144 km2). However, occupancy rates derived from large survey units rapidly reached an asymptote at 100% occupancy, suggesting that these large units are inappropriate for areas with moderate to high wolf densities (>15 wolves/1,000 km2). Virtually-derived occupancy-abundance relationships can be a useful method for monitoring wolves and other elusive wildlife if applied within certain constraints, in particular biological knowledge of the surveyed species needs to be incorporated into the design of the occupancy surveys. Further, we suggest that the applicability of this method could be extended by directly incorporating some of its assumptions into

  12. Inflammatory myofibroblastic tumor of the uterus: clinical and pathologic review of 10 cases including a subset with aggressive clinical course.

    PubMed

    Parra-Herran, Carlos; Quick, Charles M; Howitt, Brooke E; Dal Cin, Paola; Quade, Bradley J; Nucci, Marisa R

    2015-02-01

    Inflammatory myofibroblastic tumor is currently regarded as a neoplasm with intermediate biological potential and a wide anatomic distribution. Inflammatory myofibroblastic tumors of the female genital tract are rare, and to date reported cases behaved indolently. We describe, herein, 10 cases of uterine inflammatory myofibroblastic tumor, 3 of which had an aggressive clinical course. Subject age ranged from 29 to 73 years. Tumors were composed of spindle and epithelioid myofibroblastic cells admixed with lymphoplasmacytic infiltrates in a variably myxoid stroma. Two growth patterns, myxoid and fascicular (leiomyoma-like), were noted. All tumors were positive for ALK expression by immunohistochemistry, which was stronger in the myxoid areas. Smooth muscle marker and CD10 expression was variable in extent, but typically positive. Fluorescence in situ hybridization for ALK rearrangements was positive in both fascicular and myxoid areas in all 8 cases tested. Three subjects showed clinical evidence of tumor aggressiveness as defined by extrauterine spread, local recurrence, or distant metastasis. Aggressive tumors were larger, had a higher proportion of myxoid stroma, and higher mitotic activity than indolent tumors. Tumor cell necrosis was seen only in cases with adverse outcome. This is the first report to describe aggressive biological behavior in uterine inflammatory myofibroblastic tumor. This diagnosis is often underappreciated and merits inclusion in the differential diagnosis of myxoid mesenchymal lesions of the uterus, particularly because patients with an aggressive course may benefit from targeted therapy.

  13. Abundance anomalies in tidal disruption events

    NASA Astrophysics Data System (ADS)

    Kochanek, C. S.

    2016-05-01

    The ˜10 per cent of tidal disruption events (TDEs) due to stars more massive than M* ≳ M⊙ should show abundance anomalies due to stellar evolution in helium, carbon and nitrogen, but not oxygen. Helium is always enhanced, but only by up to ˜25 per cent on average because it becomes inaccessible once it is sequestered in the high-density core as the star leaves the main sequence. However, portions of the debris associated with the disrupted core of a main-sequence star can be enhanced in helium by factors of 2-3 for debris at a common orbital period. These helium abundance variations may be a contributor to the observed diversity of hydrogen and helium line strengths in TDEs. A still more striking anomaly is the rapid enhancement of nitrogen and the depletion of carbon due to the CNO cycle - stars with M* ≳ M⊙ quickly show an increase in their average N/C ratio by factors of 3-10. Because low-mass stars evolve slowly and high-mass stars are rare, TDEs showing high N/C will almost all be due to ˜1-2 M⊙ stars disrupted on the main sequence. Like helium, portions of the debris will show still larger changes in C and N, and the anomalies decline as the star leaves the main sequence. The enhanced [N/C] abundance ratio of these TDEs provides the first natural explanation for the rare, nitrogen-rich quasars and may also explain the strong nitrogen emission seen in ultraviolet spectra of ASASSN-14li.

  14. Primordial Li abundance and massive particles

    SciTech Connect

    Latin-Capital-Letter-Eth apo, H.

    2012-10-20

    The problem of the observed lithium abundance coming from the Big Bang Nucleosynthesis is as of yet unsolved. One of the proposed solutions is including relic massive particles into the Big Bang Nucleosynthesis. We investigated the effects of such particles on {sup 4}HeX{sup -}+{sup 2}H{yields}{sup 6}Li+X{sup -}, where the X{sup -} is the negatively charged massive particle. We demonstrate the dominance of long-range part of the potential on the cross-section.

  15. Abundances of Planetary Nebula NGC 5315

    NASA Technical Reports Server (NTRS)

    Pottasch, S. R.; Beintema, D. A.; Koorneef, J.; Salas, J. Bernard; Feibelman, W. A.; Oegerle, William R. (Technical Monitor)

    2002-01-01

    The ISO and IUE spectra of the elliptical nebula NGC 5315 is presented. These spectra axe combined with the spectra in the visual wavelength region to obtain a complete, extinction corrected, spectrum. The chemical composition of the nebulae is then calculated and compared to previous determinations. The HST Nicmos observations of the nebula in 3 emission lines are also presented. These observations are used to determine the helium abundance as a function of position in the nebula. A discussion is given of possible evolutionary effects.

  16. Abundances in Globular Cluster Red Giant Stars

    NASA Astrophysics Data System (ADS)

    Cavallo, R. M.

    1997-12-01

    Observations of globular cluster red giant branch (RGB) stars have shown star-to-star variations in the abundances of C, N, O, Na, Mg, and Al, contrary to predictions of standard stellar evolutionary theory. I have modeled the variations in the abundance profiles around the hydrogen-burning shell (H shell) of metal-poor red giant stars by combining four RGB stellar evolutionary sequences of different metallicities with a detailed nuclear reaction network. This approach has significant advantages over previous research: (1) it allows for the variation in the temperature and density around the H shell; (2) it follows the effects of the changing H-shell structure as the sequence evolves; (3) it accounts for the effect of the metallicity on the abundance profiles; (4) it allows the reaction rates to be varied so that their uncertainties may be explored. The results are in good qualitative agreement with the observations. All the models show a region above the H shell in which first C, then O, is depleted in the CN and ON nuclear burning cycles. Within the C-depleted region, the (12) C/(13) C ratio is reduced to its equilibrium value. Just above the O-depleted region, Na is enhanced from proton captures on (22) Ne. In brighter models, Na becomes greatly enhanced within the O-depleted region as the NeNa cycle converts (20) Ne into (23) Na before attaining equilibrium inside the H shell. The more metal-poor models also show Al being increased around the H shell, first from (25,26) Mg, then from (24) Mg in the MgAl cycle. Despite the diminution (24) Mg suffers in synthesizing Al, the models show its abundance is increased due to the NeNa-cycle breakout reaction, (23) Na(p,γ)(24) Mg. This latter result is at odds with observations that show (24) Mg is depleted in a sample of M 13 and NGC 6752 giants (Shetrone 1996, 1997).

  17. NEON AND OXYGEN ABUNDANCES AND ABUNDANCE RATIO IN THE SOLAR CORONA

    SciTech Connect

    Landi, E.; Testa, P.

    2015-02-20

    In this work we determine the Ne/O abundance ratio from Solar and Heliospheric Observatory (SOHO)/Solar Ultraviolet Measurement of Emitted Radiation (SUMER) off-disk observations of quiescent streamers over the 1996-2008 period. We find that the Ne/O ratio is approximately constant over solar cycle 23 from 1996 to 2005, at a value of 0.099 ± 0.017; this value is lower than the transition region determinations from the quiet Sun used to infer the neon photospheric abundance from the oxygen photospheric abundance. Also, the Ne/O ratio we determined from SUMER is in excellent agreement with in situ determinations from ACE/SWICS. In 2005-2008, the Ne/O abundance ratio increased with time and reached 0.25 ± 0.05, following the same trend found in the slowest wind analyzed by ACE/SWICS. Further, we measure the absolute abundance in the corona for both oxygen and neon from the data set of 1996 November 22, obtaining A {sub o} = 8.99 ± 0.04 and A {sub Ne} = 7.92 ± 0.03, and we find that both elements are affected by the first ionization potential (FIP) effect, with oxygen being enhanced by a factor of 1.4-2.1 over its photospheric abundance, and neon being changed by a factor of 0.75-1.20. We conclude that the Ne/O ratio is not constant in the solar atmosphere, both in time and at different heights, and that it cannot be reliably used to infer the neon abundance in the photosphere. Also, we argue that the FIP effect was less effective during the minimum of solar cycle 24, and that the Ne/O = 0.25 ± 0.05 value measured at that time is closer to the true photospheric value, leading to a neon photospheric abundance larger than assumed by ≈40%. We discuss the implications of these results for the solar abundance problem, for the FIP effect, and for the identification of the source regions of the solar wind.

  18. Measurements of Absolute Abundances in Solar Flares

    NASA Astrophysics Data System (ADS)

    Warren, Harry P.

    2014-05-01

    We present measurements of elemental abundances in solar flares with the EUV Variability Experiment (EVE) on the Solar Dynamics Observatory. EVE observes both high temperature Fe emission lines (Fe XV-Fe XXIV) and continuum emission from thermal bremsstrahlung that is proportional to the abundance of H. By comparing the relative intensities of line and continuum emission it is possible to determine the enrichment of the flare plasma relative to the composition of the photosphere. This is the first ionization potential or FIP bias (f). Since thermal bremsstrahlung at EUV wavelengths is relatively insensitive to the electron temperature, it is important to account for the distribution of electron temperatures in the emitting plasma. We accomplish this by using the observed spectra to infer the differential emission measure distribution and FIP bias simultaneously. In each of the 21 flares that we analyze we find that the observed composition is close to photospheric. The mean FIP bias in our sample is f = 1.17 ± 0.22. This analysis suggests that the bulk of the plasma evaporated during a flare comes from deep in the chromosphere, below the region where elemental fractionation occurs.

  19. Absolute Abundance Measurements in Solar Flares

    NASA Astrophysics Data System (ADS)

    Warren, Harry

    2014-06-01

    We present measurements of elemental abundances in solar flares with EVE/SDO and EIS/Hinode. EVE observes both high temperature Fe emission lines Fe XV-XXIV and continuum emission from thermal bremsstrahlung that is proportional to the abundance of H. By comparing the relative intensities of line and continuum emission it is possible to determine the enrichment of the flare plasma relative to the composition of the photosphere. This is the first ionization potential or FIP bias (F). Since thermal bremsstrahlung at EUV wavelengths is relatively insensitive to the electron temperature it is important to account for the distribution of electron temperatures in the emitting plasma. We accomplish this by using the observed spectra to infer the differential emission measure distribution and FIP bias simultaneously. In each of the 21 flares that we analyze we find that the observed composition is close to photospheric. The mean FIP bias in our sample is F=1.17+-0.22. Furthermore, we have compared the EVE measurements with corresponding flare observations of intermediate temperature S, Ar, Ca, and Fe emission lines taken with EIS. Our initial calculations also indicate a photospheric composition for these observations. This analysis suggests that the bulk of the plasma evaporated during a flare comes from deep in the chromosphere, below the region where elemental fractionation in the non-flaring corona occurs.

  20. Oxygen Abundances in Metal-Poor Stars

    NASA Astrophysics Data System (ADS)

    Fulbright, J. P.

    1999-05-01

    The oxygen abundances of metal-poor late-type stars can be obtained by one four methods: 1) the [O I] forbidden lines at 6300 and 6363 Angstroms, 2) the O I triplet at 7774 Angstroms, 3) OH lines at 3100-3150 Angstroms, and 4) IR CO and OH bands. Each of these methods have their strengths and weaknesses, and finding common agreement between the methods has sometimes been elusive. Recently two groups (Israelian et al, 1998, ApJ, 507, 805 and Boesgaard et al, 1999, AJ, 117, 492) have presented results from the UV OH lines and the O I triplet that suggest that the [O/Fe]-ratio continues to increase as [Fe/H] decreases. This differs from the 'traditional' result that held that [O/Fe] plateaus at +0.5 as [Fe/H] decreases. Conversely, Fulbright and Kraft (AJ, July 1999) show that in two very metal-poor stars the [O I] 6300 Angstroms line gives abundances 0.5 dex lower than obtained in the above studies. In this talk, I hope to discuss these papers and speculate on potental causes to the discrepency.

  1. MEASUREMENTS OF ABSOLUTE ABUNDANCES IN SOLAR FLARES

    SciTech Connect

    Warren, Harry P.

    2014-05-01

    We present measurements of elemental abundances in solar flares with the EUV Variability Experiment (EVE) on the Solar Dynamics Observatory. EVE observes both high temperature Fe emission lines (Fe XV-Fe XXIV) and continuum emission from thermal bremsstrahlung that is proportional to the abundance of H. By comparing the relative intensities of line and continuum emission it is possible to determine the enrichment of the flare plasma relative to the composition of the photosphere. This is the first ionization potential or FIP bias (f). Since thermal bremsstrahlung at EUV wavelengths is relatively insensitive to the electron temperature, it is important to account for the distribution of electron temperatures in the emitting plasma. We accomplish this by using the observed spectra to infer the differential emission measure distribution and FIP bias simultaneously. In each of the 21 flares that we analyze we find that the observed composition is close to photospheric. The mean FIP bias in our sample is f = 1.17 ± 0.22. This analysis suggests that the bulk of the plasma evaporated during a flare comes from deep in the chromosphere, below the region where elemental fractionation occurs.

  2. Genomic Repeat Abundances Contain Phylogenetic Signal

    PubMed Central

    Dodsworth, Steven; Chase, Mark W.; Kelly, Laura J.; Leitch, Ilia J.; Macas, Jiří; Novák, Petr; Piednoël, Mathieu; Weiss-Schneeweiss, Hanna; Leitch, Andrew R.

    2015-01-01

    A large proportion of genomic information, particularly repetitive elements, is usually ignored when researchers are using next-generation sequencing. Here we demonstrate the usefulness of this repetitive fraction in phylogenetic analyses, utilizing comparative graph-based clustering of next-generation sequence reads, which results in abundance estimates of different classes of genomic repeats. Phylogenetic trees are then inferred based on the genome-wide abundance of different repeat types treated as continuously varying characters; such repeats are scattered across chromosomes and in angiosperms can constitute a majority of nuclear genomic DNA. In six diverse examples, five angiosperms and one insect, this method provides generally well-supported relationships at interspecific and intergeneric levels that agree with results from more standard phylogenetic analyses of commonly used markers. We propose that this methodology may prove especially useful in groups where there is little genetic differentiation in standard phylogenetic markers. At the same time as providing data for phylogenetic inference, this method additionally yields a wealth of data for comparative studies of genome evolution. PMID:25261464

  3. Abundance and Distribution of Geographically Isolated ...

    EPA Pesticide Factsheets

    Geographically isolated wetlands (GIWS) are important landscape elements involved in hydrologic, biogeochemical, and biological functioning. Their influence, under certain circumstances, can significantly affect other waters of the Unites States. However, there have been no data-based estimates of the abundance of GIWs at national scales in the US, frustrating efforts to properly manage the resource. We applied a distance-based floodplain and riparian zone proxy to existing data layers from the National Hydrography Dataset (1:24,000k) and applied a geospatial buffering process to National Wetlands Inventory data to quantify the abundance of connected wetlands at significant and relevant scales. Our analyses suggest GIWs are prevalent throughout the conterminous United States, with exceptional densities in portions of the Gulf and Atlantic Coastal Plains, the Prairie Pothole Region of the Upper Midwest, and significant densities elsewhere. Indeed, over 65,000 km2 of GIWs may exist. We provide further analyses of the types, distributions, and regional extent of these systems. Lastly, we also explore additional connectivity measures associated with adjacency and relative geographic isolation to floodplains and other elements of the hydrologic landscape. Presentation at INTECOL International Wetlands Conference (Changshu, China; Sept. 2016)

  4. Fish abundance, distribution, and habitat use

    NASA Astrophysics Data System (ADS)

    Hoffnagle, Timothy L.; Valdez, Richard A.; Speas, David W.

    The 1996 controlled flood in the Colorado River, Grand Canyon, was designed, in part, to improve conditions for juvenile native fishes by reshaping habitat and displacing non-native fishes. We examined changes in abundance and distributions of native and non-native fishes immediately before and after the controlled flood and recovery of affected species 2.5 and 6 months after. Catch-per-unit-effort (CPUE) of humpback chub and flannelmouth sucker did not differ in pre- versus post-flood periods. CPUE of plains killifish, bluehead sucker and fathead minnow decreased following the flood, and CPUE of speckled dace and rainbow trout increased. Juvenile humpback chub remained primarily along talus shorelines at all discharges, while at higher discharges, speckled dace shifted from mid-channel riffles to debris fans and talus and fathead minnows used primarily vegetated shorelines. There was evidence of some downstream displacement of plains killifish, fathead minnows and rainbow trout. Catch rates of all species showed seasonal variation following the flood, with summer recruitment of young-of-the-year, particularly fathead minnows and plains killifish. Although short-term reductions in catch rates of fathead minnows and plains killifish occurred, these populations returned to pre-flood densities by 6 months after the flood. Catch rates of all species before and after the flood were similar to those recorded in previous years. We determined that the controlled flood did not significantly alter native fish distributions or abundances through Grand Canyon.

  5. Element Abundance Determination in Hot Evolved Stars

    NASA Astrophysics Data System (ADS)

    Werner, Klaus

    The hydrogen-deficiency in extremely hot post-AGB stars of spectral class PG1159 is probably caused by a (very) late helium-shell flash or a AGB final thermal pulse that consumes the hydrogen envelope, exposing the usually-hidden intershell region. Thus, the photospheric element abundances of these stars allow us to draw conclusions about details of nuclear burning and mixing processes in the precursor AGB stars. We compare predicted element abundances to those determined by quantitative spectral analyses performed with advanced non-LTE model atmospheres. A good qualitative and quantitative agreement is found for many species (He, C, N, O, Ne, F, Si, Ar) but discrepancies for others (P, S, Fe) point at shortcomings in stellar evolution models for AGB stars. Almost all of the chemical trace elements in these hot stars can only be identified in the UV spectral range. The Far Ultraviolet Spectroscopic Explorer and the Hubble Space Telescope played a crucial role for this research.

  6. Parameters and abundances in luminous stars

    SciTech Connect

    Earle Luck, R.

    2014-06-01

    Parameters and abundances for 451 stars of spectral types F, G, and K of luminosity classes I and II have been derived. Absolute magnitudes and E(B – V) have been derived for the warmer stars in order to investigate the galactic abundance gradient. The value found here: d[Fe/H]/dR ∼ –0.06 dex kpc{sup –1}, agrees well with previous determinations. Stellar evolution indicators have also been investigated with the derived C/O ratios indicating that standard CN processing has been operating. Perhaps the most surprising result found in these supposedly relatively young intermediate-mass stars is that both [O/Fe] and [C/Fe] show a correlation with [Fe/H] much the same as found in older populations. While the stars were selected based on luminosity class, there does exist a significant [Fe/H] range in the sample. The likely explanation of this is that there is a significant range in age in the sample; that is, some of the sample are low-mass red-giant stars with types that place them within the selection criteria.

  7. Occupancy as a surrogate for abundance estimation

    USGS Publications Warehouse

    MacKenzie, D.I.; Nichols, J.D.

    2004-01-01

    In many monitoring programmes it may be prohibitively expensive to estimate the actual abundance of a bird species in a defined area, particularly at large spatial scales, or where birds occur at very low densities. Often it may be appropriate to consider the proportion of area occupied by the species as an alternative state variable. However, as with abundance estimation, issues of detectability must be taken into account in order to make accurate inferences: the non?detection of the species does not imply the species is genuinely absent. Here we review some recent modelling developments that permit unbiased estimation of the proportion of area occupied, colonization and local extinction probabilities. These methods allow for unequal sampling effort and enable covariate information on sampling locations to be incorporated. We also describe how these models could be extended to incorporate information from marked individuals, which would enable finer questions of population dynamics (such as turnover rate of nest sites by specific breeding pairs) to be addressed. We believe these models may be applicable to a wide range of bird species and may be useful for investigating various questions of ecological interest. For example, with respect to habitat quality, we might predict that a species is more likely to have higher local extinction probabilities, or higher turnover rates of specific breeding pairs, in poor quality habitats.

  8. Evolutionary Dynamics of Abundant Stop Codon Readthrough

    PubMed Central

    Jungreis, Irwin; Kellis, Manolis

    2016-01-01

    Translational stop codon readthrough emerged as a major regulatory mechanism affecting hundreds of genes in animal genomes, based on recent comparative genomics and ribosomal profiling evidence, but its evolutionary properties remain unknown. Here, we leverage comparative genomic evidence across 21 Anopheles mosquitoes to systematically annotate readthrough genes in the malaria vector Anopheles gambiae, and to provide the first study of abundant readthrough evolution, by comparison with 20 Drosophila species. Using improved comparative genomics methods for detecting readthrough, we identify evolutionary signatures of conserved, functional readthrough of 353 stop codons in the malaria vector, Anopheles gambiae, and of 51 additional Drosophila melanogaster stop codons, including several cases of double and triple readthrough and of readthrough of two adjacent stop codons. We find that most differences between the readthrough repertoires of the two species arose from readthrough gain or loss in existing genes, rather than birth of new genes or gene death; that readthrough-associated RNA structures are sometimes gained or lost while readthrough persists; that readthrough is more likely to be lost at TAA and TAG stop codons; and that readthrough is under continued purifying evolutionary selection in mosquito, based on population genetic evidence. We also determine readthrough-associated gene properties that predate readthrough, and identify differences in the characteristic properties of readthrough genes between clades. We estimate more than 600 functional readthrough stop codons in mosquito and 900 in fruit fly, provide evidence of readthrough control of peroxisomal targeting, and refine the phylogenetic extent of abundant readthrough as following divergence from centipede. PMID:27604222

  9. Principal component analysis on chemical abundances spaces

    NASA Astrophysics Data System (ADS)

    Ting, Yuan-Sen; Freeman, Kenneth C.; Kobayashi, Chiaki; De Silva, Gayandhi M.; Bland-Hawthorn, Joss

    2012-04-01

    In preparation for the High Efficiency and Resolution Multi-Element Spectrograph (HERMES) chemical tagging survey of about a million Galactic FGK stars, we estimate the number of independent dimensions of the space defined by the stellar chemical element abundances [X/Fe]. This leads to a way to study the origin of elements from observed chemical abundances using principal component analysis. We explore abundances in several environments, including solar neighbourhood thin/thick disc stars, halo metal-poor stars, globular clusters, open clusters, the Large Magellanic Cloud and the Fornax dwarf spheroidal galaxy. By studying solar-neighbourhood stars, we confirm the universality of the r-process that tends to produce [neutron-capture elements/Fe] in a constant ratio. We find that, especially at low metallicity, the production of r-process elements is likely to be associated with the production of α-elements. This may support the core-collapse supernovae as the r-process site. We also verify the overabundances of light s-process elements at low metallicity, and find that the relative contribution decreases at higher metallicity, which suggests that this lighter elements primary process may be associated with massive stars. We also verify the contribution from the s-process in low-mass asymptotic giant branch (AGB) stars at high metallicity. Our analysis reveals two types of core-collapse supernovae: one produces mainly α-elements, the other produces both α-elements and Fe-peak elements with a large enhancement of heavy Fe-peak elements which may be the contribution from hypernovae. Excluding light elements that may be subject to internal mixing, K and Cu, we find that the [X/Fe] chemical abundance space in the solar neighbourhood has about six independent dimensions both at low metallicity (-3.5 ≲ [Fe/H] ≲-2) and high metallicity ([Fe/H] ≳-1). However the dimensions come from very different origins in these two cases. The extra contribution from low-mass AGB

  10. Plant abundance: the measurement and relationship with seed size

    USGS Publications Warehouse

    Guo, Q.

    2003-01-01

    There are many inconsistencies in early reports describing the relationships between plant abundance and other biotic (e.g., seed size) or abiotic variables (e.g., precipitation). It has been difficult to generalize such relationships when abundance is measured differently (e.g., density, biomass, cover). This article suggests using abundance in two broad categories: numerical abundance (e.g., number of individuals, density) and mass abundance (e.g., biomass, cover). Collective evidence indicates that when abundance is measured the same way, the observed patterns may actually be more consistent.

  11. ABUNDANCES OF GALACTIC ANTICENTER PLANETARY NEBULAE AND THE OXYGEN ABUNDANCE GRADIENT IN THE GALACTIC DISK

    SciTech Connect

    Henry, R. B. C.; Morrison, Michael A.; Kwitter, Karen B.; Jaskot, Anne E.; Balick, Bruce; Milingo, Jacquelynne B. E-mail: morrison@nhn.ou.ed E-mail: ajaskot@umich.ed E-mail: jmilingo@gettysburg.ed

    2010-11-20

    We have obtained spectrophotometric observations of 41 anticenter planetary nebulae (PNe) located in the disk of the Milky Way. Electron temperatures and densities, as well as chemical abundances for He, N, O, Ne, S, Cl, and Ar were determined. Incorporating these results into our existing database of PN abundances yielded a sample of 124 well-observed objects with homogeneously determined abundances extending from 0.9 to 21 kpc in galactocentric distance. We performed a detailed regression analysis which accounted for uncertainties in both oxygen abundances and radial distances in order to establish the metallicity gradient across the disk to be 12 + log(O/H) = (9.09 {+-} 0.05) - (0.058 {+-} 0.006) x R{sub g} , with R{sub g} in kpc. While we see some evidence that the gradient steepens at large galactocentric distances, more objects toward the anticenter need to be observed in order to confidently establish the true form of the metallicity gradient. We find no compelling evidence that the gradient differs between Peimbert Types I and II, nor is oxygen abundance related to the vertical distance from the galactic plane. Our gradient agrees well with analogous results for H II regions but is steeper than the one recently published by Stanghellini and Haywood over a similar range in galactocentric distance. A second analysis using PN distances from a different source implied a flatter gradient, and we suggest that we have reached a confusion limit which can only be resolved with greatly improved distance measurements and an understanding of the natural scatter in oxygen abundances.

  12. An Update of the Primordial Helium Abundance

    NASA Astrophysics Data System (ADS)

    Peimbert, Antonio; Peimbert, Manuel; Luridiana, Valentina

    2015-08-01

    Three of the best determinations of the primordial helium abundance (Yp) are those obtained from low metallicity HII regions by Aver, Olive, Porter, & Skillman (2013); Izotov, Thuan, & Guseva (2014); and Peimbert, Peimbert, & Luridiana (2007). In this poster we update the Yp determination by Peimbert et al. taking into account, among other aspects, recent advances in the determination of the He atomic physical parameters, the temperature structure, the collisional effects of high temperatures on the Balmer lines, as well as the effect of H and He bound-bound absorption.We compare our results with those of Aver et al. and Izotov et al. and point out possible explanations for the differences among the three determinations. We also compare our results with those obtained with the Plank satellite considering recent measurements of the neutron mean life; this comparison has implications on the determination of the number of light neutrino families.

  13. Subhalo Abundance Matching in f (R ) Gravity

    NASA Astrophysics Data System (ADS)

    He, Jian-hua; Li, Baojiu; Baugh, Carlton M.

    2016-11-01

    Using the liminality N -body simulations of Shi et al., we present the first predictions for galaxy clustering in f (R ) gravity using subhalo abundance matching. We find that, for a given galaxy density, even for an f (R ) model with fR 0=-10-6, for which the cold dark matter clustering is very similar to the cold dark matter model with a cosmological constant (Λ CDM ), the predicted clustering of galaxies in the f (R ) model is very different from Λ CDM . The deviation can be as large as 40% for samples with mean densities close to that of L* galaxies. This large deviation is testable given the accuracy that future large-scale galaxy surveys aim to achieve. Our result demonstrates that galaxy surveys can provide a stringent test of general relativity on cosmological scales, which is comparable to the tests from local astrophysical observations.

  14. Cosmological implications of light element abundances: theory.

    PubMed Central

    Schramm, D N

    1993-01-01

    Primordial nucleosynthesis provides (with the microwave background radiation) one of the two quantitative experimental tests of the hot Big Bang cosmological model (versus alternative explanations for the observed Hubble expansion). The standard homogeneous-isotropic calculation fits the light element abundances ranging from 1H at 76% and 4He at 24% by mass through 2H and 3He at parts in 105 down to 7Li at parts in 1010. It is also noted how the recent Large Electron Positron Collider (and Stanford Linear Collider) results on the number of neutrinos (Nnu) are a positive laboratory test of this standard Big Bang scenario. The possible alternate scenario of quark-hadron-induced inhomogeneities is also discussed. It is shown that when this alternative scenario is made to fit the observed abundances accurately, the resulting conclusions on the baryonic density relative to the critical density (Omegab) remain approximately the same as in the standard homogeneous case, thus adding to the robustness of the standard model and the conclusion that Omegab approximately 0.06. This latter point is the driving force behind the need for nonbaryonic dark matter (assuming total density Omegatotal = 1) and the need for dark baryonic matter, since the density of visible matter Omegavisible < Omegab. The recent Population II B and Be observations are also discussed and shown to be a consequence of cosmic ray spallation processes rather than primordial nucleosynthesis. The light elements and Nnu successfully probe the cosmological model at times as early as 1 sec and a temperature (T) of approximately 10(10) K (approximately 1 MeV). Thus, they provided the first quantitative arguments that led to the connections of cosmology to nuclear and particle physics. Images Fig. 2 PMID:11607387

  15. Earth abundant bimetallic nanoparticles for heterogeneous catalysis

    NASA Astrophysics Data System (ADS)

    Senn, Jonathan F., Jr.

    Polymer exchange membrane fuel cells have the potential to replace current fossil fuel-based technologies in terms of emissions and efficiency, but CO contamination of H2 fuel, which is derived from steam methane reforming, leads to system inefficiency or failure. Solutions currently under development are bimetallic nanoparticles comprised of earth-abundant metals in different architectures to reduce the concentration of CO by PROX during fuel cell operation. Chapter One introduces the Pt-Sn and Co-Ni bimetallic nanoparticle systems, and the intermetallic and core-shell architectures of interest for catalytic evaluation. Application, theory, and studies associated with the efficacy of these nanoparticles are briefly reviewed. Chapter Two describes the concepts of the synthetic and characterization methods used in this work. Chapter Three presents the synthetic, characterization, and catalytic findings of this research. Pt, PtSn, PtSn2, and Pt 3Sn nanoparticles have been synthesized and supported on gamma-Al2O3. Pt3Sn was shown to be an effective PROX catalyst in various gas feed conditions, such as the gas mixture incorporating 0.1% CO, which displayed a light-off temperatures of ˜95°C. Co and Ni monometallic and CoNi bimetallic nanoparticles have been synthesized and characterized, ultimately leading to the development of target Co Ni core-shell nanoparticles. Proposed studies of catalytic properties of these nanoparticles in preferential oxidation of CO (PROX) reactions will further elucidate the effects of different crystallographic phases, nanoparticle-support interactions, and architecture on catalysis, and provide fundamental understanding of catalysis with nanoparticles composed of earth abundant metals in different architectures.

  16. Cosmological implications of light element abundances: theory.

    PubMed

    Schramm, D N

    1993-06-01

    Primordial nucleosynthesis provides (with the microwave background radiation) one of the two quantitative experimental tests of the hot Big Bang cosmological model (versus alternative explanations for the observed Hubble expansion). The standard homogeneous-isotropic calculation fits the light element abundances ranging from 1H at 76% and 4He at 24% by mass through 2H and 3He at parts in 105 down to 7Li at parts in 1010. It is also noted how the recent Large Electron Positron Collider (and Stanford Linear Collider) results on the number of neutrinos (Nnu) are a positive laboratory test of this standard Big Bang scenario. The possible alternate scenario of quark-hadron-induced inhomogeneities is also discussed. It is shown that when this alternative scenario is made to fit the observed abundances accurately, the resulting conclusions on the baryonic density relative to the critical density (Omegab) remain approximately the same as in the standard homogeneous case, thus adding to the robustness of the standard model and the conclusion that Omegab approximately 0.06. This latter point is the driving force behind the need for nonbaryonic dark matter (assuming total density Omegatotal = 1) and the need for dark baryonic matter, since the density of visible matter Omegavisible < Omegab. The recent Population II B and Be observations are also discussed and shown to be a consequence of cosmic ray spallation processes rather than primordial nucleosynthesis. The light elements and Nnu successfully probe the cosmological model at times as early as 1 sec and a temperature (T) of approximately 10(10) K (approximately 1 MeV). Thus, they provided the first quantitative arguments that led to the connections of cosmology to nuclear and particle physics.

  17. Planetary nebulae near the Galactic Centre: chemical abundances

    NASA Astrophysics Data System (ADS)

    Cavichia, O.; Costa, R. D. D.; Maciel, W. J.; Mollá, M.

    2014-10-01

    In this work, we report physical parameters and abundances derived for a sample of high extinction planetary nebulae located in the Galactic bulge, near the Galactic Centre, based on low dispersion spectroscopy secured at the SOAR telescope using the Goodman spectrograph. The results show that the abundances of our sample are similar to those from other regions of the bulge. Nevertheless, the average abundances of the Galactic bulge do not follow the observed trend of the radial abundance gradient in the disk.

  18. Impaired tumor growth in colony-stimulating factor 1 (CSF-1)-deficient, macrophage-deficient op/op mouse: evidence for a role of CSF-1-dependent macrophages in formation of tumor stroma.

    PubMed

    Nowicki, A; Szenajch, J; Ostrowska, G; Wojtowicz, A; Wojtowicz, K; Kruszewski, A A; Maruszynski, M; Aukerman, S L; Wiktor-Jedrzejczak, W

    1996-01-03

    Macrophages have been suggested to play a major role in the immune response to cancer. They have also been suggested to stimulate the formation of tumor stroma and to promote tumor vascularization. The availability of the op/op mouse, which has no endogenous colony-stimulating factor 1 (CSF-1) and which possesses a profound macrophage deficiency, provides a new model to verify these notions. Subcutaneous growth of transplantable Lewis lung cancer (LLC) is markedly impaired in the op/op mice compared with normal littermates. Treatment of tumor-bearing op/op mice with human recombinant CSF-1 corrects this impairment. Histological analysis of tumors grown in op/op and normal mice revealed marked differences. Tumors grown in op/op mice display a decreased mitotic index and pronounced necrosis, particularly hemorrhagic. Moreover, particularly in the op/op tumors, peculiar sinusoid-like abortive vessels (not filled with blood) have been observed. These tumors, in contrast to tumors grown in normal mice, are almost deprived of regular arteries and veins. In contrast to tumors grown in normal mice, they exhibit almost no Sirius red-stained collagenous fibers and Gomori silver-stained reticular fibers. Our data suggest that the CSF-1-dependent macrophage subpopulation missing in op/op mice plays a primary role in supporting tumor stroma formation and tumor vascularization in murine LLC tumors.

  19. Solar-system abundances of the elements - A new table

    NASA Technical Reports Server (NTRS)

    Grevesse, Nicolas; Anders, Edward

    1989-01-01

    This paper presents an abridged version of a new abundance compilation (Anders and Grevesse, 1988), representing an update of Anders and Ebihara (1982) and Grevesse (1984). It includes revised meteoritic abundances as well as photospheric and coronal abundances, based on literature through mid-1988.

  20. Li-7 abundances in halo stars: Testing stellar evolution models and the primordial Li-7 abundance

    NASA Technical Reports Server (NTRS)

    Chaboyer, Brian; Demarque, P.

    1994-01-01

    A large number of stellar evolution models with (Fe/H) = -2.3 and -3.3 have been calculated in order to determine the primordial Li-7 abundance and to test current stellar evolution models by a comparison to the extensive database of accurate Li abundances in extremely metal-poor halo stars observed by Thorburn (1994). Standard models with gray atmospheres do a very good job of fitting the observed Li abundances in stars hotter than approximately 5600 K. They predict a primordial. Li-7 abundance of log N(Li) = 2.24 +/- 0.03. Models which include microscopic diffusion predict a downward curvature in the Li-7 destruction isochrones at hot temperatures which is not present in the observations. Thus, the observations clearly rule out models which include uninhibited microscopic diffusion of Li-7 from the surface of the star. Rotational mixing inhibits the microscopic diffusion and the (Fe/H) = -2.28 stellar models which include both diffusion and rotational mixing provide an excellent match to the mean trend in T(sub eff) which is present in the observations. Both the plateau stars and the heavily depleted cool stars are well fit by these models. The rotational mixing leads to considerable Li-7 depletion in these models and the primordial Li-7 abundance inferred from these models is log N(Li) = 3.08 +/- 0.1. However, the (Fe/H) = -3.28 isochrones reveal problems with the combined models. These isochrones predict a trend of decreasing log N(Li) with increasing T(sub eff) which is not present in the observations. Possible causes for this discrepancy are discussed.

  1. Elemental Abundances in the Galactic Disk

    NASA Astrophysics Data System (ADS)

    Reddy, B. E.; Tomkin, J.; Lambert, D. L.; Allende Prieto, C.

    Here, we discussed our recent results of elemental abundance survey of Galactic disk based on 181 F- and G-type dwarfs (published by Reddy et al. 2003, MNRAS, 340, 304). Using high-resolution and high signal-to-noise spectra we obtained quantitative abundances for 27 elements: C, N, O, Na, Mg, Al, Si, S, K, Ca, Sc, Ti, V, Cr, Mn, Co, Ni, Cu, Zn, Sr, Y, Zr, Ba, Ce, Nd, and Eu. For the entire sample we have determined kinematic (U,V,W) and the orbital parameters (peri- and apo- Galactic distances). The alpha-elements -- O, Mg, Si, Ca, and Ti -- show [α/Fe] to increase slightly with decreasing [Fe/H]. Heavy elements with dominant contributions at solar metallicity from the s-process show [s/Fe] to decrease slightly with decreasing [Fe/H]. Scatter in [X/Fe] at a fixed [Fe/H] is entirely attributable to the small measurement errors, after excluding the few thick disk stars and the s-process enriched CH subgiants. Tight limits are set on `cosmic' scatter. If a weak trend with [Fe/H] is taken into account, the composition of a thin disk star expressed as [X/Fe] is independent of the star's age and birthplace for elements contributed in different proportions by massive stars (Type II SN), exploding white dwarfs (Type Ia SN), and asymptotic red giant branch stars. By combining our sample with published studies, we deduced properties of thin and thick disk stars. Thick disk stars are primarily identified by their VLSR in the range - 40 to -100 km s-1. These are very old stars with origins in the inner Galaxy and metallicities [Fe/H] <˜-0.4. At the same [Fe/H], the sampled thin disk stars have VLSR ˜0 km s-1, and are generally younger with a birthplace at about the Sun's Galactocentric distance. In the range -0.35 ≥ [Fe/H] ≥ -0.70, well represented by present thin and thick disk samples, [X/Fe] of the thick disk stars is greater than that of thin disk stars for Mg, Al, Si, Ca, Ti, and Eu. [X/Fe] is very similar for the thin and thick disk for -- notably -- Na, and iron

  2. Barium Abundances in Omega Centauri Candidate Stars

    NASA Astrophysics Data System (ADS)

    Skipper, Joy Nicole; Sobeck, Jennifer; Majewski, Steven R.; Rochford Hayes, Christian; Cunha, Katia M. L.; Smith, Verne V.; Damke, Guillermo; García Pérez, Ana; Nidever, David L.

    2017-01-01

    The "globular cluster" omega Centauri has several peculiar features that set it apart from other Milky Way globular clusters, such as its large mass, extended size, oblate shape, internal rotation, large age and metallicity spreads, and retrograde orbit. Because of these properties it is thought that Omega Cen may be a heavily stripped remnant of a Milky Way-captured dwarf spheroidal galaxy, now currently orbiting (backwards) near the Galactic plane (e.g., Lee et al. 1999, Majewski et al. 2000). A previous search within a large, all-sky low resolution spectroscopic and photometric catalog of giant stars by Majewski et al. (2012) identified candidate retrograde stars near that plane also having kinematics consistent with being stripped debris from omega Cen, based on tidal destruction models of the system. To confirm their status as omega Centauri members, high resolution spectroscopy was undertaken of a subsample of a dozen of these candidates, and most were found by Majewski et al. to exhibit very high relative Ba abundances (as measured by the 5854 transition) — a peculiar characteristic of the omega Centauri system as originally shown by Smith et al. (2000) and Norris & Da Costa (1998). Thus, these results showed the likelihood of a connection between these widely distributed field stars and omega Centauri.We have continued this spectroscopic investigation with an expanded sample of candidate tidally-stripped omega Cen giant stars. High-resolution spectra were obtained in the wavelength region (4140~6210A) with the Ultraviolet Visual Echelle Spectrograph (UVES) on the 8.0-m Very Large Telescope (VLT) for additional candidates. For these data, we have employed multiple transitions to derive reliable [Ba/Fe] ratios. We will compare these and other derived abundances to those of the omega Cen core, other globular cluster and field stars. Any additionally-confirmed omega Cen debris stars to combine with those from the previous studies will allow for a more

  3. Manganese abundances in Galactic bulge red giants

    NASA Astrophysics Data System (ADS)

    Barbuy, B.; Hill, V.; Zoccali, M.; Minniti, D.; Renzini, A.; Ortolani, S.; Gómez, A.; Trevisan, M.; Dutra, N.

    2013-11-01

    Context. Manganese is mainly produced in type II SNe during explosive silicon burning, in incomplete Si-burning regions, and depends on several nucleosynthesis environment conditions, such as mass cut between the matter ejected and falling back onto the remnant, electron and neutron excesses, mixing fallback, and explosion energy. Manganese is also produced in type Ia SNe. Aims: The aim of this work is the study of abundances of the iron-peak element Mn in 56 bulge giants, among which 13 are red clump stars. Four bulge fields along the minor axis are inspected. The study of abundances of Mn-over-Fe as a function of metallicity in the Galactic bulge may shed light on its production mechanisms. Methods: High-resolution spectra were obtained using the FLAMES+UVES spectrograph on the Very Large Telescope. The spectra were obtained within a program to observe 800 stars using the GIRAFFE spectrograph, together with the present UVES spectra. Results: We aim at identifying the chemical evolution of manganese, as a function of metallicity, in the Galactic bulge. We find [Mn/Fe] ~ -0.7 at [Fe/H] ~ -1.3, increasing to a solar value at metallicities close to solar, and showing a spread around - 0.7 ≲ [Fe/H] ≲ -0.2, in good agreement with other work on Mn in bulge stars. There is also good agreement with chemical evolution models. We find no clear difference in the behaviour of the four bulge fields. Whereas [Mn/Fe] vs. [Fe/H] could be identified with the behaviour of the thick disc stars, [Mn/O] vs. [O/H] has a behaviour running parallel, at higher metallicities, compared to thick disc stars, indicating that the bulge enrichment might have proceeded differently from that of the thick disc. Observations collected at the European Southern Observatory, Paranal, Chile (ESO programmes 71.B-0617A, 73.B0074A, and GTO 71.B-0196).Tables 1-6 and Figs. 1-6 are available in electronic form at http://www.aanda.org

  4. Predicted correspondence between species abundances and dendrograms of niche similarities

    PubMed Central

    Sugihara, George; Bersier, Louis-Félix; Southwood, T. Richard E.; Pimm, Stuart L.; May, Robert M.

    2003-01-01

    We examine a hypothesized relationship between two descriptions of community structure: the niche-overlap dendrogram that describes the ecological similarities of species and the pattern of relative abundances. Specifically, we examine the way in which this relationship follows from the niche hierarchy model, whose fundamental assumption is a direct connection between abundances and underlying hierarchical community organization. We test three important, although correlated, predictions of the niche hierarchy model and show that they are upheld in a set of 11 communities (encompassing fishes, amphibians, lizards, and birds) where both abundances and dendrograms were reported. First, species that are highly nested in the dendrogram are on average less abundant than species from branches less subdivided. Second, and more significantly, more equitable community abundances are associated with more evenly branched dendrogram structures, whereas less equitable abundances are associated with less even dendrograms. This relationship shows that abundance patterns can give insight into less visible aspects of community organization. Third, one can recover the distribution of proportional abundances seen in assemblages containing two species by treating each branch point in the dendrogram as a two-species case. This reconstruction cannot be achieved if abundances and the dendrogram are unrelated and suggests a method for hierarchically decomposing systems. To our knowledge, this is the first test of a species abundance model based on nontrivial predictions as to the origins and causes of abundance patterns, and not simply on the goodness-of-fit of distributions. PMID:12702773

  5. Abundances in the Planetary Nebula IC 5217

    NASA Technical Reports Server (NTRS)

    Hyung, Siek; Aller, Lawrence H.; Feibelman, Walter A.; Lee, Woo-Baik; Fisher, Richard R. (Technical Monitor)

    2001-01-01

    High resolution optical wavelength spectroscopic data were secured in the optical wavelengths, 3700A - 10,050A, for the planetary nebula IC 5217 with the Hamilton Echelle Spectrograph at Lick Observatory. These optical spectra have been analyzed along with the near-UV and UV archive data. Diagnostic analyses indicate a nebular physical condition with electron temperature of about 10,700 K (from the [O III] lines) and the density of N(sub epsilon) = 5000/cm. Ionic concentrations have been derived with the representative diagnostics, and with the aid of a photoionization model construction, we derived the elemental abundances. Contrary to the previous studies found in the literature, He and C appear to be depleted compared to the average planetary nebula and to the Sun (and S marginally so), while the remaining elements appear to be close to the average value. IC 5217 may have evolved from an O-rich progenitor and the central star temperature of IC 5217 is likely to be 92,000 K.

  6. Late Embryogenesis Abundant (LEA) proteins in legumes.

    PubMed

    Battaglia, Marina; Covarrubias, Alejandra A

    2013-01-01

    Plants are exposed to different external conditions that affect growth, development, and productivity. Water deficit is one of these adverse conditions caused by drought, salinity, and extreme temperatures. Plants have developed different responses to prevent, ameliorate or repair the damage inflicted by these stressful environments. One of these responses is the activation of a set of genes encoding a group of hydrophilic proteins that typically accumulate to high levels during seed dehydration, at the last stage of embryogenesis, hence named Late Embryogenesis Abundant (LEA) proteins. LEA proteins also accumulate in response to water limitation in vegetative tissues, and have been classified in seven groups based on their amino acid sequence similarity and on the presence of distinctive conserved motifs. These proteins are widely distributed in the plant kingdom, from ferns to angiosperms, suggesting a relevant role in the plant response to this unfavorable environmental condition. In this review, we analyzed the LEA proteins from those legumes whose complete genomes have been sequenced such as Phaseolus vulgaris, Glycine max, Medicago truncatula, Lotus japonicus, Cajanus cajan, and Cicer arietinum. Considering their distinctive motifs, LEA proteins from the different groups were identified, and their sequence analysis allowed the recognition of novel legume specific motifs. Moreover, we compile their transcript accumulation patterns based on publicly available data. In spite of the limited information on these proteins in legumes, the analysis and data compiled here confirm the high correlation between their accumulation and water deficit, reinforcing their functional relevance under this detrimental conditions.

  7. High Abundance of Ions in Cosmic Ices

    NASA Technical Reports Server (NTRS)

    Gudipati, Murthy S.; Allamandola, Louis J.; Fonda, Mark (Technical Monitor)

    2002-01-01

    Water-rich, mixed molecular ices and polycyclic aromatic hydrocarbons (PAHs) are common throughout interstellar molecular clouds and the Solar System. Vacuum ultraviolet (VUV) irradiation and particle bombardment of these abiotic ices produces complex organic species, including important biogenic molecules such as amino acids and functionalized PAHs which may have played a role in the origin of life. This ability of such water-rich, oxygen dominated ices to promote production of complex organic species is surprising and points to an important, unusual, but previously overlooked mechanism at play within the ice. Here we report the nature of this mechanism using electronic spectroscopy. VUV-irradiation of PAH/H2O ices leads to an unprecedented and efficient (greater than 70 %) conversion of the neutral PAHs to their cation form (PAH+). Further, these H2O/PAH+ ices are stabile at temperatures below 50 K, a temperature domain common throughout interstellar clouds and the Solar System. Between 50 and 125 K they react to form the complex organics. In view of this, we conclude that charged PAHs and other molecular ions should be common and abundant in many cosmic ices. The chemical, spectroscopic and physical properties of these ion-rich ices can be of fundamental importance for objects as diverse as comets, planets, and molecular clouds and may account for several poorly understood phenomena associated with each of these object classes.

  8. Detailed abundances in EMP dwarfs from SDSS

    NASA Astrophysics Data System (ADS)

    Sbordone, Luca; Caffau, Elisabetta; Bonifacio, Piercarlo

    2012-09-01

    We report on the current status of an ongoing survey to select extremely metal poor (EMP) turn-off (TO) stars from Sloan Digital Sky Survey (SDSS) spectra, and determine their detailed chemical composition through high resolution follow-up. So far, 26 stars have been observed with UVESatVLT and X-SHOOTERatVLT, all but two showing an iron content below [Fe/H]=-3. Among them we detected the current record holder for the lowest total metallicity (SDSS J102915+172927, Z=10-5 Zsolar), four carbon-enhanced extremely metal poor objects (CEMP), as well as subsets with enhanced Ni and Mn. Lithium abundances or upper limits were derived, confirming the previously detected ``meltdown'' of the Spite plateau for metallicities below about [Fe/H]=-2.8. SDSS J102915+172927 in particular shows no detectable Li I 670.8 doublet, leading to an upper limit of A(Li)<1.1, hinting to an even deeper Li depletion in TO stars below [Fe/H]=-4. Spectroscopic follow-up is currently being prosecuted by the recently started ESO large program TOPoS, aiming to observe about 80 more EMP candidates.

  9. Beryllium abundances in Hg-Mn stars

    SciTech Connect

    Boesgaard, A.M.; Heacox, W.D.; Wolff, S.C.; Borsenberger, J.; Praderie, F.

    1982-08-15

    The Hg-Mn stars show anomalous line strengths of many chemical elements including Be. We have observed the Be ii resonance doublet at lambdalambda 3130, 3131 at 6.7 A mm/sup -1/ in 43 Hg-Mn stars and 10 normal stars in the same temperature range with the coude spectrograph of the 2.24 m University of Hawaii telescope at Mauna Kea. Measured equivalent widths of the two lines and/or the blend of the doublet have been compared with predictions from (1) LTE model atmospheres and (2) non-LTE line formation on non-LTE model atmospheres. (For strong Be ii lines, the LTE calculations result in more Be by factors of 2 to 4 than do the non-LTE calculations.) Overabundances of factors of 20--2 x 10/sup 4/ relative to solar have been found for 75% of the Hg-Mn stars. The 25% with little or no Be are typically among the cooler Hg-Mn stars, but for the stars with Be excesses, there is only marginal evidence for a correlationi of the size of the overabundance and temperature. It is suggested that diffusion driven by radiation pressure is responsible for the observed Be abundance anomalies.

  10. Late Embryogenesis Abundant (LEA) proteins in legumes

    PubMed Central

    Battaglia, Marina; Covarrubias, Alejandra A.

    2013-01-01

    Plants are exposed to different external conditions that affect growth, development, and productivity. Water deficit is one of these adverse conditions caused by drought, salinity, and extreme temperatures. Plants have developed different responses to prevent, ameliorate or repair the damage inflicted by these stressful environments. One of these responses is the activation of a set of genes encoding a group of hydrophilic proteins that typically accumulate to high levels during seed dehydration, at the last stage of embryogenesis, hence named Late Embryogenesis Abundant (LEA) proteins. LEA proteins also accumulate in response to water limitation in vegetative tissues, and have been classified in seven groups based on their amino acid sequence similarity and on the presence of distinctive conserved motifs. These proteins are widely distributed in the plant kingdom, from ferns to angiosperms, suggesting a relevant role in the plant response to this unfavorable environmental condition. In this review, we analyzed the LEA proteins from those legumes whose complete genomes have been sequenced such as Phaseolus vulgaris, Glycine max, Medicago truncatula, Lotus japonicus, Cajanus cajan, and Cicer arietinum. Considering their distinctive motifs, LEA proteins from the different groups were identified, and their sequence analysis allowed the recognition of novel legume specific motifs. Moreover, we compile their transcript accumulation patterns based on publicly available data. In spite of the limited information on these proteins in legumes, the analysis and data compiled here confirm the high correlation between their accumulation and water deficit, reinforcing their functional relevance under this detrimental conditions. PMID:23805145

  11. Proteomics characterization of abundant Golgi membrane proteins.

    PubMed

    Bell, A W; Ward, M A; Blackstock, W P; Freeman, H N; Choudhary, J S; Lewis, A P; Chotai, D; Fazel, A; Gushue, J N; Paiement, J; Palcy, S; Chevet, E; Lafrenière-Roula, M; Solari, R; Thomas, D Y; Rowley, A; Bergeron, J J

    2001-02-16

    A mass spectrometric analysis of proteins partitioning into Triton X-114 from purified hepatic Golgi apparatus (84% purity by morphometry, 122-fold enrichment over the homogenate for the Golgi marker galactosyl transferase) led to the unambiguous identification of 81 proteins including a novel Golgi-associated protein of 34 kDa (GPP34). The membrane protein complement was resolved by SDS-polyacrylamide gel electrophoresis and subjected to a hierarchical approach using delayed extraction matrix-assisted laser desorption ionization mass spectrometry characterization by peptide mass fingerprinting, tandem mass spectrometry to generate sequence tags, and Edman sequencing of proteins. Major membrane proteins corresponded to known Golgi residents, a Golgi lectin, anterograde cargo, and an abundance of trafficking proteins including KDEL receptors, p24 family members, SNAREs, Rabs, a single ARF-guanine nucleotide exchange factor, and two SCAMPs. Analytical fractionation and gold immunolabeling of proteins in the purified Golgi fraction were used to assess the intra-Golgi and total cellular distribution of GPP34, two SNAREs, SCAMPs, and the trafficking proteins GBF1, BAP31, and alpha(2)P24 identified by the proteomics approach as well as the endoplasmic reticulum contaminant calnexin. Although GPP34 has never previously been identified as a protein, the localization of GPP34 to the Golgi complex, the conservation of GPP34 from yeast to humans, and the cytosolically exposed location of GPP34 predict a role for a novel coat protein in Golgi trafficking.

  12. Chloroflexi bacteria are more diverse, abundant, and similar in high than in low microbial abundance sponges.

    PubMed

    Schmitt, Susanne; Deines, Peter; Behnam, Faris; Wagner, Michael; Taylor, Michael W

    2011-12-01

    Some marine sponges harbor dense and phylogenetically complex microbial communities [high microbial abundance (HMA) sponges] whereas others contain only few and less diverse microorganisms [low microbial abundance (LMA) sponges]. We focused on the phylum Chloroflexi that frequently occurs in sponges to investigate the different associations with three HMA and three LMA sponges from New Zealand. By applying a range of microscopical and molecular techniques a clear dichotomy between HMA and LMA sponges was observed: Chloroflexi bacteria were more abundant and diverse in HMA than in LMA sponges. Moreover, different HMA sponges contain similar Chloroflexi communities whereas LMA sponges harbor different and more variable communities which partly resemble Chloroflexi seawater communities. A comprehensive phylogenetic analysis of our own and publicly available sponge-derived Chloroflexi 16S rRNA gene sequences (> 780 sequences) revealed the enormous diversity of this phylum within sponges including 29 sponge-specific and sponge-coral clusters (SSC/SCC) as well as a 'supercluster' consisting of > 250 sponge-derived and a single nonsponge-derived 16S rRNA gene sequence. Interestingly, the majority of sequences obtained from HMA sponges, but only a few from LMA sponges, fell into SSC/SCC clusters. This indicates a much more specific association of Chloroflexi bacteria with HMA sponges and suggests an ecologically important role for these prominent bacteria.

  13. The Open Cluster Chemical Abundances and Mapping (OCCAM) Survey: Galactic Neutron Capture Abundance Gradients

    NASA Astrophysics Data System (ADS)

    O'Connell, Julia; Frinchaboy, Peter M.; Shetrone, Matthew D.; Melendez, Matthew; Cunha, Katia M. L.; Majewski, Steven R.; Zasowski, Gail; APOGEE Team

    2017-01-01

    The evolution of elements, as a function or age, throughout the Milky Way disk provides a key constraint for galaxy evolution models. In an effort to provide these constraints, we have conducted an investigation into the r- and s- process elemental abundances for a large sample of open clusters as part of an optical follow-up to the SDSS-III/APOGEE-1 survey. Stars were identified as cluster members by the Open Cluster Chemical Abundance & Mapping (OCCAM) survey, which culls member candidates by radial velocity, metallicity, and proper motion from the observed APOGEE sample. To obtain data for neutron capture elements in these clusters, we conducted a long-term observing campaign covering three years (2013-2016) using the McDonald Observatory Otto Struve 2.1-m telescope and Sandiford Cass Echelle Spectrograph (R ~ 60,000). We present Galactic neutron-capture abundance gradients using 30+ clusters, within 6 kpc of the Sun, covering a range of ages from ~80 Myr to ~10 Gyr .

  14. Spatial and temporal abundance patterns of oceanic chaetognaths in the western North Atlantic—I. Hydrographic and seasonal abundance patterns

    NASA Astrophysics Data System (ADS)

    Cheney, Jerry

    1985-09-01

    Chaetognath abundance was measured from 38 MOCNESS tows collected in the western North Atlantic from August 1975 to November 1977. Twenty-one species were identified from 18 slope water (SW), 18 northern Sargasso Sea (NSS) and two Gulf Stream (GS) tows. Sagitta elegans, S. hispida and S. megalophthalma were collected in only one or two tows. Eukrohnia bathypelagica, E. fowleri, E. hamata, Sagitta helenae, S. macrocephala, S. maxima and S. tasmanica are significantly more abundant in the SW than in the NSS. Krohnitta subtilis, Pterosagitta draco, Sagitta bipunctata, S. decipiens, S. hexaptera, S. lyra, S. minima, S. planctonis and S. serratodentata are significantly more abundant in the NSS. Krohnitta pacifica and Sagitta enflata show no significant abundance differences between the SW and NSS. Most species show at least an order of magnitude abundance difference between the SW and NSS, with intermediate GS abundances. A simple mixing model and previous reports of chaetognath distributions in the North Atlantic indicate that most species have expatriate populations in either the SW or NSS or in both regions. Increased temperature and food abundance probably limit SW species from the NSS, while decreased temperature and increased predator abundance probably limit NSS species from the SW. Spring abundance peaks were observed for many species in the NSS, but no seasonal peaks were detected for species in the SW. The spring abundance peaks in the NSS are probably due to increased food abundance, although temperature could not be ruled out as an important factor.

  15. Abundance models improve spatial and temporal prioritization of conservation resources.

    PubMed

    Johnston, Alison; Fink, Daniel; Reynolds, Mark D; Hochachka, Wesley M; Sullivan, Brian L; Bruns, Nicholas E; Hallstein, Eric; Merrifield, Matt S; Matsumoto, Sandi; Kelling, Steve

    2015-10-01

    Conservation prioritization requires knowledge about organism distribution and density. This information is often inferred from models that estimate the probability of species occurrence rather than from models that estimate species abundance, because abundance data are harder to obtain and model. However, occurrence and abundance may not display similar patterns and therefore development of robust, scalable, abundance models is critical to ensuring that scarce conservation resources are applied where they can have the greatest benefits. Motivated by a dynamic land conservation program, we develop and assess a general method for modeling relative abundance using citizen science monitoring data. Weekly estimates of relative abundance and occurrence were compared for prioritizing times and locations of conservation actions for migratory waterbird species in California, USA. We found that abundance estimates consistently provided better rankings of observed counts than occurrence estimates. Additionally, the relationship between abundance and occurrence was nonlinear and varied by species and season. Across species, locations prioritized by occurrence models had only 10-58% overlap with locations prioritized by abundance models, highlighting that occurrence models will not typically identify the locations of highest abundance that are vital for conservation of populations.

  16. The Origin of Element Abundance Variations in Solar Energetic Particles

    NASA Astrophysics Data System (ADS)

    Reames, Donald V.

    2016-08-01

    Abundance enhancements, during acceleration and transport in both gradual and impulsive solar energetic particle (SEP) events, vary approximately as power laws in the mass-to-charge ratio [A/Q] of the ions. Since the Q-values depend upon the electron temperature of the source plasma, this has allowed a determination of this temperature from the pattern of element-abundance enhancements and a verification of the expected inverse-time dependence of the power of A/Q for diffusive transport of ions from the SEP events, with scattering mean free paths found to be between 0.2 and 1 AU. SEP events derived from plasma of different temperatures map into different regions in typical cross-plots of abundances, spreading the distributions. In comparisons of SEP events with temperatures above 2 MK, impulsive events show much broader non-thermal variation of abundances than do gradual events. The extensive shock waves accelerating ions in gradual events may average over much of an active region where numerous but smaller magnetic reconnections, "nanojets", produce suprathermal seed ions, thus averaging over varying abundances, while an impulsive SEP event only samples one local region of abundance variations. Evidence for a reference He/O-abundance ratio of 91, rather than 57, is also found for the hotter plasma. However, while this is similar to the solar-wind abundance of He/O, the solar-wind abundances otherwise provide an unacceptably poor reference for the SEP-abundance enhancements, generating extremely large errors.

  17. Differential expression and regulation of vitamin D hydroxylases and inflammatory genes in prostate stroma and epithelium by 1,25-dihydroxyvitamin D in men with prostate cancer and an in vitro model.

    PubMed

    Giangreco, Angeline A; Dambal, Shweta; Wagner, Dennis; Van der Kwast, Theodorus; Vieth, Reinhold; Prins, Gail S; Nonn, Larisa

    2015-04-01

    Previous work on vitamin D in the prostate has focused on the prostatic epithelium, from which prostate cancer arises. Prostatic epithelial cells are surrounded by stroma, which has well-established regulatory control over epithelial proliferation, differentiation, and the inflammatory response. Here we examined the regulation of vitamin D-related genes and inflammatory genes by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D) in laser-capture microdissected prostate tissue from a vitamin D3 clinical trial and in an in vitro model that facilitates stromal-epithelial crosstalk. Analysis of the trial tissues showed that VDR was present in both cell types, whereas expression of the hydroxylases was the highest in the epithelium. Examination of gene expression by prostatic (1,25(OH)2D) concentrations showed that VDR was significantly lower in prostate tissues with the highest concentration of 1,25(OH)2D, and down-regulation of VDR by 1,25(OH) 2D was confirmed in the primary cell cultures. Analysis of inflammatory genes in the patient tissues revealed that IL-6 expression was the highest in the prostate stroma while PTGS2 (COX2) levels were lowest in the prostate cancer tissues from men in the highest tertile of prostatic 1,25(OH)2D. In vitro, TNF-α, IL-6 and IL-8 were suppressed by 1,25 (OH)2D in the primary epithelial cells, whereas TNF-α and PTGS2 were suppressed by 1,25(OH) 2D in the stromal cells. Importantly, the ability of 1,25(OH)2D to alter pro-inflammatory-induced changes in epithelial cell growth were dependent on the presence of the stromal cells. In summary, whereas both stromal and epithelial cells of the prostate express VDR and can presumably respond to 1,25(OH)2D, the prostatic epithelium appears to be the main producer of 1,25(OH)2D. Further, while the prostate epithelium was more responsive to the anti-inflammatory activity of 1,25 (OH)2D than stromal cells, stroma-epithelial crosstalk enhanced the phenotypic effects of 1,25(OH)2D and the inflammatory

  18. Abundances, planetary nebulae, and stellar evolution

    NASA Astrophysics Data System (ADS)

    Aller, Lawrence H.

    1994-09-01

    Among Henry Norris Russell's many achievements were his contributions to solar and stellar spectroscopy, in particular, to an analysis of the chemical composition of the solar atmosphere. The question of composition differences between stars was hotly debated; some distinguished astronomers argued that all stars had the solar composition. Some early challenges to this doctrine are described. Determinations of chemical compositions of gaseous nebulae were much more difficult. If we observe the lines of a given chemical element in one ionization stage in a stellar spectrum, we can deduce readily the abundance of that element. No such luxury is available for a planetary or diffuse gaseous nebula. We must measure lines of as many ionization stages as we can. Furthermore, a nebula is an extended object. Often detailed spectroscopy is at hand only for narrow pencil columns taken through the image. Different observers use a variety of apertures. Fortunately it is possible to calculate theoretical spectra for any arbitrary cross section taken through a symmetrical model, so UV, optical, and IR observations all can be compared properly with a prediction. The value of high-resolution spectra obtained with instruments such as the Hamilton Echelle Spectrograph at Lick Observatory is emphasized. Improved fluxes for weak but important transitions are found. Close blends of lines of different ions can be resolved, and checks can be made on predictions of atomic parameters such as Einstein A-values and collision strengths. High spectral resolution data have been obtained and reduced for 22 planetary nebulae of varying size, structure, stellar population membership, dustiness, level of excitation, evolutionary status, and chemical compositions. The promise seems justified that with such extensive, high quality data, additional insights on nebular genesis and late states of stellar evolution can be found. The present survey is confined to nebulae of high surface brightness, but

  19. Comparing halo bias from abundance and clustering

    NASA Astrophysics Data System (ADS)

    Hoffmann, K.; Bel, J.; Gaztañaga, E.

    2015-06-01

    We model the abundance of haloes in the ˜(3 Gpc h-1)3 volume of the MICE Grand Challenge simulation by fitting the universal mass function with an improved Jackknife error covariance estimator that matches theory predictions. We present unifying relations between different fitting models and new predictions for linear (b1) and non-linear (c2 and c3) halo clustering bias. Different mass function fits show strong variations in their performance when including the low mass range (Mh ≲ 3 × 1012 M⊙ h-1) in the analysis. Together with fits from the literature, we find an overall variation in the amplitudes of around 10 per cent in the low mass and up to 50 per cent in the high mass (galaxy cluster) range (Mh > 1014 M⊙ h-1). These variations propagate into a 10 per cent change in b1 predictions and a 50 per cent change in c2 or c3. Despite these strong variations, we find universal relations between b1 and c2 or c3 for which we provide simple fits. Excluding low-mass haloes, different models fitted with reasonable goodness in this analysis, show per cent level agreement in their b1 predictions, but are systematically 5-10 per cent lower than the bias directly measured with two-point halo-mass clustering. This result confirms previous findings derived from smaller volumes (and smaller masses). Inaccuracies in the bias predictions lead to 5-10 per cent errors in growth measurements. They also affect any halo occupation distribution fitting or (cluster) mass calibration from clustering measurements.

  20. Abundances, planetary nebulae, and stellar evolution

    NASA Technical Reports Server (NTRS)

    Aller, Lawrence H.

    1994-01-01

    Among Henry Norris Russell's many achievements were his contributions to solar and stellar spectroscopy, in particular, to an analysis of the chemical composition of the solar atmosphere. The question of composition differences between stars was hotly debated; some distinguished astronomers argued that all stars had the solar composition. Some early challenges to this doctrine are described. Determinations of chemical compositions of gaseous nebulae were much more difficult. If we observe the lines of a given chemical element in one ionization stage in a stellar spectrum, we can deduce readily the abundance of that element. No such luxury is available for a planetary or diffuse gaseous nebula. We must measure lines of as many ionization stages as we can. Furthermore, a nebula is an extended object. Often detailed spectroscopy is at hand only for narrow pencil columns taken through the image. Different observers use a variety of apertures. Fortunately it is possible to calculate theoretical spectra for any arbitrary cross section taken through a symmetrical model, so UV, optical, and IR observations all can be compared properly with a prediction. The value of high-resolution spectra obtained with instruments such as the Hamilton Echelle Spectrograph at Lick Observatory is emphasized. Improved fluxes for weak but important transitions are found. Close blends of lines of different ions can be resolved, and checks can be made on predictions of atomic parameters such as Einstein A-values and collision strengths. High spectral resolution data have been obtained and reduced for 22 planetary nebulae of varying size, structure, stellar population membership, dustiness, level of excitation, evolutionary status, and chemical compositions. The promise seems justified that with such extensive, high quality data, additional insights on nebular genesis and late states of stellar evolution can be found. The present survey is confined to nebulae of high surface brightness, but

  1. On the sodium abundance in cometary meteoroids

    NASA Astrophysics Data System (ADS)

    Trigo-Rodriguez, J. M.; Llorca, J.

    We have obtained the chemical abundances of Na, Mg, Ca, Ti, Cr, Mn, Fe, Co and Ni relative to Si for thirteen fireballs, most of them produced by cometary meteoroids. We used a model developed by Borovicka (1993) to determine realistic physical parameters in the meteor column and the relative chemical abundances along the fireball path (Trigo-Rodriguez et al., 2003). Although most of the relative elemental chemical abundances in meteoroids fit well with chondritic values, we have noted that sodium is overabundant in meteor columns (Trigo-Rodriguez et al., 2004). This overabundance is accompanied by other interesting patterns: (i) The spectral lines associated with multiplet 1 of Na I usually appear before the lines of other elements. This could be related to some volatile phase that is easily removed from the meteoroid in the first steps of ablation. Different reservoirs of easily-removable Na may be present in cometary meteoroids, such as organics or phyllosilicates (Trigo-Rodriguez et al., 2004); (ii) The intensity of the Na I lines increases in bright flares associated with the process of fragmentation of the incoming meteoroid. If the structure of cometary meteoroids is similar to the dustball model invoked by Hawkes & Jones (1975), Na could be present as a mineral phase "gluing" mineral grains and, in consequence, it would be released easily during fragmentation events. Although Na is practically omnipresent in cometary meteor spectra, Na-bearing phases are rare in aggregate and cluster Interplanetary Dust Particles (IDPs) and usually the Na/Si ratio is clearly below the chondritic value (Rietmeijer, 2002). Our analysis, however, shows that sodium is overabundant in cometary meteoroids (Trigo-Rodriguez et al., 2004). One possibility, as proposed by Rietmeijer (1999), is that the accepted cosmic ratio of Na/Si is not accurate, being two times the currently accepted value. In any case, our idea is that an important part of the sodium present in meteoroids is

  2. Abiotic mediation of a mutualism drives herbivore abundance.

    PubMed

    Mooney, Emily H; Phillips, Joseph S; Tillberg, Chadwick V; Sandrow, Cheryl; Nelson, Annika S; Mooney, Kailen A

    2016-01-01

    Species abundance is typically determined by the abiotic environment, but the extent to which such effects occur through the mediation of biotic interactions, including mutualisms, is unknown. We explored how light environment (open meadow vs. shaded understory) mediates the abundance and ant tending of the aphid Aphis helianthi feeding on the herb Ligusticum porteri. Yearly surveys consistently found aphids to be more than 17-fold more abundant on open meadow plants than on shaded understory plants. Manipulations demonstrated that this abundance pattern was not due to the direct effects of light environment on aphid performance, or indirectly through host plant quality or the effects of predators. Instead, open meadows had higher ant abundance and per capita rates of aphid tending and, accordingly, ants increased aphid population growth in meadow but not understory environments. The abiotic environment thus drives the abundance of this herbivore exclusively through the mediation of a protection mutualism.

  3. 3D model atmospheres and the solar photospheric oxygen abundance

    NASA Astrophysics Data System (ADS)

    Caffau, E.; Ludwig, H.-G.

    2008-10-01

    In recent years the photospheric solar oxygen abundance experienced a significant downward revision. However, a low photospheric abundance is incompatible with the value in the solar interior inferred from helioseismology. For contributing to the dispute whether the solar oxygen abundance is “high” or “low”, we re-derived its photospheric abundance independently of previous analyses. We applied 3D (CO5BOLD) as well as 1D model atmospheres. We considered standard disc-centre and disc-integrated spectral atlases, as well as newly acquired solar intensity spectra at different heliocentric angles. We determined the oxygen abundances from equivalent width and/or line profile fitting of a number of atomic lines. As preliminary result, we find an oxygen abundance in the range 8.73 8.79, encompassing the value obtained by Holweger (2001), and somewhat higher than the value obtained by Asplund et al. (2005).

  4. Light-element abundances in 20 F and G dwarfs

    NASA Astrophysics Data System (ADS)

    Tomkin, J.; Lambert, D. L.; Balachandran, S.

    1985-03-01

    Red and near-IR spectral lines of the Galaxy are analyzed to extract Na, Mg, Al, Si and Ca abundances. The data were obtained using a 2.7 m telescope fitted with a coudespectrograph and a Reticon photodiode array tuned to the 6160, 6350, 6570, 6696, 7860 and 8740 wavelengths of 20 F and G dwarfs in the disk and halo. The abundances were then compared to recorded Fe abundances, particularly the forbidden Fe/H ratio. Even numbered atomic number elemental abundances followed the ratio down to values of -0.4, then increased relative to Fe in the transition from disk to halo. The abundances of odd-numbered elements more closely tracked the abundance of Mg in the disk, and experienced a fairly abrupt decrease in the disk-halo transition.

  5. Heavy Element Abundances in NGC 5846

    NASA Technical Reports Server (NTRS)

    Jones, Christine

    2000-01-01

    In this paper we analyze the diffuse X-ray coronae surrounding the elliptical galaxy NGC 5846, combining measurements from two observatories, ROSAT and the Advanced Satellite for Cosmology and Astrophysics. We map the gas temperature distribution and find a central cool region within an approximately isothermal gas halo extending to a radius of about 50 kpc and evidence for a temperature decrease at larger radii. With a radially falling temperature profile, the total mass converges to (9.6 +/- 1.0) x 10(exp 12) solar mass at 230 kpc radius. This corresponds to a total mass to blue light ratio of 53 +/- 5 solar mass/solar luminosity. As in other early type galaxies, the gas mass is only a few percent of the total mass. Using the spectroscopic measurements, we also derive radial distributions for the heavy elements silicon and iron and find that the abundances of both decrease with galaxy radius. The mass ratio of Si to Fe lies between the theoretical predictions for element production in SN Ia and SN II, suggesting an important role for SN Ia, as well as SN II, for gas enrichment in ellipticals. Using the 2 SN la yield of Si, we set an upper limit of 0.012 h(sup 2, sub 50) solar neutrino units (SNU) for the SN Ia rate at radii >50 kpc, which is independent of possible uncertainties in the iron L-shell modeling. We compare our observations with the theoretical predictions for the chemical evolution of ellipticals. We conclude that the metal content in stars, if explained by the star formation duration, requires a significant decline in the duration of star formation with galaxy radius, ranging from 1 Gyr at the center to 0.01 Gyr at 100 kpc radius. Alternatively, the decline in metallicity with galaxy radius may be caused by a similar drop with radius in the efficiency of star formation. Based on the Si and Fe measurements presented in this paper, we conclude that the latter scenario is preferred unless a dependence of the SN Ia rate on stellar metallicity is invoked.

  6. Origin of Stellar Abundances in the early Galaxy

    SciTech Connect

    Montes, F.; Beers, T. C.; Cowan, J.; Elliot, T.; Schatz, H.; Farouqi, K.; Gallino, R.; Heil, M.; Kratz, K.-L.; Pfeiffer, B.; Pignatari, M.

    2007-10-26

    Observations of metal-poor stars in the last decade have revealed an abundance pattern that have recently been explained as the result of two nucleosynthesis processes, a strong r-process that creates most of the Z{>=}56 and some 38{<=}Z{<=}47 abundances and a light element primary process (LEPP) responsible for creating the remaining 38{<=}Z{<=}47 abundances and some small contribution to heavier elements. We review some of the current literature on the LEPP and show a derived abundance pattern as a function of mass number.

  7. Abundance of birds in Fukushima as judged from Chernobyl.

    PubMed

    Møller, Anders Pape; Hagiwara, Atsushi; Matsui, Shin; Kasahara, Satoe; Kawatsu, Kencho; Nishiumi, Isao; Suzuki, Hiroyuki; Ueda, Keisuke; Mousseau, Timothy A

    2012-05-01

    The effects of radiation on abundance of common birds in Fukushima can be assessed from the effects of radiation in Chernobyl. Abundance of birds was negatively related to radiation, with a significant difference between Fukushima and Chernobyl. Analysis of 14 species common to the two areas revealed a negative effect of radiation on abundance, differing between areas and species. The relationship between abundance and radiation was more strongly negative in Fukushima than in Chernobyl for the same 14 species, demonstrating a negative consequence of radiation for birds immediately after the accident on 11 March 2011 during the main breeding season in March-July, when individuals work close to their maximum sustainable level.

  8. Digestion and depletion of abundant proteins improves proteomic coverage

    PubMed Central

    Fonslow, Bryan R.; Stein, Benjamin D.; Webb, Kristofor J.; Xu, Tao; Choi, Jeong; Park, Sung Kyu; Yates, John R.

    2012-01-01

    Two major challenges in proteomics are the large number of proteins and their broad dynamic range within the cell. We exploited the abundance-dependent Michaelis-Menten kinetics of trypsin digestion to selectively digest and deplete abundant proteins with a method we call DigDeAPr. We validated the depletion mechanism with known yeast protein abundances and observed greater than 3-fold improvement in low abundance human protein identification and quantitation metrics. This methodology should be broadly applicable to many organisms, proteases, and proteomic pipelines. PMID:23160281

  9. Prognostic value of the International Neuroblastoma Pathology Classification in Neuroblastoma (Schwannian stroma-poor) and comparison with other prognostic factors: a study of 182 cases from the Spanish Neuroblastoma Registry.

    PubMed

    Burgues, Octavio; Navarro, Samuel; Noguera, Rosa; Pellín, Antonio; Ruiz, Amparo; Castel, Victoria; Llombart-Bosch, Antonio

    2006-10-01

    In addition to clinical and biological factors, further valuable prognostic information in neuroblastoma (Schwannian stroma-poor) (NB) patients is provided by the histopathologic analysis and the application of the International Neuroblastoma Pathology Classification (INPC) system. The objective of this study was to assess the prognostic impact of the INPC classification in a series of NB (Schwannian stroma-poor) and its relation with other prognostic factors. One hundred eighty-two cases of NB were collected from the files of the Spanish Neuroblastoma Registry. Slides were reviewed, and NB cases were grouped into favorable and unfavorable categories according to INPC criteria, taking into account morphological features (mitosis-karyorrhexis index, histological subtype) and patient's age at diagnosis. Other pathological [presence of calcifications, tissular components, and number of mitotic cells per 10 high-power field (HPF)], immunohistochemical (P-glycoprotein and Ki-67 protein expression) and genetic (MYCN amplification and chromosome 1p deletion) features were also studied. Statistical analyses of overall survival with Kaplan-Meier curves and a multivariate study using Cox regression were performed (40.3% of NBs were considered favorable and 59.7% unfavorable). Unfavorable NB showed a mean survival time of 57 months compared with 89 months in favorable cases. Advanced stage, more than ten mitoses per 10 HPF, Ki-67 expression in more than 30% of tumor cells, MYCN oncogene amplification and chromosome 1p deletion were observed more frequently in unfavorable NB. The Cox regression analysis demonstrated that clinical stage (International Neuroblastoma Staging System stage 4) and histological subtype (undifferentiated NB) were the most important factors that influence the overall survival (p<0.001). INPC classification results are major prognostic indicators in NB and should be considered in the therapeutic stratification of NB patients.

  10. [Myxoid liposarcoma of the lumbosacral spine. Clinical case report].

    PubMed

    Granados-López, Sandy Lucero; Tavares-García, Juana Sonia; Pérez-Contreras, Alberto

    2013-01-01

    Introducción: el liposarcoma es un tumor maligno de tejidos blandos que constituye el grupo más numeroso de sarcomas en el adulto. La variante mixoide representa 30 a 35 % de todos los liposarcomas. Comúnmente se observa en los muslos. En la literatura se han informado solo dos pacientes con liposarcoma en la columna vertebral. Caso clínico: mujer de 28 años de edad con síntomas de compresión medular (marcha claudicante, fuerza en la extremidad derecha 4/5, disminución de la sensibilidad). La imagen por resonancia magnética confirmó una masa paravertebral derecha que se extendía desde L4 hasta S2, multinodular, sólido quística, que seguía el trayecto de los forámenes de conjunción de S1 y S2 hacia el espacio presacro, con señales hipointensas en T1 e hiperintensas en T2. Con los estudios radiológicos se concluyó que presentaba un neurofibroma. Se realizó resección extra e intrarraquídea, de la que se extrajo un tumor. El estudio histopatológico definitivo indicó que se trataba de un liposarcoma mixoide. Conclusiones: la columna vertebral es una localización poco frecuente para esta neoplasia, así como para sus metástasis. Es difícil lograr una resección completa en este sitio, por lo que la tasa de recurrencia es alta.

  11. Mediastinal Myxoid Liposarcoma with Intrapericardial Involvement and Large Pericardial Effusion.

    PubMed

    Endara, Santiago Adolfo; Davalos, Gerardo Augusto; Vinueza, Ana Lucia; Montalvo, Nelson; Duran, Patricia Graciela; Barzallo, David Esteban

    2015-10-28

    Liposarcoma is the name given to a group of soft tissue sarcomas (STSs) with adipocytic differentiation. As a group, liposarcomas are the second most common STSs in adults. In 1951 Kozonis et al published that in the English language only four cases of liposarcomas originating in the mediastinum had been described. Primary mediastinal liposarcoma is an uncommon neoplasm of intrathoracic origin. We present the case of a 47-year-old woman diagnosed with a large mediastinal mass with intrapericardial invasion and massive pericardial effusion; biopsies showed a mediastinal liposarcoma.

  12. Stellar oxygen abundances. I - A resolution to the 7774 A O I abundance discrepancy

    NASA Astrophysics Data System (ADS)

    King, Jeremy R.

    1993-09-01

    We investigate the discrepancy between O/Fe abundance ratios of metal-poor stars derived from the 7774 A O I triplet and O/Fe ratios determined from other oxygen lines. We propose a possible resolution to this discrepancy which also eliminates the correlation of O/Fe and T(eff) found in a recent 7774 A O I analysis. The equivalent widths of Abia & Rebolo (1989) are found to be systematically too high by 25 percent. Arguments are presented that current temperature estimates for halo stars are 150-200 K too low. Using the guidance of both model atmospheres and other empirical color-T(eff) relations, we construct new color temperature relations for metal-poor stars. These relations are tied to the temperature scale of Saxner & Hammarback (1985) for metal-rich stars. We use (b-y) and (V-K) indices to redetermine values of T(eff) for a handful of halo stars. (B-V)-T(eff) relations which do not take into account the effects of metallicity are found to be inadequate. Revised O/Fe ratios are determined using the new temperature scale. The mean abundance ratio of the reanalyzed halo dwarfs is about +0.52. There is no trend of O/Fe with Fe/H or T(eff).

  13. Herbivore regulation of plant abundance in aquatic ecosystems.

    PubMed

    Wood, Kevin A; O'Hare, Matthew T; McDonald, Claire; Searle, Kate R; Daunt, Francis; Stillman, Richard A

    2017-05-01

    Herbivory is a fundamental process that controls primary producer abundance and regulates energy and nutrient flows to higher trophic levels. Despite the recent proliferation of small-scale studies on herbivore effects on aquatic plants, there remains limited understanding of the factors that control consumer regulation of vascular plants in aquatic ecosystems. Our current knowledge of the regulation of primary producers has hindered efforts to understand the structure and functioning of aquatic ecosystems, and to manage such ecosystems effectively. We conducted a global meta-analysis of the outcomes of plant-herbivore interactions using a data set comprised of 326 values from 163 studies, in order to test two mechanistic hypotheses: first, that greater negative changes in plant abundance would be associated with higher herbivore biomass densities; second, that the magnitude of changes in plant abundance would vary with herbivore taxonomic identity. We found evidence that plant abundance declined with increased herbivore density, with plants eliminated at high densities. Significant between-taxa differences in impact were detected, with insects associated with smaller reductions in plant abundance than all other taxa. Similarly, birds caused smaller reductions in plant abundance than echinoderms, fish, or molluscs. Furthermore, larger reductions in plant abundance were detected for fish relative to crustaceans. We found a positive relationship between herbivore species richness and change in plant abundance, with the strongest reductions in plant abundance reported for low herbivore species richness, suggesting that greater herbivore diversity may protect against large reductions in plant abundance. Finally, we found that herbivore-plant nativeness was a key factor affecting the magnitude of herbivore impacts on plant abundance across a wide range of species assemblages. Assemblages comprised of invasive herbivores and native plant assemblages were associated with

  14. Climatic effects on mosquito abundance in Mediterranean wetlands

    PubMed Central

    2014-01-01

    Background The impact of climate change on vector-borne diseases is highly controversial. One of the principal points of debate is whether or not climate influences mosquito abundance, a key factor in disease transmission. Methods To test this hypothesis, we analysed ten years of data (2003–2012) from biweekly surveys to assess inter-annual and seasonal relationships between the abundance of seven mosquito species known to be pathogen vectors (West Nile virus, Usutu virus, dirofilariasis and Plasmodium sp.) and several climatic variables in two wetlands in SW Spain. Results Within-season abundance patterns were related to climatic variables (i.e. temperature, rainfall, tide heights, relative humidity and photoperiod) that varied according to the mosquito species in question. Rainfall during winter months was positively related to Culex pipiens and Ochlerotatus detritus annual abundances. Annual maximum temperatures were non-linearly related to annual Cx. pipiens abundance, while annual mean temperatures were positively related to annual Ochlerotatus caspius abundance. Finally, we modelled shifts in mosquito abundances using the A2 and B2 temperature and rainfall climate change scenarios for the period 2011–2100. While Oc. caspius, an important anthropophilic species, may increase in abundance, no changes are expected for Cx. pipiens or the salt-marsh mosquito Oc. detritus. Conclusions Our results highlight that the effects of climate are species-specific, place-specific and non-linear and that linear approaches will therefore overestimate the effect of climate change on mosquito abundances at high temperatures. Climate warming does not necessarily lead to an increase in mosquito abundance in natural Mediterranean wetlands and will affect, above all, species such as Oc. caspius whose numbers are not closely linked to rainfall and are influenced, rather, by local tidal patterns and temperatures. The final impact of changes in vector abundance on disease frequency

  15. Pleomorphic adenoma (formerly chondroid syringoma) of the eyelid margin with a pseudocystic appearance.

    PubMed

    Palioura, Sotiria; Jakobiec, Frederick A; Zakka, Fouad R; Iwamoto, Mami

    2013-01-01

    Among the adenomas and adenocarcinomas spawned by the adnexal glands of the eyelids, pleomorphic adenoma (also referred to as benign mixed tumor or chondroid syringoma in dermatopathology) is among the rarest. Pleomorphic adenomas (PAs) can arise from sweat glands in the dermis of the eyelid skin and must be distinguished from those of the accessory lacrimal glands of Krause and Wolfring. We describe an eyelid margin skin PA that appeared clinically to be a cyst and was not associated with an accessory lacrimal gland. Histopathologically, the lesion was circumscribed but nonencapsulated and composed of branching ductular structures with a double layer of epithelial cells set in a myxoid and sclerotic stroma that did not contain cartilage. The outer ductular (myoepithelial) cells delaminated to populate the stroma. Histochemistry disclosed abundant extracellular mucopolysaccharides that conferred the "cystic" character clinically. The inner ductular cells were uniformly positive for cytokeratin 7 and focally for gross cystic fluid disease protein-15, an apocrine marker. The inner and outer ductular cells were negative for alpha-smooth muscle actin. These pathologic findings support an apocrine (gland of Moll) origin for this tumor, which is consistent with the fact that there are no eccrine glands at the eyelid margin.

  16. Nucleosynthesis: Stellar and Solar Abundances and Atomic Data

    NASA Technical Reports Server (NTRS)

    Cowan, John J.; Lawler, James E.; Sneden, Christopher; DenHartog, E. A.; Collier, Jason; Dodge, Homer L.

    2006-01-01

    Abundance observations indicate the presence of often surprisingly large amounts of neutron capture (i.e., s- and r-process) elements in old Galactic halo and globular cluster stars. These observations provide insight into the nature of the earliest generations of stars in the Galaxy the progenitors of the halo stars responsible for neutron-capture synthesis. Comparisons of abundance trends can be used to understand the chemical evolution of the Galaxy and the nature of heavy element nucleosynthesis. In addition age determinations, based upon long-lived radioactive nuclei abundances, can now be obtained. These stellar abundance determinations depend critically upon atomic data. Improved laboratory transition probabilities have been recently obtained for a number of elements. These new gf values have been used to greatly refine the abundances of neutron-capture elemental abundances in the solar photosphere and in very metal-poor Galactic halo stars. The newly determined stellar abundances are surprisingly consistent with a (relative) Solar System r-process pattern, and are also consistent with abundance predictions expected from such neutron-capture nucleosynthesis.

  17. Elemental abundances of the B6 IV star Xi Octantis

    NASA Technical Reports Server (NTRS)

    Adelman, Saul J.; Robinson, Richard D.; Wahlgren, Glenn M.

    1993-01-01

    An elemental abundance study used AAT echelle spectrograms of the ultrasharp-lined, superficially normal B6 IV star Xi Octantis. The derived abundances fall within the trends of values derived for normal B main-sequence band stars. On average, they are 0.28 dex less than solar.

  18. The Abundance and Distribution of Presolar Materials in Cluster IDPS

    NASA Technical Reports Server (NTRS)

    Messenger, Scott; Keller, Lindsay; Nakamura-Messenger, Keiko; Ito, Motoo

    2007-01-01

    Presolar grains and remnants of interstellar organic compounds occur in a wide range of primitive solar system materials, including meteorites, interplanetary dust particles (IDPs), and comet Wild-2 samples. Among the most abundant presolar phases are silicate stardust grains and molecular cloud material. However, these materials have also been susceptible to destruction and alteration during parent body and nebular processing. In addition to their importance as direct samples of remote and ancient astrophysical environments, presolar materials thus provide a measure of how well different primitive bodies have preserved the original solar system starting materials. The matrix normalized abundances of presolar silicate grains in meteorites range from 20 ppm in Semarkona and Bishunpur to 170 ppm for Acfer 094. The lower abundances of presolar silicates in Bishunpur and Semarkona has been ascribed to the destruction of presolar silicates during aqueous processes. Presolar silicates appear to be significantly more abundant in anhydrous IDPs, possibly because these materials did not experience parent body hydrothermal alteration. Among IDPs the estimated abundances of presolar silicates vary by more than an order of magnitude, from 480 to 5500 ppm. The wide disparity in the abundances of presolar silicates of IDPs may be a consequence of the relatively small total area analyzed in those studies and the fine grain sizes of the IDPs. Alternatively, there may be a wide range in presolar silicate abundances between different IDPs. This view is supported by the observation that 15N-rich IDPs have higher presolar silicate abundances than those with isotopically normal N.

  19. Ionized Gaseous Nebulae Abundance Determination from the Direct Method

    NASA Astrophysics Data System (ADS)

    Pérez-Montero, Enrique

    2017-04-01

    This tutorial explains the procedure used to analyze an optical emission-line spectrum produced by a nebula ionized by massive star formation. Particularly, the methodology used to derive physical properties, such as electron density and temperature, and the ionic abundances of the most representative elements whose emission lines are present in the optical spectrum is described. The main focus is on the direct method, which is based on the measurement of the electron temperature to derive the abundances, given that the ionization and thermal equilibrium of the ionized gas is dominated by the metallicity. The ionization correction factors used to obtain total abundances from the abundances of some of their ions are also given. Finally, some strong-line methods to derive abundances are described. Such methods are used when no estimation of the temperature can be derived, but which can be consistent with the direct method if they are empirically calibrated.

  20. Three energy variables predict ant abundance at a geographical scale.

    PubMed Central

    Kaspari, M; Alonso, L; O'Donnell, S

    2000-01-01

    Energy theory posits three processes that link local abundance of ectotherms to geographical gradients in temperature. A survey of 49 New World habitats found a two order of magnitude span in the abundance (nests m(-2)) of ground nesting ants (Formicidae). Abundance increased with net primary productivity (r2=0.55), a measure of the baseline supply of harvestable energy. Abundance further increased with mean temperature (r2=0.056), a constraint on foraging activity for this thermophilic taxon. Finally for a given mean temperature, ants were more abundant in seasonal sites with longer, colder winters (r2 = 0.082) that help ectotherm taxa sequester harvested energy in non-productive months. All three variables are currently changing on a global scale. All should be useful in predicting biotic responses to climate change. PMID:10737406

  1. Interstellar Dust Models Consistent with Extinction, Emission, and Abundance Constraints

    NASA Technical Reports Server (NTRS)

    Zubko, Viktor; Dwek, Eli; Arendt, Richard G.

    2004-01-01

    We present new interstellar dust models which have been derived by simultaneously fitting the far ultraviolet to near infrared extinction, the diffuse infrared emission, and, unlike previous models, the elemental abundances in dust for the diffuse interstellar medium. We found that dust models consisting of a mixture of spherical graphite and silicate grains, polycyclic aromatic hydrocarbon (PAH) molecules, in addition to porous composite particles containing silicate, organic refractory, and water ice, provide an improved .t to the UV-to-infrared extinction and infrared emission measurements, while consuming the amounts of elements well within the uncertainties of adopted interstellar abundances, including B star abundances. These models are a signi.cant improvement over the recent Li & Draine (2001, ApJ, 554, 778) model which requires an excessive amount of silicon to be locked up in dust: 48 ppm (atoms per million of H atoms), considerably more than the solar abundance of 34 ppm or the B star abundance of 19 ppm.

  2. Carbon and nitrogen abundances determined from transition layer lines

    NASA Technical Reports Server (NTRS)

    Boehm-Vitense, Erika; Mena-Werth, Jose

    1992-01-01

    The possibility of determining relative carbon, nitrogen, and silicon abundances from the emission-line fluxes in the lower transition layers between stellar chromospheres and coronae is explored. Observations for main-sequence and luminosity class IV stars with presumably solar element abundances show that for the lower transition layers Em = BT sup -gamma. For a given carbon abundance the constants gamma and B in this relation can be determined from the C II and C IV emission-line fluxes. From the N V and S IV lines, the abundances of these elements relative to carbon can be determined from their surface emission-line fluxes. Ratios of N/C abundances determined in this way for some giants and supergiants agree within the limits of errors with those determined from molecular bands. For giants, an increase in the ratio of N/C at B-V of about 0.8 is found, as expected theoretically.

  3. An "Andesitic" Component in Shergottites with Restored LREE Abundances?

    NASA Technical Reports Server (NTRS)

    Nyquist, L. E.; Shih, C.-Y.; Wiesmann, H.; Barrat, J. A.

    2002-01-01

    The shergottite Martian meteorites present a variety of oft-confusing petrologic features. In particular, represented among this subgroup are basalts with very depleted LREE abundances, as well as those with nearly chondritic overall REE abundances. The LREE-depleted basalts appear to more closely record the REE and isotopic features of their mantle source legions. Those basalts with more nearly chondritic REE abundances appear to contain an extra component often referred to as a "crustal" component. The addition of the crustal component tends to restore the overall REE abundance pattern towards chondritic relative abundances. Here we suggest that the crustal component could derive from andesitic rocks observed remotely to occur on the Martian surface, and which were analysed at the Pathfinder site.

  4. An "Andestic" Component in Shergottites with Restored LREE Abundances?

    NASA Technical Reports Server (NTRS)

    Nyquist, L. E.; Shih, C.-Y.; Wiesmann, H.; Barrat, J. A.

    2002-01-01

    The shergottite Martian meteorites present a variety of oft-confusing petrologic features. In particular, represented among this subgroup are basalts with very depleted LREE abundances, as well as those with nearly chondritic overall REE abundances. The LREE-depleted basalts appear to more closely record the REE and isotopic features of their mantle source regions. Those basalts with more nearly chondritic REE abundances appear to contain an extra component often referred to as a "crustal" component. The addition of the crustal component tends to restore the overall REE abundance pattern towards chondritic relative abundances. Here we suggest that the crustal component could derive from "andesitic" rocks observed remotely to occur on the Martian surface, and which were analysed at the Pathfinder site.

  5. Abundances of the elements in the solar system

    NASA Technical Reports Server (NTRS)

    Cameron, A. G. W.

    1973-01-01

    The present status of abundance information for elements in meteorites and in the sun is reviewed, and a new table of abundances of the elements, which should be characteristic of the primitive solar nebula, is compiled and presented. Special attention is called to the elemental abundances in the silicon-to-calcium region, where many of the abundances are rather poorly determined, and where these abundances have an impact on theories of nucleosynthesis of the elements. To each elemental isotope is assigned a mechanism of nucleosynthesis which may have been responsible for production of most of that isotope, and brief comments are made concerning the present status of understanding of the different mechanisms of nucleosynthesis.

  6. The lithium abundances of a large sample of red giants

    SciTech Connect

    Liu, Y. J.; Tan, K. F.; Wang, L.; Zhao, G.; Li, H. N.; Sato, Bun'ei; Takeda, Y. E-mail: gzhao@nao.cas.cn

    2014-04-20

    The lithium abundances for 378 G/K giants are derived with non-local thermodynamic equilibrium correction considered. Among these are 23 stars that host planetary systems. The lithium abundance is investigated, as a function of metallicity, effective temperature, and rotational velocity, as well as the impact of a giant planet on G/K giants. The results show that the lithium abundance is a function of metallicity and effective temperature. The lithium abundance has no correlation with rotational velocity at v sin i < 10 km s{sup –1}. Giants with planets present lower lithium abundance and slow rotational velocity (v sin i < 4 km s{sup –1}). Our sample includes three Li-rich G/K giants, 36 Li-normal stars, and 339 Li-depleted stars. The fraction of Li-rich stars in this sample agrees with the general rate of less than 1% in the literature, and the stars that show normal amounts of Li are supposed to possess the same abundance at the current interstellar medium. For the Li-depleted giants, Li-deficiency may have already taken place at the main sequence stage for many intermediate mass (1.5-5 M {sub ☉}) G/K giants. Finally, we present the lithium abundance and kinematic parameters for an enlarged sample of 565 giants using a compilation of the literature, and confirm that the lithium abundance is a function of metallicity and effective temperature. With the enlarged sample, we investigate the differences between the lithium abundance in thin-/thick-disk giants, which indicate that the lithium abundance in thick-disk giants is more depleted than that in thin-disk giants.

  7. Influence of deer abundance on the abundance of questing adult Ixodes scapularis (Acari: Ixodidae)

    USGS Publications Warehouse

    Ginsberg, H.S.; Zhioua, E.

    1999-01-01

    Nymphal and adult Ixodes scapularis Say were sampled by flagging at 2 sites on a barrier island, Fire Island, NY, and at 2 sites on the nearby mainland. Nymphal densities did not differ consistently between island and mainland sites, but adult densities were consistently lower on the island. We tested whether lower adult densities on the island resulted from greater nymphal mortality on the island than the mainland, or whether adult ticks on the island were poorly sampled by flagging because they had attached abundantly to deer, which were common on Fire Island. Differential nymphal mortality on islands vs. mainland did not explain this difference in adult densities because survival of flat and engorged nymphs in enclosures was the same at island and mainland sites. Ticks were infected by parasitic wasps on the island and not the mainland, but the infection rate (4.3%) was too low to explain the difference in adult tick densities. In contrast, exclusion of deer by game fencing on Fire Island resulted in markedly increased numbers of adult ticks in flagging samples inside compared to samples taken outside the exclosures. Therefore, the scarcity of adult ticks in flagging samples on Fire Island resulted, at least in part, from the ticks being unavailable to flagging samples because they were on deer hosts. Differences in the densities of flagged ticks inside and outside the exclosures were used to estimate the percentage of questing adults on Fire Island that found deer hosts, excluding those that attached to other host species. Approximately 56% of these questing adult ticks found deer hosts in 1995 and 50% found deer hosts in 1996. Therefore, in areas where vertebrate hosts are highly abundant, large proportions of the questing tick population can find hosts. Moreover, comparisons of tick densities at different sites by flagging can potentially be biased by differences in host densities among sites.

  8. Geographical Range and Local Abundance of Tree Species in China

    PubMed Central

    Ren, Haibao; Condit, Richard; Chen, Bin; Mi, Xiangcheng; Cao, Min; Ye, Wanhui; Hao, Zhanqing; Ma, Keping

    2013-01-01

    Most studies on the geographical distribution of species have utilized a few well-known taxa in Europe and North America, with little research in China and its wide range of climate and forest types. We assembled large datasets to quantify the geographic ranges of tree species in China and to test several biogeographic hypotheses: 1) whether locally abundant species tend to be geographically widespread; 2) whether species are more abundant towards their range-centers; and 3) how abundances are correlated between sites. Local abundances of 651 species were derived from four tree plots of 20–25 ha where all individuals ≥1 cm in stem diameter were mapped and identified taxonomically. Range sizes of these species across China were then estimated from over 460,000 geo-referenced records; a Bayesian approach was used, allowing careful measures of error of each range estimate. The log-transformed range sizes had a bell-shaped distribution with a median of 703,000 km2, and >90% of 651 species had ranges >105 km2. There was no relationship between local abundance and range size, and no evidence for species being more abundant towards their range-centers. Finally, species’ abundances were positively correlated between sites. The widespread nature of most tree species in China suggests few are vulnerable to global extinction, and there is no indication of the double-peril that would result if rare species also had narrow ranges. PMID:24130772

  9. A Semi-automated Abundance Survey of Ap Stars

    NASA Astrophysics Data System (ADS)

    Hall, Martin P.; Kurtz, Don; Elkin, Vladimir; Bruntt, Hans

    2015-08-01

    We have carried out an abundance analysis on the high-resolution spectra of approximately 350 Ap stars collected between 2007 and 2010 on the FEROS Echelle (Fibre-led, Extended Range, Echelle ) spectrograph housed at the 2.2-m telescope at European Southern Observatory at La Silla, Chile. We employed the VWA package (vsin I, wavelength shift, abundance analysis) for preliminary selection of spectral lines, and a semi-automated set of routines which we developed in the programming language IDL, to calculate the equivalent widths and abundances of ions of Iron and the rare earth elements Neodymium and Praseodymium using the WIDTH program and NEMO model atmospheres. Initial results are presented, which reinforce the correlation between iron abundance and effective temperature, from an over-abundance in the late Bp stars, to under-abundant in the early F stars. Results also suggest that the disequilibrium in abundances of the first and second ionisation stages of these ions in the rapidly oscillating Ap (roAp) stars may a consequence of the relatively cool temperatures of those stars, rather than a signature of pulsation.

  10. Dam removal increases American eel abundance in distant headwater streams

    USGS Publications Warehouse

    Hitt, Nathaniel P.; Eyler, Sheila; Wofford, John E.B.

    2012-01-01

    American eel Anguilla rostrata abundances have undergone significant declines over the last 50 years, and migration barriers have been recognized as a contributing cause. We evaluated eel abundances in headwater streams of Shenandoah National Park, Virginia, to compare sites before and after the removal of a large downstream dam in 2004 (Embrey Dam, Rappahannock River). Eel abundances in headwater streams increased significantly after the removal of Embrey Dam. Observed eel abundances after dam removal exceeded predictions derived from autoregressive models parameterized with data prior to dam removal. Mann–Kendall analyses also revealed consistent increases in eel abundances from 2004 to 2010 but inconsistent temporal trends before dam removal. Increasing eel numbers could not be attributed to changes in local physical habitat (i.e., mean stream depth or substrate size) or regional population dynamics (i.e., abundances in Maryland streams or Virginia estuaries). Dam removal was associated with decreasing minimum eel lengths in headwater streams, suggesting that the dam previously impeded migration of many small-bodied individuals (<300 mm TL). We hypothesize that restoring connectivity to headwater streams could increase eel population growth rates by increasing female eel numbers and fecundity. This study demonstrated that dams may influence eel abundances in headwater streams up to 150 river kilometers distant, and that dam removal may provide benefits for eel management and conservation at the landscape scale.

  11. OH Column Abundance Apparent Response to Solar Cycle 23

    NASA Astrophysics Data System (ADS)

    Burnett, C. R.; Minschwaner, K. R.

    2009-12-01

    The 33-year series of high spectral resolution measurements of absorption of sunlight by OH at 308 nm has exhibited temporary decreases of column abundances in 1986, 1997, and 2008 near the times of minimum solar activity. These observations and analyses are of significance as they encompass three complete solar cycles for comparison. During solar cycle 23, the annual average abundances increased approximately 20% from the minimum abundance in 1997 to high-sun enhanced values in 2000-2006, then dropped approximately 15% in 2008. The abundances exhibited a pronounced reduction at solar minimum in August-October 2008, similar to that seen in fall 1986 and fall 1997. The average morning abundances on those occasions were 13% smaller than the 1980-88 corresponding average, about 0.9 x 1013 cm-2, with minimum values broadly consistent with model results. In contrast, high-sun OH abundances observed during periods of solar maximum are approximately 33% larger than modeled abundances. This discrepancy cannot be explained by reasonable adjustments of reaction rates or modeled constituent concentrations in the stratosphere or mesosphere. However, the observed responses to a tropopause fold event in 1988 and to the Pinatubo aerosol in 1991 do suggest an important contribution to the total OH column from the lower stratosphere. In addition to the apparent variations with solar activity, this OH column database contains a number of other effects such as diurnal and seasonal patterns, and geographic differences between observations from Colorado, Florida, Alaska, Micronesia, New Zealand, and New Mexico.

  12. (Un)true deuterium abundance in the Galactic disk

    NASA Astrophysics Data System (ADS)

    Prodanović, Tijana; Steigman, Gary; Fields, Brian D.

    2010-04-01

    Deuterium has a special place in cosmology, nuclear astrophysics, and galactic chemical evolution, because of its unique property that it is only created in the big bang nucleosynthesis while all other processes result in its net destruction. For this reason, among other things, deuterium abundance measurements in the interstellar medium (ISM) allow us to determine the fraction of interstellar gas that has been cycled through stars, and set constraints and learn about different Galactic chemical evolution (GCE) models. However, recent indications that deuterium might be preferentially depleted onto dust grains complicate our understanding about the meaning of measured ISM deuterium abundances. For this reason, recent estimates by Linsky et al. (2006) have yielded a lower bound to the “true”, undepleted, ISM deuterium abundance that is very close to the primordial abundance, indicating a small deuterium astration factor contrary to the demands of many GCE models. To avoid any prejudice about deuterium dust depletion along different lines of sight that are used to determine the “true” D abundance, we propose a model-independent, statistical Bayesian method to address this issue and determine in a model-independent manner the undepleted ISM D abundance. We find the best estimate for the gas-phase ISM deuterium abundance to be (D/H)ISM ≥ (2.0 ± 0.1) × 10-5. Presented are the results of Prodanović et al. (2009).

  13. Stellar abundances in the solar neighborhood: The Hypatia Catalog

    SciTech Connect

    Hinkel, Natalie R.; Timmes, F.X.; Young, Patrick A.; Pagano, Michael D.; Turnbull, Margaret C.

    2014-09-01

    We compile spectroscopic abundance data from 84 literature sources for 50 elements across 3058 stars in the solar neighborhood, within 150 pc of the Sun, to produce the Hypatia Catalog. We evaluate the variability of the spread in abundance measurements reported for the same star by different surveys. We also explore the likely association of the star within the Galactic disk, the corresponding observation and abundance determination methods for all catalogs in Hypatia, the influence of specific catalogs on the overall abundance trends, and the effect of normalizing all abundances to the same solar scale. The resulting stellar abundance determinations in the Hypatia Catalog are analyzed only for thin-disk stars with observations that are consistent between literature sources. As a result of our large data set, we find that the stars in the solar neighborhood may reveal an asymmetric abundance distribution, such that a [Fe/H]-rich group near the midplane is deficient in Mg, Si, S, Ca, Sc II, Cr II, and Ni as compared to stars farther from the plane. The Hypatia Catalog has a wide number of applications, including exoplanet hosts, thick- and thin-disk stars, and stars with different kinematic properties.

  14. Seasonal Abundance of Aphids and Aphidophagous Insects in Pecan.

    PubMed

    Dutcher, James D; Karar, Haider; Abbas, Ghulam

    2012-12-05

    Seasonal occurrence of aphids and aphidophagous insects was monitored for six years (2006-2011) from full leaf expansion in May to leaf fall in October in "Desirable" variety pecan trees that were not treated with insecticides. Aphid outbreaks occurred two times per season, once in the spring and again in the late summer. Yellow pecan and blackmargined aphids exceeded the recommended treatment thresholds one time and black pecan aphids exceeded the recommended treatment levels three times over the six seasons. Increases in aphidophagous insect abundance coincided with aphid outbreaks in five of the six seasons. Among aphidophagous insects Harmonia axyridis and Olla v-nigrum were frequently collected in both the tree canopy and at the ground level, whereas, Coccinella septempunctata, Hippodamia convergens were rarely found in the tree canopy and commonly found at the ground level. Green lacewing abundance was higher in the ground level than in the tree canopy. Brown lacewings were more abundant in the tree canopy than at the ground level. Dolichopodid and syrphid fly abundance, at the ground level increased during peak aphid abundance in the tree canopy. Application of an aqueous solution of fermenting molasses to the pecan foliage during an aphid outbreak significantly increased the abundance of ladybeetles and lacewings and significantly reduced the abundance of yellow pecan, blackmargined and black pecan aphids.

  15. Geographical range and local abundance of tree species in China.

    PubMed

    Ren, Haibao; Condit, Richard; Chen, Bin; Mi, Xiangcheng; Cao, Min; Ye, Wanhui; Hao, Zhanqing; Ma, Keping

    2013-01-01

    Most studies on the geographical distribution of species have utilized a few well-known taxa in Europe and North America, with little research in China and its wide range of climate and forest types. We assembled large datasets to quantify the geographic ranges of tree species in China and to test several biogeographic hypotheses: 1) whether locally abundant species tend to be geographically widespread; 2) whether species are more abundant towards their range-centers; and 3) how abundances are correlated between sites. Local abundances of 651 species were derived from four tree plots of 20-25 ha where all individuals ≥1 cm in stem diameter were mapped and identified taxonomically. Range sizes of these species across China were then estimated from over 460,000 geo-referenced records; a Bayesian approach was used, allowing careful measures of error of each range estimate. The log-transformed range sizes had a bell-shaped distribution with a median of 703,000 km(2), and >90% of 651 species had ranges >10(5) km(2). There was no relationship between local abundance and range size, and no evidence for species being more abundant towards their range-centers. Finally, species' abundances were positively correlated between sites. The widespread nature of most tree species in China suggests few are vulnerable to global extinction, and there is no indication of the double-peril that would result if rare species also had narrow ranges.

  16. Implications of Abundant Gas and Oil for Climate Forcing

    NASA Astrophysics Data System (ADS)

    Edmonds, J.

    2015-12-01

    Perhaps the most important development in the field of energy over the past decade has been the advent of technologies that enable the production of larger volumes of natural gas and oil at lower cost. The availability of more abundant gas and oil is reshaping the global energy system, with implications for both evolving emissions of CO2 and other climate forcers. More abundant gas and oil will also transform the character of greenhouse gas emissions mitigation. We review recent findings regarding the impact of abundant gas and oil for climate forcing and the challenge of emissions mitigation. We find strong evidence that, absent policies to limits its penetration against renewable energy, abundant gas has little observable impact on CO2 emissions, and tends to increase overall climate forcing, though the latter finding is subject to substantial uncertainty. The presence of abundant gas also affects emissions mitigation. There is relatively little literature exploring the implication of expanded gas availability on the difficulty in meeting emissions mitigation goals. However, preliminary results indicate that on global scales abundant gas does not substantially affect the cost of emissions mitigation, even though natural gas could have an expanded role in emissions mitigation scenarios as compared with scenarios in which natural gas is less abundant.

  17. Aggregative response in bats: prey abundance versus habitat.

    PubMed

    Müller, Jörg; Mehr, Milenka; Bässler, Claus; Fenton, M Brock; Hothorn, Torsten; Pretzsch, Hans; Klemmt, Hans-Joachim; Brandl, Roland

    2012-07-01

    In habitats where prey is either rare or difficult to predict spatiotemporally, such as open habitats, predators must be adapted to react effectively to variations in prey abundance. Open-habitat foraging bats have a wing morphology adapted for covering long distances, possibly use information transfer to locate patches of high prey abundance, and would therefore be expected to show an aggregative response at these patches. Here, we examined the effects of prey abundance on foraging activities of open-habitat foragers in comparison to that of edge-habitat foragers and closed-habitat foragers. Bat activity was estimated by counting foraging calls recorded with bat call recorders (38,371 calls). Prey abundance was estimated concurrently at each site using light and pitfall traps. The habitat was characterized by terrestrial laser scanning. Prey abundance increased with vegetation density. As expected, recordings of open-habitat foragers clearly decreased with increasing vegetation density. The foraging activity of edge- and closed-habitat foragers was not significantly affected by the vegetation density, i.e., these guilds were able to forage from open habitats to habitats with dense vegetation. Only open-habitat foragers displayed a significant and proportional aggregative response to increasing prey abundance. Our results suggest that adaptations for effective and low-cost foraging constrains habitat use and excludes the guild of open-habitat foragers from foraging in habitats with high prey abundance, such as dense forest stands.

  18. A revised DDO abundance calibration for population I red giants

    NASA Astrophysics Data System (ADS)

    Piatti, A. E.; Claria, J. J.; Minniti, D.

    1993-12-01

    Several arguments that justify establishing a revised abundance calibration for DDO photometry of population I red giants are presented. The components of the blanketing vector in the DDO C(45-48) vs C(42-45) diagram are determined for late-type dwarfs and giants. We have redefined the DDO cyanogen anomaly and calibrated it against metallicity. The sample of field giants now available with abundances derived from high dispersion spectroscopy is substantially larger than previously available, leading to a more accurate abundance calibration. Iso-abundance lines in the C(41-42) vs C(42-45) diagram have been determined for population IG and K giants and an iterative method for deriving abundances of these stars is described. We show that the new DDO abundances are in very good agreement with those derived from high dispersion spectroscopy. The new method improves by about 0.1 dex the DDO abundances derived for early G and/or late K giants, with respect to the delta(CN) method of Janes (1975).

  19. Model reduction for stochastic chemical systems with abundant species.

    PubMed

    Smith, Stephen; Cianci, Claudia; Grima, Ramon

    2015-12-07

    Biochemical processes typically involve many chemical species, some in abundance and some in low molecule numbers. We first identify the rate constant limits under which the concentrations of a given set of species will tend to infinity (the abundant species) while the concentrations of all other species remains constant (the non-abundant species). Subsequently, we prove that, in this limit, the fluctuations in the molecule numbers of non-abundant species are accurately described by a hybrid stochastic description consisting of a chemical master equation coupled to deterministic rate equations. This is a reduced description when compared to the conventional chemical master equation which describes the fluctuations in both abundant and non-abundant species. We show that the reduced master equation can be solved exactly for a number of biochemical networks involving gene expression and enzyme catalysis, whose conventional chemical master equation description is analytically impenetrable. We use the linear noise approximation to obtain approximate expressions for the difference between the variance of fluctuations in the non-abundant species as predicted by the hybrid approach and by the conventional chemical master equation. Furthermore, we show that surprisingly, irrespective of any separation in the mean molecule numbers of various species, the conventional and hybrid master equations exactly agree for a class of chemical systems.

  20. Model reduction for stochastic chemical systems with abundant species

    SciTech Connect

    Smith, Stephen; Cianci, Claudia; Grima, Ramon

    2015-12-07

    Biochemical processes typically involve many chemical species, some in abundance and some in low molecule numbers. We first identify the rate constant limits under which the concentrations of a given set of species will tend to infinity (the abundant species) while the concentrations of all other species remains constant (the non-abundant species). Subsequently, we prove that, in this limit, the fluctuations in the molecule numbers of non-abundant species are accurately described by a hybrid stochastic description consisting of a chemical master equation coupled to deterministic rate equations. This is a reduced description when compared to the conventional chemical master equation which describes the fluctuations in both abundant and non-abundant species. We show that the reduced master equation can be solved exactly for a number of biochemical networks involving gene expression and enzyme catalysis, whose conventional chemical master equation description is analytically impenetrable. We use the linear noise approximation to obtain approximate expressions for the difference between the variance of fluctuations in the non-abundant species as predicted by the hybrid approach and by the conventional chemical master equation. Furthermore, we show that surprisingly, irrespective of any separation in the mean molecule numbers of various species, the conventional and hybrid master equations exactly agree for a class of chemical systems.

  1. How Ants Drop Out: Ant Abundance on Tropical Mountains

    PubMed Central

    Longino, John T.; Branstetter, Michael G.; Colwell, Robert K.

    2014-01-01

    In tropical wet forests, ants are a large proportion of the animal biomass, but the factors determining abundance are not well understood. We characterized ant abundance in the litter layer of 41 mature wet forest sites spread throughout Central America (Chiapas, Guatemala, Honduras, Nicaragua, and Costa Rica) and examined the impact of elevation (as a proxy for temperature) and community species richness. Sites were intentionally chosen to minimize variation in precipitation and seasonality. From sea level to 1500 m ant abundance very gradually declined, community richness declined more rapidly than abundance, and the local frequency of the locally most common species increased. These results suggest that within this elevational zone, density compensation is acting, maintaining high ant abundance as richness declines. In contrast, in sites above 1500 m, ant abundance dropped abruptly to much lower levels. Among these high montane sites, community richness explained much more of the variation in abundance than elevation, and there was no evidence of density compensation. The relative stability of abundance below 1500 m may be caused by opposing effects of temperature on productivity and metabolism. Lower temperatures may decrease productivity and thus the amount of food available for consumers, but slower metabolisms of consumers may allow maintenance of higher biomass at lower resource supply rates. Ant communities at these lower elevations may be highly interactive, the result of continuous habitat presence over geological time. High montane sites may be ephemeral in geological time, resulting in non-interactive communities dominated by historical and stochastic processes. Abundance in these sites may be determined by the number of species that manage to colonize and/or avoid extinction on mountaintops. PMID:25098722

  2. High chemical abundances in stripped Virgo spiral galaxies

    NASA Astrophysics Data System (ADS)

    Skillman, E. D.; Kennicutt, R. C.; Shields, G. A.

    1993-01-01

    Based on a comparison of the oxygen abundances in H 2 regions in field and Virgo cluster late type spiral galaxies, Shields, Skillman, & Kennicutt (1991) suggested that the highly stripped spiral galaxies in the Virgo cluster have systematically higher abundances than comparable field galaxies. In April 1991 and May 1992 we used the blue channel spectrograph on the MMT to obtain new observations of 30 H 2 regions in Virgo spiral galaxies. These spectra cover the wavelength range from (O II) lambda 3727 to (S II) lambda 6731. We now have observed at least 4 H II regions in 9 spiral galaxies in the Virgo cluster. Combining (O II) and (O III) line strengths, we calculate the H II region oxygen abundances based on the empirical calibration of Edmunds & Pagel (1984). These observations show: (1) The stripped, low luminosity Virgo spirals (N4689, N4571) truly have abundances characteristic of much more luminous field spirals; (2) Virgo spirals which show no evidence of stripping (N4651, N4713) have abundances comparable to field galaxies; and (3) Evidence for transition galaxies (e.g., N4254, N4321), with marginally stripped disks and marginal abundance enhancements. The new observations presented here confirm the validity of the oxygen over-abundances in the stripped Virgo spirals. Shields et al. (1991) discussed two different mechanisms for producing the higher abundances in the disks of stripped galaxies in Virgo. The first is the supression of infall of near-primordial material, the second is the suppression of radial inflow of metal-poor gas. Distinguishing between the two cases will require more observations of the Virgo cluster spirals and a better understanding of which parameters determine the variation of abundance with radius in field spirals (cf., Garnett & Shields 1987).

  3. Understanding and reducing statistical uncertainties in nebular abundance determinations

    NASA Astrophysics Data System (ADS)

    Wesson, R.; Stock, D. J.; Scicluna, P.

    2012-06-01

    Whenever observations are compared to theories, an estimate of the uncertainties associated with the observations is vital if the comparison is to be meaningful. However, many or even most determinations of temperatures, densities and abundances in photoionized nebulae do not quote the associated uncertainty. Those that do typically propagate the uncertainties using analytical techniques which rely on assumptions that generally do not hold. Motivated by this issue, we have developed Nebular Empirical Analysis Tool (NEAT), a new code for calculating chemical abundances in photoionized nebulae. The code carries out a standard analysis of lists of emission lines using long-established techniques to estimate the amount of interstellar extinction, calculate representative temperatures and densities, compute ionic abundances from both collisionally excited lines and recombination lines, and finally to estimate total elemental abundances using an ionization correction scheme. NEATuses a Monte Carlo technique to robustly propagate uncertainties from line flux measurements through to the derived abundances. We show that, for typical observational data, this approach is superior to analytic estimates of uncertainties. NEAT also accounts for the effect of upward biasing on measurements of lines with low signal-to-noise ratio, allowing us to accurately quantify the effect of this bias on abundance determinations. We find not only that the effect can result in significant overestimates of heavy element abundances derived from weak lines, but also that taking it into account reduces the uncertainty of these abundance determinations. Finally, we investigate the effect of possible uncertainties in R, the ratio of selective-to-total extinction, on abundance determinations. We find that the uncertainty due to this parameter is negligible compared to the statistical uncertainties due to typical line flux measurement uncertainties.

  4. Short-scale variations of the solar wind helium abundance

    SciTech Connect

    Šafránková, J.; Němeček, Z.; Cagaš, P.; Přech, L.; Pavlů, J.; Zastenker, G. N.; Riazantseva, M. O.; Koloskova, I. V.

    2013-11-20

    Abrupt changes of the relative He abundance in the solar wind are usually attributed to encounters with boundaries dividing solar wind streams from different sources in the solar corona. This paper presents a systematic study of fast variations of the He abundance that supports the idea that a majority of these variations on short timescales (3-30 s) are generated by in-transit turbulence that is probably driven by the speed difference between the ion species. This turbulence contributes to the solar wind heating and leads to a correlation of the temperature with He abundance.

  5. Chemical evolution models for NGC 6822 using planetary nebulae abundances

    NASA Astrophysics Data System (ADS)

    Hernández-Martínez, Liliana; Carigi, Leticia; Peña, Miriam; Peimbert, Manuel

    2012-08-01

    We present chemical evolution models for the dwarf irregular NGC 6822, using chemical abundances of Planetary Nebulae (PNe) and HII regions and also the mass of gas (M gas ) as observational constraints. Chemical evolution models have been calculated to reproduce the abundances as derived from both, collisionally excited lines (CELs) and recombination lines (RLs). In our models, the chemical contribution of low and intermediate mass stars (LIMS) is time delayed, while for the massive stars the chemical contribution is instantaneous, as in Franco & Carigi (2008). The chemical contribution of SNIa is included in our model, thus we are also able to reproduce the observational Fe/H abundance obtained from A stars.

  6. On the abundance of Europium. [in Ap and Am stars

    NASA Technical Reports Server (NTRS)

    Hartoog, M. R.; Cowley, C. R.; Adelman, S. J.

    1974-01-01

    The inclusion of the effects of hyperfine splitting can significantly lower the abundance estimate of Eu from singly ionized lines which lie on the flat portion of the curve of growth. In the 21 cool Ap stars studied by Adelman and the five Am stars studied by Smith, the Eu abundance was reduced by 0.4 dex on the average. In individual cases, the reductions were as great as 0.9 dex. This makes the Eu abundance comparable to that of its neighboring rare earths Sm and Gd in the Ap stars and less than Sm and Gd in the Am stars, but still substantially overabundant with respect to solar values.

  7. Trace-element abundances in several new ureilites

    NASA Technical Reports Server (NTRS)

    Boynton, William V.; Hill, Dolores H.

    1993-01-01

    Four new ureilites are analyzed for trace-element abundances. Frontier Mountain (FRO) 90054 is an augite-rich ureilite and has high rare earth element (REE) abundances with a pattern expected of augite. FRO 90036 and Acfer 277 have REE patterns similar to the V-shape pattern of other ureilites. Nuevo Mercurio (b) has very high REE abundances, but they look like they are due to terrestrial alteration. The siderophile-element pattern of these ureilites are similar to those of known ureilites.

  8. Ecological niche structure and rangewide abundance patterns of species

    PubMed Central

    Martínez-Meyer, Enrique; Díaz-Porras, Daniel; Peterson, A. Townsend; Yáñez-Arenas, Carlos

    2013-01-01

    Spatial abundance patterns across species' ranges have attracted intense attention in macroecology and biogeography. One key hypothesis has been that abundance declines with geographical distance from the range centre, but tests of this idea have shown that the effect may occur indeed only in a minority of cases. We explore an alternative hypothesis: that species' abundances decline with distance from the centroid of the species' habitable conditions in environmental space (the ecological niche). We demonstrate consistent negative abundance–ecological distance relationships across all 11 species analysed (turtles to wolves), and that relationships in environmental space are consistently stronger than relationships in geographical space. PMID:23134784

  9. The determination of electron abundances in interstellar clouds

    NASA Technical Reports Server (NTRS)

    Wootten, A.; Snell, R.; Glassgold, A. E.

    1979-01-01

    An independent method is proposed for the determination of electron abundances in dense clouds based upon the abundance ratio of HCO(+) and CO. The method is derived from a simple application of gas phase ion molecule interstellar chemistry. It is noted that unlike the fractionation of deuterated molecules, it applies to warm as well as to cool clouds. The method is illustrated with the results of the recent abundance survey of Wooten et al. (1978). Finally, it is shown that in cases where deuterium enhancement is measured, an upper limit can be obtained for the cosmic ray ionization rate.

  10. Coronal element abundances derived from solar energetic particles

    NASA Technical Reports Server (NTRS)

    Reames, Donald V.

    1994-01-01

    The large gradual solar-energetic-particle (SEP) events, where abundances are commonly measured, are produced when coronal mass ejections (CMEs) drive shock waves through the corona and the interplanetary medium. The shock accelerates particles from the highly-ionized, approximately 1.5 MK, plasma in a manner that depends only weakly upon the Q/A of the ion, except at very high energies. Averaging the approximately 1 MeV/amu abundances over many events compensates for the acceleration effects to produce abundances that appear to correspond directly to those in the coronal source for all observed elements, including H. The resulting abundances reflect the 4 x enhancement of ions with low values of first ionization potential (FIP) arising from ion-neutral fractionation that occurs as the atoms are transported up from the photosphere. A different pattern of fractionation is found for ions that are shock-accelerated from the high speed solar wind emerging from coronal holes.

  11. Relative abundance of desert tortoises on the Nevada Test Site

    SciTech Connect

    Rautenstrauch, K.R.; O`Farrell, T.P.

    1993-12-31

    Seven hundred fifty-nine transects having a total length of 1,191 km were walked during 1981--1986 to determine the distribution and relative abundance of desert tortoises (Gopherus agassizii) on the Nevada Test Site (NTS). The abundance of tortoises on NTS was low to very low relative to other populations in the Mojave Desert. Sign of tortoises was found from 880 to 1,570 m elevation and was more abundant above 1,200 m than has been reported previously for Nevada. Tortoises were more abundant on NTS on the upper alluvial fans and slopes of mountains than in valley bottoms. They also were more common on or near limestone and dolomite mountains than on mountains of volcanic origin.

  12. THE ATOMIC WEIGHTS COMMISSION AND ISOTOPIC ABUNDANCE RATIO DETERMINATIONS.

    SciTech Connect

    HOLDEN, N.E.

    2005-08-07

    Following Thomson's discovery of stable isotopes in non-radioactive chemical elements, the derivation of atomic weight values from mass spectrometric measurements of isotopic abundance ratios moved very slowly. Forty years later, only 3 1/2 % of the recommended values were based on mass spectrometric measurements and only 38% in the first half century. It might be noted that two chemical elements (tellurium and mercury) are still based on chemical measurements, where the atomic weight value calculated from the relative isotopic abundance measurement either agrees with the value from the chemical measurement or the atomic weight value calculated from the relative isotopic abundance measurement falls within the uncertainty of the chemical measurement of the atomic weight. Of the 19 chemical elements, whose atomic weight is based on non-corrected relative isotopic abundance measurements, five of these are two isotope systems (indium, iridium, lanthanum, lutetium and tantalum) and one is a three-isotope system (oxygen).

  13. Why abundant tropical tree species are phylogenetically old.

    PubMed

    Wang, Shaopeng; Chen, Anping; Fang, Jingyun; Pacala, Stephen W

    2013-10-01

    Neutral models of species diversity predict patterns of abundance for communities in which all individuals are ecologically equivalent. These models were originally developed for Panamanian trees and successfully reproduce observed distributions of abundance. Neutral models also make macroevolutionary predictions that have rarely been evaluated or tested. Here we show that neutral models predict a humped or flat relationship between species age and population size. In contrast, ages and abundances of tree species in the Panamanian Canal watershed are found to be positively correlated, which falsifies the models. Speciation rates vary among phylogenetic lineages and are partially heritable from mother to daughter species. Variable speciation rates in an otherwise neutral model lead to a demographic advantage for species with low speciation rate. This demographic advantage results in a positive correlation between species age and abundance, as found in the Panamanian tropical forest community.

  14. Oxygen and nitrogen abundances in Virgo and field spirals

    NASA Astrophysics Data System (ADS)

    Pilyugin, L. S.; Mollá, M.; Ferrini, F.; Vílchez, J. M.

    2002-01-01

    The oxygen and nitrogen abundances in the H II regions of the nine Virgo spirals of the sample from Skillman et al. (1996) and in nine field spiral galaxies are re-determined with the recently suggested P-method. We confirm that there is an abundance segregation in the sample of Virgo spirals in the sense that the H I deficient Virgo spirals near the core of the cluster have higher oxygen abundances in comparison to the spirals at the periphery of the Virgo cluster. At the same time both the Virgo periphery and core spirals have counterparts among field spirals. Some field spirals have H I to optical radius ratios, similar to that in H I deficient Virgo core spirals. We conclude that if there is a difference in the abundance properties of the Virgo and field spirals, this difference appears to be small and masked by the observational errors.

  15. Abundance of Asymmetric Dark Matter in Brane World Cosmology

    NASA Astrophysics Data System (ADS)

    Abdusattar, Haximjan; Iminniyaz, Hoernisa

    2016-09-01

    Relic abundance of asymmetric Dark Matter particles in brane world cosmological scenario is investigated in this article. Hubble expansion rate is enhanced in brane world cosmology and it affects the relic abundance of asymmetric Dark Matter particles. We analyze how the relic abundance of asymmetric Dark Matter is changed in this model. We show that in such kind of nonstandard cosmological scenario, indirect detection of asymmetric Dark Matter is possible if the cross section is small enough which let the anti-particle abundance kept in the same amount with the particle. We show the indirect detection signal constraints can be used to such model only when the cross section and the 5-dimensional Planck mass scale are in appropriate values. Supported by the National Natural Science Foundation of China under Grant No. 11365022

  16. Dark Energy and The Dark Matter Relic Abundance

    SciTech Connect

    Rosati, Francesca

    2004-11-17

    Two mechanisms by which the quintessence scalar could enhance the relic abundance of dark matter particles are discussed. These effects can have an impact on supersymmetric candidates for dark matter.

  17. A SOLAR SPECTROSCOPIC ABSOLUTE ABUNDANCE OF ARGON FROM RESIK

    SciTech Connect

    Sylwester, J.; Sylwester, B.; Phillips, K. J. H.; Kuznetsov, V. D. E-mail: kjhp@mssl.ucl.ac.u

    2010-09-10

    Observations of He-like and H-like Ar (Ar XVII and Ar XVIII) lines at 3.949 A and 3.733 A, respectively, with the RESIK X-ray spectrometer on the CORONAS-F spacecraft, together with temperatures and emission measures from the two channels of GOES, have been analyzed to obtain the abundance of Ar in flare plasmas in the solar corona. The line fluxes per unit emission measure show a temperature dependence like that predicted from theory and lead to spectroscopically determined values for the absolute Ar abundance, A(Ar) = 6.44 {+-} 0.07 (Ar XVII) and 6.49 {+-} 0.16 (Ar XVIII), which are in agreement to within uncertainties. The weighted mean is 6.45 {+-} 0.06, which is between two recent compilations of the solar Ar abundance and suggests that the photospheric and coronal abundances of Ar are very similar.

  18. Aquifer water abundance evaluation using a fuzzy- comprehensive weighting method

    NASA Astrophysics Data System (ADS)

    Wei, Z.

    2016-08-01

    Aquifer water abundance evaluation is a highly relevant issue that has been researched for many years. Despite prior research, problems with the conventional evaluation method remain. This paper establishes an aquifer water abundance evaluation method that combines fuzzy evaluation with a comprehensive weighting method to overcome both the subjectivity and lack of conformity in determining weight by pure data analysis alone. First, this paper introduces the principle of a fuzzy-comprehensive weighting method. Second, the example of well field no. 3 (of a coalfield) is used to illustrate the method's process. The evaluation results show that this method is can more suitably meet the real requirements of aquifer water abundance assessment, leading to more precise and accurate evaluations. Ultimately, this paper provides a new method for aquifer water abundance evaluation.

  19. Stellar oxygen abundances. 3: The oxygen abundance of the very metal poor halo star BD -13 deg 3442

    NASA Technical Reports Server (NTRS)

    King, Jeremy R.

    1994-01-01

    A spectrum of the very metal poor ((Fe/H) approximately -3) halo star BD -13 deg 3442 is presented and used to determine this star's oxygen abundance. Our determination makes BD -13 deg 3442 the most metal poor dwarf (though a somewhat evolved one) with an O abundance determination. The O abundance (determined from the 7774 A O I triped) and (O/Fe) ratio is compared to that of two other metal-poor stars. The (O/Fe) ratio of BD -13 deg 3442 is found to be approximately 0.35 dex larger than that of the other two halo stars. Possible implications of this result are discussed.

  20. Early nucleosynthesis and chemical abundances of stars in globular clusters.

    NASA Astrophysics Data System (ADS)

    Gratton, R. G.

    This cycle of lectures presents a self consistent sketch of current understanding about chemcial composition of globular clusters and its aftermaths. The first two lectures give basic about nucleosynthesis, chemical models, and abundance determinations. Main results for globular clusters are presented in the next two lectures. In the final lecture the author reviews various indices used to derive abundances from photometry and low dispersion spectroscopy.

  1. Abundance analysis of the outer halo globular cluster Palomar 14

    NASA Astrophysics Data System (ADS)

    Çalışkan, Ş.; Christlieb, N.; Grebel, E. K.

    2012-01-01

    We determine the elemental abundances of nine red giant stars belonging to Palomar 14 (Pal 14). Pal 14 is an outer halo globular cluster (GC) at a distance of ~70 kpc. Our abundance analysis is based on high-resolution spectra and one-dimensional stellar model atmospheres. We derived the abundances for the iron peak elements Sc, V, Cr, Mn, Co, Ni, the α-elements O, Mg, Si, Ca, Ti, the light odd element Na, and the neutron-capture elements Y, Zr, Ba, La, Ce, Nd, Eu, Dy, and Cu. Our data do not permit us to investigate light element (i.e., O to Mg) abundance variations. The neutron-capture elements show an r-process signature. We compare our measurements with the abundance ratios of inner and other outer halo GCs, halo field stars, GCs of recognized extragalactic origin, and stars in dwarf spheroidal galaxies (dSphs). The abundance pattern of Pal 14 is almost identical to those of Pal 3 and Pal 4, the next distant members of the outer halo GC population after Pal 14. The abundance pattern of Pal 14 is also similar to those of the inner halo GCs, halo field stars, and GCs of recognized extragalactic origin, but differs from what is customarily found in dSphs field stars. The abundance properties of Pal 14, as well as those of the other outer halo GCs, are thus compatible with an accretion origin from dSphs. Whether or not GC accretion played a role, it seems that the formation conditions of outer halo GCs and GCs in dSphs were similar. Based on observations collected at the European Southern Observatory, Chile (Program IDs 077.B-0769).Tables A.1 and A.2 are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/537/A83

  2. Literature survey of isotopic abundance data for 1987-1989

    SciTech Connect

    Holden, N.E. )

    1989-08-09

    I have compiled all of the data on isotopic abundance measurements and their variation in nature for the time period since the last General Assembly. Most of the data deals with the variations in the abundances as given by per mil deviations from some standard. As such, they are not of major interest to the Atomic Weights Commission. However, there were some measurements which are of general interest in this list.

  3. Solar-system abundances and processes of nucleosynthesis

    NASA Technical Reports Server (NTRS)

    Woolum, Dorothy S.

    1988-01-01

    The origin of the elements is studied. The average elemental composition of the solar system is examined and used to infer the primordial solar system abundances of the individual nuclides. Patterns in these nuclide abundances are used as clues to their origin. The possible cosmic significance of the patterns are considered. The astrophysical settings for nucleosynthesis and the chemical evolution of the Galaxy and information based on observed isotopic anomalies in meteorites are taken into account.

  4. THE EFFECTS OF INITIAL ABUNDANCES ON NITROGEN IN PROTOPLANETARY DISKS

    SciTech Connect

    Schwarz, Kamber R.; Bergin, Edwin A.

    2014-12-20

    The dominant form of nitrogen provided to most solar system bodies is currently unknown, though available measurements show that the detected nitrogen in solar system rocks and ices is depleted with respect to solar abundances and the interstellar medium. We use a detailed chemical/physical model of the chemical evolution of a protoplanetary disk to explore the evolution and abundance of nitrogen-bearing molecules. Based on this model, we analyze how initial chemical abundances provided as either gas or ice during the early stages of disk formation influence which species become the dominant nitrogen bearers at later stages. We find that a disk with the majority of its initial nitrogen in either atomic or molecular nitrogen is later dominated by atomic and molecular nitrogen as well as NH{sub 3} and HCN ices, where the dominant species varies with disk radius. When nitrogen is initially in gaseous ammonia, it later becomes trapped in ammonia ice except in the outer disk where atomic nitrogen dominates. For a disk with the initial nitrogen in the form of ammonia ice, the nitrogen remains trapped in the ice as NH{sub 3} at later stages. The model in which most of the initial nitrogen is placed in atomic N best matches the ammonia abundances observed in comets. Furthermore, the initial state of nitrogen influences the abundance of N{sub 2}H{sup +}, which has been detected in protoplanetary disks. Strong N{sub 2}H{sup +} emission is found to be indicative of an N{sub 2} abundance greater than n{sub N{sub 2}}/n{sub H{sub 2}}>10{sup −6} in addition to tracing the CO snow line. Our models also indicate that NO is potentially detectable, with lower N gas abundances leading to higher NO abundances.

  5. Estimating site occupancy and abundance using indirect detection indices

    USGS Publications Warehouse

    Stanley, T.R.; Royle, J. Andrew

    2005-01-01

    Knowledge of factors influencing animal distribution and abundance is essential in many areas of ecological research, management, and policy-making. Because common methods for modeling and estimating abundance (e.g., capture-recapture, distance sampling) are sometimes not practical for large areas or elusive species, indices are sometimes used as surrogate measures of abundance. We present an extension of the Royle and Nichols (2003) generalization of the MacKenzie et al. (2002) site-occupancy model that incorporates length of the sampling interval into the, model for detection probability. As a result, we obtain a modeling framework that shows how useful information can be extracted from a class of index methods we call indirect detection indices (IDIs). Examples of IDIs include scent station, tracking tube, snow track, tracking plate, and hair snare surveys. Our model is maximum likelihood, and it can be used to estimate site occupancy and model factors influencing patterns of occupancy and abundance in space. Under certain circumstances, it can also be used to estimate abundance. We evaluated model properties using Monte Carlo simulations and illustrate the method with tracking tube and scent station data. We believe this model will be a useful tool for determining factors that influence animal distribution and abundance.

  6. Stronger warming effects on microbial abundances in colder regions

    DOE PAGES

    Chen, Ji; Luo, Yiqi; Xia, Jianyang; ...

    2015-12-10

    Soil microbes play critical roles in regulating terrestrial carbon (C) cycle and its feedback to climate change. However, it is still unclear how the soil microbial community and abundance respond to future climate change scenarios. In this meta-analysis, we synthesized the responses of microbial community and abundance to experimental warming from 64 published field studies. Our results showed that warming significantly increased soil microbial abundance by 7.6% on average. When grouped by vegetation or soil types, tundras and histosols had the strongest microbial responses to warming with increased microbial, fungal, and bacterial abundances by 15.0%, 9.5% and 37.0% in tundra,more » and 16.5%, 13.2% and 13.3% in histosols, respectively. We found significant negative relationships of the response ratios of microbial, fungal and bacterial abundances with the mean annual temperature, indicating that warming had stronger effects in colder than warmer regions. Moreover, the response ratios of microbial abundance to warming were positively correlated with those of soil respiration. Our results therefore indicate that the large quantities of C stored in colder regions are likely to be more vulnerable to climate warming than the soil C stored in other warmer regions.« less

  7. DIRECT EVALUATION OF THE HELIUM ABUNDANCES IN OMEGA CENTAURI

    SciTech Connect

    Dupree, A. K.; Avrett, E. H. E-mail: eavrett@cfa.harvard.edu

    2013-08-20

    A direct measure of the helium abundances from the near-infrared transition of He I at 1.08 {mu}m is obtained for two nearly identical red giant stars in the globular cluster Omega Centauri. One star exhibits the He I line; the line is weak or absent in the other star. Detailed non-local thermal equilibrium semi-empirical models including expansion in spherical geometry are developed to match the chromospheric H{alpha}, H{beta}, and Ca II K lines, in order to predict the helium profile and derive a helium abundance. The red giant spectra suggest a helium abundance of Y {<=} 0.22 (LEID 54064) and Y = 0.39-0.44 (LEID 54084) corresponding to a difference in the abundance {Delta}Y {>=} 0.17. Helium is enhanced in the giant star (LEID 54084) that also contains enhanced aluminum and magnesium. This direct evaluation of the helium abundances gives observational support to the theoretical conjecture that multiple populations harbor enhanced helium in addition to light elements that are products of high-temperature hydrogen burning. We demonstrate that the 1.08 {mu}m He I line can yield a helium abundance in cool stars when constraints on the semi-empirical chromospheric model are provided by other spectroscopic features.