Science.gov

Sample records for batiments gdf suez

  1. 75 FR 57911 - Application To Export Electric Energy; GDF SUEZ Energy Marketing NA, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-23

    ... Application To Export Electric Energy; GDF SUEZ Energy Marketing NA, Inc. AGENCY: Office of Electricity Delivery and Energy Reliability, DOE. ACTION: Notice of application. SUMMARY: GDF SUEZ Energy Marketing NA... utilities, Federal power marketing agencies and other entities within the United States. The existing...

  2. Cost estimate for a proposed GDF Suez LNG testing program

    SciTech Connect

    Blanchat, Thomas K.; Brady, Patrick Dennis; Jernigan, Dann A.; Luketa, Anay Josephine; Nissen, Mark R.; Lopez, Carlos; Vermillion, Nancy; Hightower, Marion Michael

    2014-02-01

    At the request of GDF Suez, a Rough Order of Magnitude (ROM) cost estimate was prepared for the design, construction, testing, and data analysis for an experimental series of large-scale (Liquefied Natural Gas) LNG spills on land and water that would result in the largest pool fires and vapor dispersion events ever conducted. Due to the expected cost of this large, multi-year program, the authors utilized Sandia's structured cost estimating methodology. This methodology insures that the efforts identified can be performed for the cost proposed at a plus or minus 30 percent confidence. The scale of the LNG spill, fire, and vapor dispersion tests proposed by GDF could produce hazard distances and testing safety issues that need to be fully explored. Based on our evaluations, Sandia can utilize much of our existing fire testing infrastructure for the large fire tests and some small dispersion tests (with some modifications) in Albuquerque, but we propose to develop a new dispersion testing site at our remote test area in Nevada because of the large hazard distances. While this might impact some testing logistics, the safety aspects warrant this approach. In addition, we have included a proposal to study cryogenic liquid spills on water and subsequent vaporization in the presence of waves. Sandia is working with DOE on applications that provide infrastructure pertinent to wave production. We present an approach to conduct repeatable wave/spill interaction testing that could utilize such infrastructure.

  3. 77 FR 39689 - Application To Export Electric Energy; IPR-GDF SUEZ Energy Marketing North America, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-05

    ...; IPR-GDF SUEZ Energy Marketing North America, Inc. AGENCY: Office of Electricity Delivery and Energy Reliability, DOE. ACTION: Notice of application. SUMMARY: IPR-GDF SUEZ Energy Marketing North America, Inc... Mexico would be surplus energy purchased from electric utilities, Federal power marketing agencies, and...

  4. ASTER Suez Canal

    NASA Image and Video Library

    2000-10-06

    One of the most important waterways in the world, the Suez Canal runs north to south across the Isthmus of Suez in northeastern Egypt. This image of the canal covers an area 36 kilometers (22 miles) wide and 60 kilometers (47 miles) long in three bands of the reflected visible and infrared wavelength region. It shows the northern part of the canal, with the Mediterranean Sea just visible in the upper right corner. The Suez Canal connects the Mediterranean Sea with the Gulf of Suez, an arm of the Red Sea. The artificial canal provides an important shortcut for ships operating between both European and American ports and ports located in southern Asia, eastern Africa, and Oceania. With a length of about 195 kilometers (121 miles) and a minimum channel width of 60 meters (197 feet), the Suez Canal is able to accommodate ships as large as 150,000 tons fully loaded. Because no locks interrupt traffic on this sea level waterway, the transit time only averages about 15 hours. ASTER acquired this scene on May 19, 2000. http://photojournal.jpl.nasa.gov/catalog/PIA02661

  5. Gulf of Suez, Egypt

    SciTech Connect

    Schuetz, K.I. )

    1988-08-01

    The Gulf of Suez is an intracratonic rift basin which originated in the early Miocene on the once-continuous Arabo-African plate. The Precambrian crystalline basement is overlain by a platform cover of Early Cambrian to Eocene age. There is no evidence of tectonic precursors to the Miocene breakup. Marine transgressions, for example during the Carboniferous and Cretaceous, followed wide embayments caused by long-wavelength oscillations trending northwest-southeast on the North African craton. This article discusses the geologic history of the Gulf.

  6. ASTER Suez Canal

    NASA Technical Reports Server (NTRS)

    2000-01-01

    One of the most important waterways in the world, the Suez Canal runs north to south across the Isthmus of Suez in northeastern Egypt. This image of the canal covers an area 36 kilometers (22 miles) wide and 60 kilometers (47 miles) long in three bands of the reflected visible and infrared wavelength region. It shows the northern part of the canal, with the Mediterranean Sea just visible in the upper right corner. The Suez Canal connects the Mediterranean Sea with the Gulf of Suez, an arm of the Red Sea. The artificial canal provides an important shortcut for ships operating between both European and American ports and ports located in southern Asia, eastern Africa, and Oceania. With a length of about 195 kilometers (121 miles) and a minimum channel width of 60 meters (197 feet), the Suez Canal is able to accommodate ships as large as 150,000 tons fully loaded. Because no locks interrupt traffic on this sea level waterway, the transit time only averages about 15 hours. ASTER acquired this scene on May 19, 2000.

    Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) is one of five Earth-observing instruments launched December 18, 1999, on NASA's Terra satellite. The instrument was built by Japan's Ministry of International Trade and Industry. A joint U.S./Japan science team is responsible for validation and calibration of the instrument and the data products. Dr. Anne Kahle at NASA's Jet Propulsion Laboratory, Pasadena, California, is the U.S. science team leader; Moshe Pniel of JPL is the project manager. ASTER is the only high-resolution imaging sensor on Terra. The primary goal of the ASTER mission is to obtain high-resolution image data in 14 channels over the entire land surface, as well as black and white stereo images. With revisit time of between 4 and 16 days, ASTER will provide the capability for repeat coverage of changing areas on Earth's surface. Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) is one of five

  7. ASTER Suez Canal

    NASA Technical Reports Server (NTRS)

    2000-01-01

    One of the most important waterways in the world, the Suez Canal runs north to south across the Isthmus of Suez in northeastern Egypt. This image of the canal covers an area 36 kilometers (22 miles) wide and 60 kilometers (47 miles) long in three bands of the reflected visible and infrared wavelength region. It shows the northern part of the canal, with the Mediterranean Sea just visible in the upper right corner. The Suez Canal connects the Mediterranean Sea with the Gulf of Suez, an arm of the Red Sea. The artificial canal provides an important shortcut for ships operating between both European and American ports and ports located in southern Asia, eastern Africa, and Oceania. With a length of about 195 kilometers (121 miles) and a minimum channel width of 60 meters (197 feet), the Suez Canal is able to accommodate ships as large as 150,000 tons fully loaded. Because no locks interrupt traffic on this sea level waterway, the transit time only averages about 15 hours. ASTER acquired this scene on May 19, 2000.

    Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) is one of five Earth-observing instruments launched December 18, 1999, on NASA's Terra satellite. The instrument was built by Japan's Ministry of International Trade and Industry. A joint U.S./Japan science team is responsible for validation and calibration of the instrument and the data products. Dr. Anne Kahle at NASA's Jet Propulsion Laboratory, Pasadena, California, is the U.S. science team leader; Moshe Pniel of JPL is the project manager. ASTER is the only high-resolution imaging sensor on Terra. The primary goal of the ASTER mission is to obtain high-resolution image data in 14 channels over the entire land surface, as well as black and white stereo images. With revisit time of between 4 and 16 days, ASTER will provide the capability for repeat coverage of changing areas on Earth's surface. Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) is one of five

  8. Suez Canal, Gulf of Suez, Sinai Peninsula, Egypt, as seen from the Apollo 7

    NASA Technical Reports Server (NTRS)

    1968-01-01

    Suez Canal, Gulf of Suez, Sinai Peninsula, United Arab Republic (Egypt), Mediterranean Sea, as seen from the Apollo 7 spacecraft during its 13th revolution of the earth. Photographed from an altitude of 126 nautical miles, at ground elapsed time of 19 hours and 42 minutes.

  9. Suez Canal, Gulf of Suez, Sinai Peninsula, Egypt, as seen from the Apollo 7

    NASA Image and Video Library

    1968-10-12

    Suez Canal, Gulf of Suez, Sinai Peninsula, United Arab Republic (Egypt), Mediterranean Sea, as seen from the Apollo 7 spacecraft during its 13th revolution of the earth. Photographed from an altitude of 126 nautical miles, at ground elapsed time of 19 hours and 42 minutes.

  10. GDF v2.0, an enhanced version of GDF

    NASA Astrophysics Data System (ADS)

    Tsoulos, Ioannis G.; Gavrilis, Dimitris; Dermatas, Evangelos

    2007-12-01

    An improved version of the function estimation program GDF is presented. The main enhancements of the new version include: multi-output function estimation, capability of defining custom functions in the grammar and selection of the error function. The new version has been evaluated on a series of classification and regression datasets, that are widely used for the evaluation of such methods. It is compared to two known neural networks and outperforms them in 5 (out of 10) datasets. Program summaryTitle of program: GDF v2.0 Catalogue identifier: ADXC_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADXC_v2_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 98 147 No. of bytes in distributed program, including test data, etc.: 2 040 684 Distribution format: tar.gz Programming language: GNU C++ Computer: The program is designed to be portable in all systems running the GNU C++ compiler Operating system: Linux, Solaris, FreeBSD RAM: 200000 bytes Classification: 4.9 Does the new version supersede the previous version?: Yes Nature of problem: The technique of function estimation tries to discover from a series of input data a functional form that best describes them. This can be performed with the use of parametric models, whose parameters can adapt according to the input data. Solution method: Functional forms are being created by genetic programming which are approximations for the symbolic regression problem. Reasons for new version: The GDF package was extended in order to be more flexible and user customizable than the old package. The user can extend the package by defining his own error functions and he can extend the grammar of the package by adding new functions to the function repertoire. Also, the new version can perform function estimation of multi

  11. Association of plasma GDF-9 or GDF-15 levels with bone parameters in polycystic ovary syndrome.

    PubMed

    Berberoglu, Zehra; Aktas, Aynur; Fidan, Yasemin; Yazici, Ayse Canan; Aral, Yalcin

    2015-01-01

    We aimed to determine plasma levels of growth and differentiation factor (GDF)-9 and GDF-15, and their possible association with bone turnover parameters and bone mineral density (BMD), in patients with polycystic ovary syndrome (PCOS). Forty-two obese PCOS women aged 25-35 years, 23 women with idiopathic hirsutism (IH) and 20 healthy controls matched for age and body mass index were enrolled. Anthropometric, metabolic and hormonal patterns, plasma GDF-9 and GDF-15 concentrations, bone turnover markers and BMD were measured. No significant differences were observed in bone turnover markers, BMD measurements, plasma GDF-9 and GDF-15 levels in subjects with PCOS compared with the other two groups. In the combined population of all three groups, GDF-15 concentrations were negatively correlated with osteocalcin (r = -0.317, p < 0.01). Analysis of PCOS patients showed a significant correlation of GDF-15 concentrations with age and homeostasis model assessment index (r = 0.319, p < 0.05, and r = 0.312, p < 0.05, respectively). In addition, GDF-15 concentrations were negatively correlated with osteocalcin (r = -0.395, p < 0.01) and positively correlated with urine deoxypyridinoline (r = 0.353, p < 0.05). GDF-9 did not correlate with bone markers and BMD measurements. In conclusion, plasma GDF-9 and GDF-15 levels as well as bone turnover markers and BMD measurements in subjects with PCOS (25-35 years of age) were comparable with those either in subjects with IH or in healthy controls with similar anthropometric and metabolic profiles. GDF-15 might be a marker of a crossregulation between bone and energy metabolism.

  12. Distinct and cooperative roles of mammalian Vg1 homologs GDF1 and GDF3 during early embryonic development.

    PubMed

    Andersson, Olov; Bertolino, Philippe; Ibáñez, Carlos F

    2007-11-15

    Vg1, a member of the TGF-beta superfamily of ligands, has been implicated in the induction of mesoderm, formation of primitive streak, and left-right patterning in Xenopus and chick embryos. In mice, GDF1 and GDF3 - two TGF-beta superfamily ligands that share high sequence identity with Vg1 - have been shown to independently mimic distinct aspects of Vg1's functions. However, the extent to which the developmental processes controlled by GDF1 and GDF3 and the underlying signaling mechanisms are evolutionarily conserved remains unclear. Here we show that phylogenetic and genomic analyses indicate that Gdf1 is the true Vg1 ortholog in mammals. In addition, and similar to GDF1, we find that GDF3 signaling can be mediated by the type I receptor ALK4, type II receptors ActRIIA and ActRIIB, and the co-receptor Cripto to activate Smad-dependent reporter genes. When expressed in heterologous cells, the native forms of either GDF1 or GDF3 were incapable of inducing downstream signaling. This could be circumvented by using chimeric constructs carrying heterologous prodomains, or by co-expression with the Furin pro-protein convertase, indicating poor processing of the native GDF1 and GDF3 precursors. Unexpectedly, co-expression with Nodal - another TGF-beta superfamily ligand involved in mesoderm formation - could also expose the activities of native GDF1 and GDF3, suggesting a potentially novel mode of cooperation between these ligands. Functional complementarity between GDF1 and GDF3 during embryonic development was investigated by analyzing genetic interactions between their corresponding genes. This analysis showed that Gdf1(-/-);Gdf3(-/-) compound mutants are more severely affected than either Gdf1(-/-) or Gdf3(-/-) single mutants, with defects in the formation of anterior visceral endoderm and mesoderm that recapitulate Vg1 loss of function, suggesting that GDF1 and GDF3 together represent the functional mammalian homologs of Vg1.

  13. The versatility and paradox of GDF 11.

    PubMed

    Jamaiyar, A; Wan, W; Janota, D M; Enrick, M K; Chilian, W M; Yin, L

    2017-02-14

    In addition to its roles in embryonic development, Growth and Differentiation Factor 11 (GDF 11) has recently drawn much interest about its roles in other processes, such as aging. GDF 11 has been shown to play pivotal roles in the rescue of the proliferative and regenerative capabilities of skeletal muscle, neural stem cells and cardiomyocytes. We would be remiss not to point that some controversy exists regarding the role of GDF 11 in biological processes and whether it will serve as a therapeutic agent. The latest studies have shown that the level of circulating GDF 11 correlates with the outcomes of patients with cardiovascular diseases, cancer and uremia. Based on these studies, GDF 11 is a promising candidate to serve as a novel biomarker of diseases. This brief review gives a detailed and concise view of the regulation and functions of GDF 11 and its roles in development, neurogenesis and erythropoiesis as well as the prospect of using this protein as an indicator of cardiac health and aging.

  14. GDF15 — EDRN Public Portal

    Cancer.gov

    GDF15, also known as macrophage inhibitory cytokine 1, or MIC1, is a bone morphogenetic protein (BMP) belonging to the transforming growth factor-beta (TGF-beta) superfamily. The bone morphogenetic proteins regulate tissue differentiation and maintenance. GDF15 is a secreted protein that is highly expressed in placenta, with lower levels in prostate and colon and some expression in kidney. Bone morphogenetic protein precursor molecules are cleaved at a dibasic site to release C-terminal domains with 7 conserved cysteines in the mature protein.

  15. GDF15 promotes EMT and metastasis in colorectal cancer.

    PubMed

    Li, Chen; Wang, Jingyu; Kong, Jianlu; Tang, Jinlong; Wu, Yihua; Xu, Enping; Zhang, Honghe; Lai, Maode

    2016-01-05

    Metastasis is the major cause of cancer deaths, and the epithelial-mesenchymal transition (EMT) has been considered to be a fundamental event in cancer metastasis. However, the role of growth differentiation factor 15 (GDF15) in colorectal cancer (CRC) metastasis and EMT remains poorly understood. Here, we showed that GDF15 promoted CRC cell metastasis both in vitro and in vivo. In addition, the EMT process was enhanced by GDF15 through binding to TGF-β receptor to activate Smad2 and Smad3 pathways. Clinical data showed GDF15 level in tumor tissues, and the serum was significantly increased, in which high GDF15 level correlated with a reduced overall survival in CRC. Thus, GDF15 may promote colorectal cancer metastasis through activating EMT. Promisingly, GDF15 could be considered as a novel prognostic marker for CRC in the clinic.

  16. Mechanisms of GDF-5 action during skeletal development.

    PubMed

    Francis-West, P H; Abdelfattah, A; Chen, P; Allen, C; Parish, J; Ladher, R; Allen, S; MacPherson, S; Luyten, F P; Archer, C W

    1999-03-01

    Mutations in GDF-5, a member of the TGF-beta superfamily, result in the autosomal recessive syndromes brachypod (bp) in mice and Hunter-Thompson and Grebe-type chondrodysplasias in humans. These syndromes are all characterised by the shortening of the appendicular skeleton and loss or abnormal development of some joints. To investigate how GDF-5 controls skeletogenesis, we overexpressed GDF-5 during chick limb development using the retrovirus, RCASBP. This resulted in up to a 37.5% increase in length of the skeletal elements, which was predominantly due to an increase in the number of chondrocytes. By injecting virus at different stages of development, we show that GDF-5 can increase both the size of the early cartilage condensation and the later developing skeletal element. Using in vitro micromass cultures as a model system to study the early steps of chondrogenesis, we show that GDF-5 increases chondrogenesis in a dose-dependent manner. We did not detect changes in proliferation. However, cell suspension cultures showed that GDF-5 might act at these stages by increasing cell adhesion, a critical determinant of early chondrogenesis. In contrast, pulse labelling experiments of GDF-5-infected limbs showed that at later stages of skeletal development GDF-5 can increase proliferation of chondrocytes. Thus, here we show two mechanisms of how GDF-5 may control different stages of skeletogenesis. Finally, our data show that levels of GDF-5 expression/activity are important in controlling the size of skeletal elements and provides a possible explanation for the variation in the severity of skeletal defects resulting from mutations in GDF-5.

  17. Rift offsets, Gulf of Suez, Egypt

    SciTech Connect

    Patton, T.L.; Nelson, R.A.

    1988-02-01

    Structure and stratigraphic mapping in the northern half of the Gulf of Suez (GOS) documents two en echelon, rift-parallel (Clysmic trend) rift segments. The segments are right stepping and share a zone of overlap, which extends southward from the southern border of the Wadi Araba structure on the western shore of the gulf to the north end of the Abu Durba block on the east side of the gulf. The spatial relationship of the two segments defines the central GOS rift offset, and the structural depression linking the segments in the area of overlap forms a rift-offset zone. Another potential rift offset, though less well constrained, also with a north-south trend may be present south of Gebel Zeit. This rift and the central GOS rift offset provide a model for the opening of the GOS in which north-south rift-offset zones link Clysmic-trending rift segments, imparting a regional zig-zag pattern to the initial rift configuration. Recognition of offset zones and their associated fault fabrics is essential for effective exploration of rift basins. For example, the alignment of producing fields and elongation directions of individual fields in the central GOS offset are anomalous relative to those of other producing trends in the Gulf.

  18. Adlai Stevenson and the Suez Crisis of 1956.

    ERIC Educational Resources Information Center

    Graff, Leo W., Jr.

    1982-01-01

    This study examines Adlai Stevenson's response to the Suez crisis, the Arab-Israeli conflict, and the struggle between the nationalism emerging in Third World countries and the imperialism fading in Europe. It also looks at Stevenson's stance toward Israel and his relations with American Zionists during the 1956 presidential campaign. (AM)

  19. GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation

    PubMed Central

    Liu, Weiqing; Zhou, Liyan; Zhou, Chenchen; Zhang, Shiwen; Jing, Junjun; Xie, Liang; Sun, Ningyuan; Duan, Xiaobo; Jing, Wei; Liang, Xing; Zhao, Hu; Ye, Ling; Chen, Qianming; Yuan, Quan

    2016-01-01

    Osteoporosis is an age-related disease that affects millions of people. Growth differentiation factor 11 (GDF11) is a secreted member of the transforming growth factor beta (TGF-β) superfamily. Deletion of Gdf11 has been shown to result in a skeletal anterior–posterior patterning disorder. Here we show a role for GDF11 in bone remodelling. GDF11 treatment leads to bone loss in both young and aged mice. GDF11 inhibits osteoblast differentiation and also stimulates RANKL-induced osteoclastogenesis through Smad2/3 and c-Fos-dependent induction of Nfatc1. Injection of GDF11 impairs bone regeneration in mice and blocking GDF11 function prevents oestrogen-deficiency-induced bone loss and ameliorates age-related osteoporosis. Our data demonstrate that GDF11 is a previously unrecognized regulator of bone remodelling and suggest that GDF11 is a potential target for treatment of osteoporosis. PMID:27653144

  20. Foxg1 promotes olfactory neurogenesis by antagonizing Gdf11

    PubMed Central

    Kawauchi, Shimako; Kim, Joon; Santos, Rosaysela; Wu, Hsiao-Huei; Lander, Arthur D.; Calof, Anne L.

    2009-01-01

    Summary Foxg1, a winged-helix transcription factor, promotes the development of anterior neural structures; in mice lacking Foxg1, development of the cerebral hemispheres and olfactory epithelium (OE) is severely reduced. It has been suggested that Foxg1 acts by positively regulating the expression of growth factors, such as Fgf8, which support neurogenesis. However, Foxg1 also binds Smad transcriptional complexes, allowing it to negatively regulate the effects of TGFβ family ligands. Here, we provide evidence that this latter effect explains much of the ability of Foxg1 to drive neurogenesis in the OE. We show that Foxg1 is expressed in developing OE at the same time as the gene encoding growth differentiation factor 11 (Gdf11), a TGFβ family member that mediates negative-feedback control of OE neurogenesis. Mutations in Gdf11 rescue, to a considerable degree, the major defects in Foxg1-/- OE, including the early, severe loss of neural precursors and olfactory receptor neurons, and the subsequent collapse of both neurogenesis and nasal cavity formation. Rescue is gene-dosage dependent, with loss of even one allele of Gdf11 restoring substantial neurogenesis. Notably, we find no evidence for a disruption of Fgf8 expression in Foxg1-/- OE. However, we do observe both a failure of expression of follistatin (Fst), which encodes a secreted Gdf11 antagonist normally expressed in and around OE, and an increase in the expression of Gdf11 itself within the remaining OE in these mutants. Fst expression is rescued in Foxg1-/-;Gdf11-/- and Foxg1-/-;Gdf11+/- mice. These data suggest that the influence of Foxg1 on Gdf11-mediated negative feedback of neurogenesis may be both direct and indirect. In addition, defects in development of the cerebral hemispheres in Foxg1-/- mice are not rescued by mutations in Gdf11, nor is Gdf11 expressed at high levels within these structures. Thus, the pro-neurogenic effects of Foxg1 are likely to be mediated through different signaling

  1. Mites (acari) infesting commensal rats in Suez Canal zone, Egypt.

    PubMed

    el Kady, G A; Shoukry, A; Ragheb, D A; el Said, A M; Habib, K S; Morsy, T A

    1995-08-01

    Mites are arthropods distinguished from ticks by usually being microscopical in size and have a hypostome unarmed with tooth-like anchoring processes. They are group in a number of suborders, each with super-families and families including many genera of medical and economic importance. In this paper, commensal rodents (Rattus norvegicus, R. r. alexandrinus and R. r. frugivorous) were surveyed in the Suez Canal Zone for their acari ectoparasites. Four species of mites were recovered. In a descending order of mite indices, they were Eulaelaps stabularis (4.83 on 6 rats), Laelaps nuttalli (3.11 on 27 rats), Ornithonyssus bacoti (1.66 on 9 rats) and Dermanyssus gallinae (0.66 on 24 rats). The overall mite indices in the three governorates were 3.66 in Suez, 2.82 in Ismailia and zero in Port Said. The medical and economic importance of the mites were discussed.

  2. Geology of the Warda discovery, Gulf of Suez, Egypt

    SciTech Connect

    Vargo, J.N.; Greet, M.J.; Collings, B.P.; Davis, C.B.; Miller, M.H. )

    1991-08-01

    British Gas, as operator for its partners, Yukong Ltd., and Union Pacific Petroleum Suez Ltd., recently discovered the Warda field in the Gulf of Suez in November 1990. Discovery well Hb78-2, located 4 km off the mouth of the Wadi Araba on the west side of the north-central Gulf of Suez, reached a total depth of 8,400 ft in Nubia clastics. Oil was tested in the Hb78-2 from five separate clastic intervals at a cumulative flow rate of approximately 7,000 BOPD of 20-24{degree} API with no water. Currently, an appraisal well program is underway to extend the limits of the field. This significant new-field discovery is located in a part of the Suez basin that previously considered to have limited oil potential. Geophysical assessment of the structure used exploration 3-D seismic coverage and concurrently acquired potential-fields datasets. The Warda structure at Kareen-Rudeis levels is a broad four-way closure, trending northwest-southeast, which drapes over older pre-Miocene tilted fault blocks. The Warda structure lies downthrown to a major Clysmic shoulder fault and is bounded on the northeast by another Clysmic down-to-the-basin normal fault. Cross faulting is noted at the deeper levels, and particularly influences the rift boundary faults. According to burial-history modeling, oil generation occurred within 4-5 million years after the Eocene-Senonian carbonate source rocks achieved onset of oil generation at a birthline of 10,000-11,000 ft subsea. The Cretaceous-Carboniferous Nubia sandstones apparently have acted as a conduit for oil migration from the adjacent Lagia hydrocarbon kitchen a few kilometers to the northeast.

  3. The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL.

    PubMed

    Emmerson, Paul J; Wang, Feng; Du, Yong; Liu, Qian; Pickard, Richard T; Gonciarz, Malgorzata D; Coskun, Tamer; Hamang, Matthew J; Sindelar, Dana K; Ballman, Kimberly K; Foltz, Lisa A; Muppidi, Avinash; Alsina-Fernandez, Jorge; Barnard, Gavin C; Tang, Jason X; Liu, Xilin; Mao, Xudong; Siegel, Robert; Sloan, John H; Mitchell, Pamela J; Zhang, Bei B; Gimeno, Ruth E; Shan, Bei; Wu, Xinle

    2017-08-28

    Growth/differentiation factor 15 (GDF15), also known as MIC-1, is a distant member of the transforming growth factor-β (TGF-β) superfamily and has been implicated in various biological functions, including cancer cachexia, renal and heart failure, atherosclerosis and metabolism. A connection between GDF15 and body-weight regulation was initially suggested on the basis of an observation that increasing GDF15 levels in serum correlated with weight loss in individuals with advanced prostate cancer. In animal models, overexpression of GDF15 leads to a lean phenotype, hypophagia and other improvements in metabolic parameters, suggesting that recombinant GDF15 protein could potentially be used in the treatment of obesity and type 2 diabetes. However, the signaling and mechanism of action of GDF15 are poorly understood owing to the absence of a clearly identified cognate receptor. Here we report that GDNF-family receptor α-like (GFRAL), an orphan member of the GFR-α family, is a high-affinity receptor for GDF15. GFRAL binds to GDF15 in vitro and is required for the metabolic actions of GDF15 with respect to body weight and food intake in vivo in mice. Gfral(-/-) mice were refractory to the effects of recombinant human GDF15 on body-weight, food-intake and glucose parameters. Blocking the interaction between GDF15 and GFRAL with a monoclonal antibody prevented the metabolic effects of GDF15 in rats. Gfral mRNA is highly expressed in the area postrema of mouse, rat and monkey, in accordance with previous reports implicating this region of the brain in the metabolic actions of GDF15 (refs. 4,5,6). Together, our data demonstrate that GFRAL is a receptor for GDF15 that mediates the metabolic effects of GDF15.

  4. 46 CFR 69.7 - Vessels transiting the Panama and Suez Canals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Vessels transiting the Panama and Suez Canals. 69.7... MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS General § 69.7 Vessels transiting the Panama and Suez Canals. (a) All vessels intending to transit the Panama Canal, other than vessels of war, must be measured and...

  5. 46 CFR 69.7 - Vessels transiting the Panama and Suez Canals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Vessels transiting the Panama and Suez Canals. 69.7... MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS General § 69.7 Vessels transiting the Panama and Suez Canals. (a) All vessels intending to transit the Panama Canal, other than vessels of war, must be measured and...

  6. 46 CFR 69.7 - Vessels transiting the Panama and Suez Canals.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Vessels transiting the Panama and Suez Canals. 69.7... MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS General § 69.7 Vessels transiting the Panama and Suez Canals. (a) All vessels intending to transit the Panama Canal, other than vessels of war, must be measured and...

  7. 46 CFR 69.7 - Vessels transiting the Panama and Suez Canals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Vessels transiting the Panama and Suez Canals. 69.7... MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS General § 69.7 Vessels transiting the Panama and Suez Canals. (a) All vessels intending to transit the Panama Canal, other than vessels of war, must be measured and...

  8. 46 CFR 69.7 - Vessels transiting the Panama and Suez Canals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Vessels transiting the Panama and Suez Canals. 69.7... MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS General § 69.7 Vessels transiting the Panama and Suez Canals. (a) All vessels intending to transit the Panama Canal, other than vessels of war, must be measured and...

  9. [Inhibiting GDF-8 expression by retrovirus-based RNAi stably].

    PubMed

    Liu, Chaowu; Yang, Zhuo; Zhao, Bin; Liu, Changmei

    2008-02-01

    We cloned human U6 promoter from pAVU6 + 27 vector into pXSN to transcripe small RNA. Meanwhile, a shRNA targeting GDF-8 was cloned down-stream of the hU6 promoter to construct recombinant vector. Then the packing cell GP-293 was co-transfected the recombinant with pVSV-G to gernarate virus particle. Resistant C2C12 cell pools were screened using G418. Levels of mRNA and protein of GDF-8 were tested by Real-Time PCR and western blotting. Cell proliferation and cell cycle were analyzed using MTT and FACS. The expression of GDF-8 was dramatically decreased by the retrovirus-based system in C2C12 cells. Cells proliferated effectively after integrating the recombinant. The cells in G0/G1 phase decreased by 13.7%, while cells in S phase increased by 14.9%. In conclusion, the retrovirus-based RNAi could be used to stably silence GDF-8. It can be a powerful tool in curing muscle atrophy.

  10. GDF 15 as an anti-apoptotic, diagnostic and prognostic marker in oral squamous cell carcinoma.

    PubMed

    Schiegnitz, E; Kämmerer, P W; Koch, F P; Krüger, M; Berres, M; Al-Nawas, B

    2012-07-01

    Growth-differentiation factor 15 (GDF 15) is involved in tumor pathogenesis and its expression is increased in many types of cancers. Functional effects of GDF 15 on oncogenesis of oral squamous cell carcinoma (OSCC) remain unclear. Therefore, the aim of this study was to examine the apoptotic characteristics of GDF 15 in OSCC cell lines in vitro and to analyze serum GDF 15 concentrations as a diagnostic and prognostic tumor marker for OSCC in vivo. Caspase activity was assessed in OSCC cell lines with the Caspase-Glo 3/7 system. Serum GDF 15 concentrations from 64 patients with histopathological proven OSCC and from 30 healthy volunteers were measured using an enzyme-linked immunosorbent assay. In 21 patients, serum GDF 15 was also analyzed postoperatively. In vitro, treatment of OSCC cell lines with GDF 15 reduced Caspase 3/7 activity significantly (p<0.05). In vivo, serum GDF 15 concentrations of the OSCC patients in all stages of OSCC were significantly higher than those of the healthy subjects (p<0.0001). After surgery, GDF 15 concentrations declined significantly from 1545±774pg/ml preoperative to 953±438pg/ml postoperative (p=0.003). The median survival time of OSCC patients with GDF 15 levels below 875pg/ml was significantly higher than of OSCC patients with GDF 15 levels above or equal 875pg/ml (p=0.031). Determination of receiver operating characteristic curves (ROC) showed a respective area under the ROC curve (AUC) of 0.943. The anti-apoptotic effect of GDF 15 in OSCC cell lines was shown in vitro. In vivo, significant elevated serum GDF 15 levels with prognostic value in OSCC-patients were seen for the first time. The results indicate that GDF15 may be used as a potential marker for diagnosis and prognosis of this entity.

  11. Roles of GASP-1 and GDF-11 in Dental and Craniofacial Development

    PubMed Central

    Lee, Yun-Sil; Lee, Se-Jin

    2016-01-01

    Purpose Growth and differentiation factor-11 (GDF-11) is a TGF-β family member that plays important regulatory roles in development of multiple tissues which include axial skeletal patterning, palatal closure, and tooth formation. Proteins that have been identified as GDF-11 inhibitors include GDF-associated serum protein-1 (GASP-1) and GASP-2. Recently, we found that mice genetically engineered to lack both Gasp1 and Gdf11 have an increased frequency of cleft palate. The goal of this study was to investigate the roles of GDF-11 and its inhibitors, GASP-1 and GASP-2, during dental and craniofacial development and growth. Methods Mouse genetic studies were used in this study. Homozygous knockout mice for Gasp1 (Gasp1−/−) and Gasp2 (Gasp2−/−) were viable and fertile, but Gdf11 homozygous knockout (Gdf11−/−) mice died within 24 hours after birth. The effect of either Gasp1 or Gasp2 deletion in Gdf11−/− mice during embryogenesis was evaluated in Gasp1−/−;Gdf11−/− and Gasp2−/−;Gdf11−/− mouse embryos at 18.5 days post-coitum (E18.5). For the analysis of adult tissues, we used Gasp1−/−;Gdf11+/− and Gasp2−/−;Gdf11+/− mice to evaluate the potential haploinsufficiency of Gdf11 in Gasp1−/− and Gasp2−/− mice. Results Although Gasp2 expression decreased after E10.5, Gasp1 expression was readily detected in various ectodermal tissues at E17.5, including hair follicles, epithelium in nasal cavity, retina, and developing tooth buds. Interestingly, Gasp1−/−;Gdf11−/− mice had abnormal formation of lower incisors: tooth buds for lower incisors were under-developed or missing. Although Gdf11+/− mice were viable and had mild transformations of the axial skeleton, no specific defects in the craniofacial development have been observed in Gdf11+/− mice. However, loss of Gasp1 in Gdf11+/− mice occasionally resulted in small and abnormally shaped auricles. Conclusions These findings suggest that both GASP-1 and GDF-11 play

  12. Graben infilling in Gulf of Suez and Red Sea

    SciTech Connect

    Burollet, P.F.

    1986-05-01

    During the last 4 years, the French research group Genegass has completed geological and geophysical studies in the Red Sea and the Gulf of Suez. Neogene infilling of the basin is related with basement quality and volume of clastic supply, and inherited structural features are important to the development of Miocene rifting. The Neogene series may be divided into four major groups (Listed A-D), each limited by unconformities that seem to reflect the major stages of rifting. (A) The lowermost formations begin with a conglomerate and are followed by a variegated unit of sand and clay. In the Gulf of Suez, especially on the eastern bank, these formations are marine. Along the Red Sea, tilted blocks may be capped by stromatolites, and the valleys between them are the site of shale and evaporite sedimentation (lower Miocene). (B) The main extension phase results in an invasion of marine shales. The lower zones contain coarse clastics, and the high zones contain reefs and bioclastic limestone (late Burdigalian to early Serravallian). (C) The middle to late Miocene corresponds to a regional basinward tilting. Stromatolites coat the slopes, and conglomerate fans are found in the lower zones. Evaporite sedimentation dominates; anhydrite is found on the borders, and in the basin, thick halite is overlain by a clastic series. Basement shoulders are uplifted. (D) During the Pliocene and Pleistocene, the central part of the graben showed an important subsidence, and salt tectonism was active with diapirs and collapses.

  13. Biochemistry and Biology of GDF11 and Myostatin: Similarities, Differences, and Questions for Future Investigation.

    PubMed

    Walker, Ryan G; Poggioli, Tommaso; Katsimpardi, Lida; Buchanan, Sean M; Oh, Juhyun; Wattrus, Sam; Heidecker, Bettina; Fong, Yick W; Rubin, Lee L; Ganz, Peter; Thompson, Thomas B; Wagers, Amy J; Lee, Richard T

    2016-04-01

    Growth differentiation factor 11 (GDF11) and myostatin (or GDF8) are closely related members of the transforming growth factor β superfamily and are often perceived to serve similar or overlapping roles. Yet, despite commonalities in protein sequence, receptor utilization and signaling, accumulating evidence suggests that these 2 ligands can have distinct functions in many situations. GDF11 is essential for mammalian development and has been suggested to regulate aging of multiple tissues, whereas myostatin is a well-described negative regulator of postnatal skeletal and cardiac muscle mass and modulates metabolic processes. In this review, we discuss the biochemical regulation of GDF11 and myostatin and their functions in the heart, skeletal muscle, and brain. We also highlight recent clinical findings with respect to a potential role for GDF11 and/or myostatin in humans with heart disease. Finally, we address key outstanding questions related to GDF11 and myostatin dynamics and signaling during development, growth, and aging.

  14. Evaluation of growth differentiation factor 11 (GDF11) levels in dogs with chronic mitral valve insufficiency.

    PubMed

    Ahn, Sung-Taek; Suh, Sang-Il; Moon, Hyeongsun; Hyun, Changbaig

    2016-01-01

    Growth differentiation factor 11 (GDF11) regulates cell growth and differentiation in both embryonic and adult tissues. Circulating GDF11 levels have recently been reported to be significantly lower in aging mice and restoration of GDF11 reversed age-related cardiac hypertrophy in old mice. Here, we evaluated the potential of serum levels of GDF11 as a circulating biomarker in dogs at different stages of heart failure, due to chronic mitral valve insufficiency (CMVI). We found no significant differences in serum GDF11 levels between dogs at different stages of CMVI-associated heart failure. Furthermore, the circulating levels of GDF11 did not correlate with age, body weight, echocardiographic variables, and the severity of CMVI-induced heart failure in dogs.

  15. Egypt, Nile Valley, Gulf of Suez, Sinai as seen from Gemini 12 spacecraft

    NASA Image and Video Library

    1966-11-13

    S66-63477 (13 Nov. 1966) --- United Arab Republic (Egypt), the Nile Valley from Luxor to Cairo, El Payium, Gulf of Suez, Sinai as seen from Gemini-12 spacecraft on its 25th revolution of Earth. Photo credit: NASA

  16. Growing backwards: an inverted role for the shrimp ortholog of vertebrate myostatin and GDF11.

    PubMed

    De Santis, Christian; Wade, Nicholas M; Jerry, Dean R; Preston, Nigel P; Glencross, Brett D; Sellars, Melony J

    2011-08-15

    Myostatin (MSTN) and growth differentiation factor-11 (GDF11) are closely related proteins involved in muscle cell growth and differentiation as well as neurogenesis of vertebrates. Both MSTN and GDF11 negatively regulate their functions. Invertebrates possess a single ortholog of the MSTN/GDF11 family. In order to understand the role of MSTN/GDF11 in crustaceans, the gene ortholog was identified and characterized in the penaeid shrimp Penaeus monodon. The overall protein sequence and specific functional sites were highly conserved with other members of the MSTN/GDF11 family. Gene transcripts of pmMstn/Gdf11, assessed by real-time PCR, were detected in a variety of tissue types and were actively regulated in muscle across the moult cycle. To assess phenotypic function in shrimp, pmMstn/Gdf11 gene expression was downregulated by tail-muscle injection of sequence-specific double-stranded RNA. Shrimp with reduced levels of pmMstn/Gdf11 transcripts displayed a dramatic slowing in growth rate compared with control groups. Findings from this study place the MSTN/GDF11 gene at the centre of growth regulation in shrimp, but suggest that, compared with higher vertebrates, this gene has an opposite role in invertebrates such as shrimp, where levels of gene expression may positively regulate growth.

  17. Modulation of GDF11 expression and synaptic plasticity by age and training.

    PubMed

    De Domenico, Emanuela; D'Arcangelo, Giovanna; Faraoni, Isabella; Palmieri, Mattia; Tancredi, Virginia; Graziani, Grazia; Grimaldi, Paola; Tentori, Lucio

    2017-08-29

    The Growth Differentiation Factor 11 (GDF11) has been controversially involved in the aging/rejuvenation process. To clarify whether GDF11 is differently expressed during aging, we have evaluated GDF11 levels in skeletal muscles and hippocampi of young and old mice, sedentary or subjected to a 12-weeks triweekly training protocol. The results of real-time PCR and Western blot analyses indicate that skeletal muscles of sedentary old mice express higher levels of GDF11 compared to young animals (p < 0.05). Conversely, in hippocampi no significant differences of GDF11 expression are detected. Analysis of long-term potentiation, a synaptic plasticity phenomenon, reveals that population spikes in response to a tetanic stimulus are significantly higher in sedentary young mice than in old animals (p < 0.01). Training induces a significant improvement of long-term potentiation in both young and old animals (p < 0.05), an increase (p < 0.05) of skeletal muscle GDF11 levels in young mice and a reduction of GDF11 expression in hippocampi of old mice (p < 0.05). Overall, data suggest that GDF11 can be considered an aging biomarker for skeletal muscles. Moreover, physical exercise has a positive impact on long-term potentiation in both young and old mice, while it has variable effects on GDF11 expression depending on age and on the tissue analyzed.

  18. Biogenic Films at the Mouth of the Suez Canal

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Astronauts aboard the Space Shuttle Discovery used the sunglint off the surface of the Mediterranean Sea to reveal biogenic films on the ocean surface. ('Biogenic film' refers to a thin layer of biologically-produced film resting on the surface. Click for more details.) The films dampen surface capillary waves, creating brighter and darker reflections, which, in turn, trace the complex surface water movements along the coast. The sunglint also highlights coastal features (jetties, submerged coastal areas) near the Port of Suez. Image STS105-331-18, taken in August 2001, was provided by the Earth Sciences and Image Analysis Laboratory at Johnson Space Center. Additional images taken by astronauts and cosmonauts can be viewed at the NASA-JSC Gateway to Astronaut Photography of Earth.

  19. Miocene platform-margin reefs, Gulf of Suez, Egypt

    SciTech Connect

    James, N.P.; Rosen, B.; Coniglio, M.

    1988-02-01

    Jebel Abu Shaar is a completely dolomitized carbonate platform atop a crystalline basement horst on the western side of the Gulf of Suez. Margins of the platform, where not removed by synsedimentary faulting, are formed by well-developed coral reefs. The massive reef carbonates consistently illustrate two stages of growth: a basal paucispecific unit of branching coral bafflestone, mostly Stylophora and a thicker upper unit of diverse coral framestone, dominated by faviids. A deep-water, slope-parallel biostrome of ahermatypic corals, dominated by Dendrophyllia and containing numerous Balanophyllia and Madracis, is present 10 km north of Abu Shaar. Corals are well cemented by numerous rinds of marine cement which is overlain by geopetal internal sediment containing planktonic foraminifers and pteropods.

  20. Biogenic Films at the Mouth of the Suez Canal

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Astronauts aboard the Space Shuttle Discovery used the sunglint off the surface of the Mediterranean Sea to reveal biogenic films on the ocean surface. ('Biogenic film' refers to a thin layer of biologically-produced film resting on the surface. Click for more details.) The films dampen surface capillary waves, creating brighter and darker reflections, which, in turn, trace the complex surface water movements along the coast. The sunglint also highlights coastal features (jetties, submerged coastal areas) near the Port of Suez. Image STS105-331-18, taken in August 2001, was provided by the Earth Sciences and Image Analysis Laboratory at Johnson Space Center. Additional images taken by astronauts and cosmonauts can be viewed at the NASA-JSC Gateway to Astronaut Photography of Earth.

  1. cDNA cloning and expression analysis of myostatin/GDF11 in shrimp, Litopenaeus vannamei.

    PubMed

    Qian, Zhaoying; Mi, Xiao; Wang, Xianzong; He, Shulin; Liu, Yongjie; Hou, Fujun; Liu, Qiao; Liu, Xiaolin

    2013-05-01

    Myostatin (MSTN) and growth differentiation factor-11 (GDF11) are closely related proteins belonging to the transforming growth factor-β (TGF-β) superfamily. In vertebrates, MSTN is known to negatively regulate skeletal muscle growth, and GDF11 is found to inhibit neurogenesis. In invertebrates, only one ortholog of vertebrate MSTN and GDF11 (MSTN/GDF11) existed. Little attention has been paid on its role to date. In this study, the cDNA that encodes a 422-amino-acid MSTN/GDF11 protein (LvMSTN/GDF11) was characterized from a crustacean species, the Pacific white shrimp (Litopenaeus vannamei). Sequence analysis revealed that the overall protein sequence and specific functional sites of LvMSTN/GDF11 were highly conserved with those in other crustacean species. Expression analysis by quantitative real-time reverse transcription polymerase chain reaction technique demonstrated its tissue-specific, larval developmental stage-specific, and molt stage-specific expression pattern, respectively. After in vivo injections of 20 hydroxyecdysone (20E), LvMSTN/GDF11 transcripts were declined in the abdominal (A) and pleopod (P1) muscles, increased in the pereiopod (P2) muscle, and not affected in the thoracic (T) muscle. The observed expression profiles suggest multiple functions of LvMSTN/GDF11 in L. vannamei and its role differs during the larval development and natural molt cycle. The different responses of LvMSTN/GDF11 to acute increases of 20E in the A, P1, P2 and T muscles may indicate that LvMSTN/GDF11 is transcriptionally regulated via ecdysteroids to coincide with its specific roles in the former three muscles, while its role may be independent of 20E regulation in the T muscle.

  2. Exogenous GDF11 induces cardiac and skeletal muscle dysfunction and wasting.

    PubMed

    Zimmers, Teresa A; Jiang, Yanling; Wang, Meijing; Liang, Tiffany W; Rupert, Joseph E; Au, Ernie D; Marino, Francesco E; Couch, Marion E; Koniaris, Leonidas G

    2017-07-01

    Growth differentiation factor 11 (GDF11), a TGF-beta superfamily member, is highly homologous to myostatin and essential for embryonic patterning and organogenesis. Reports of GDF11 effects on adult tissues are conflicting, with some describing anti-aging and pro-regenerative activities on the heart and skeletal muscle while others opposite or no effects. Herein, we sought to determine the in vivo cardiac and skeletal muscle effects of excess GDF11. Mice were injected with GDF11 secreting cells, an identical model to that used to initially identify the in vivo effects of myostatin. GDF11 exposure in mice induced whole body wasting and profound loss of function in cardiac and skeletal muscle over a 14-day period. Loss of cardiac mass preceded skeletal muscle loss. Cardiac histologic and echocardiographic evaluation demonstrated loss of ventricular muscle wall thickness, decreased cardiomyocyte size, and decreased cardiac function 10 days following initiation of GDF11 exposure. Changes in skeletal muscle after GDF11 exposure were manifest at day 13 and were associated with wasting, decreased fiber size, and reduced strength. Changes in cardiomyocytes and skeletal muscle fibers were associated with activation of SMAD2, the ubiquitin-proteasome pathway and autophagy. Thus, GDF11 over administration in vivo results in cardiac and skeletal muscle loss, dysfunction, and death. Here, serum levels of GDF11 by Western blotting were 1.5-fold increased over controls. Although GDF11 effects in vivo are likely dose, route, and duration dependent, its physiologic changes are similar to myostatin and other Activin receptors ligands. These data support that GDF11, like its other closely related TGF-beta family members, induces loss of cardiac and skeletal muscle mass and function.

  3. GDF11 improves tubular regeneration after acute kidney injury in elderly mice

    PubMed Central

    Zhang, Ying; Li, Qinggang; Liu, Dong; Huang, Qi; Cai, Guangyan; Cui, Shaoyuan; Sun, Xuefeng; Chen, Xiangmei

    2016-01-01

    The GDF11 expression pattern and its effect on organ regeneration after acute injury in the elderly population are highly controversial topics. In our study, GDF11/8 expression increased after kidney ischemia–reperfusion injury (IRI), and the relatively lower level of GDF11/8 in the kidneys of aged mice was associated with a loss of proliferative capacity and a decline in renal repair, compared to young mice. In vivo, GDF11 supplementation in aged mice increased vimentin and Pax2 expression in the kidneys as well as the percentage of 5-ethynyl-2′-deoxyuridine (EdU)-positive proximal tubular epithelial cells. GDF11 improved the renal repair, recovery of renal function, and survival of elderly mice at 72 h after IRI. Moreover, the addition of recombinant GDF11 to primary renal epithelial cells increased proliferation, migration, and dedifferentiation by upregulating the ERK1/2 pathway in vitro. Our study indicates that GDF11/8 in the kidney decreases with age and that GDF11 can increase tubular cell dedifferentiation and proliferation as well as improve tubular regeneration after acute kidney injury (AKI) in old mice. PMID:27703192

  4. Combined use of bFGF and GDF-5 enhances the healing of medial collateral ligament injury

    SciTech Connect

    Saiga, Kenta; Furumatsu, Takayuki; Yoshida, Aki; Masuda, Shin; Takihira, Shota; Abe, Nobuhiro; Ozaki, Toshifumi

    2010-11-12

    Research highlights: {yields} bFGF/GDF-5 treatment increases cellular proliferation and migration of MCL fibroblasts. {yields} bFGF/GDF-5 hydrogels stimulate the healing of MCL injury in vivo. {yields} bFGF/GDF-5 hydrogels stimulate Col1a1 expression and type I collagen synthesis. {yields} Combined use of bFGF/GDF-5 enhances MCL healing. -- Abstract: Basic fibroblast growth factor (bFGF) and growth and differentiation factor (GDF)-5 stimulate the healing of medial collateral ligament (MCL) injury. However, the effect of isolated and combined use of bFGF/GDF-5 remains still unclear. We investigated cellular proliferation and migration responding to bFGF/GDF-5 using rabbit MCL fibroblasts. Rabbit MCL injury was treated by bFGF and/or GDF-5 with peptide hydrogels. Gene expression and deposition of collagens in healing tissues were evaluated. bFGF/GDF-5 treatment additively enhanced cell proliferation and migration. bFGF/GDF-5 hydrogels stimulated Col1a1 expression without increasing Col3a1 expression. Combined use of bFGF/GDF-5 stimulated type I collagen deposition and the reorganization of fiber alignment, and induced better morphology of fibroblasts in healing MCLs. Our study indicates that combined use of bFGF/GDF-5 might enhance MCL healing by increasing proliferation and migration of MCL fibroblasts, and by regulating collagen synthesis and connective fiber alignment.

  5. Growth Differentiation Factor-15 (GDF-15) is a potential marker of radiation response and radiation sensitivity.

    PubMed

    Sándor, Nikolett; Schilling-Tóth, Boglárka; Kis, Enikő; Benedek, Anett; Lumniczky, Katalin; Sáfrány, Géza; Hegyesi, Hargita

    2015-11-01

    We have investigated the importance of GDF-15 (secreted cytokine belonging to the TGF-β superfamily) in low and high dose radiation-induced cellular responses. A telomerase immortalized human fibroblast cell line (F11hT) was used in the experiments. A lentiviral system encoding small hairpin RNAs (shRNA) was used to establish GDF-15 silenced cells. Secreted GDF-15 levels were measured in culture medium by ELISA. Cell cycle analysis was performed by flow cytometry. The experiments demonstrated that in irradiated human fibroblasts GDF-15 expression increased with dose starting from 100mGy. Elevated GDF-15 expression was not detected in bystander cells. The potential role of GDF-15 in radiation response was investigated by silencing GDF-15 in immortalized human fibroblasts with five different shRNA encoded in lentiviral vectors. Cell lines with considerably reduced GDF-15 levels presented increased radiation sensitivity, while a cell line with elevated GDF-15 was more radiation resistant than wild type cells. We have investigated how the reduced GDF-15 levels alter the response of several known radiation inducible genes. In F11hT-shGDF-15 cells the basal expression level of CDKN1A was unaltered relative to F11hT cells, while GADD45A and TGF-β1 mRNA levels were slightly higher, and TP53INP1 was considerably reduced. The radiation-induced expression of TP53INP1 was lower in the silenced than in wild type fibroblast cells. Cell cycle analysis indicated that radiation-induced early G2/M arrest was abrogated in GDF-15 silenced cells. Moreover, radiation-induced bystander effect was less pronounced in GDF-15 silenced fibroblasts. In conclusion, the results suggest that GDF-15 works as a radiation inducible radiation resistance increasing factor in normal human fibroblast cells, acts by regulating the radiation-induced transcription of several genes and might serve as a radiation-induced early biomarker in exposed cells.

  6. GDF11 does not improve the palmitate induced insulin resistance in C2C12.

    PubMed

    Jing, Y-Y; Li, D; Wu, F; Gong, L-L; Li, R

    2017-04-01

    GDF11 (Growth Differentiation factor 11) has been reported to rejuvenate skeletal muscle, heart and brain in aged mice, and the aged skeletal muscle is closely related to insulin resistance. We wondered whether GDF11 has an effect on skeletal muscle insulin resistance. High fat diet induced obese mice with insulin resistance were established in vivo. Palmitate-induced insulin resistance in C2C12 myotubes was established in vitro. The mRNA expression of GDF11, GLUT4, IRS-1 (insulin receptor substrate-1) and PGC-1α (peroxisome proliferator-activated receptor-gamma coactivator 1) were tested by reverse transcriptase-polymerase chain reaction (RT-PCR). The protein level of GDF11 and PGC-1α were detected by Western blot. The glucose uptake was measured by 2NBDG uptake assay. In high fat diet induced obese mice, both serum level of GDF11 and the expression of GDF11 in skeletal muscle decreased. Similarly, the expression of GDF11 also reduced in palmitate-treated C2C12 myotubes. In vitro, the glucose uptake and the expression of GLUT4, IRS-1 and PGC-1α significantly decreased after palmitate intervention, but GDF11 treatment did not reverse the reduction of glucose uptake and the expression of GLUT4, IRS-1 and PGC-1α in C2C12 myotubes. We firstly confirmed that the expression of GDF11 decreased both in the skeletal muscle of obese mice and palmitate-treated myotubes, but supplementation GDF11 does not ameliorate the palmitate-induced insulin resistance in C2C12 myotubes.

  7. Controle sismique d'un batiment en acier de 1 etage par amortisseurs elastomeres et contreventements en Chevron

    NASA Astrophysics Data System (ADS)

    Girard, Olivier

    Actuellement, le principe de dimensionnement a la capacite est fortement utilise dans le domaine du genie parasismique. De maniere simplifiee, cette methode de dimensionnement consiste a dissiper l'energie injectee a une structure lors d'une secousse sismique par la deformation inelastique d'un element structural sacrificiel. Cette methode de dimensionne-ment permet d'obtenir des structures economiques, car cette dissipation d'energie permet de reduire substantiellement les efforts qui se retrouvent a l'interieur de la structure. Or, la consequence de ce dimensionnement est la presence de degats importants a la structure qui suivent a la secousse sismique. Ces degats peuvent engendrer des couts superieurs aux couts d'erection de la structure. Bien entendu, sachant que les secousses sismiques d'importances sont des phenomenes rares, l'ingenieur est pret a accepter ce risque afin de diminuer les couts initiaux de construction. Malgre que cette methode ait permis d'obtenir des constructions economiques et securitaires, il serait interessant de developper un systeme qui permettrait d'obtenir des performances de controle des efforts sismiques comparables a un systeme dimensionne selon un principe de dimensionnement a la capacite sans les consequences negatives de ces systemes. En utilisant les principes d'isolation a la base, il a ete possible de developper un systeme de reprise des forces sismiques (SRFS). qui permet d'obtenir un controle des efforts sismiques concurrentiels tout en gardant une structure completement elastique. Ce systeme consiste u inserer un materiel elastomere entre l'assemblage de la poutre et des contreventements a l'interieur d'un cadre contrevente conventionnel. Cette insertion permet de diminuer substantiellement la rigidite laterale du batiment, ce qui a pour consequence d'augmenter la valeur de la periode fondamentale du batiment dans lequel ces cadres sont inseres. Ce phenomene est appele le saut de periode. Ce saut de periode permet de

  8. GDF-15 Is Elevated in Children with Mitochondrial Diseases and Is Induced by Mitochondrial Dysfunction

    PubMed Central

    Montero, Raquel; Yubero, Delia; Villarroya, Joan; Henares, Desiree; Jou, Cristina; Rodríguez, Maria Angeles; Ramos, Federico; Nascimento, Andrés; Ortez, Carlos Ignacio; Campistol, Jaume; Perez-Dueñas, Belen; O'Callaghan, Mar; Pineda, Mercedes; Garcia-Cazorla, Angeles; Oferil, Jaume Colomer; Montoya, Julio; Ruiz-Pesini, Eduardo; Emperador, Sonia; Meznaric, Marija; Campderros, Laura; Kalko, Susana G.; Villarroya, Francesc; Artuch, Rafael; Jimenez-Mallebrera, Cecilia

    2016-01-01

    Background We previously described increased levels of growth and differentiation factor 15 (GDF-15) in skeletal muscle and serum of patients with mitochondrial diseases. Here we evaluated GDF-15 as a biomarker for mitochondrial diseases affecting children and compared it to fibroblast-growth factor 21 (FGF-21). To investigate the mechanism of GDF-15 induction in these pathologies we measured its expression and secretion in response to mitochondrial dysfunction. Methods We analysed 59 serum samples from 48 children with mitochondrial disease, 19 samples from children with other neuromuscular diseases and 33 samples from aged-matched healthy children. GDF-15 and FGF-21 circulating levels were determined by ELISA. Results Our results showed that in children with mitochondrial diseases GDF-15 levels were on average increased by 11-fold (mean 4046pg/ml, 1492 SEM) relative to healthy (350, 21) and myopathic (350, 32) controls. The area under the curve for the receiver-operating-characteristic curve for GDF-15 was 0.82 indicating that it has a good discriminatory power. The overall sensitivity and specificity of GDF-15 for a cut-off value of 550pg/mL was 67.8% (54.4%-79.4%) and 92.3% (81.5%-97.9%), respectively. We found that elevated levels of GDF-15 and or FGF-21 correctly identified a larger proportion of patients than elevated levels of GDF-15 or FGF-21 alone. GDF-15, as well as FGF-21, mRNA expression and protein secretion, were significantly induced after treatment of myotubes with oligomycin and that levels of expression of both factors significantly correlated. Conclusions Our data indicate that GDF-15 is a valuable serum quantitative biomarker for the diagnosis of mitochondrial diseases in children and that measurement of both GDF-15 and FGF-21 improves the disease detection ability of either factor separately. Finally, we demonstrate for the first time that GDF-15 is produced by skeletal muscle cells in response to mitochondrial dysfunction and that its levels

  9. Growth differentiation factor 11 (GDF11) - a promising anti-ageing factor - is highly concentrated in platelets.

    PubMed

    Bueno, J L; Ynigo, M; de Miguel, C; Gonzalo-Daganzo, R M; Richart, A; Vilches, C; Regidor, C; García-Marco, J A; Flores-Ballester, E; Cabrera, J R

    2016-11-01

    Recent research suggests that growth differentiation factor 11 (GDF11) could reverse age-related diseases and that its blood concentration decreases with age. This poses plasma from young donors as a therapeutic GDF11 source to treat age-related diseases. In addition, the tissue source of circulating GDF11 remains unknown. We analysed GDF11 levels in paired samples of serum, plasma and platelet lysate (PL) from 23 volunteers. Plasma and PL were collected by plateletpheresis. Here, we show that GDF11 is highly concentrated in platelets and that the circulating levels reported in previous studies could be biased as a result of serum sample manipulation.

  10. Miocene platform-margin reefs, Gulf of Suez, Egypt

    SciTech Connect

    Noel, J.P.; Rosen, B.; Coniglio, M.

    1988-01-01

    Jebel Abu Shaar is a completely dolomitized carbonate platform atop a crystalline basement horst on the western side of the Gulf of Suez. Margins of the platform, where not removed by synsedimentary faulting, are formed by well-developed coral reefs. The massive reef carbonates consistently illustrate two stages of growth: a basal paucispecific unit of branching coral bafflestone, mostly Stylophora and a thicker upper unit of diverse coral framestone, dominated by faviids. In the upper unit, the reef crest is massive columnar Porites and less common Caulastrea framestone. The back-reef is a framestone of diverse faviids, mainly Montastrea Favites, and Tarbellastrea, and interbedded reef-flat rhodolite rudstones. The back-reef and reef-flat facies grade onshelf into Stylophora bafflestone biostromers and faviid bioherms. The reef front is a shallow to intermediate depth zone of numerous and diverse faviids, dominated by Montastrea and Acanthastrea framestones, bioclastic sands, and hardgrounds. Deeper zones are mostly small Acanthastrea mounds or rhodolite/bivalve rudstones with scattered faviids and Acanthastrea. Synsedimentary lithification, internal sedimentationm, and bioerosion prevail throughout. A deep-water, slope-parallel biostrome of ahermatypic corals, dominated by Dendrophyllia and containing numerous Balanophyllia and Madracis, is present 10 km north of Abu Shaar. Corals are well cemented by numerous rinds of marine cement which is overlain by geopetal internal sediment containing planktonic foraminifers and pteropods.

  11. Extensional tectonics and collapse structures in the Suez Rift (Egypt)

    NASA Technical Reports Server (NTRS)

    Chenet, P. Y.; Colletta, B.; Desforges, G.; Ousset, E.; Zaghloul, E. A.

    1985-01-01

    The Suez Rift is a 300 km long and 50 to 80 km wide basin which cuts a granitic and metamorphic shield of Precambrian age, covered by sediments of Paleozoic to Paleogene age. The rift structure is dominated by tilted blocks bounded by NW-SE normal faults. The reconstruction of the paleostresses indicates a N 050 extension during the whole stage of rifting. Rifting began 24 My ago with dikes intrusions; main faulting and subsidence occurred during Early Miocene producing a 80 km wide basin (Clysmic Gulf). During Pliocene and Quaternary times, faulting is still active but subsidence is restricted to a narrower area (Present Gulf). On the Eastern margin of the gulf, two sets of fault trends are predominant: (1) N 140 to 150 E faults parallel to the gulf trend with pure dip-slip displacement; and (2) cross faults, oriented NOO to N 30 E that have a strike-slip component consistent with the N 050 E distensive stress regime. The mean dip cross fault is steeper (70 to 80 deg) than the dip of the faults parallel to the Gulf (30 to 70 deg). These two sets of fault define diamond shaped tilted block. The difference of mechanical behavior between the basement rocks and the overlying sedimentary cover caused structural disharmony and distinct fault geometries.

  12. Relationship of serum GDF11 levels with bone mineral density and bone turnover markers in postmenopausal Chinese women

    PubMed Central

    Chen, Yusi; Guo, Qi; Zhang, Min; Song, Shumin; Quan, Tonggui; Zhao, Tiepeng; Li, Hongliang; Guo, Lijuan; Jiang, Tiejian; Wang, Guangwei

    2016-01-01

    Growth differentiation factor 11 (GDF11) is an important circulating factor that regulates aging. However, the role of GDF11 in bone metabolism remains unclear. The present study was undertaken to investigate the relationship between serum GDF11 level, bone mass, and bone turnover markers in postmenopausal Chinese women. Serum GDF11 level, bone turnover biochemical markers, and bone mineral density (BMD) were determined in 169 postmenopausal Chinese women (47–78 years old). GDF11 serum levels increased with aging. There were negative correlations between GDF11 and BMD at the various skeletal sites. After adjusting for age and body mass index (BMI), the correlations remained statistically significant. In the multiple linear stepwise regression analysis, age or years since menopause, BMI, GDF11, and estradiol were independent predictors of BMD. A significant negative correlation between GDF11 and bone alkaline phosphatase (BAP) was identified and remained significant after adjusting for age and BMI. No significant correlation was noted between cross-linked N-telopeptides of type I collagen (NTX) and GDF11. In conclusion, GDF11 is an independent negative predictor of BMD and correlates with a biomarker of bone formation, BAP, in postmenopausal Chinese women. GDF11 potentially exerts a negative effect on bone mass by regulating bone formation. PMID:27408764

  13. GDF 15 - A Novel Biomarker in the Offing for Heart Failure

    PubMed Central

    George, Melvin; Jena, Amrita; Srivatsan, Varsha; Muthukumar, Rajaram; Dhandapani, VE

    2016-01-01

    Background: Several diagnostic and prognostic biomarkers are being explored in heart failure. GDF-15 belongs to the transforming growth factor β (TGF-β) cytokine family that is highly up regulated in inflammatory conditions. We undertook this systematic review to summarize the current evidence on the utility of GDF-15 as a biomarker in heart failure. Design and Methods: Multiple electronic databases for studies that reported the association between GDF- 15 and heart failure were searched using different electronic databases such as MEDLINE, Science Direct, Springer Link, Scopus, Cochrane Reviews, and Google Scholar using pre-defined inclusion- exclusion criteria. Results: Twenty one original studies were identified that included data from 20,920 study participants. GDF 15 was found to be a strong prognosticator of all-cause mortality in heart failure patients. Several studies found the benefit of using GDF-15 as a component of a multi-biomarker strategy in prognosticating patients with heart failure. Conclusion: More studies are warranted to elucidate the molecular pathways involving GDF-15 and to see how knowledge about GDF-15 can be used to make therapeutic decisions in the clinic. PMID:26750722

  14. GDF10 Is a Signal for Axonal Sprouting and Functional Recovery after Stroke

    PubMed Central

    Li, S; Nie, EH; Yin, Y; Benowitz, LI; Tung, S; Vinters, HV; Bahjat, FR; Stenzel-Poore, MP; Kawaguchi, R; Coppola, G; Carmichael, ST

    2016-01-01

    Stroke produces a limited process of neural repair. Axonal sprouting in cortex adjacent to the infarct is part of this recovery process, but the signal that initiates axonal sprouting is not known. Growth and Differentiation Factor 10 (GDF10) is induced in peri-infarct neurons in mouse, non-human primate and human. GDF10 promotes axonal outgrowth in vitro in mouse, rat and human neurons through TGFβRI/II signaling. Using pharmacogenetic gain and loss of function studies, GDF10 produces axonal sprouting and enhanced functional recovery after stroke; knocking down GDF10 blocks axonal sprouting and reduces recovery. RNA-seq from peri-infarct cortical neurons indicates that GDF10 downregulates PTEN and upregulates PI3 kinase signaling and induces specific axonal guidance molecules. Unsupervised genome-wide association analysis of the GDF10 transcriptome shows that it is not related to neurodevelopment but may partially overlap with other CNS injury patterns. GDF10 is a stroke-induced signal for axonal sprouting and functional recovery. PMID:26502261

  15. Regulation of GDF-11 and myostatin activity by GASP-1 and GASP-2

    PubMed Central

    Lee, Yun-Sil; Lee, Se-Jin

    2013-01-01

    Myostatin (MSTN) and growth and differentiation factor-11 (GDF-11) are highly related TGF-β family members that have distinct biological functions. MSTN is expressed primarily in skeletal muscle and acts to limit muscle growth. GDF-11 is expressed more widely and plays multiple roles, including regulating axial skeletal patterning during development. Several MSTN and GDF-11 binding proteins have been identified, including GDF-associated serum protein-1 (GASP-1) and GASP-2, which are capable of inhibiting the activities of these ligands. Here, we show that GASP-1 and GASP-2 act by blocking the initial signaling event (namely, the binding of the ligand to the type II receptor). Moreover, we show that mice lacking Gasp1 and Gasp2 have phenotypes consistent with overactivity of MSTN and GDF-11. Specifically, we show that Gasp2−/− mice have posteriorly directed transformations of the axial skeleton, which contrast with the anteriorly directed transformations seen in Gdf11−/− mice. We also show that both Gasp1−/− and Gasp2−/− mice have reductions in muscle weights, a shift in fiber type from fast glycolytic type IIb fibers to fast oxidative type IIa fibers, and impaired muscle regeneration ability, which are the reverse of what are seen in Mstn−/− mice. All of these findings suggest that both GASP-1 and GASP-2 are important modulators of GDF-11 and MSTN activity in vivo. PMID:24019467

  16. GDF11 administration does not extend lifespan in a mouse model of premature aging

    PubMed Central

    Freitas-Rodríguez, Sandra; Rodríguez, Francisco; Folgueras, Alicia R.

    2016-01-01

    GDF11 has recently emerged as a powerful anti-aging candidate, found in young blood, capable of rejuvenating a number of aged tissues, such as heart, skeletal muscle and brain. However, recent reports have shown contradictory data questioning its capacity to reverse age-related tissue dysfunction. The availability of a mouse model of accelerated aging, which shares most of the features occurring in physiological aging, gives us an excellent opportunity to test in vivo therapies aimed at extending lifespan both in pathological and normal aging. On this basis, we wondered whether the proposed anti-aging functions of GDF11 would have an overall effect on longevity. We first confirmed the existence of a reduction in GDF11/8 levels in our mouse model of accelerated aging compared with wild-type littermates. However, we show herein that GDF11 daily administration does not extend lifespan of premature-aged mice. PMID:27507054

  17. Adenovirus-mediated GDF-5 promotes the extracellular matrix expression in degenerative nucleus pulposus cells*

    PubMed Central

    Luo, Xu-wei; Liu, Kang; Chen, Zhu; Zhao, Ming; Han, Xiao-wei; Bai, Yi-guang; Feng, Gang

    2016-01-01

    Objective: To construct a recombinant adenovirus vector-carrying human growth and differentiation factor-5 (GDF-5) gene, investigate the biological effects of adenovirus-mediated GDF-5 (Ad-GDF-5) on extracellular matrix (ECM) expression in human degenerative disc nucleus pulposus (NP) cells, and explore a candidate gene therapy method for intervertebral disc degeneration (IDD). Methods: Human NP cells of a degenerative disc were isolated, cultured, and infected with Ad-GDF-5 using the AdEasy-1 adenovirus vector system. On Days 3, 7, 14, and 21, the contents of the sulfated glycosaminoglycan (sGAG), deoxyribonucleic acid (DNA) and hydroxyproline (Hyp), synthesis of proteoglycan and collagen II, gene expression of collagen II and aggrecan, and NP cell proliferation were assessed. Results: The adenovirus was an effective vehicle for gene delivery with prolonged expression of GDF-5. Biochemical analysis revealed increased sGAG and Hyp contents in human NP cells infected by Ad-GDF-5 whereas there was no conspicuous change in basal medium (BM) or Ad-green fluorescent protein (GFP) groups. Only cells in the Ad-GDF-5 group promoted the production of ECM, as demonstrated by the secretion of proteoglycan and up-regulation of collagen II and aggrecan at both protein and mRNA levels. The NP cell proliferation was significantly promoted. Conclusions: The data suggest that Ad-GDF-5 gene therapy is a potential treatment for IDD, which restores the functions of degenerative intervertebral disc through enhancing the ECM production of human NP cells. PMID:26739524

  18. Altered hypertrophic chondrocyte kinetics in GDF-5 deficient murine tibial growth plates.

    PubMed

    Mikic, B; Clark, R T; Battaglia, T C; Gaschen, V; Hunziker, E B

    2004-05-01

    The growth/differentiation factors (GDFs) are a subgroup of the bone morphogenetic proteins best known for their role in joint formation and chondrogenesis. Mice deficient in one of these signaling proteins, GDF-5, exhibit numerous skeletal abnormalities, including shortened limb bones. The primary aim of this study was determine whether GDF-5 deficiency would alter the growth rate in growth plates from the long bones in mice and, if so, how this is achieved. Stereologic and cell kinetic parameters in proximal tibial growth plates from 5-week-old female GDF-5 -/- mice and control littermates were examined. GDF-5 deficiency resulted in a statistically significant reduction in growth rate (-14%, p=0.03). The effect of genotype on growth rate was associated with an altered hypertrophic phase duration, with hypertrophic cells from GDF-5 deficient mice exhibiting a significantly longer phase duration compared to control littermates (+25%, p=0.006). These data suggest that one way in which GDF-5 might modulate the rate of endochondral bone growth could be by affecting the duration of the hypertrophic phase in growth plate chondrocytes.

  19. The Suez Canal as a habitat and pathway for marine algae and seagrasses

    NASA Astrophysics Data System (ADS)

    Aleem, A. A.

    The Suez Canal supports a diversified benthic algal flora; 133 species of benthic algae are now known from the Canal, as compared with only 24 in 1924. The vertical and horizontal distribution of algae is considered in relation to hydrographic factors. The algae display zonation and 3-4 algal belts are distinguished on the Canal banks on buoys and pier supports. Associated fauna include Balanus amphitrite and Brachidontes variabilis, together with various hydroids, sponges, ascidians, asteroids, ophiuroids and crustaceans. Merceriella enigmatica thrives well in brackish water habitats. The algal flora in the Bitter Lakes resembles that in the Red Sea. The number of Red Sea species decreases from Suez to Port Said in the littoral zone. On the other hand, bottom algae predominantly belong to Red Sea flora. Thirty of the species of algae found belong to the Indo-Pacific flora; half of these are new records to the Canal. Several of these Indo-Pacific algae have recently become established in the Eastern Mediterranean, whereas only two of the Mediterranean macro-algal flora (viz. Caulerpa prolifera and Halopteris scoparia) have been found in the Gulf of Suez. Two seagrasses, Halopia ovalis and Thalassia hemprichii, are recorded for the first time in the Canal. Only Halophila stipulacea has found its way into the Mediterranean via the Suez Canal, but none of the Mediterranean seagrasses is found either in the Canal or in the Red Sea.

  20. Reservoir assessment of the Nubian sandstone reservoir in South Central Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    El-Gendy, Nader; Barakat, Moataz; Abdallah, Hamed

    2017-05-01

    The Gulf of Suez is considered as one of the most important petroleum provinces in Egypt and contains the Saqqara and Edfu oil fields located in the South Central portion of the Gulf of Suez. The Nubian sandstone reservoir in the Gulf of Suez basin is well known for its great capability to store and produce large volumes of hydrocarbons. The Nubian sandstone overlies basement rocks throughout most of the Gulf of Suez region. It consists of a sequence of sandstones and shales of Paleozoic to Cretaceous age. The Nubian sandstone intersected in most wells has excellent reservoir characteristics. Its porosity is controlled by sedimentation style and diagenesis. The cementation materials are mainly kaolinite and quartz overgrowths. The permeability of the Nubian sandstone is mainly controlled by grain size, sorting, porosity and clay content especially kaolinite and decreases with increase of kaolinite. The permeability of the Nubian Sandstone is evaluated using the Nuclear Magnetic Resonance (NMR technology) and formation pressure data in addition to the conventional logs and the results were calibrated using core data. In this work, the Nubian sandstone was investigated and evaluated using complete suites of conventional and advanced logging techniques to understand its reservoir characteristics which have impact on economics of oil recovery. The Nubian reservoir has a complicated wettability nature which affects the petrophysical evaluation and reservoir productivity. So, understanding the reservoir wettability is very important for managing well performance, productivity and oil recovery.

  1. Thermochronological investigation of the timing of rifting and rift segmentation in the Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Bosworth, W.; Stockli, D. F.

    2006-12-01

    The Tertiary Gulf of Suez rift system is one of the best-studied continental rift systems and has inspired many fundamental geodynamic models for continental rifting. However, our limited knowledge of how extensional strain is spatially and temporally distributed has made it difficult to adequately evaluate models for the dynamic evolution of this rift. A critical aspect of constraining the evolution of rifting and rift segmentation in the Gulf of Suez involves acquiring reliable geochronological constraints on extensional faulting. This study has commenced a systematic investigation of the timing and spatial distribution of rifting, lateral rift segmentation, and rift localization within the Gulf of Suez, Egypt, employing apatite and zircon (U-Th)/He thermochronometry. (U-Th)/He thermochronometric analysis of sample transects from exhumed fault blocks within the rift integrated with structural data will allow us to directly determine the timing, distribution, and magnitude of extension. The onset of major rifting (~24-19 Ma) in the Gulf of Suez was marked by the development of crustal domino-style tilt blocks and syn-rift deposition of the late Oligocene non-marine Abu Zenima Fm and non-marine to restricted marine Nukhul Fm. Development of the Gulf of Aqaba-Dead Sea transform cut off the rift from the Red Sea rift at an early extensional stage. Apatite (AHe) and zircon (ZHe) (U- Th)/He data were collected from basement and pre-rift sedimentary sample transects from the central and southern Sinai Peninsula portion and the Gebel El Zeit area in the southern Gulf of Suez as well as from basement samples from selected drill cores off Gebel El Zeit. Preliminary data exhibit partially reset ages trending as old as ~70 Ma (AHe) and ~450 Ma (ZHe) from shallower structural levels (Proterozoic basement and Phanerozoic cover sequence). Structurally deeper samples yield abundant AHe ages of ~22-24 Ma, indicative of rapid cooling and exhumation during the early Miocene. More

  2. Nodal·Gdf1 Heterodimers with Bound Prodomains Enable Serum-independent Nodal Signaling and Endoderm Differentiation

    PubMed Central

    Fuerer, Christophe; Nostro, M. Cristina; Constam, Daniel B.

    2014-01-01

    The TGFβ family member Nodal is central to control pluripotent stem cell fate, but its use as a stem cell differentiation factor is limited by low specific activity. During development, Nodal depends on growth and differentiation factor (Gdf)-1 and on the shared co-receptor Cryptic to specify visceral left-right axis asymmetry. We therefore asked whether the functionality of Nodal can be augmented by Gdf1. Because Nodal and Gdf1 coimmunoprecipitate each other, they were predicted to form heterodimers, possibly to facilitate diffusion or to increase the affinity for signaling receptors. Here, we report that Gdf1 suppresses an unexpected dependence of Nodal on serum proteins and that it is critically required for non-autonomous signaling in cells expressing Cryptic. Nodal, Gdf1, and their cleaved propeptides copurified as a heterodimeric low molecular weight complex that stimulated Activin receptor (Acvr) signaling far more potently than Nodal alone. Although heterodimerization with Gdf1 did not increase binding of Nodal to Fc fusions of co-receptors or Acvr extracellular domains, it was essential for soluble Acvr2 to inhibit Nodal signaling. This implies that Gdf1 potentiates Nodal activity by stabilizing a low molecular weight fraction that is susceptible to neutralization by soluble Acvr2. Finally, in differentiating human ES cells, endodermal markers were more efficiently induced by Nodal·Gdf1 than by Nodal, suggesting that Nodal·Gdf1 is an attractive new reagent to direct stem cell differentiation. PMID:24798330

  3. Combined effects of engineered tendon matrix and GDF-6 on bone marrow mesenchymal stem cell-based tendon regeneration.

    PubMed

    Jiang, Dapeng; Gao, Peng; Zhang, Yubo; Yang, Shulong

    2016-05-01

    To examine whether an engineered tendon matrix (ETM) environment and growth and differentiation factor-6 (GDF-6) have synergistic effects on the tenogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the quality of tendon repair. ETM and GDF-6 promote tenogenic differentiation of BMSCs in vitro. Implantation of GDF-6-incorporated ETM containing BMSCs into a tendon injury model significantly improved the histological and mechanical properties of the repaired tendon. GDF-6-incorporated ETM containing BMSCs represents a promising strategy for tendon injury repair.

  4. The effect of a bioactive collagen membrane releasing PDGF or GDF-5 on bone regeneration.

    PubMed

    Yamano, Seiichi; Haku, Ken; Yamanaka, Takuto; Dai, Jisen; Takayama, Tadahiro; Shohara, Ryutaro; Tachi, Keita; Ishioka, Mika; Hanatani, Shigeru; Karunagaran, Sanjay; Wada, Keisuke; Moursi, Amr M

    2014-03-01

    Regenerative procedures using barrier membrane technology are presently well established in periodontal/endodontic surgery. The objective of this study was to compare the subsequent effects of the released platelet-derived growth factor (PDGF) and growth/differentiation factor 5 (GDF-5) from collagen membranes (CMs) on bone regeneration in vitro and in vivo. In vitro studies were conducted using MC3T3-E1 mouse preosteoblasts cultured with or without factors. Cell viability, cell proliferation, alkaline phosphatase (ALP) activity and bone marker gene expression were then measured. In vivo studies were conducted by placing CMs with low or high dose PDGF or GDF-5 in rat mandibular defects. At 4 weeks after surgery new bone formation was measured using μCT and histological analysis. The results of in vitro studies showed that CM/GDF-5 significantly increased ALP and cell proliferation activities without cytotoxicity in MC3T3-E1 cells when compared to CM/PDGF or CM alone. Gene expression analysis revealed that Runx2 and Osteocalcin were significantly increased in CM/GDF-5 compared to CM/PDGF or control. Quantitative and qualitative μCT and histological analysis for new bone formation revealed that although CM/PDGF significantly enhanced bone regeneration compared to CM alone or control, CM/GDF-5 significantly accelerated bone regeneration to an even greater extent than CM/PDGF. The results also showed that GDF-5 induced new bone formation in a dose-dependent manner. These results suggest that this strategy, using a CM carrying GDF-5, might lead to an improvement in the current clinical treatment of bone defects for periodontal and implant therapy.

  5. GDF: A tool for function estimation through grammatical evolution

    NASA Astrophysics Data System (ADS)

    Tsoulos, Ioannis G.; Gavrilis, Dimitris; Dermatas, Evangelos

    2006-04-01

    This article introduces a tool for data fitting that is based on genetic programming and especially on the grammatical evolution technique. The user needs to input a series of points and the accompanied dimensionality n and the tool will produce via the genetic programming paradigm a function f:R→R which is an approximate solution to the symbolic regression problem. The tool is entirely written in ANSI C++ and it can be installed in any UNIX system. Program summaryTitle of program: GDF Catalogue identifier:ADXC Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADXC Computer for which the program is designed and others on which is has been tested:The tool is designed to be portable in all systems running the GNU C++ compiler Installation: University of Ioannina and University of Patras, Greece Programming language used:GNU-C++ Memory required to execute with typical data:200 KB No. of bits in a word: 32 No. of processors used: 1 Has the code been vectorized or parallelized?: No No. of bytes in distributed program, including test data, etc.: 33 469 No. of lines in distributed program, including test data, etc.: 5704 Distribution format: tar.gz Solution method: Functional forms are being created by genetic programming which are approximations for the symbolic regression problem.

  6. Microbial pollution indicators along the Egyptian coastal waters of Suez and Aqaba Gulfs and Red Sea.

    PubMed

    Ibrahim, Hassan A H; Farag, Aida M; Beltagy, Ehab A; El-Shenawy, Mohamed A

    2011-01-01

    Nowadays, the Egyptian coasts of the Aqaba and Suez Gulfs, and the Red Sea proper, are under the direct effects of many recreational resorts, urban agglomeration, marine shipping, activity of the phosphate industry, fishing ports, and limited freshwater and sewage surfaces. Therefore, the water, especially those used for recreational activities, must be of a very good quality to be able to increase the national income. To investigate the conventional water-quality bacteria, total coliforms (TC), Escherichia coli (EC), and fecal streptococci (FS), in the Egyptian coastal waters of Suez and Aqaba Gulfs and the Red Sea. A total of 2372 surface water samples were collected from 42 sampling sites during 12 years (1998-2009) to detect and estimate TC, EC, and FS using the membrane filtration method. On the basis of the national and international bacterial standards, 540 samples (22.8%) out of 2372 were found to exceed the guide values (positive samples) and were not accepted for marine recreational purposes. During the course of the study, Suez Gulf showed the highest positive records of 54 and 96 for TC and EC, respectively, whereas FS recorded 94 and 88 positive samples in the Red Sea and Suez Gulf, respectively. The lowest positive records were found in 1998 and 2009, whereas the highest were in 2000 and 2002-2004. The highest polluted sampling sites were recorded in Su7 (Suez Gulf), Aq2 (Aqaba Gulf), and Re15 (Red Sea), and were generally affected by sewage disposal and/or anthropogenic influences. The most polluted sites were in the Suez Gulf, reaching 238 sites, followed by 194 sites in the Red Sea, whereas the Aqaba Gulf had only 108 polluted sites. Moreover, the most polluted sample locations throughout the study were Su7, Aq2, and Re15, without implementation of corrective actions from authorized organizations. The data of the current study must be taken into consideration by the government for a safer and cleaner seawater in the eastern Egyptian coasts

  7. Acute exercise in elite rugby players increases the circulating level of the cardiovascular biomarker GDF-15.

    PubMed

    Galliera, Emanuela; Lombardi, Giovanni; Marazzi, Monica G; Grasso, Dalila; Vianello, Elena; Pozzoni, Roberto; Banfi, Giuseppe; Corsi Romanelli, Massimiliano M

    2014-09-01

    Intense training can lead to a pathophysiological change in serum concentration of a variety of biomarkers. Traditional biomarkers of cardiac injury are very useful in monitoring CVD patients, but in healthy subjects or athletes they cannot be informative enough about the cardiovascular risk, because in these cases their serum levels do not increase over the pathological limit. Therefore novel cardiovascular biomarkers are required in order to allow a better monitoring of sport performance, prediction of overtraining and diagnosis of sport-related cardiac injuries. Growth differentiation factor-15 (GDF-15) is emerging as a powerful cardiovascular injury risk indicator. In this study we investigate the effect of intense physical training of on the circulating levels of GDF-15 in rugby professional players. Serum GDF-15, Erythropoietin, IL-6, the cardiovascular parameter ST-2, NT-proBNP and routine hematological parameters were measured in a group of 30 rugby players before and after a session of intense training. While ST-2, IL-6 and hsCRP displayed no significant changes after intense training, NT-proBNP and GDF-15 showed a significant increase, even without reaching the pathological level. The measure of GDF-15 in professional rugby players could be a useful tool to monitoring their cardiovascular status during training and competition session in order to prevent the onset of collateral cardiovascular adverse event due to the intense training and, in the case of cardiac injury, it could possibly allow a very early diagnosis at the beginning of the pathogenic process.

  8. POLYMORPHISM IN THE CODING REGION SEQUENCE OF GDF8 GENE IN INDIAN SHEEP.

    PubMed

    Pothuraju, M; Mishra, S K; Kumar, S N; Mohamed, N F; Kataria, R S; Yadav, D K; Arora, R

    2015-11-01

    The present study was undertaken to identify polymorphism in the coding sequence of GDF8gene across indigenous meat type sheep breeds. A 1647 bp sequence was generated, encompassing 208 bp of the 5'UTR, 1128 bp of coding region (exon1, 2 and 3) as well as 311 bp of 3'UTR. The sheep and goat GDF8 gene sequences were observed to be highly conserved as compared to cattle, buffalo, horse and pig. Several nucleotide variations were observed across coding sequence of GDF8 gene in Indian sheep. Three polymorphic sites were identified in the 5'UTR, one in exon 1 and one in the exon 2 regions. Both SNPs in the exonic region were found to be non-synonymous. The mutations c.539T > G and c.821T > A discovered in this study in the exon 1 and exon 2, respectively, have not been previously reported. The information generated provides preliminary indication of the functional diversity present in Indian sheep at the coding region of GDF8gene. The novel as well as the previously reported SNPs discovered in the Indian sheep warrant further analysis to see whether they affect the phenotype. Future studies will need to establish the affect of reported SNPs in the expression of the GDF8 gene in Indian sheep population.

  9. The GDF5 SNP is associated with meniscus injury and function recovery in male Chinese soldiers.

    PubMed

    Ge, W; Mu, J; Huang, C

    2014-06-01

    Genetic factor have previously been shown to play an important role in sports injuries and recovery. GDF5 Single-Nucleotide Polymorphism rs143383 has been recently reported to be associated with fracture susceptibility. Furthermore, the effect of GDF5 during the recovery processes of trauma is increased. In the present study, we aimed to evaluate whether this SNP was associated with susceptibility to the meniscus injury and postoperative recovery in Chinese male soldiers. GDF5 SNP was genotyped in 135 male soldiers with meniscus injury and 400 healthy male controls. Moreover, the function recovery of the soldiers suffering from the meniscal repair was also assessed. Our data showed that the GDF5 TT genotype (60.0 vs. 47.25%; P=0.010) and T allele (76.3 vs. 68.75%; P=0.019) were significantly over-represented in the meniscus injury group compared with the control group. We found that the TC (P<0.05), CC (P<0.05) and C carriers (P<0.05) genotype exhibited significantly higher Lysholm Scores than the TT genotype at 1 month postoperative. In addition, the CC (P<0.05) genotype also demonstrated significantly higher Lysholm Scores than the TT genotype 2 months postoperative. Taken together, our results revealed that the GDF5 SNP was associated with susceptibility to the meniscus injury and postoperative function recovery in Chinese male soldiers. © Georg Thieme Verlag KG Stuttgart · New York.

  10. BMP15 Mutations Associated With Primary Ovarian Insufficiency Reduce Expression, Activity, or Synergy With GDF9.

    PubMed

    Patiño, Liliana C; Walton, Kelly L; Mueller, Thomas D; Johnson, Katharine E; Stocker, William; Richani, Dulama; Agapiou, David; Gilchrist, Robert B; Laissue, Paul; Harrison, Craig A

    2017-03-01

    Bone morphogenetic protein (BMP)15 is an oocyte-specific growth factor, which, together with growth differentiation factor (GDF) 9, regulates folliculogenesis and ovulation rate. Multiple mutations in BMP15 have been identified in women with primary ovarian insufficiency (POI), supporting a pathogenic role; however, the underlying biological mechanism of many of these mutants remains unresolved. To determine how mutations associated with ovarian dysfunction alter the biological activity of human BMP15. The effects of 10 mutations in BMP15 on protein production, activation of granulosa cells, and synergy with GDF9 were assessed. Sequencing of 35 patients with POI identified both an unrecognized BMP15 variant (c.986G>A, R329H) and a variant (c.581T>C, F194S) previously associated with the condition. Assessing expression and activity of these and 8 other BMP15 mutants identified: (1) multiple variants, including L148P, F194S, and Y235C, with reduced mature protein production; (2) three variants (R138H, A180T, and R329H) with ∼fourfold lower activity than wild-type BMP15; and (3) 3 variants (R68W, F194S, and N196K) with a significantly reduced ability to synergize with GDF9. Mutations in BMP15 associated with POI reduce mature protein production, activity, or synergy with GDF9. The latter effect is perhaps most interesting given that interactions with GDF9 most likely underlie the physiology of BMP15 in the human ovary.

  11. Molecular cloning of porcine growth differentiation factor 9 (GDF-9) cDNA and its role in early folliculogenesis: direct ovarian injection of GDF-9 gene fragments promotes early folliculogenesis.

    PubMed

    Shimizu, Takashi; Miyahayashi, Yasunori; Yokoo, Masaki; Hoshino, Yumi; Sasada, Hiroshi; Sato, Eimei

    2004-11-01

    Growth differentiation factor-9 (GDF-9) is a growth factor secreted by oocytes in growing ovarian follicles. To investigate the ovarian function of GDF-9 in pigs, we first cloned porcine GDF-9 complementary DNA (cDNA), and then injected its gene fragments into the ovary in gilts. Porcine GDF-9 has open reading frame (ORF) homologies of 81.4%, 84.6%, 84.2%, 72.7% and 72.6% with its human, bovine, ovine, rat and mouse counterparts respectively. Regarding the deduced amino-acid sequence of the mature protein, the corresponding homologies reach 92.1%, 97.8%, 97.0%, 89.6% and 88.1% respectively. To investigate the role of GDF-9 in early folliculogenesis, the ovaries of 2-month-old prepubertal gilts were injected with GDF-9 gene fragments. The injection of porcine GDF-9 gene fragments resulted in an increase in the number of primary, secondary and tertiary follicles, concomitant with a decrease in the number of primordial follicles. These results indicated that exogenous GDF-9 can promote early folliculogenesis in the porcine ovary, and that a technique for direct ovarian injection of GFD-9 gene fragments may contribute to a novel therapy for prevention and treatment of infertility associated with ovarian dysfunction.

  12. A study of Salmonella typhi isolated in Suez Canal area. Biotyping, phage typing and colicinogenic property.

    PubMed

    Shoeb, S; Khalifa, I; el Daly, O; Heiba, A; Farmer, J; Brenner, F; el Batawi, Y

    1989-01-01

    In this work a total of 82 strains of Salmonella typhi were isolated from Egyptian patients diagnosed as quiry enteric fever. These cases were from Ismalia, Suez and port Said Areas. The strains fell in 16 phage types. Phage types N, 40, E1, and degraded Vi were the commonest phage type in Ismailia, while phage types degraded Vi and C1 were the commonest in Port Said. Phage types Di-N, degraded Vi, A and C1 were the commonest in Suez. Chemotyping of Salmonella typhi showed that the majority of the strains belonged to chemotype I (82%), and the rest belonged to chemotype II (18%). Colicin production was negative and all the strains were susceptible to the currently used antibiotics.

  13. Interpretation of multispectral and infrared thermal surveys of the Suez Canal Zone, Egypt

    NASA Technical Reports Server (NTRS)

    Elshazly, E. M.; Hady, M. A. A. H.; Hafez, M. A. A.; Salman, A. B.; Morsy, M. A.; Elrakaiby, M. M.; Alaassy, I. E. E.; Kamel, A. F.

    1977-01-01

    Remote sensing airborne surveys were conducted, as part of the plan of rehabilitation, of the Suez Canal Zone using I2S multispectral camera and Bendix LN-3 infrared passive scanner. The multispectral camera gives four separate photographs for the same scene in the blue, green, red, and near infrared bands. The scanner was operated in the microwave bands of 8 to 14 microns and the thermal surveying was carried out both at night and in the day time. The surveys, coupled with intensive ground investigations, were utilized in the construction of new geological, structural lineation and drainage maps for the Suez Canal Zone on a scale of approximately 1:20,000, which are superior to the maps made by normal aerial photography. A considerable number of anomalies belonging to various types were revealed through the interpretation of the executed multispectral and infrared thermal surveys.

  14. Association between Growth Differentiation Factor 15 (GDF15) and Cardiovascular Risk in Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

    PubMed

    Shin, Min Young; Kim, Ji Min; Kang, Yea Eun; Kim, Min Kyeong; Joung, Kyong Hye; Lee, Ju Hee; Kim, Koon Soon; Kim, Hyun Jin; Ku, Bon Jeong; Shong, Minho

    2016-09-01

    We investigated an association between serum Growth Differentiation Factor 15 (GDF15) level and cardiovascular risk in patients with newly diagnosed type 2 diabetes mellitus (T2D). A total of 107 participants were screened for T2D and divided into a T2D group and a control group (without diabetes). We used the Framingham risk score (FRS) and the New Pooled Cohort Equation score to estimate the 10-year risk of atherosclerotic cardiovascular disease. Serum GDF15 levels were measured using an enzyme-linked immunosorbent assay. Correlation analyses were performed to evaluate the associations between GDF15 level and cardiovascular risk scores. The mean serum GDF15 level was elevated in the T2D group compared to the control group (P < 0.001). A positive correlation was evident between serum GDF15 level and age (r = 0.418, P = 0.001), the FRS (r = 0.457, P < 0.001), and the Pooled Cohort Equation score (r = 0.539, P < 0.001). After adjusting for age, LDL-C level, and body mass index (BMI), the serum GDF15 level was positively correlated with the FRS and the New Pooled Cohort Equation score. The serum GDF15 level is independently associated with cardiovascular risk scores of newly diagnosed T2D patients. This suggests that the level of GDF15 may be a useful predictive biomarker of cardiovascular risk in newly diagnosed T2D patients.

  15. Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation

    PubMed Central

    Liu, Jia; Saito, Kan; Maruya, Yuriko; Nakamura, Takashi; Yamada, Aya; Fukumoto, Emiko; Ishikawa, Momoko; Iwamoto, Tsutomu; Miyazaki, Kanako; Yoshizaki, Keigo; Ge, Lihong; Fukumoto, Satoshi

    2016-01-01

    Bone morphogenetic proteins (BMPs) regulate hard tissue formation, including bone and tooth. Growth differentiation factor 5 (GDF5), a known BMP, is expressed in cartilage and regulates chondrogenesis, and mutations have been shown to cause osteoarthritis. Notably, GDF5 is also expressed in periodontal ligament tissue; however, its role during tooth development is unclear. Here, we used cell culture and in vivo analyses to determine the role of GDF5 during tooth development. GDF5 and its associated BMP receptors are expressed at the protein and mRNA levels during postnatal tooth development, particularly at a stage associated with enamel formation. Furthermore, whereas BMP2 was observed to induce evidently the differentiation of enamel-forming ameloblasts, excess GDF5 induce mildly this differentiation. A mouse model harbouring a mutation in GDF5 (W408R) showed enhanced enamel formation in both the incisors and molars, but not in the tooth roots. Overexpression of the W408R GDF5 mutant protein was shown to induce BMP2-mediated mRNA expression of enamel matrix proteins and downstream phosphorylation of Smad1/5/8. These results suggest that mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-signalling. PMID:27030100

  16. GDF15 contributes to radiation-induced senescence through the ROS-mediated p16 pathway in human endothelial cells.

    PubMed

    Park, Hyejin; Kim, Chun-Ho; Jeong, Jae-Hoon; Park, Myungjin; Kim, Kwang Seok

    2016-03-01

    Growth differentiation factor 15 (GDF15) is an emerging biomarker of cardiovascular risk and disease. Microarray analyses revealed that GDF15 levels were increased during cellular senescence induced by ionizing radiation (IR) in human aortic endothelial cells (HAECs). However, the role of GDF15 in HAEC cellular senescence remains unclear. This study demonstrated that downregulation of GDF15 in HAECs partially prevented cellular senescence triggered by IR, which was confirmed by recovery of cell proliferation and reverse senescence-associated β-galactosidase (SA-β-gal) staining. Conversely, upregulation of GDF15-induced cellular senescence in HAECs, confirmed by G0/G1 cell cycle arrest, decreased during cell proliferation and increased SA-β-gal staining. GDF15-induced cellular senescence was observed in p16-knockdown cells but not in p53-knockdown cells. GDF15 expression in endothelial cells also generated reactive oxygen species (ROS), which led to activation of extracellular signal-regulated kinases (ERKs) and induction of senescence by oxidative stress. These results suggested that GDF15 might play an important role in cellular senescence through a ROS-mediated p16 pathway and contribute to the pathogenesis of atherosclerosis via pro-senescent activity.

  17. Risk assessment during transport of radioactive materials through the Suez Canal

    NASA Astrophysics Data System (ADS)

    Sabek, M. G.; El-Shinawy, R. M. K.; Gomaa, M.

    1997-03-01

    In this paper a study for risk assessment of the impact of transporting radioactive materials, during the period 1986-1992, through the Suez Canal of Egypt is given. The code RADTRAN-IV was used for this study. The results of the code, for a normal case, show that the transportation of low activity materials such as uranium (U 3O 8) represent the main items that contribute significantly to the collective dose within the Suez Canal area (Port-Said, Ismailia and Suez). The values of the annual collective dose due to transportation of all radionuclide materials was found to be at a maximum in Suez town and is equal to 5.04 × 10 -8 Man-Sv for the whole populations. If we only consider the workder at the harbour (estimated to be 50 persons), the value of the annual collective dose is about 3.33 × 10 -4 Man-Sv. These values are less than the exemption value of 1 Man-Sv recommended by the IAEA. For the accident case, the following pathways are considered by the code: ground-shine, direct inhalation, inhalation of resuspended material and cloud-shine. The total values of the estimated risks for each radionuclide material are presented in table form and, in addition, health effects (genetic effects, GE, and latent cancer fatality), LCF) are discussed. The calculated values of the radiological risks are very low for the three towns, showing that no radiation-induced early deaths are to be expected.

  18. Mobility and Fate of Pollutants in the Aquifer System of the Northwestern Suez Gulf, Egypt.

    PubMed

    Snousy, Moustafa Gamal; Zawrah, M F; Abdel-Moghny, Th; Ebiad, M A; Rashad, A M; Khalil, Mahmoud M; Abu El Ella, E M; El-Sayed, E; Tantawy, M A

    The northwestern part of Suez Gulf region is a strategic area in Egypt. It includes important sources of national income. To achieve the development goals, the government has established huge projects in this area (e.g. establishment and expanding of a large commercial port at Ain Sokhna, many industrial zones as well as tourism projects). The utilization of the Suez Gulf resources and their continuing development mainly depend on the creation of actual pollution control programs. The environmental quality control and pollution reduction activities are important ingredients of any economic development program. These different activities in this area depend mainly on the groundwater that is pumped intensively from different water bearing formations or aquifers. The main objective of the present work is compiling the previous studies from the 1980s up to 2015. These studies are concerned with estimating the concentrations of different pollutants in various ecosystems in the northwestern Suez Gulf region. Also, to provide an explanation for the movement of different pollutants such as organic and heavy metals from contaminated land to ground and surface (Gulf) waters. This issue has not been extensively surveyed before, and this review, gives specific directions for future monitoring and remediation strategies in this region.

  19. Synrift sedimentation in the Gulf of Suez rift controlled by eustatic sea level variations

    SciTech Connect

    Perry, S.K.; Schamel, S.

    1985-01-01

    Laterally persistent stratigraphic variations in the southern Gulf of Suez rift indicate that eustatic variations in sea level predominate over local tectonic effects in controlling Neogene basin-fill sedimentation. Low sea level allows extensive erosion of tilt-block crests and rift shoulders, sending clastic aprons into the intervening subbasins and allowing evaporite deposition. High sea level minimizes clastic input, allowing marls and shales to build up off structure and reefs to form on and around tilt blocks. Thus variations in sediment character indicate relative sea level. Early rifting events in the upper Oligocene are marked by deposition of continental red beds. Overlying lowest Miocene clastics and evaporites are cut by a lower Burdigalian unconformity, indicating a minor transgression in the Aquitanian. Above a disconformity, laterally varying clastics and evaporites suggest regression followed by intermittent shallow-water conditions. A higher unconformity is overlain by thick cyclic evaporites representing periodic flooding and drying of the rift, a result of sea level remaining close to the height of the Suez sill to the north. A major Messinian unconformity cuts the section, indicating major regression, and is overlain by largely clastic sediments of both continental and marine affinities, showing rapid sea level fluctuations. Regional synrift sedimentation has been controlled more by eustatic sea level change, modified by the Suez sill to the north, than by tectonic movements within the rift.

  20. Association of GDF1 rs4808863 with fetal congenital heart defects: a case–control study

    PubMed Central

    Zhang, Juan; Wu, Qingqing; Wang, Li; Li, Xiaofei; Ma, Yuqing; Yao, Ling

    2015-01-01

    Background Congenital heart defects (CHDs) are the most common fetal defects and the most important cause of child mortality and morbidity. Objective To investigate the association between growth/differentiation factor 1 (GDF1) polymorphisms and fetal CHDs, by evaluating the association of GDF1 rs4808863 with fetal CHDs. Design A case–control study. Setting Beijing, China. Participants We selected 124 fetuses with a CHD and a normal karyotype and normal array-based comparative genomic hybridisation analysis and compared them with 124 normal fetuses matched for gestational age and sex. Fetuses with a CHD, from 20 to 32 weeks of gestation were included. Fetuses with any chromosomal abnormalities, and fetuses from multiple pregnancies and those carried by pregnant women with chronic diseases, were excluded from this research. DNA extraction and genotyping were carried out for all cases to investigate the genotype distributions of GDF1 rs4808863. Results A significant difference was noted for the CT phenotype of GDF1 rs4808863 between the controls and the fetuses with CHDs using homozygote and heterozygote comparisons. The minor allele (T allele) of GDF1 rs4808863 was associated with an increased risk of CHD (p<0.05). A statistically significant difference between controls and fetuses with CHDs was noted in a comparison with the mutation genotype CT+TT and wild-type genotype CC (p<0.05) using dominant modal analysis. After stratification analysis, the CT phenotype, the minor allele (T allele) and the mutation genotype CT+TT of the rs4808863 polymorphism were associated with atrioventricular septal defect (AVSD), left ventricular outflow tract obstruction (LVOTO) and left–right laterality defects (p<0.05). Conclusions Our results suggest that the GDF1 rs4808863 polymorphism contributes to an increased risk of fetal CHDs, especially the subtypes of AVSD, LVOTO and left–right laterality defects. PMID:26656983

  1. MAP3K11/GDF15 axis is a critical driver of cancer cachexia

    PubMed Central

    Tao, Julie; Liu, Qing; Nicoletti, Richard; Feng, Bin; Krieger, Brian; Mazsa, Elizabeth; Siddiquee, Zakir; Wang, Ruoji; Huang, Lucia; Shen, Luhua; Lin, Jie; Vigano, Antonio; Chiu, M. Isabel; Weng, Zhigang; Winston, William; Weiler, Solly

    2015-01-01

    Abstract Background Cancer associated cachexia affects the majority of cancer patients during the course of the disease and thought to be directly responsible for about a quarter of all cancer deaths. Current evidence suggests that a pro‐inflammatory state may be associated with this syndrome although the molecular mechanisms responsible for the development of cachexia are poorly understood. The purpose of this work was the identification of key drivers of cancer cachexia that could provide a potential point of intervention for the treatment and/or prevention of this syndrome. Methods Genetically engineered and xenograft tumour models were used to dissect the molecular mechanisms driving cancer cachexia. Cytokine profiling from the plasma of cachectic and non‐cachectic cancer patients and mouse models was utilized to correlate circulating cytokine levels with the cachexia phenotype. Results Utilizing engineered tumour models we identified MAP3K11/GDF15 pathway activation as a potent inducer of cancer cachexia. Increased expression and high circulating levels of GDF15 acted as a key mediator of this process. In animal models, tumour‐produced GDF15 was sufficient to trigger the cachexia phenotype. Elevated GDF15 circulating levels correlated with the onset and progression of cachexia in animal models and in patients with cancer. Inhibition of GDF15 biological activity with a specific antibody reversed body weight loss and restored muscle and fat tissue mass in several cachectic animal models regardless of their complex secreted cytokine profile. Conclusions The combination of correlative observations, gain of function, and loss of function experiments validated GDF15 as a key driver of cancer cachexia and as a potential therapeutic target for the treatment and/or prevention of this syndrome. PMID:27239403

  2. Expression of the osteoarthritis-associated gene GDF5 is modulated epigenetically by DNA methylation.

    PubMed

    Reynard, Louise N; Bui, Catherine; Canty-Laird, Elizabeth G; Young, David A; Loughlin, John

    2011-09-01

    GDF5 is involved in synovial joint development, maintenance and repair, and the rs143383 C/T single nucleotide polymorphism (SNP) located in the 5'UTR of GDF5 is associated, at the genome-wide significance level, with osteoarthritis susceptibility, and with other musculoskeletal phenotypes including height, congenital hip dysplasia and Achilles tendinopathy. There is a significant reduction in the expression of the disease-associated T allele relative to the C allele in synovial joint tissues, an effect influenced by a second SNP (rs143384, C/T) also within the 5'UTR. The differential allelic expression (DAE) imbalance of the C and T alleles of rs143383 varies intra- and inter-individually, suggesting that DAE may be modulated epigenetically. The C alleles of both SNPs form CpG dinucleotides that are potentially amenable to regulation by methylation. Here, we have examined whether DNA methylation regulates GDF5 expression and the allelic imbalance caused by rs143383. We observed methylation of the GDF5 promoter and 5'UTR in cell lines and joint tissues, with demethylation correlating with increased GDF5 expression. The CpG sites created by the C alleles at rs143383 and rs143384 were variably methylated, and treatment of a heterozygous cell line with a demethylating agent further increased the allelic expression imbalance between the C and T alleles. This demonstrates that the genetic effect of the rs143383 SNP on GDF5 expression is modulated epigenetically by DNA methylation. The variability in DAE of rs143383 is therefore partly accounted for by differences in DNA methylation that could influence the penetrance of this allele in susceptibility to common musculoskeletal diseases.

  3. TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and body weight regulator.

    PubMed

    Tsai, Vicky Wang-Wei; Macia, Laurence; Johnen, Heiko; Kuffner, Tamara; Manadhar, Rakesh; Jørgensen, Sebastian Beck; Lee-Ng, Ka Ki Michelle; Zhang, Hong Ping; Wu, Liyun; Marquis, Christopher Peter; Jiang, Lele; Husaini, Yasmin; Lin, Shu; Herzog, Herbert; Brown, David A; Sainsbury, Amanda; Breit, Samuel N

    2013-01-01

    The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1(-/-)) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1(-/-) mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1(-/-) mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage.

  4. Small molecules dorsomorphin and LDN-193189 inhibit myostatin/GDF8 signaling and promote functional myoblast differentiation.

    PubMed

    Horbelt, Daniel; Boergermann, Jan H; Chaikuad, Apirat; Alfano, Ivan; Williams, Eleanor; Lukonin, Ilya; Timmel, Tobias; Bullock, Alex N; Knaus, Petra

    2015-02-06

    GDF8, or myostatin, is a member of the TGF-β superfamily of secreted polypeptide growth factors. GDF8 is a potent negative regulator of myogenesis both in vivo and in vitro. We found that GDF8 signaling was inhibited by the small molecule ATP competitive inhibitors dorsomorphin and LDN-193189. These compounds were previously shown to be potent inhibitors of BMP signaling by binding to the BMP type I receptors ALK1/2/3/6. We present the crystal structure of the type II receptor ActRIIA with dorsomorphin and demonstrate that dorsomorphin or LDN-193189 target GDF8 induced Smad2/3 signaling and repression of myogenic transcription factors. As a result, both inhibitors rescued myogenesis in myoblasts treated with GDF8. As revealed by quantitative live cell microscopy, treatment with dorsomorphin or LDN-193189 promoted the contractile activity of myotubular networks in vitro. We therefore suggest these inhibitors as suitable tools to promote functional myogenesis.

  5. Evaluation of poly-aromatic hydrocarbons (PAHs) in the aquatic species of Suez Gulf water along El-Sokhna area to the Suez refineries.

    PubMed

    Ali, Nabila A; Ahmed, Omayma E; Doheim, Mamdouh M

    2014-02-01

    The Egyptian Red Sea environment especially along El-Sokhna area to the Suez refineries (Suez) is severely contaminated with organic compounds, as well as overfishing. This may be well contributory to recent serious declines in fish stocks. Fish embryos are also particularly vulnerable to oil exposure, even at extremely low concentrations of less than one part per billion. Consequently, even traces of oil pollution at levels often considered safe for wildlife can cause severe damage to fish. Sixteen polycyclic aromatic hydrocarbons (PAHs) were investigated in ten fish species of aquatic species by high performance liquid chromatography (HPLC). The compositions of PAHs determined in all samples were measured in order to use them as chemical markers for identifying different sources of PAH pollutants in the studied region. The total content of these16 PAHs ranged from 399.616 up to 67,631.779 ng/g wet weight. The data show that these values are considered to be alarmingly high enough to cause lethal toxicity effect by accumulation. All studied aquatic species samples are characterized by relatively high concentrations of the six-membered ring PAHs. The origin of PAHs in the collected samples is either petrogenic, biogenic, or mixed petrogenic and biogenic.

  6. Release of active and depot GDF-5 after adenovirus-mediated overexpression stimulates rabbit and human intervertebral disc cells.

    PubMed

    Wang, Haili; Kroeber, Markus; Hanke, Michael; Ries, Rainer; Schmid, Carsten; Poller, Wolfgang; Richter, Wiltrud

    2004-02-01

    To develop new therapeutic options for the treatment of disc degeneration we tested the possibility of overexpression of active growth and differentiation factor (GDF) 5 and of transforming growth factor (TGF) beta(1) by adenoviral gene transfer and characterized its effect on cell proliferation and matrix synthesis of cultured rabbit and human intervertebral disc cells. Recombinant adenovirus encoding for GDF-5 or TGF-beta(1) was developed and transgene expression characterized by RT-PCR, western blot and ELISA. Growth and matrix synthesis of transduced cells was measured by [(3)H]thymidine or [(35)S]sulfate incorporation. Disc cells expressed the receptors BMPR1A, BMPR1B, and BMPR2, which are relevant for GDF-5 action. Adenovirus efficiently transferred the GDF-5 gene or the TGF-beta(1) gene to rabbit and human intervertebral disc cells. About 50 ng GDF-5 protein/10(6 )cells per 24 h or 7 ng TGF-beta(1) protein/10(6 )cells per 24 h was produced. According to western blotting, two GDF-5 forms, with molecular weights consistent with the activated GDF-5 dimer and the proform, were secreted over the 3 weeks following gene transfer. Overexpressed GDF-5 and TGF-beta(1) were bioactive and promoted growth of rabbit disc cells in monolayer culture. Our results suggest that ex vivo gene delivery of GDF-5 and TGF-beta(1) is an attractive approach for the release of mature and pre-GDF-5 in surrounding tissue. This leads us to hope that it will prove possible to improve the treatment of degenerative disc disease by means of ex vivo gene transfer of single or multiple growth factors.

  7. Simulation of strong ground motion parameters of the 1 June 2013 Gulf of Suez earthquake, Egypt

    NASA Astrophysics Data System (ADS)

    Toni, Mostafa

    2017-06-01

    This article aims to simulate the ground motion parameters of the moderate magnitude (ML 5.1) June 1, 2013 Gulf of Suez earthquake, which represents the largest instrumental earthquake to be recorded in the middle part of the Gulf of Suez up to now. This event was felt in all cities located on both sides of the Gulf of Suez, with minor damage to property near the epicenter; however, no casualties were observed. The stochastic technique with the site-dependent spectral model is used to simulate the strong ground motion parameters of this earthquake in the cities located at the western side of the Gulf of Suez and north Red Sea namely: Suez, Ain Sokhna, Zafarana, Ras Gharib, and Hurghada. The presence of many tourist resorts and the increase in land use planning in the considered cities represent the motivation of the current study. The simulated parameters comprise the Peak Ground Acceleration (PGA), Peak Ground Velocity (PGV), and Peak Ground Displacement (PGD), in addition to Pseudo Spectral Acceleration (PSA). The model developed for ground motion simulation is validated by using the recordings of three accelerographs installed around the epicenter of the investigated earthquake. Depending on the site effect that has been determined in the investigated areas by using geotechnical data (e.g., shear wave velocities and microtremor recordings), the investigated areas are classified into two zones (A and B). Zone A is characterized by higher site amplification than Zone B. The ground motion parameters are simulated at each zone in the considered areas. The results reveal that the highest values of PGA, PGV, and PGD are observed at Ras Gharib city (epicentral distance ∼ 11 km) as 67 cm/s2, 2.53 cm/s, and 0.45 cm respectively for Zone A, and as 26.5 cm/s2, 1.0 cm/s, and 0.2 cm respectively for Zone B, while the lowest values of PGA, PGV, and PGD are observed at Suez city (epicentral distance ∼ 190 km) as 3.0 cm/s2, 0.2 cm/s, and 0.05 cm/s respectively for Zone A

  8. Endometriosis-associated infertility: GDF-9, AMH, and AMHR2 genes polymorphisms.

    PubMed

    De Conto, Emily; Matte, Úrsula; Bilibio, João Paolo; Genro, Vanessa Krebs; Souza, Carlos Augusto; Leão, Delva Pereira; Cunha-Filho, João Sabino

    2017-08-22

    The purpose of this paper is to determine whether there is a correlation between polymorphisms in the growth differentiation factor-9 (GDF-9) gene and anti-Müllerian hormone (AMH) gene and its receptor, AMHR2, and endometriosis-associated infertility. This is a case-control study to evaluate whether there is a correlation between polymorphisms in the GDF-9 gene (SNPs determined by direct sequencing), AMH gene, AMHR2 (both SNPs determined by genotyping using TaqMan Allelic Discrimination), and endometriosis-associated infertility. The study included 74 infertile women with endometriosis and 70 fertile women (tubal ligation) as a control group. Patient age and the mean FSH levels were similar between the infertile with endometriosis and fertile without endometriosis groups. The frequency of genotypes between the groups for GDF-9 gene polymorphisms did not show statistical significance, nor did the AMHR2 gene polymorphism. However, the AMH gene polymorphism did show statistical significance, relating the polymorphic allele with infertility in endometriosis. We demonstrate that an SNP in the AMH gene is associated with infertility in endometriosis, whereas several SNPs in the GDF-9 gene and the - 482A G SNP in the AMHR2 gene were found to be unrelated.

  9. GDF15/MIC1 and MMP9 Cerebrospinal Fluid Levels in Parkinson's Disease and Lewy Body Dementia.

    PubMed

    Maetzler, Walter; Deleersnijder, Willy; Hanssens, Valérie; Bernard, Alice; Brockmann, Kathrin; Marquetand, Justus; Wurster, Isabel; Rattay, Tim W; Roncoroni, Lorenzo; Schaeffer, Eva; Lerche, Stefanie; Apel, Anja; Deuschle, Christian; Berg, Daniela

    2016-01-01

    Based on animal and ex-vivo experiments, Growth/Differentiation Factor-15 (GDF15, also called Macrophage Inhibitory Cytokine-1, MIC1), a member of the transforming growth factor-beta family, and Matrix Metalloproteinase-9 (MMP9), a member of the matrix metalloprotease family may be potential markers for Lewy body disorders, i.e. Parkinson's disease with (PDD) and without dementia (PDND) and Lewy body dementia (DLB). GDF15 has a prominent role in development, cell proliferation, differentiation, and repair, whereas MMP9 degrades, as a proteolytic enzyme, components of the extracellular matrix. In this study, cerebrospinal fluid GDF15 and MMP9 levels of 59 PDND, 17 PDD and 23 DLB patients, as well as of 95 controls were determined, and associated with demographic, clinical and biochemical parameters. Our analysis confirmed the already described association of GDF15 levels with age and gender. Corrected GDF15 levels were significantly higher in PDD than in PDND patients, and intermediate in DLB patients. Within Lewy body disorders, GDF15 levels correlated positively with age at onset of Parkinsonism and dementia, Hoehn & Yahr stage and cerebrospinal fluid t-Tau and p-Tau levels, and negatively with the Mini Mental State Examination. Remarkably, it does not relevantly correlate with disease duration. MMP9 was not relevantly associated with any of these parameters. Cerebrospinal GDF15, but not MMP9, may be a potential marker of and in Lewy body disorders.

  10. GDF15/MIC1 and MMP9 Cerebrospinal Fluid Levels in Parkinson’s Disease and Lewy Body Dementia

    PubMed Central

    Bernard, Alice; Brockmann, Kathrin; Marquetand, Justus; Wurster, Isabel; Rattay, Tim W.; Roncoroni, Lorenzo; Schaeffer, Eva; Lerche, Stefanie; Apel, Anja; Deuschle, Christian; Berg, Daniela

    2016-01-01

    Based on animal and ex-vivo experiments, Growth/Differentiation Factor-15 (GDF15, also called Macrophage Inhibitory Cytokine-1, MIC1), a member of the transforming growth factor-beta family, and Matrix Metalloproteinase-9 (MMP9), a member of the matrix metalloprotease family may be potential markers for Lewy body disorders, i.e. Parkinson’s disease with (PDD) and without dementia (PDND) and Lewy body dementia (DLB). GDF15 has a prominent role in development, cell proliferation, differentiation, and repair, whereas MMP9 degrades, as a proteolytic enzyme, components of the extracellular matrix. In this study, cerebrospinal fluid GDF15 and MMP9 levels of 59 PDND, 17 PDD and 23 DLB patients, as well as of 95 controls were determined, and associated with demographic, clinical and biochemical parameters. Our analysis confirmed the already described association of GDF15 levels with age and gender. Corrected GDF15 levels were significantly higher in PDD than in PDND patients, and intermediate in DLB patients. Within Lewy body disorders, GDF15 levels correlated positively with age at onset of Parkinsonism and dementia, Hoehn & Yahr stage and cerebrospinal fluid t-Tau and p-Tau levels, and negatively with the Mini Mental State Examination. Remarkably, it does not relevantly correlate with disease duration. MMP9 was not relevantly associated with any of these parameters. Cerebrospinal GDF15, but not MMP9, may be a potential marker of and in Lewy body disorders. PMID:26938614

  11. Enhanced reconstruction of long bone architecture by a growth factor mutant combining positive features of GDF-5 and BMP-2.

    PubMed

    Kleinschmidt, Kerstin; Ploeger, Frank; Nickel, Joachim; Glockenmeier, Julia; Kunz, Pierre; Richter, Wiltrud

    2013-08-01

    Non healing bone defects remain a worldwide health problem and still only few osteoinductive growth factors are available for clinical use in bone regeneration. By introducing BMP-2 residues into growth and differentiation factor (GDF)-5 we recently produced a mutant GDF-5 protein BB-1 which enhanced heterotopic bone formation in mice. Designed to combine positive features of GDF-5 and BMP-2, we suspected that this new growth factor variant may improve long bone healing compared to the parent molecules and intended to unravel functional mechanisms behind its action. BB-1 acquired an increased binding affinity to the BMP-IA receptor, mediated enhanced osteogenic induction of human mesenchymal stem cells versus GDF-5 and higher VEGF secretion than BMP-2 in vitro. Rabbit radius defects treated with a BB-1-coated collagen carrier healed earlier and with increased bone volume compared to BMP-2 and GDF-5 according to in vivo micro-CT follow-up. While BMP-2 callus often remained spongy, BB-1 supported earlier corticalis and marrow cavity formation, showing no pseudojoint persistence like with GDF-5. Thus, by combining positive angiogenic and osteogenic features of GDF-5 and BMP-2, only BB-1 restored a natural bone architecture within 12 weeks, rendering this promising growth factor variant especially promising for long bone regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Circulating GDF-15 levels predict future secondary manifestations of cardiovascular disease explicitly in women but not men with atherosclerosis.

    PubMed

    Gohar, Aisha; Gonçalves, Isabel; Vrijenhoek, Joyce; Haitjema, Saskia; van Koeverden, Ian; Nilsson, Jan; de Borst, Gert J; de Vries, Jean-Paul; Pasterkamp, Gerard; den Ruijter, Hester M; Björkbacka, Harry; de Jager, Saskia C A

    2017-08-15

    Elevated serum levels of growth differentiation factor-15 (GDF-15), is an established risk factor for a range of cardiovascular diseases. We aimed to evaluate the predictive value of plasma GDF-15 as a biomarker for secondary cardiovascular events (CVE) in patients with atherosclerosis undergoing carotid endarterectomy (CEA). Secondly, we determined whether plasma GDF-15 was associated with carotid plaque characteristics. Circulating GDF-15 levels were determined by Luminex assay in a cohort of 1056 patients from the Athero-Express biobank. Composite endpoint was defined as major CVE, death and peripheral vascular interventions. Findings were validated in 473 patients from the independent Carotid Plaque Imaging Project biobank. GDF-15 levels did not associate with secondary CVE in the total cohort. However, following a significant interaction with sex, it was found to be strongly, independently predictive of secondary CVE in women but not men (quartile 4 vs. quartile 1: HR 3.04 [95% CI 1.35-6.86], p=0.007 in women vs. HR 0.96 [95% CI 0.66-1.40], p=0.845 in men). This was also observed in the validation cohort (women: HR 2.28 [95% CI 1.04-5.05], p=0.041), albeit dependent upon renal function. In addition, GDF-15 was associated with the presence of plaque smooth muscle cells and calcification. High circulating GDF-15 levels are predictive of secondary CVE in women but not in men with carotid atherosclerotic disease undergoing CEA, suggesting a potential use for GDF-15 as a biomarker for secondary prevention in women. Sex differences in the role of GDF-15 in atherosclerotic disease deserve further interest. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Growth and differentiation factor 10 (Gdf10) is involved in Bergmann glial cell development under Shh regulation.

    PubMed

    Mecklenburg, Nora; Martinez-Lopez, Jesus E; Moreno-Bravo, Juan Antonio; Perez-Balaguer, Ariadna; Puelles, Eduardo; Martinez, Salvador

    2014-10-01

    Growth differentiation factor 10 (Gdf10), also known as Bmp3b, is a member of the transforming growth factor (TGF)-ß superfamily. Gdf10 is expressed in Bergmann glial cells, which was investigated by single-cell transcriptional profiling (Koirala and Corfas, (2010) PLoS ONE 5: e9198). Here we provide a detailed characterization of Gdf10 expression from E14, the stage at which Gdf10 is expressed for the first time in the cerebellum, until P28. We detected Gdf10 expression in both germinal zones: in the ventricular zone (VZ) of the 4th ventricle as well as in the rhombic lip (RL). The VZ has been postulated to give rise to GABAergic neurons and glial cells, whereas the RL gives rise to glutamatergic neurons. Thus, it was very surprising to discover a gene that is expressed exclusively in glial cells and is not restricted to an expression in the VZ, but is also present in the RL. At postnatal stages Gdf10 was distributed equally in Bergmann glial cells of the cerebellum. Furthermore, we found Gdf10 to be regulated by Sonic hedgehog (Shh), which is secreted by Purkinje cells of the cerebellum. In the conditional Shh mutants, glial cells showed a reduced expression of Gdf10, whereas the expression of Nestin and Vimentin was unchanged. Thus, we show for the first time, that Gdf10, expressed in Bergmann glial cells, is affected by the loss of Shh as early as E18.5, suggesting a regulation of glial development by Shh.

  14. Reference change values and determinants of variability of NT-proANP and GDF15 in stable chronic heart failure.

    PubMed

    Frankenstein, Lutz; Remppis, Andrew; Frankenstein, Joerdis; Hess, Georg; Zdunek, Dietmar; Gut, Simon; Slottje, Karen; Katus, Hugo A; Zugck, Christian

    2009-11-01

    Biovariability, reference change values (RCV), and index of individuality (IOI) have not been previously described for NT-proANP or GDF15. Also, the relation of changes of these markers to other clinical variables or biomarkers is unknown. In 41 patients with stable chronic systolic dysfunction, NT-proANP and GDF15 were measured alongside with clinical variables/markers comprising NT-proBNP, hsTnT, and hsCRP at four sampling intervals (2 weeks, 1-, 2-, 3-month intervals). At 2 weeks, 1-, 2-, and 3-month-follow-up, individual NT-proANP variations were 27.1, 22.5, 28.9, 15.6%, respectively, corresponding to RCVs of 53.2, 62.4, 80.2, and 43.2%, respectively. For GDF15, the respective individual variations were 6.8, 4.1, 5.5, 6.8%, corresponding to RCVs of 18.8, 11.5, 15.3 and 18.8%. Neither changes of NT-proANP or GDF15 correlated with changes in any of the clinical variables or biomarkers examined except for GDF15 with renal function. Baseline hormonal levels and clinical variables did not consistently influence the extent of change. The IOI was 0.19-0.35 according to interval for NT-proANP and 0.06-0.09 for GDF 15. In patients with CHF preselected for clinical stability changes of NT-proANP at intermediate follow-up do not correlate with changes in other variables; changes of GDF15 inversely correlate with renal function. The extent of change in both markers is not related to baseline hormonal levels or other baseline variables. RCVs are high for NT-proANP and low for GDF15, while inter-individual variation is high in GDF15 and intermediate in NT-proANP.

  15. SOX11 contributes to the regulation of GDF5 in joint maintenance

    PubMed Central

    2013-01-01

    Background Individual skeletal elements of the vertebrate limbs arise through a segmentation process introducing joints in specific locations. However, the molecular pathways controlling joint formation and subsequent joint maintenance are largely unknown. In this study, we focused on SOX11, and its contribution to the regulation of GDF5, a secreted signal necessary for proper joint formation and postnatal joint homeostasis. Results Sox11 is initially expressed broadly in the murine cartilage condensations at early stages of skeletal development, but its expression is specifically increased in the forming joint interzone as is forms. SOX11 overexpression can directly activate GDF5 expression both in vitro and in micromass cell cultures prepared from chick limb buds. Conserved SOX family binding sites are present in the 5’ UTR region of the GDF5 gene and we show SOX11 can specifically bind to one of them. While misexpression of Sox11 in developing chick limbs through RCAS virus infection does not induce Gdf5 expression in ectopic locations, it does enhance its expression. To explore the roles of Sox11 in joint homeostasis, we analyzed adult knee joints in an osteoarthritis mouse model where the medial meniscus and the medial collateral ligament were removed. We also analyzed knee joints from human subjects who underwent total knee replacement surgery. We find that SOX11 is mainly expressed in the weight-bearing areas of knee joints, and its expression is decreased in degraded cartilage during progression of knee osteoarthritis in both mice and humans. Conclusions This work implicates SOX11 as a potential regulator of GDF5 expression in joint maintenance and suggests a possible role in the pathogenesis of osteoarthritis. PMID:23356643

  16. October field: The latest giant under development in Egypt's Gulf of Suez

    SciTech Connect

    Lelek, J.J.; Abdine, A.S. )

    1990-09-01

    October field, the third largest oil field in Egypt, produced 378 MMBO from its discovery in 1977 until January 1990. It is the northernmost giant oil field in the Gulf of Suez Rift basin. Twenty wells from five platforms in approximately 190 ft (58 m) of water currently drain over 3,238 ha. Recent successful field extensions demonstrate the viability of continuing exploration in this oil-rich area. This structurally trapped field is a complex of rotated fault blocks typical of rift basins worldwide. A northwest-trending normal fault with an approximate throw of 1,220 m has trapped an 335-m oil column on the upthrown eastern side. On the upthrown side, the Carboniferous through Oligocene prerift section dips gently to the northeast and is unconformably overlain by generally flat Miocene to Holocene clastics, carbonates, and evaporites. Severe multiple problems result from thick Miocene evaporites hampering seismic definition of the highly productive prerift section. These same evaporites serve as the ultimate seal in October field and throughout the Gulf of Suez. Although four layers are productive, approximately 95% of field reserves are within Carboniferous to Lower Cretaceous massive Nubia Sandstones. The remaining reserves are in more stratified Upper Cretaceous sandstones, basal Miocene rift-fill Nukhul Formation clastics, and a Lower Miocene clastic in the upper Rudeis Formation. Several distinct reservoir accumulations exist, with the deepest and most significant original oil-water contact at {minus}10,670 ft subsea. October field oil gravities range from 14 to 34{degree} API, with an initial solution GOR of 134 to 474 SCF/STB. The hydrocarbon source for all October field oil as well as most Gulf of Suez oil is believed to be the Campanian Brown Limestone Member of the Sudr Formation. Average reservoir parameters for the Nubia Formation are 16% porosity, 236 md permeability, 137 m net pay thickness, and 5,506 psi original reservoir pressure.

  17. Depositional setting and hydrocarbon source potential of the Miocene Gulf of Suez syn-rift evaporites

    SciTech Connect

    Richardson, M.; Arthur, M.A.; Quinn, J.S.; Whelan, J.K.; Katz, B.J. )

    1988-08-01

    The Red Sea rift basin and its northern continuation, the Gulf of Suez, has experienced continuous deposition of marine evaporites throughout much of its development from the early Miocene to the Pliocene resulting in the accumulation of up to 5 km of evaporite strata in the rift. In this paper, the geologic history of these evaporites are discussed, along with their petroleum source rock potential. The authors hypothesize that rapid deposition of organic matter occurred during episodic storms and freshening events in which a less saline surface layer developed.

  18. Current motion and short-term deformations in the Suez Sinai area from GPS observations

    NASA Astrophysics Data System (ADS)

    Riguzzi, Federica; Pietrantonio, Grazia; Piersanti, Antonio; Mahmoud, Salah M.

    2006-07-01

    We analyze observations from eight GPS campaigns carried out between 1997 and 2005 on a network of 13 sites in the Suez-Sinai area, where separation between the African and the Arabian plates takes place. This is the key area to understand if and in which way Sinai behaves like a sub-plate of the African plate and the role played by seismic and geodetic (long-term) deformation release. Our analysis shows that, on average, the Suez-Sinai area motion, in terms of ITRF00 velocities, matches the African plate motion defined by the NNR-NUVEL-1A model. The horizontal principal strain rate axes estimated separately in the Gulf of Suez area and in the northern Sinai vary from compression across the Gulf (-2.2 ± 1.2) × 10 -8 year -1 to NE extension (1.0 ± 1.5) × 10 -8 year -1 in the North, showing the presence of two distinct domains, so that in our opinion Sinai cannot be considered simply a unique rigid block. The analysis of GPS baseline length variations shows short-term deformations across the Gulf of Suez, reaching up a maximum value of more than 1 cm in 8 years. Since current geodynamical models do not predict significant tectonic deformation in this area, we work under the hypothesis that a contribute may be expected by post-seismic relaxation effects. Under this hypothesis, we compare the baselines length variations with the post-seismic relaxation field associated with five major local earthquakes occurred in the area, testing two different viscoelastic models. Our results show that the detected short-term deformations are better modeled for viscosity values of 10 18 Pa s in the lower crust and 10 20 Pa s in the asthenosphere. However, since the modeled post-seismic effect results modest and a certain amount of the detected deformation is not accounted for, we think that an improved modeling should take into account the lateral heterogeneities of crust and upper mantle structures.

  19. Phytoplankton variability in relation to some environmental factors in the eastern coast of Suez Gulf, Egypt.

    PubMed

    Nassar, Mohamed Z; El-Din, Nihal G Shams; Gharib, Samiha M

    2015-10-01

    Water samples were seasonally collected from 12 stations of the eastern coast of Suez Gulf during autumn of 2012 and winter, spring, and summer of 2013 in order to investigate phytoplankton community structure in relation to some physicochemical parameters. The study area harbored a diversified phytoplankton community (138 species), belonging to 67 genera. Four algal groups were represented and classified as Bacillariophyceae (90 species), Dinophyceae (28 species), Cyanophyceae (16 species), and Chlorophyceae (4 species). The results indicated a relative high occurrence of some species namely.; Pleurotaenium trabecula of green algae; Chaetoceros lorenzianus, Proboscia alata var. gracillima, Pseudosolenia calcar-avis, and Pseudo-nitzschia pungens of diatoms; Trichodesmium erythraeum and Pseudoanabaena limnetica of cyanophytes. Most of other algal species were fairly distributed at the selected stations of the study area. The total abundance of phytoplankton was relatively low (average of 2989 unit/L) in the eastern coast of Suez Gulf, as compared its western coast and the northern part of the Red Sea. The diversity of phytoplankton species was relatively high (2.35-3.82 nats) with an annual average of 3.22 nats in the present study. The results concluded that most of eastern coast of Suez Gulf is still healthy, relatively unpolluted, and oligotrophic area, which is clearly achieved by the low values of dissolved phosphate (0.025-0.3 μM), nitrate (0.18-1.26 μM), and dissolved ammonium (0.81-5.36 μM). Even if the occurrence of potentially harmful algae species was low, the study area should be monitored continuously. The dissolved oxygen ranged between 1.77 and 8.41 mg/L and pH values between 7.6 and 8.41. The multiple regression analysis showed that the dissolved nitrate and pH values were the most effective factors that controlled the seasonal fluctuations of phytoplankton along the eastern coast of Suez Gulf during 2012-2013.

  20. Growth differentiation factor 9 (Gdf9) was localized in the female as well as male germ cells in a protogynous hermaphroditic teleost fish, ricefield eel Monopterus albus.

    PubMed

    He, Zhi; Wu, Yangsheng; Xie, Jun; Wang, Taixin; Zhang, Lihong; Zhang, Weimin

    2012-09-01

    Growth differentiation factor 9 (GDF9) is a member of the transforming growth factor beta (TGFb) superfamily. As an oocyte-derived growth factor, GDF9 plays key roles in regulating follicle development. In the present study, we identified a gdf9 homologue from the ovary of ricefield eel, and analyzed its expression both at the mRNA and protein levels. Ricefield eel Gdf9 showed high homologies with those of other teleosts, especially perciformes fish. RT-PCR analysis revealed that ricefield eel gdf9 was expressed exclusively in the ovary and testis. The mRNA levels of gdf9 in the ovary were increased significantly at the pre-vitellogenic (PV) stage and then decreased significantly along with vitellogenesis. During the natural sex change, expression of ricefield eel gdf9 was peaked at the intersexual stages. The immunoreactivity for Gdf9 was localized exclusively in the cytoplasm of the oocytes in the ovary, particularly the oocytes at early stages, but not in the oogonia. Interestingly, strong immunoreactive signals were also detected in the degenerating oocytes in the intersexual gonad. Furthermore, the Gdf9 immunoreactivity was demonstrated for the first time to be localized in the cytoplasm of spermatogonia and spermatocytes of ricefield eel, a teleost fish. Taken together, the results of present study suggested that Gdf9 may play important roles in the folliculogenesis as well as spermatogenesis in ricefield eels.

  1. GDF-15 gene expression alterations in human lymphoblastoid cells and peripheral blood lymphocytes following exposure to ionizing radiation

    PubMed Central

    Li, Shuang; Zhang, Qing-Zhao; Zhang, De-Qin; Feng, Jiang-Bin; Luo, Qun; Lu, Xue; Wang, Xin-Ru; Li, Kun-Peng; Chen, De-Qing; Mu, Xiao-Feng; Gao, Ling; Liu, Qing-Jie

    2017-01-01

    The identification of rapid, sensitive and high-throughput biomarkers is imperative in order to identify individuals harmed by radiation accidents, and accurately evaluate the absorbed doses of radiation. DNA microarrays have previously been used to evaluate the alterations in growth/differentiation factor 15 (GDF15) gene expression in AHH-1 human lymphoblastoid cells, following exposure to γ-rays. The present study aimed to characterize the relationship between the dose of ionizing radiation and the produced effects in GDF-15 gene expression in AHH-1 cells and human peripheral blood lymphocytes (HPBLs). GDF-15 mRNA and protein expression levels following exposure to γ-rays and neutron radiation were assessed by reverse transcription-quantitative polymerase chain reaction and western blot analysis in AHH-1 cells. In addition, alterations in GDF-15 gene expression in HPBLs following ex vivo irradiation were evaluated. The present results demonstrated that GDF-15 mRNA and protein expression levels in AHH-1 cells were significantly upregulated following exposure to γ-ray doses ranging between 1 and 10 Gy, regardless of the dose rate. A total of 48 h following exposure to neutron radiation, a dose-response relationship was identified in AHH-1 cells at γ-ray doses between 0.4 and 1.6 Gy. GDF-15 mRNA levels in HPBLs were significantly upregulated following exposure to γ-ray doses between 1 and 8 Gy, within 4–48 h following irradiation. These results suggested that significant time- and dose-dependent alterations in GDF-15 mRNA and protein expression occur in AHH-1 cells and HPBLs in the early phases following exposure to ionizing radiation. In conclusion, alterations in GDF-15 gene expression may have potential as a biomarker to evaluate radiation exposure. PMID:28440431

  2. GDF-15 enhances intracellular Ca2+ by increasing Cav1.3 expression in rat cerebellar granule neurons

    PubMed Central

    Lu, Jun-Mei; Wang, Chang-Ying; Hu, Changlong; Fang, Yan-Jia; Mei, Yan-Ai

    2016-01-01

    GDF-15 (growth/differentiation factor 15) is a novel member of the TGF (transforming growth factor)-β superfamily that has critical roles in the central and peripheral nervous systems. We reported previously that GDF-15 increased delayed rectifier outward K+ currents and Kv2.1 α subunit expression through TβRII (TGF-β receptor II) to activate Src kinase and Akt/mTOR (mammalian target of rapamycin) signalling in rat CGNs (cerebellar granule neurons). In the present study, we found that treatment of CGNs with GDF-15 for 24 h increased the intracellular Ca2+ concentration ([Ca2+]i) in response to membrane depolarization, as determined by Ca2+ imaging. Whole-cell current recordings indicated that GDF-15 increased the inward Ca2+ current (ICa) without altering steady-state activation of Ca2+ channels. Treatment with nifedipine, an inhibitor of L-type Ca2+ channels, abrogated GDF-15-induced increases in [Ca2+]i and ICa. The GDF-15-induced increase in ICa was mediated via up-regulation of the Cav1.3 α subunit, which was attenuated by inhibiting Akt/mTOR and ERK (extracellular-signal-regulated kinase) pathways and by pharmacological inhibition of Src-mediated TβRII phosphorylation. Given that Cav1.3 is not only a channel for Ca2+ influx, but also a transcriptional regulator, our data confirm that GDF-15 induces protein expression via TβRII and activation of a non-Smad pathway, and provide novel insight into the mechanism of GDF-15 function in neurons. PMID:27114559

  3. Heads, Shoulders, Elbows, Knees, and Toes: Modular Gdf5 Enhancers Control Different Joints in the Vertebrate Skeleton

    PubMed Central

    Schoor, Michael; Mortlock, Doug P.; Reddi, A. Hari; Kingsley, David M.

    2016-01-01

    Synovial joints are crucial for support and locomotion in vertebrates, and are the frequent site of serious skeletal defects and degenerative diseases in humans. Growth and differentiation factor 5 (Gdf5) is one of the earliest markers of joint formation, is required for normal joint development in both mice and humans, and has been genetically linked to risk of common osteoarthritis in Eurasian populations. Here, we systematically survey the mouse Gdf5 gene for regulatory elements controlling expression in synovial joints. We identify separate regions of the locus that control expression in axial tissues, in proximal versus distal joints in the limbs, and in remarkably specific sub-sets of composite joints like the elbow. Predicted transcription factor binding sites within Gdf5 regulatory enhancers are required for expression in particular joints. The multiple enhancers that control Gdf5 expression in different joints are distributed over a hundred kilobases of DNA, including regions both upstream and downstream of Gdf5 coding exons. Functional rescue tests in mice confirm that the large flanking regions are required to restore normal joint formation and patterning. Orthologs of these enhancers are located throughout the large genomic region previously associated with common osteoarthritis risk in humans. The large array of modular enhancers for Gdf5 provide a new foundation for studying the spatial specificity of joint patterning in vertebrates, as well as new candidates for regulatory regions that may also influence osteoarthritis risk in human populations. PMID:27902701

  4. Heads, Shoulders, Elbows, Knees, and Toes: Modular Gdf5 Enhancers Control Different Joints in the Vertebrate Skeleton.

    PubMed

    Chen, Hao; Capellini, Terence D; Schoor, Michael; Mortlock, Doug P; Reddi, A Hari; Kingsley, David M

    2016-11-01

    Synovial joints are crucial for support and locomotion in vertebrates, and are the frequent site of serious skeletal defects and degenerative diseases in humans. Growth and differentiation factor 5 (Gdf5) is one of the earliest markers of joint formation, is required for normal joint development in both mice and humans, and has been genetically linked to risk of common osteoarthritis in Eurasian populations. Here, we systematically survey the mouse Gdf5 gene for regulatory elements controlling expression in synovial joints. We identify separate regions of the locus that control expression in axial tissues, in proximal versus distal joints in the limbs, and in remarkably specific sub-sets of composite joints like the elbow. Predicted transcription factor binding sites within Gdf5 regulatory enhancers are required for expression in particular joints. The multiple enhancers that control Gdf5 expression in different joints are distributed over a hundred kilobases of DNA, including regions both upstream and downstream of Gdf5 coding exons. Functional rescue tests in mice confirm that the large flanking regions are required to restore normal joint formation and patterning. Orthologs of these enhancers are located throughout the large genomic region previously associated with common osteoarthritis risk in humans. The large array of modular enhancers for Gdf5 provide a new foundation for studying the spatial specificity of joint patterning in vertebrates, as well as new candidates for regulatory regions that may also influence osteoarthritis risk in human populations.

  5. Structural evolution of the southern transfer zone of the Gulf of Suez rift, Egypt

    NASA Astrophysics Data System (ADS)

    Abd-Allah, Ali M. A.; Abdel Aal, Mohamed H.; El-Said, Mohamed M.; Abd El-Naby, Ahmed

    2014-08-01

    We present a detailed study about the initiation and reactivations of Zeit-El Tor transfer zone, south Gulf of Suez rift, and its structural setting and tectonic evolution with respect to the Cretaceous-Cenozoic tectonic movements in North Egyptian margin. NE trending zone of opposed-dipping faults (22 km wide) has transferred the NE and SW rotations of the sub-basins in central and south Gulf of Suez rift, respectively. The evolution of this zone started by reactivation of the NE oriented late Neoproterozoic fractures that controlled the occurrence of Dokhan Volcanics in the rift shoulders. Later, the Syrian Arc contraction reactivated these fractures by a sinistral transpression during the Late Cretaceous-Eocene time. N64°E extension of the Oligo-Miocene rift reactivated the NE fractures by a sinistral transtension. During this rifting, the NE trending faults forming the transfer zone were more active than the rift-bounding faults; the Upper Cretaceous reverse faults in the blocks lying between these NE trending faults were rotated; and drape-related reverse faults and the positive flower structures were formed. Tectonic inversion from contraction to extension controlled the distribution and thickness of the Upper Cretaceous-Miocene rocks.

  6. Ascidian introductions through the Suez Canal: The case study of an Indo-Pacific species.

    PubMed

    Rius, Marc; Shenkar, Noa

    2012-10-01

    Although marine biological invasions via the Suez Canal have been extensively documented, little is known about the introduction of non-indigenous ascidians (Chordata, Ascidiacea), a group containing particularly aggressive invasive species. Here, we used a multidisciplinary approach to study the introduction of the ascidian Herdmania momus into the Mediterranean Sea. We reviewed its taxonomy and global distribution, and analyzed how genetic variation is partitioned between sides of the Suez Canal. The taxonomic revision showed that H. momus currently has a wide Indo-Pacific distribution. Genetic data indicated two well-differentiated colonization histories across the eastern Mediterranean. Our findings suggest that the range expansion of H. momus has been greatly facilitated by the combined effect of human-mediated transport and the species' ability to adapt to different environments. The integrative approach presented here is critical to attain a holistic understanding of marine biological invasions, especially when studying groups with a poorly resolved taxonomy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Relationship between sediment morphology and oil pollution along the Suez Canal beaches, Egypt

    SciTech Connect

    Barakat, M.A.K.; Shimy, T.M.; Mostafa, Y.M.

    1996-10-01

    In this study, marine surface sediments are collected from nine locations along the Suez Canal in order to investigate the relationship between the morphology of sands in the studied beaches and pollution by oil. Basically, the studied samples were analyzed by three techniques: grains-size analysis, microscopic examination, and gas chromatographic (GC) analysis. This study concluded that medium sand is the major class represented in the studied marine sediments. Pollution in these sand grains increases in the irregular grains more so than in the more rounded grains. Also, deep surface points, pitting, and fissures are considered to be good sites to precipitate oil contamination. Also, the presence of iron oxides may be taken as evidence for tanker ballast washings. The heavy fraction (zircon) shows more contamination than the light fraction (quartz) in these samples. Finally, GC profiles have shown two types of samples: one typical of weathered or highly weathered crude oil patterns and the other for samples with very highly weathered profiles. The relationship obtained between morphology studies and both oil content and GC chromatogram profiles indicates that all of the studied locations are suffering from pollution of oil that is spilled while shipping petroleum through the Suez Canal.

  8. Marine Radioactivity Studies in the Suez Canal, Part I: Hydrodynamics and Transit Times

    NASA Astrophysics Data System (ADS)

    Abril, J. M.; Abdel-Aal, M. M.

    2000-04-01

    This paper describes work carried out under the IAEA Project EGY/07/002 to study the dispersion of radioactive material in the Suez Canal. This effort is linked with the increased public concern about radiation safety through this important trade route. To follow the fate of radioactive wastes along this waterway, we had to solve the hydrodynamics of the water, governed mainly by tides, atmospheric forcing and the drift currents produced by horizontal salinity gradients and by differences in mean sea level (MSL) at the two entrances of the Canal. The hydrodynamics has been studied using both 1-D and 2-D modelling approaches, and a reasonable calibration has been possible from the data set prepared with the collaboration of the Suez Canal Authority. Dispersion of conservative pollutants has been preliminarily studied by using a 1-D-Gaussian approach. Thus, we are computing the path of the plumes and the time evolution of concentrations for different scenarios of discharges and under different seasonal conditions. The transit times can vary enormously during the year, ranging from a few days to several months, depending on the differences in MSL at the two entrances of the Canal.

  9. Oil prospect of the Gulf of Suez, Egypt - a case study

    SciTech Connect

    Elzarka, M.H.; Mostafa, A.R. )

    1988-01-01

    Four groups of rocks, having more than 0.5% of organic carbon are defined within the subsurface section of Rahmi area, Gulf of Suez. The deduced types of indigenous kerogen are: algal-amorphous, inertinite-woody, and herbaceous. The algal-amorphous kerogen of Rudeis/Nukhul Formations (Lower Miocene), Eocene and pre-Eocene rocks is recognized as being oil prone, that is having high capacity for generating oil. The application of hydrocarbon liquid window concept shows that the LOM values fall within the range from 8.6 to 10.8, and the thermal alteration index for the different units is not extended into oil generation window, where it ranges from immature (Kareem Formation-Lower Miocene), to moderately mature (Paleocene), to the beginning of the thermal phase of oil generation (Senonian). The vitrinite reflectance values indicate a low level of thermal maturity. The formational temperatures increase towards the depocentral part of the basin and eastwards to the present Gulf of Suez. The thermal maturity index increases towards ancient stratigraphic units. The study of organic richness, quality and maturity revealed that, where the Nukhul, Eocene and Senonian rocks are buried deeper in the study area, would have been excellent source rocks for oil.

  10. Surface expression of an accommodation zone within the Gulf of Suez rift, Egypt

    NASA Astrophysics Data System (ADS)

    Coffield, Dana Q.; Schamel, Steven

    1989-01-01

    The Gebel Gharamul region in the western Gulf of Suez offers an excellent outcrop example of the structural geometries associated with an accommodation zone termination. The surface expression of the accommodation zone is dominated by a basement promontory, which protrudes from the rift shoulder and underlies the junction of oblique ramps from two adjacent half-grabens, both of which face the Gulf of Suez. The southern half-graben represents the breakaway fault of the southwest-dipping tilt-block domain, and the northern half-graben represents the collapse of the upper plate above the northeast-dipping tilt-block domain. Basement and Nubian rocks in the hanging walls above the opposing low-angle detachments on either side of the accommodation zone are broken by gulf-parallel synthetic normal faults and orthogonal transfer faults, which act as block terminations and incrementally accommodate the large-scale rotation and displacement between adjacent blocks. The prerift and synrift stratigraphic succession is draped over this fault template, resulting in a complex and variable distribution of structures, the product of an inhomogeneous stratigraphic succession within an accommodation zone.

  11. Subsurface structural mapping of Gebel El-Zeit area, Gulf of Suez, Egypt using aeromagnetic data

    NASA Astrophysics Data System (ADS)

    Aboud, Essam; Salem, Ahmed; Ushijima, Keisuke

    2005-08-01

    The Gebel El-Zeit area is located on the western coast of the Gulf of Suez, Egypt. The areas in/and around the Gulf of Suez are generally important due to their hydrocarbon resources. In this study, we have applied gradient interpretation techniques (Euler deconvolution and analytic signal) to the aeromagnetic data of the Gebel El-Zeit area. The main objective of this study is to identify and delineate the possible subsurface structure of the area that may assist in locating new hydrocarbon prospects. Results of Euler method suggested that, on the eastern and western parts of the area, the basement could be observed on the ground (~50 m over the ground) and became more deeper on the central part to reach depth of 5 km (from the ground level). Results from the analytic signal method indicated that, the depth to the basement has an average value of 156 m on the eastern side and 758 m on the western side. Generally, the area is characterized by a graben structure bounded by major faults striking in the NW-SE direction.

  12. [The corvette "Nordstjernen's" voyage to the opening of the Suez Canal--naval medicine in 1869].

    PubMed

    Ongre, Aksel; Pettersen, Jan Sommerfelt; Munch, Johan Storm

    2002-06-30

    When the Norwegian corvette Nordstjernen was in the North Sea bound for Port Said to be present at the opening of the Suez Canal on 17 November 1869, an officer suffered a rupture of m. triceps brachii when he was drawn into the machinery during a storm. He was put ashore in Harwich; four days after the injury he was hospitalized in Colchester. The voyage was eventful in other ways too. Another officer died from typhoid fever in Ismailia. On the Swedish frigate Vanadis, also present at the opening of the Suez Canal, one of the doctors died from lung infection and was buried in Smyrna; a twelve-feet high column of white marble was taken from the ruins of Aesculap's temple and put on his grave. Denmark was represented by the frigate Sjaelland. During a storm in the North Sea, one seaman fell down on the deck from the foresail yard and suffered contusions and a fracture of the left clavicle. These cases illustrate challenges that faced our ancestors. The accident happened when the ship was in the Netherlands sector of the North Sea as we know it today. Today the Coast Guard could have arranged transport by helicopter and hospitalized the patient in about two hours.

  13. GDF9 and BMP15 Expressions and Fine Structure Changes during Folliculogenesis in Polycystic Ovary Syndrome.

    PubMed

    Karagül, Meryem İlkay; Aktaş, Savaş; Coşkun Yılmaz, Banu; Yılmaz, Mustafa; Örekiçi Temel, Gülhan

    2017-09-13

    Polycystic Ovary Syndrome (PCOS) is the most frequently seen endocrine disorder in women of the reproductive age with the prevalence of about 10%. To investigate the efficiency of the growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) during folliculogenesis in a dehydroepiandrosterone (DHEA)-induced mouse PCOS model. Animal experimentation. Mice were divided into three groups; control, vehicle and PCOS group. PCOS model mice was developed by the injection of DHEA dissolved in 0.1 ml sesame oil. Ovarian tissues were examined for GDF9 and BMP15 immunofluorescent labeling and electron microscopic examinations. The immunoreactivity of GDF9 and BMP15 proteins decreased (p<0.05) in PCOS group (27.73±8.43 and 24.85±7.03, respectively) compared with control group (33.72±11.22 and 31.12±11.05, respectively) and vehicle group (33.95±10.75 and 29.99±10.72, respectively). Apoptotic changes were observed in granulosa cells, lipid vacuoles increased in theca cells, there was a thickening and irregularities in basal lamina of granulosa cells, increased electron density in zona pellucida (ZP) in some of the multilaminar primary and secondary follicles in the PCOS model, at the ultrastructural level. These results suggest that the decrease in GDF9 and BMP15 expressions starting from the primary follicle stage effect the follicle development and the ZP structure and it may cause subfertility or infertility in PCOS.

  14. BMP15 and GDF9 Gene Mutations in Premature Ovarian Failure

    PubMed Central

    Kumar, Ravindra; Alwani, Madhuri; Kosta, Susmit; Kaur, Ravjyot; Agarwal, Sarita

    2017-01-01

    Background: Premature ovarian failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles before the age of 40, representing one major cause of female infertility. Mutations in bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) have been shown to be associated with POF. Methods: Genomic DNA was isolated from 52 idiopathic premature ovarian failure patients and 100 normal control individuals. Exons of BMP15 and GDF9 gene were amplified using PCR method and subjected to directed sequencing. Variants were identified by comparing the sequences obtained with normal sequences from NCBI database. Results: Four BMP15 gene variants were identified in 6 patients in heterozygous condition. Out of these 4 variants, 3 variants namely, c.165A>T (p.Glu55Asp), c.538 G>T (p.Aln180 Ser) and c. 510_512 delT were novel variants. In silico analysis using SIFT, Provean and Polyphen 2 score predicted the non-deleterious effect of c.165A>T and c.538 G>T variant. 788insTCT variant was identified in 3 patients. No variant was identified in GDF9 gene in any patients and controls. Conclusion: Although the variant has been identified in BMP15 gene but it may not be associated with the premature ovarian failure.

  15. Growth differentiation factor-15 (GDF-15), novel biomarker for assessing atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease.

    PubMed

    Zhou, Yong-Ming; Li, Ming-Jiang; Zhou, Yan-Li; Ma, Le-Le; Yi, Xin

    2015-01-01

    Growth differentiation factor-15 (GDF-15) has been identified as a strong biomarker of cardiovascular diseases; however, no evidence are available concerning the relationship of GDF-15 and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD). Twenty patients with rheumatic heart disease were divided into two groups, 10 cases with AF and 10 cases with sinus rhythm (SR). Clinical data and blood samples were collected; left atrial appendage was taken by the surgeon in the process of valve replacement. Masson stained sections and mRNA levels of cardiac fibrosis biomarkers were used to determine the level of cardiac fibrosis, the expression level of GDF-15 was evaluated via immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). Compared with SR group, more collagen deposited in the atrial tissue of AF group. The distribution of GDF-15 in the AF group was significantly higher than SR group (P<0.05). In addition, plasma GDF-15 level and mRNA level of GDF-15 in atrial tissue of AF showed the same trend as the result of immunohistochemistry. After linear correlation analysis, the expression level of GDF-15 was found to be positively related to the degree of cardiac fibrosis. GDF-15 might involve in the development and maintenance of atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease, and GDF-15 could be used as a novel biomarker to evaluate myocardial fibrosis in the future.

  16. Growth differentiation factor (GDF)-15 blocks norepinephrine-induced myocardial hypertrophy via a novel pathway involving inhibition of epidermal growth factor receptor transactivation.

    PubMed

    Xu, Xin-ye; Nie, Ying; Wang, Fang-fang; Bai, Yan; Lv, Zhi-zhen; Zhang, You-yi; Li, Zi-jian; Gao, Wei

    2014-04-04

    Accumulating evidence suggests that growth differentiation factor 15 (GDF-15) is associated with the severity and prognosis of various cardiovascular diseases. However, the effect of GDF-15 on the regulation of cardiac remodeling is still poorly understood. In this present study, we demonstrate that GDF-15 blocks norepinephrine (NE)-induced myocardial hypertrophy through a novel pathway involving inhibition of EGFR transactivation. Both in vivo and in vitro assay indicate that NE was able to stimulate the synthesis of GDF-15. The up-regulation of GDF-15 feedback inhibits NE-induced myocardial hypertrophy, including quantitation of [(3)H]leucine incorporation, protein/DNA ratio, cell surface area, and ANP mRNA level. Further research shows that GDF-15 could inhibit the phosphorylation of EGF receptor and downstream kinases (AKT and ERK1/2) induced by NE. Clinical research also shows that serum GDF-15 levels in hypertensive patients were significant higher than in healthy volunteers and were positively correlated with the thickness of the posterior wall of the left ventricle, interventricular septum, and left ventricular mass, as well as the serum level of norepinephrine. In conclusion, NE induces myocardial hypertrophy and up-regulates GDF-15, and this up-regulation of GDF-15 negatively regulates NE-induced myocardial hypertrophy by inhibiting EGF receptor transactivation following NE stimulation.

  17. Geodynamic of the Gulf of Suez-Red Sea rifting and origin of within plate magmatism

    NASA Astrophysics Data System (ADS)

    Ragab, A. I.; El-Kaliouby, B. A.

    1992-04-01

    This study is an attempt to follow up the overall picture of the geologic processes of the "Wilson Cycle" in the Gulf of Suez Red Sea region. A plate-tectonic model is suggested covering the Pan-African collisional tectonics, post-Pan-African magmatism in space and time, and rifting stages in the Red Sea region. Field relations, petrography, and petrochemistry of the Tertiary basalt sheets of Abu Zenima area, Sinai, have been studied and correlated with some petrochemical data of Phanerozoic magmatic activities in the Red Sea region. The sequence of events of the tectonics and magmatic activities in the Gulf of Suez-Red Sea rift system may belong to six stages post Pan-African orogeny: (1) Paleozoic-Cretaceous continental bimodal alkaline magmatism resulting from the sinking of detached subducted oceanic plates, in the late stages of the Pan-African collisional tectonics. Consequently causing convection currents around them and partial melting of a deep undepleted mantle source; (2) Paleogene crustal doming and stretching as a result of asthenosphere upwelling activated by a long period of (≅ 300 m.y.) within plate alkaline magmatism; (3) Late Oligocene fissure-eruption of transitional (T-type MORBs) plateau basalts, dykes and sills on a regional scale. The transitional character of this basaltic activity is attributed to the soaking of the asthenosphere, during its slow upwelling, in the rising alkaline magmatism; (4) Early Miocene narrow long continental rifting in the Gulf of Suez-Red Sea region, probably due to a thermal contraction process resulting from the eruption of the Tertiary transitional, fissure-eruption basalts in large volumes from the upwelled asthenosphere; (5) Initiation of crustal separation of the very early stage of seafloor spreading, which is most probably characterized by mafic igneous rocks underplating of the crustal faulted blocks by dyke injection and related plutonic rocks; (6) Pliocene oceanic rifting and seafloor spreading

  18. Penetrating evaporites - new information from old seismic data in Suez Rift, Egypt

    SciTech Connect

    Perry, S.K.; Gawarecki, S.L.; Schamel, S.

    1987-05-01

    Structures in the prerift sediments, Gulf of Suez, are of primary interest for petroleum exploration. However, the overlying thick blanket of Miocene synrift evaporites severely limits resolution of deep structures in seismic reflection lines. A technique for maximizing accuracy of prerift maps and sections is illustrated by examples from the south-central Gulf of Suez. Preliminary structural maps of prerift units are generated from limited well data, good seismically derived maps of the base evaporite, and fragmentary deep seismic data. Through rigorous application of conventional cross section balancing techniques and geometric rules for listric normal fault-block rotation, trial cross sections are constructed. Construction of trial cross sections relies heavily on the following information from seismic lines: (1) thickness variations of synrift fill; (2) sequence boundaries representing unconformities over buried tilt blocks; (3) dip domains faintly visible beneath Miocene evaporites; and (4) faulting in Miocene sediments in response to deeper normal faults. The integration of well data allows control of seismic interpretation and of depth to prerift rocks. The sections are refined through iteration and are then used in conjunction with areal balancing methods to correct the structure maps. The subsequent serialization of balanced sections results in an internally consistent, geometrically constrained, three-dimensional picture of the basin which best fits all the available data. Important information on prerift structures which results from this technique includes location of normal faults and the magnitude of their throw, attitude of deep tilt blocks, and location of tilt-block terminations. Using this methodology, old prospects can be refined and new plays and prospects generated. These can then be tested by local detailed seismic work or by the drill.

  19. Risk factors of falls among elderly living in urban Suez--Egypt.

    PubMed

    Kamel, Mohammed Hany; Abdulmajeed, Abdulmajeed Ahmed; Ismail, Sally El-Sayed

    2013-01-01

    Falling is one of the most common geriatric syndromes threatening the independence of older persons. Falls result from a complex and interactive mix of biological or medical, behavioral and environmental factors, many of which are preventable. Studying these diverse risk factors would aid early detection and management of them at the primary care level. This is a cross sectional study about risk factors of falls was conducted to 340 elders in Urban Suez. Those are all patients over 60 who attended two family practice centers in Urban Suez. When asked about falling during the past 12 months, 205 elders recalled at least one incident of falling. Of them, 36% had their falls outdoors and 24% mentioned that stairs was the most prevalent site for indoor falls. Falls were also reported more among dependant than independent elderly. Using univariate regression analysis, almost all tested risk factors were significantly associated with falls in the studied population. These risk factors include: living alone, having chronic diseases, using medications, having a physical deficit, being in active, and having a high nutritional risk. However, the multivariate regression analysis proved that the strongest risk factors are low level of physical activity with OR 0.6 and P value 0.03, using a cane or walker (OR 1.69 and P value 0.001) and Impairment of daily living activities (OR 1.7 and P value 0.001). Although falls is a serious problem among elderly with many consequences, it has many preventable risk factors. Health care providers should advice people to remain active and more research is needed in such an important area of Family Practice.

  20. Growth Differentiation Factor 9 (GDF9) Suppresses Follistatin and Follistatin-Like 3 Production in Human Granulosa-Lutein Cells

    PubMed Central

    Shi, Feng-Tao; Cheung, Anthony P.; Huang, He-Feng; Leung, Peter C. K.

    2011-01-01

    Background We have demonstrated that growth differentiation factor 9 (GDF9) enhances activin A-induced inhibin βB-subunit mRNA levels in human granulosa-lutein (hGL) cells by regulating receptors and key intracellular components of the activin signaling pathway. However, we could not exclude its effects on follistatin (FST) and follistatin-like 3 (FSTL3), well recognized extracellular inhibitors of activin A. Methodology hGL cells from women undergoing in vitro fertilization (IVF) treatment were cultured with and without siRNA transfection of FST, FSTL3 or GDF9 and then treated with GDF9, activin A, FST, FSTL3 or combinations. FST, FSTL3 and inhibin βB-subunit mRNA, and FST, FSTL3 and inhibin B protein levels were assessed with real-time RT-PCR and ELISA, respectively. Data were log transformed before ANOVA followed by Tukey's test. Principal Findings GDF9 suppressed basal FST and FSTL3 mRNA and protein levels in a time- and dose-dependent manner and inhibited activin A-induced FST and FSTL3 mRNA and protein expression, effects attenuated by BMPR2 extracellular domain (BMPR2 ECD), a GDF9 antagonist. After GDF9 siRNA transfection, basal and activin A-induced FST and FSTL3 mRNA and protein levels increased, but changes were reversed by adding GDF9. Reduced endogenous FST or FSTL3 expression with corresponding siRNA transfection augmented activin A-induced inhibin βB-subunit mRNA levels as well as inhibin B levels (P values all <0.05). Furthermore, the enhancing effects of GDF9 in activin A-induced inhibin βB-subunit mRNA and inhibin B production were attenuated by adding FST. Conclusion GDF9 decreases basal and activin A-induced FST and FSTL3 expression, and this explains, in part, its enhancing effects on activin A-induced inhibin βB-subunit mRNA expression and inhibin B production in hGL cells. PMID:21829661

  1. In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate

    PubMed Central

    Essalmani, Rachid; Zaid, Ahmed; Marcinkiewicz, Jadwiga; Chamberland, Ann; Pasquato, Antonella; Seidah, Nabil G.; Prat, Annik

    2008-01-01

    The proprotein convertase PC5/6 cleaves protein precursors after basic amino acids and is essential for implantation in CD1/129/Sv/C57BL/6 mixed-background mice. Conditional inactivation of Pcsk5 in the epiblast but not in the extraembryonic tissue bypassed early embryonic lethality but resulted in death at birth. PC5/6-deficient embryos exhibited Gdf11-related phenotypes such as altered anteroposterior patterning with extra vertebrae and lack of tail and kidney agenesis. They also exhibited Gdf11-independent phenotypes, such as a smaller size, multiple hemorrhages, collapsed alveoli, and retarded ossification. In situ hybridization revealed overlapping PC5/6 and Gdf11 mRNA expression patterns. In vitro and ex vivo analyses showed that the selectivity of PC5/6 for Gdf11 essentially resides in the presence of a P1′ Asn in the RSRR↓N cleavage motif. This work identifies Gdf11 as a likely in vivo specific substrate of PC5/6 and opens the way to the identification of other key substrates of this convertase. PMID:18378898

  2. Small Molecules Dorsomorphin and LDN-193189 Inhibit Myostatin/GDF8 Signaling and Promote Functional Myoblast Differentiation*

    PubMed Central

    Horbelt, Daniel; Boergermann, Jan H.; Chaikuad, Apirat; Alfano, Ivan; Williams, Eleanor; Lukonin, Ilya; Timmel, Tobias; Bullock, Alex N.; Knaus, Petra

    2015-01-01

    GDF8, or myostatin, is a member of the TGF-β superfamily of secreted polypeptide growth factors. GDF8 is a potent negative regulator of myogenesis both in vivo and in vitro. We found that GDF8 signaling was inhibited by the small molecule ATP competitive inhibitors dorsomorphin and LDN-193189. These compounds were previously shown to be potent inhibitors of BMP signaling by binding to the BMP type I receptors ALK1/2/3/6. We present the crystal structure of the type II receptor ActRIIA with dorsomorphin and demonstrate that dorsomorphin or LDN-193189 target GDF8 induced Smad2/3 signaling and repression of myogenic transcription factors. As a result, both inhibitors rescued myogenesis in myoblasts treated with GDF8. As revealed by quantitative live cell microscopy, treatment with dorsomorphin or LDN-193189 promoted the contractile activity of myotubular networks in vitro. We therefore suggest these inhibitors as suitable tools to promote functional myogenesis. PMID:25368322

  3. A General Approach for Identifying Distant Regulatory Elements Applied to the Gdf6 Gene

    PubMed Central

    Mortlock, Douglas P.; Guenther, Catherine; Kingsley, David M.

    2003-01-01

    Regulatory sequences in higher genomes can map large distances from gene coding regions, and cannot yet be identified by simple inspection of primary DNA sequence information. Here we describe an efficient method of surveying large genomic regions for gene regulatory information, and subdividing complex sets of distant regulatory elements into smaller intervals for detailed study. The mouse Gdf6 gene is expressed in a number of distinct embryonic locations that are involved in the patterning of skeletal and soft tissues. To identify sequences responsible for Gdf6 regulation, we first isolated a series of overlapping bacterial artificial chromosomes (BACs) that extend varying distances upstream and downstream of the gene. A LacZ reporter cassette was integrated into the Gdf6 transcription unit of each BAC using homologous recombination in bacteria. Each modified BAC was injected into fertilized mouse eggs, and founder transgenic embryos were analyzed for LacZ expression mid-gestation. The overlapping segments defined by the BAC clones revealed five separate regulatory regions that drive LacZ expression in 11 distinct anatomical locations. To further localize sequences that control expression in developing skeletal joints, we created a series of BAC constructs with precise deletions across a putative joint-control region. This approach further narrowed the critical control region to an area containing several stretches of sequence that are highly conserved between mice and humans. A distant 2.9-kilobase fragment containing the highly conserved regions is able to direct very specific expression of a minimal promoter/LacZ reporter in proximal limb joints. These results demonstrate that even distant, complex regulatory sequences can be identified using a combination of BAC scanning, BAC deletion, and comparative sequencing approaches. PMID:12915490

  4. First Behavioural Characterisation of a Knockout Mouse Model for the Transforming Growth Factor (TGF)-β Superfamily Cytokine, MIC-1/GDF15

    PubMed Central

    Low, Jac Kee; Ambikairajah, Ananthan; Shang, Kani; Brown, David A.; Tsai, Vicky W. W.; Breit, Samuel N.; Karl, Tim

    2017-01-01

    Macrophage inhibitory cytokine-1 (MIC-1), also known as growth differentiation factor 15 (GDF15), is a stress response cytokine. MIC-1/GDF15 is secreted into the cerebrospinal fluid and increased levels of MIC-1/GDF15 are associated with a variety of diseases including cognitive decline. Furthermore, Mic-1/Gdf15 knockout mice (Mic-1 KO) weigh more, have increased adiposity, associated with increased spontaneous food intake, and exhibit reduced basal energy expenditure and physical activity. The current study was designed to comprehensively determine the role of MIC-1/GDF15 on behavioural domains of male and female knockout mice including locomotion, exploration, anxiety, cognition, social behaviours, and sensorimotor gating. Mic-1 KO mice exhibited a task-dependent increase in locomotion and exploration and reduced anxiety-related behaviours across tests. Spatial working memory and social behaviours were not affected by Mic-1/Gdf15 deficiency. Interestingly, knockout mice formed an increased association with the conditioned stimulus in fear conditioning testing and also displayed significantly improved prepulse inhibition. Overall sex effects were evident for social behaviours, fear conditioning, and sensorimotor gating. This is the first study defining the role of Mic-1/Gdf15 in a number of behavioural domains. Whether the observed impact is based on direct actions of Mic-1/Gdf15 deficiency on the CNS or whether the behavioural effects are mediated by indirect actions on e.g. other neurotransmitter systems must be clarified in future studies. PMID:28081177

  5. EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1.

    PubMed

    Cheng, Simon K; Olale, Felix; Bennett, James T; Brivanlou, Ali H; Schier, Alexander F

    2003-01-01

    The TGF-beta signals Nodal, Activin, GDF1, and Vg1 have been implicated in mesoderm induction and left-right patterning. Nodal and Activin both activate Activin receptors, but only Nodal requires EGF-CFC coreceptors for signaling. We report that Vg1 and GDF1 signaling in zebrafish also depends on EGF-CFC proteins, but not on Nodal signals. Correspondingly, we find that in Xenopus Vg1 and GDF1 bind to and signal through Activin receptors only in the presence of EGF-CFC proteins. These results establish that multiple TGF-beta signals converge on Activin receptor/EGF-CFC complexes and suggest a more widespread requirement for coreceptors in TGF-beta signaling than anticipated previously.

  6. EGF-CFC proteins are essential coreceptors for the TGF-β signals Vg1 and GDF1

    PubMed Central

    Cheng, Simon K.; Olale, Felix; Bennett, James T.; Brivanlou, Ali H.; Schier, Alexander F.

    2003-01-01

    The TGF-β signals Nodal, Activin, GDF1, and Vg1 have been implicated in mesoderm induction and left-right patterning. Nodal and Activin both activate Activin receptors, but only Nodal requires EGF-CFC coreceptors for signaling. We report that Vg1 and GDF1 signaling in zebrafish also depends on EGF-CFC proteins, but not on Nodal signals. Correspondingly, we find that in Xenopus Vg1 and GDF1 bind to and signal through Activin receptors only in the presence of EGF-CFC proteins. These results establish that multiple TGF-β signals converge on Activin receptor/EGF-CFC complexes and suggest a more widespread requirement for coreceptors in TGF-β signaling than anticipated previously. PMID:12514096

  7. Reproductive biology of the Suez Canal spider crab Schizophrys aspera (H. Milne Edwards, 1834: Crustacea: Brachyura: Majidae).

    PubMed

    El-Serehy, Hamed A; Al-Rasheid, Khaled A; Ibrahim, Nesreen K; Al-Misned, Fahad A

    2015-11-01

    A reproductive biology study of the spider crab Schizophrys aspera (H. Milne Edwards, 1834) was conducted in the Suez Canal from July 2012 to June 2013. The annual sex ratio (Male:Female) of S. aspera was female biased with values of 1:1.25. Out of the four ovarian development stages of this crab, two stages were observed in the Suez Canal throughout the whole year. The ovigerous crab's carapace width varied from 28 to 52 mm. This crab species can spawn during most of the year in the canal water, with a peak during late spring and early winter. The fecundity of ovigerous females ranged between 2349 and 13600 eggs with a mean of 5494 ± 1486 eggs. Female crabs that reached sexual maturity exhibited a minimum carapace width varying between 22 and 46 mm, and fifty percentage of all ovigerous females showed a carapace width of 36 mm.

  8. Transcriptional Basis for the Inhibition of Neural Stem Cell Proliferation and Migration by the TGFβ-Family Member GDF11

    PubMed Central

    Gajendra, Sangeetha; Sonego, Martina; Doherty, Patrick; Lalli, Giovanna

    2013-01-01

    Signalling through EGF, FGF and endocannabinoid (eCB) receptors promotes adult neurogenesis, and this can be modelled in culture using the Cor-1 neural stem cell line. In the present study we show that Cor-1 cells express a TGFβ receptor complex composed of the ActRIIB/ALK5 subunits and that a natural ligand for this receptor complex, GDF11, activates the canonical Smad2/3 signalling cascade and significantly alters the expression of ∼4700 gene transcripts within a few hours of treatment. Many of the transcripts regulated by GDF11 are also regulated by the EGF, FGF and eCB receptors and by the MAPK pathway – however, in general in the opposite direction. This can be explained to some extent by the observation that GDF11 inhibits expression of, and signalling through, the EGF receptor. GDF11 regulates expression of numerous cell-cycle genes and suppresses Cor-1 cell proliferation; interestingly we found down-regulation of Cyclin D2 rather than p27kip1 to be a good molecular correlate of this. GDF11 also inhibited the expression of numerous genes linked to cytoskeletal regulation including Fascin and LIM and SH3 domain protein 1 (LASP1) and this was associated with an inhibition of Cor-1 cell migration in a scratch wound assay. These data demonstrate GDF11 to be a master regulator of neural stem cell transcription that can suppress cell proliferation and migration by regulating the expression of numerous genes involved in both these processes, and by suppressing transcriptional responses to factors that normally promote proliferation and/or migration. PMID:24244313

  9. Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems.

    PubMed

    James, R; Kumbar, S G; Laurencin, C T; Balian, G; Chhabra, A B

    2011-04-01

    Tendon tissue engineering with a biomaterial scaffold that mimics the tendon extracellular matrix (ECM) and is biomechanically suitable, and when combined with readily available autologous cells, may provide successful regeneration of defects in tendon. Current repair strategies using suitable autografts and freeze-dried allografts lead to a slow repair process that is sub-optimal and fails to restore function, particularly in difficult clinical situations such as zone II flexor tendon injuries of the hand. We have investigated the effect of GDF-5 on cell proliferation and gene expression by primary rat adipose-derived stem cells (ADSCs) that were cultured on a poly(DL-lactide-co-glycolide) PLAGA fiber scaffold and compared to a PLAGA 2D film scaffold. The electrospun scaffold mimics the collagen fiber bundles present in native tendon tissue, and supports the adhesion and proliferation of multipotent ADSCs. Gene expression of scleraxis, the neotendon marker, was upregulated seven- to eightfold at 1 week with GDF-5 treatment when cultured on a 3D electrospun scaffold, and was significantly higher at 2 weeks compared to 2D films with or without GDF-5 treatment. Expression of the genes that encode the major tendon ECM protein, collagen type I, was increased by fourfold starting at 1 week on treatment with 100 ng mL(-1) GDF-5, and at all time points the expression was significantly higher compared to 2D films irrespective of GDF-5 treatment. Thus stimulation with GDF-5 can modulate primary ADSCs on a PLAGA fiber scaffold to produce a soft, collagenous musculoskeletal tissue that fulfills the need for tendon regeneration.

  10. Genetic defects of GDF6 in the zebrafish out of sight mutant and in human eye developmental anomalies

    PubMed Central

    2010-01-01

    Background The size of the vertebrate eye and the retina is likely to be controlled at several stages of embryogenesis by mechanisms that affect cell cycle length as well as cell survival. A mutation in the zebrafish out of sight (out) locus results in a particularly severe reduction of eye size. The goal of this study is to characterize the outm233 mutant, and to determine whether mutations in the out gene cause microphthalmia in humans. Results In this study, we show that the severe reduction of eye size in the outm233 mutant is caused by a mutation in the zebrafish gdf6a gene. Despite the small eye size, the overall retinal architecture appears largely intact, and immunohistochemical studies confirm that all major cell types are present in outm233 retinae. Subtle cell fate and patterning changes are present predominantly in amacrine interneurons. Acridine orange and TUNEL staining reveal that the levels of apoptosis are abnormally high in outm233 mutant eyes during early neurogenesis. Mutation analysis of the GDF6 gene in 200 patients with microphthalmia revealed amino acid substitutions in four of them. In two patients additional skeletal defects were observed. Conclusions This study confirms the essential role of GDF6 in the regulation of vertebrate eye size. The reduced eye size in the zebrafish outm233 mutant is likely to be caused by a transient wave of apoptosis at the onset of neurogenesis. Amino acid substitutions in GDF6 were detected in 4 (2%) of 200 patients with microphthalmia. In two patients different skeletal defects were also observed, suggesting pleitrophic effects of GDF6 variants. Parents carrying these variants are asymptomatic, suggesting that GDF6 sequence alterations are likely to contribute to the phenotype, but are not the sole cause of the disease. Variable expressivity and penetrance suggest a complex non-Mendelian inheritance pattern where other genetic factors may influence the outcome of the phenotype. PMID:21070663

  11. Targeted myocardial delivery of GDF11 gene rejuvenates the aged mouse heart and enhances myocardial regeneration after ischemia-reperfusion injury.

    PubMed

    Du, Guo-Qing; Shao, Zheng-Bo; Wu, Jie; Yin, Wen-Juan; Li, Shu-Hong; Wu, Jun; Weisel, Richard D; Tian, Jia-Wei; Li, Ren-Ke

    2017-01-01

    Ischemic cardiac injury is the main contributor to heart failure, and the regenerative capacity of intrinsic stem cells plays an important role in tissue repair after injury. However, stem cells in aged individuals have reduced regenerative potential and aged tissues lack the capacity to renew. Growth differentiation factor 11 (GDF11), from the activin-transforming growth factor β superfamily, has been shown to promote stem cell activity and rejuvenation. We carried out non-invasive targeted delivery of the GDF11 gene to the heart using ultrasound-targeted microbubble destruction (UTMD) and cationic microbubble (CMB) to investigate the ability of GDF11 to rejuvenate the aged heart and improve tissue regeneration after injury. Young (3 months) and old (21 months) mice were used to evaluate the expression of GDF11 mRNA in the myocardium at baseline and after ischemia/reperfusion (I/R) and myocardial infarction. GDF11 expression decreased with age and following myocardial injury. UTMD-mediated delivery of the GDF11 plasmid to the aged heart after I/R injury effectively and selectively increased GDF11 expression in the heart, and improved cardiac function and reduced infarct size. Over-expression of GDF11 decreased senescence markers, p16 and p53, as well as the number of p16(+) cells in old mouse hearts. Furthermore, increased proliferation of cardiac stem cell antigen 1 (Sca-1(+)) cells and increased homing of endothelial progenitor cells and angiogenesis in old ischemic hearts occurred after GDF11 over-expression. Repetitive targeted delivery of the GDF11 gene via UTMD can rejuvenate the aged mouse heart and protect it from I/R injury.

  12. Effective RNA-silencing strategy of Lv-MSTN/GDF11 gene and its effects on the growth in shrimp, Litopenaeus vannamei.

    PubMed

    Lee, Ji-Hyun; Momani, Jalal; Kim, Young Mog; Kang, Chang-Keun; Choi, Jung-Hwa; Baek, Hae-Ja; Kim, Hyun-Woo

    2015-01-01

    Myostatin (MSTN), also known as GDF8, is a member of the transforming growth factor-β (TGF-β) superfamily and plays an important role in muscle growth, development, and differentiation. Recently, Lv-MSTN/GDF11, the primitive isoform of MSTN and GDF11, was identified from the shrimp Litopenaeus vannamei. The major production site for Lv-MSTN/GDF11 is in the heart, not the tail muscle, which differs from MSTNs in mammals. Among the three injected RNAs, long dsRNA was the most effective for Lv-MSTN/GDF11 knockdown and transcripts of Lv-MSTN/GDF11 decreased in both the heart (88.85%) and skeletal muscles (43.36%) 72h after injection of 10pmol of long dsRNA. We also found that higher doses of dsRNA did not lead to greater decreases in Lv-MSTN/GDF11 transcripts for amounts between 1pmol and 100pmol. Injection of Lv-MSTN/GDF11 dsRNA did not affect the upregulation of the skeletal actin gene (Lv-ACTINSK) in the tail muscle, but the expression of cytoplasmic and cardiac actins were upregulated in both the heart and tail muscle. Over the course of 8weeks of dsRNA injection, considerably higher mortality (~71%) was seen in the dsRNA-injected group compared to the control group (40%). Surviving shrimp in the dsRNA injected group had a lower growth rate due to the adverse effects of Lv-MSTN/GDF11 knockdown. Lv-MSTN/GDF11 appears to be involved in muscular or neuronal development, but not in doubling muscle fibers, as is the case with mammalian MSTN. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Energy transfer and tunable multicolor emission and paramagnetic properties of GdF3:Dy(3+),Tb(3+),Eu(3+) phosphors.

    PubMed

    Guan, Hongxia; Sheng, Ye; Xu, Chengyi; Dai, Yunzhi; Xie, Xiaoming; Zou, Haifeng

    2016-07-20

    A series of Dy(3+), Tb(3+), Eu(3+) singly or doubly or triply doped GdF3 phosphors were synthesized by a glutamic acid assisted one-step hydrothermal method. The samples were characterized by X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM) and photoluminescence (PL) spectroscopy. The results show that the synthesized samples are all pure GdF3. The obtained samples have a peanut-like morphology with a diameter of about 270 nm and a length of about 600 nm. Under UV excitation, GdF3:Dy(3+), GdF3:Tb(3+) and GdF3:Eu(3+) samples exhibit strong blue, green and red emissions, respectively. By adjusting their relative doping concentrations in the GdF3 host, the different color hues of green and red light are obtained by co-doped Dy(3+), Tb(3+) and Tb(3+), Eu(3+) ions in the GdF3 host, respectively. Besides, there exist two energy transfer pairs in the GdF3 host: (1) Dy(3+) → Tb(3+) and (2) Tb(3+) → Eu(3+). More significantly, in the Dy(3+), Tb(3+), and Eu(3+) tri-doped GdF3 phosphors, white light can also be achieved upon excitation of UV light by adjusting the doping concentration of Eu(3+). In addition, the obtained samples also exhibit paramagnetic properties at room temperature (300 K) and low temperature (2 K). It is obvious that multifunctional Dy(3+), Tb(3+), Eu(3+) tri-doped GdF3 materials including tunable multicolors and intrinsic paramagnetic properties may have potential applications in the field of full-color displays.

  14. Controls on erosional retreat of the uplifted rift flanks at the Gulf of Suez and northern Red Sea

    NASA Technical Reports Server (NTRS)

    Steckler, Michael S.; Omar, Gomaa I.

    1994-01-01

    The Gulf of Suez and the Red Sea rigts are currently bordered by large asymmetric uplifts that are undergoing erosion. We find that the amount and timing of erosion vary systematically along the strike of the margin and have been controlled by variations in the perift stratigraphy. The perfit strata are compsoed of cliff-forming Eocene-Cretaceous carbonates overlaying the easily eroded Cretaceous-Cambrian 'Nubian' sandstone. This lithologic succession promotes scarp retreat of the sedimentary section, follwed by dissection of the underlying basement. The perift section thins from over 2000 m at the northern end of the rift to less htan 400 m at its junction with the Red Sea. Thus, at the northern part of the Gulf of Suez, the Nubian sandstone is minimally exposed, and the carbonates form a scarp at the rift border fault. Farther south, undercuttin of hte carbonates by erosion of the sandstion has resulted in scarp retreat. The escarpment cuts diagonally away from the border fault andis over 100 km inland from the border fault at the southernmost Gulf of Suez. The amount of retreat varies inversely with the sediment thickness. Exposure and erosion of basement are initiated by the retreate of the escarpment, and the depth of erosion, as indicated by fission track ages, increases with distance from the escarpment. These observations are explained by a model in which erosion along the Gulf of Suez is initiated as rift flank uplift becomes sufficiently large ot expose the friable sandstones. Undercutting the escarpment and exhumation of basement has been propagating northward and westward for at least 20 m.y. The average rate of scarp retreat has been 6 km/m.y. and the along-strike propagation of the erosion has been 12 km/m.y. The diachronous erosion of the rift flanks at the Gulf of Suez highlights the importance of distinguishing between the timing of uplift and of erosion. Both thermochronometric and stratigraphic data primarily indicate the timing of erosion, which

  15. Controls on erosional retreat of the uplifted rift flanks at the Gulf of Suez and northern Red Sea

    NASA Technical Reports Server (NTRS)

    Steckler, Michael S.; Omar, Gomaa I.

    1994-01-01

    The Gulf of Suez and the Red Sea rigts are currently bordered by large asymmetric uplifts that are undergoing erosion. We find that the amount and timing of erosion vary systematically along the strike of the margin and have been controlled by variations in the perift stratigraphy. The perfit strata are compsoed of cliff-forming Eocene-Cretaceous carbonates overlaying the easily eroded Cretaceous-Cambrian 'Nubian' sandstone. This lithologic succession promotes scarp retreat of the sedimentary section, follwed by dissection of the underlying basement. The perift section thins from over 2000 m at the northern end of the rift to less htan 400 m at its junction with the Red Sea. Thus, at the northern part of the Gulf of Suez, the Nubian sandstone is minimally exposed, and the carbonates form a scarp at the rift border fault. Farther south, undercuttin of hte carbonates by erosion of the sandstion has resulted in scarp retreat. The escarpment cuts diagonally away from the border fault andis over 100 km inland from the border fault at the southernmost Gulf of Suez. The amount of retreat varies inversely with the sediment thickness. Exposure and erosion of basement are initiated by the retreate of the escarpment, and the depth of erosion, as indicated by fission track ages, increases with distance from the escarpment. These observations are explained by a model in which erosion along the Gulf of Suez is initiated as rift flank uplift becomes sufficiently large ot expose the friable sandstones. Undercutting the escarpment and exhumation of basement has been propagating northward and westward for at least 20 m.y. The average rate of scarp retreat has been 6 km/m.y. and the along-strike propagation of the erosion has been 12 km/m.y. The diachronous erosion of the rift flanks at the Gulf of Suez highlights the importance of distinguishing between the timing of uplift and of erosion. Both thermochronometric and stratigraphic data primarily indicate the timing of erosion, which

  16. ZrO₂ surface chemically coated with hyaluronic acid hydrogel loading GDF-5 for osteogenesis in dentistry.

    PubMed

    Bae, Min Soo; Kim, Ji Eun; Lee, Jung Bok; Heo, Dong Nyoung; Yang, Dae Hyeok; Kim, Jin-Ho; Kwon, Kung-Rock; Bang, Jae Beum; Bae, Hojae; Kwon, Il Keun

    2013-01-30

    The objective of this study was to modify zirconium dioxide (ZrO(2)) with photo-cured hyaluronic acid hydrogel (pcHAgel), and to subsequently evaluate the bone regeneration potential of the modified ZrO(2). In the present study, HA grafted onto a ZrO(2) substrate was investigated for its biocompatibility and other properties. We describe the positive influences of ZrO(2) surface-modified with pcHAgel (Zr-3) containing two different loads of growth and differentiation factor-5 (GDF-5) to aid new bone formation as compared to the same amount of BMP-2 (Zr-4-7). We characterized the Zr-3 for their surface morphology and chemical properties. Atomic force microscopy (AFM), scanning electron microscope (SEM), and X-ray photoelectron spectroscopy (XPS) showed that the pcHAgel was successfully grafted onto the ZrO(2) surface. The sustained release of GDF-5 and BMP-2 were observed to occur in the Zr-4-7. In vitro cell tests showed a higher level of MG63 cell proliferation and differentiation on Zr-4-7 than on Zr-3. The Zr-3 is a good biomaterial to deliver osteogenic differentiation factors such as BMP-2 and GDF-5, and GDF-5 can be useful as an effective alternative to aid new bone formation as compared to BMP-2.

  17. Highly uniform hollow GdF3 spheres: controllable synthesis, tuned luminescence, and drug-release properties.

    PubMed

    Lv, Ruichan; Gai, Shili; Dai, Yunlu; Niu, Na; He, Fei; Yang, Piaoping

    2013-11-13

    In this paper, uniform hollow mesoporous GdF3 micro/nanospheres were successfully prepared by a facile two-step synthesis route without using any surfactant, catalyst, and further calcination process. The precursor Gd(OH)CO3 spheres are prepared by a coprecipitation process. After that, uniform and size-tunable GdF3 hollow spheres were easily coprecipitated with NaBF4 at the sacrifice of the precursor with low temperature and short reaction time. X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution TEM, N2 adsorption/desorption, and up-conversion (UC) photoluminescence spectra were used to characterize the as-obtained products. It is found that the initial pH value and NaBF4/Gd(3+) molar ratios play important roles in the structures, sizes, and phases of the hollow products. The growth mechanism of the hollow spheres has been systematically investigated based on the Kirkendall effect. Under 980 nm IR laser excitation, UC luminescence of the as-prepared Yb(3+)/Er(3+)-codoped GdF3 hollow spheres can be changed by a simple adjustment of the concentration of the Yb(3+) ion. Enhanced red emission is obtained by introducing Li(+) ions in GdF3:Yb(3+)/Er(3+). Furthermore, a doxorubicin release experiment and a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide cytotoxicity assay reveal that the product has potential application in drug delivery and targeted cancer therapy.

  18. Polymorphism identification in BMP15 and GDF9 genes and their association with egg production in chickens.

    PubMed

    Huang, H Y; Liang, Z; Li, S F; Li, C M; Zhao, Z H; Wang, Q B

    2015-01-01

    1. Mutations in growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are significantly associated with reproductive performance in mammals and the objective of the present study was to identify polymorphic sites and elucidate the association between genotypes in BMP15 and GDF9 and egg production. 2. Polymorphisms in BMP15 exon1 and GDF9 exon2 were detected by DNA sequencing and PCR-RFLP. Three SNPs were detected in each of BMP15 (A111G, C231T and C34T) and GDF9 (G593A, T824C and C896T). C34T leads to the substitution of Leu by Phe, which was predicted to affect protein function. 3. Results of the association analysis indicated that C34T had an effect on total egg production at 300 d of age (EN) and age at first laying (AFE). G593A affected EN and both C231T and C896T influenced AFE. The TGC1TGC1 diplotype in BMP15 had the highest EN. 4. In conclusion, EN may be significantly improved by marker-assisted selection of the BMP15 genotypes in maternal lines of Shaobo hens.

  19. Structure of Gremlin-2 in Complex with GDF5 Gives Insight into DAN-Family-Mediated BMP Antagonism.

    PubMed

    Nolan, Kristof; Kattamuri, Chandramohan; Rankin, Scott A; Read, Randy J; Zorn, Aaron M; Thompson, Thomas B

    2016-08-23

    The DAN family, including Gremlin-1 and Gremlin-2 (Grem1 and Grem2), represents a large family of secreted BMP (bone morphogenetic protein) antagonists. However, how DAN proteins specifically inhibit BMP signaling has remained elusive. Here, we report the structure of Grem2 bound to GDF5 at 2.9-Å resolution. The structure reveals two Grem2 dimers binding perpendicularly to each GDF5 monomer, resembling an H-like structure. Comparison to the unbound Grem2 structure reveals a dynamic N terminus that undergoes significant transition upon complex formation, leading to simultaneous interaction with the type I and type II receptor motifs on GDF5. Binding studies show that DAN-family members can interact with BMP-type I receptor complexes, whereas Noggin outcompetes the type I receptor for ligand binding. Interestingly, Grem2-GDF5 forms a stable aggregate-like structure in vitro that is not clearly observed for other antagonists, including Noggin and Follistatin. These findings exemplify the structural and functional diversity across the various BMP antagonist families. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. Controllable synthesis and upconversion emission of ultrasmall lanthanide-doped Sr2GdF7 nanocrystals

    NASA Astrophysics Data System (ADS)

    Xiang, Lijun; Ren, Guozhong; Mao, Yifu; He, Jin; Su, Rui

    2015-11-01

    The effect of rare-earth ions content on the phase structure, crystal size and morphology of SrF2-GdF3 system were studied under solvothermal conditions. By tuning the molar ratio of reactants, tetragonal phase Sr2GdF7 nanocrystals (NCs) were synthesized via solvothermal method using oleic acid as capping ligands. The effects of reaction conditions on the phase structure, crystal size, morphology, and upconversion (UC) emission properties of the products were investigated. The results reveal that apropos Gd3+ ions content (0.30-0.45 mmol) is favorable to the formation of pure phase Sr2GdF7 NCs with more uniform size distribution. The average crystalline size of the products can be controlled less than 10 nm. The energy transfer UC mechanisms for the fluorescent intensity were also investigated. Following Yb3+, Er3+, Tm3+ and Ho3+ ions doping, the Sr2GdF7 NCs show intense green, yellow, and white-color UC emission under the excitation of a 980 nm laser, and the doping concentration of lanthanide ions was optimized, which makes the NCs show maximum intensities under the excitation of a 980 nm laser.

  1. Crystal structure analysis reveals a spring-loaded latch as molecular mechanism for GDF-5–type I receptor specificity

    PubMed Central

    Kotzsch, Alexander; Nickel, Joachim; Seher, Axel; Sebald, Walter; Müller, Thomas D

    2009-01-01

    Dysregulation of growth and differentiation factor 5 (GDF-5) signalling, a member of the TGF-β superfamily, is strongly linked to skeletal malformation. GDF-5-mediated signal transduction involves both BMP type I receptors, BMPR-IA and BMPR-IB. However, mutations in either GDF-5 or BMPR-IB lead to similar phenotypes, indicating that in chondrogenesis GDF-5 signalling seems to be exclusively mediated through BMPR-IB. Here, we present structural insights into the GDF-5:BMPR-IB complex revealing how binding specificity for BMPR-IB is generated on a molecular level. In BMPR-IB, a loop within the ligand-binding epitope functions similar to a latch allowing high-affinity binding of GDF-5. In BMPR-IA, this latch is in a closed conformation leading to steric repulsion. The new structural data now provide also a molecular basis of how phenotypically relevant missense mutations in GDF-5 might impair receptor binding and activation. PMID:19229295

  2. Miocene salt structures as exploration indicators in the offshore B-Trend, Gulf of Suez, Egypt

    SciTech Connect

    Saoudi, A.M. )

    1991-03-01

    The B-Trend is a structural horst block extending in a northwest-southeast direction for about 40 km in the southern offshore area of the Gulf of Suez. It contains six individual sub-structures (six oil fields) oriented along strike and dipping toward the southwest. Subsurface geologic data from 60 wells together with the available seismic data in the area were integrated to explain the development of salt structures along this belt and their influence on oil exploration. These salt structures are restricted to the Belayim and South Gharib formations of middle and upper Miocene age, respectively. Moreover, they are arranged as linear features along the trend. Thickening in the Belayim salt is due in some cases to injection and in others to deposition. The apexes of the Belayim injected salt bodies are located down-dip from the crest of the underlying structures and are shifted westward from the apexes of the overlying larger South Gharib salt bulges. The highset corner of the pre-Miocene structures is located to the east of the injected Belayim salt pillows. Thick Belayim salt of depositional origin usually exists on the downthrown side of the leading edge fault to the east. The thickness ratios between the different members of the Belayim Formation help to differentiate between the injected and deposited salt bodies. These ratios can be used to orient well tracks to the optimum structural target while drilling.

  3. Physico-chemical conditions for plankton in Lake Timsah, a saline lake on the Suez Canal

    NASA Astrophysics Data System (ADS)

    El-Serehy, H. A. H.; Sleigh, M. A.

    1992-02-01

    Lake Timsah receives high salinity water from the Suez Canal, mainly from the south, and freshwater from a Nile canal and other sources, producing a salinity stratification with surface salinities of 20-40‰ and over 40‰ in deeper water. Water temperature at a depth of 50-70 cm fell to below 20 °C in winter and rose to above 30 °C in summer; oxygen concentration at the same depth ranged between 6-10 mg l -1 and the pH was 8·1-8·3, and at mid-day this water was supersaturated with oxygen through 6-8 months of the year. The main chemical nutrients reached their highest levels in winter (December-February) and their lowest levels in summer (May-August), silicate varying between 1-7 μ M, phosphate between 0·1 and 0·8 μ M and nitrate between 4-10 μ M; nitrite varied in a more complex manner, usually between 0·25 and 0·4 μ M. The atomic ratio of N/P was generally well above the Redfield ratio level, except for a few months in midwinter. These nutrient concentrations are high in comparison with those of unpolluted seas of the region, but are typical of the more eutrophic coastal waters in most parts of the world.

  4. Tectonic and structural setting of the northeastern central Gulf of Suez area using aeromagnetic data

    NASA Astrophysics Data System (ADS)

    Zahra, Hesham Shaker; Nakhla, Adel Mokhles

    2016-03-01

    Cumulative qualitative and quantitative analysis of the filtered regional and residual magnetic components of the northeastern central area of the Gulf of Suez, as well as images of the second vertical derivatives of the reduced to the northern magnetic pole map of the total magnetic intensity field images, supplemented with the available geologic information, enabled the precise delineation of the detailed structural configuration of the basement complex, which consequently illustrated the structural deformational pattern of the overlying sedimentary succession. The basement tectonic map reflects a series of N-S to NNW-SSE oriented belts of high and low basement structures. These structures are interrupted by a set of NE-SW crossing diagonal faults having varying throws and creating promising blocks for exploration. An often remarkable correlation between the reduced to the magnetic pole map and the basement relief map is noted, in particular the outline of various oil fields. A larger number of the tilted fault blocks and basement culminations have been outlined and numerous interesting exploration prospects are indicated, which appear to warrant further follow up investigation.

  5. A phase IIa randomized controlled pilot study evaluating the safety and clinical outcomes following the use of rhGDF-5/β-TCP in regenerative periodontal therapy.

    PubMed

    Windisch, Péter; Stavropoulos, Andreas; Molnár, Bálint; Szendröi-Kiss, Dóra; Szilágyi, Emese; Rosta, Péter; Horváth, Attila; Capsius, Björn; Wikesjö, Ulf M E; Sculean, Anton

    2012-08-01

    To present the safety profile, the early healing phase and the clinical outcomes at 24 weeks following treatment of human intrabony defects with open flap debridement (OFD) alone or with OFD and rhGDF-5 adsorbed onto a particulate β-tricalcium phosphate (β-TCP) carrier. Twenty chronic periodontitis patients, each with at least one tooth exhibiting a probing depth ≥6 mm and an associated intrabony defect ≥4 mm entered the study. Ten subjects (one defect/patient) were randomized to receive OFD alone (control) and ten subjects OFD combined with rhGDF-5/β-TCP. Blood samples were collected at screening, and at weeks 2 and 24 to evaluate routine hematology and clinical chemistry, rhGDF-5 plasma levels, and antirhGDF-5 antibody formation. Plaque and gingival indices, bleeding on probing, probing depth, clinical attachment level, and radiographs were recorded pre- and 24 weeks postsurgery. Comparable safety profiles were found in the two treatment groups. Neither antirhGDF-5 antibody formation nor relevant rhGDF-5 plasma levels were detected in any patient. At 6 months, treatment with OFD + rhGDF-5/β-TCP resulted in higher but statistically not significant PD reduction (3.7 ± 1.2 vs. 3.1 ± 1.8 mm; p = 0.26) and CAL gain (3.2 ± 1.7 vs. 1.7 ± 2.2 mm; p = 0.14) compared to OFD alone. In the tested concentration, the use of rhGDF-5/β-TCP appeared to be safe and the material possesses a sound biological rationale. Thus, further adequately powered, randomized controlled clinical trials are warranted to confirm the clinical relevance of this new approach in regenerative periodontal therapy. rhGDF-5/β-TCP may represent a promising new techology in regenerative periodontal therapy.

  6. Sex-specific differences in the modulation of Growth Differentiation Factor 15 (GDF15) by hyperoxia in vivo and in vitro: Role of Hif-1α.

    PubMed

    Zhang, Yuhao; Jiang, Weiwu; Wang, Lihua; Lingappan, Krithika

    2017-10-01

    Male premature neonates are more susceptible than females to the development of bronchopulmonary dysplasia (BPD). The reasons underlying sexually dimorphic outcomes in premature neonates are not known. GDF15 (Growth and differentiation factor 15) is a secreted cytokine and plays a role in cell proliferation, apoptosis, and angiogenesis. In this study, we sought to elucidate the sex-specific expression of Gdf15 in the lung in vivo in neonatal hyperoxic lung injury and its regulation by Hif-1α, and to delineate the differences in GDF15 expression in male and female human umbilical venous endothelial cells in an in vitro model of oxygen toxicity. Following hyperoxia exposure (95% FiO2, PND (postnatal day 1-5: saccular stage of lung development), neonatal male mice (C57BL/6) show increased GDF15 and decreased HIF-1α expression compared to female mice. For the in vitro experiments, male and female HUVECs were exposed to room air condition (21% O2, 5% CO2) or in hyperoxia condition (95% O2, 5% CO2) for up to 72h. Male HUVECs had greater expression of GDF15 mRNA and protein. To study the inter-relationship between GDF15 and HIF-1α, we measured the expression of GDF15 in H441 cells after HIF-1α knockdown using promoter dual luciferase reporter assay, which showed that HIF-1α and GDF15 expression are inversely related under normoxia and hyperoxia. The results indicate that sex differences exist in the expression and modulation of GDF15 by HIF-1α in neonatal hyperoxic injury both in vivo and in vitro. These differences could explain in part the mechanisms behind sex-specific differences in BPD. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The Role of NAG-1/GDF15 in the Inhibition of Intestinal Polyps in APC/Min Mice by Sulindac

    PubMed Central

    Wang, Xingya; Kingsley, Philip J.; Marnett, Larry J.; Eling, Thomas E.

    2014-01-01

    The antitumor effects of nonsteroidal anti-inflammatory drugs (NSAID) are assumed to be due to the inhibition of COX activity, but COX-independent mechanisms may also play an important role. NSAID-activated gene (NAG-1/GDF15) is induced by NSAIDs and has antitumorigenic activities. To determine the contribution of COX-2 inhibition and NAG-1/GDF15 expression to the prevention of colon carcinogenesis by NSAIDs, we evaluated several sulindac derivatives [des-methyl (DM)-sulindac sulfide and its prodrug DM-sulindac] that do not inhibit COX-2 activity. Sulindac sulfide and DM-sulindac induced the expression of NAG-1/GDF15 in HCT116 cells as determined by quantitative real-time PCR and Western blot. We fed APC/Min mice with 320 ppm of sulindac and doses of DM-sulindac. Only sulindac significantly inhibited tumor formation in APC/Min mice. To determine the pharmacokinetic properties of sulindac and DM-sulindac in vivo, wild-type C57/B6 mice were fed with sulindac and DM-sulindac at 80, 160, and 320 ppm. High-performance liquid chromatography analysis revealed that the conversion of DM-sulindac to DM-sulindac sulfide (active form) was less efficient than the conversion of sulindac to sulindac sulfide (active form) in the mice. Lower levels of DM-sulindac sulfide accumulated in intestinal and colon tissues in comparison with sulindac sulfide. In addition, NAG-1/GDF15 was induced in the liver of sulindac-fed mice but not in the DM-sulindac–fed mice. Collectively, our results suggest that the tumor-inhibitory effects of sulindac in APC/Min mice may be due to, in part, NAG-1/GDF15 induction in the liver. Our study also suggests that pharmacologic properties should be carefully evaluated when developing drug candidates. PMID:21205743

  8. The role of NAG-1/GDF15 in the inhibition of intestinal polyps in APC/Min mice by sulindac.

    PubMed

    Wang, Xingya; Kingsley, Philip J; Marnett, Larry J; Eling, Thomas E

    2011-01-01

    The antitumor effects of nonsteroidal anti-inflammatory drugs (NSAID) are assumed to be due to the inhibition of COX activity, but COX-independent mechanisms may also play an important role. NSAID-activated gene (NAG-1/GDF15) is induced by NSAIDs and has antitumorigenic activities. To determine the contribution of COX-2 inhibition and NAG-1/GDF15 expression to the prevention of colon carcinogenesis by NSAIDs, we evaluated several sulindac derivatives [des-methyl (DM)-sulindac sulfide and its prodrug DM-sulindac] that do not inhibit COX-2 activity. Sulindac sulfide and DM-sulindac induced the expression of NAG-1/GDF15 in HCT116 cells as determined by quantitative real-time PCR and Western blot. We fed APC/Min mice with 320 ppm of sulindac and doses of DM-sulindac. Only sulindac significantly inhibited tumor formation inAPC/Min mice. To determine the pharmacokinetic properties of sulindac and DM-sulindac in vivo, wild-type C57/B6 mice were fed with sulindac and DM-sulindac at 80, 160, and 320 ppm. High-performance liquid chromatography analysis revealed that the conversion of DM-sulindac to DM-sulindac sulfide (active form) was less efficient than the conversion of sulindac to sulindac sulfide (active form) in the mice. Lower levels of DM-sulindac sulfide accumulated in intestinal and colon tissues in comparison with sulindac sulfide. In addition, NAG-1/GDF15 was induced in the liver of sulindac-fed mice but not in the DM-sulindac-fed mice. Collectively, our results suggest that the tumor-inhibitory effects of sulindac in APC/Min mice may be due to, in part, NAG-1/GDF15 induction in the liver. Our study also suggests that pharmacologic properties should be carefully evaluated when developing drug candidates. ©2011 AACR.

  9. Digital outcrop characterisation and fracture modelling for a GDF in a crystalline basement.

    NASA Astrophysics Data System (ADS)

    Head, William S.; Hodgetts, David; Smith, Nicholas T.

    2013-04-01

    Plans to dispose of the UK's legacy nuclear waste in a Geological Disposal Facility (GDF) depend heavily on the geological suitability of the host bedrock. Characterising the geology at the proposed depth of the GDF (500 m to 1 km) is a major challenge facing the industry. Clastic surface outcrop analogues are used in the hydrocarbon industry to characterise potential reservoirs that do not outcrop at the surface. The same approach has, to our knowledge, never been applied to crystalline rocks: one of the proposed settings for a GDF. This project utilises terrestrial lidar scanning to create 3D Digital Outcrop Models (DOM's) of geological exposures which form part of the Borrowdale Volcanic Group (BVG) exposed in several localities around the Lake District of the UK. The BVG is a laterally extensive, highly heterogeneous 6 km thick unit, comprising mainly igneous rocks with associated sedimentary and metamorphic rocks. The rocks, which have a complex tectonic history, were formed by explosive caldera-type eruptions in the Late Ordovician (Caradoc) period, and include lavas, ignimbrites, sills and dykes. Using the lidar data collected with a Riegl LMS-Z420i terrestrial laser scanner, a DOM has been constructed and the fracture distributions mapped using a combination of manual and automated approaches. The resulting fracture data are analysed to give statistical information on fracture dimension, distribution and spacing. Stochastically generated Discrete Fracture Networks (DFN's) have then been modelled from these fractures statistical data. Uncertainties in the data include biases due to exposure orientation and extent, resolution of lidar data and whether fractures are open or closed at depth (which may be estimated from the current stress regime). Multiple realisations of the DFN are generated to help take into account uncertainty in the fracture-derived statistics. The DFN is then used to calculate porosity and permeability values for the fracture network

  10. Synthesis and Luminescence Properties of Transparent Nanocrystalline GdF3:Tb Glass-Ceramic Scintillator

    PubMed Central

    Lee, Gyuhyon; Savage, Nicholas; Wagner, Brent; Zhang, Yuelan; Jacobs, Benjamin; Menkara, Hisham; Summers, Christopher; Kang, Zhitao

    2014-01-01

    Transparent glass-ceramic containing rare-earth doped halide nanocrystals exhibits enhanced luminescence performance. In this study, a glass-ceramic with Tb doped gadolinium fluoride nanocrystals embedded in an aluminosilicate glass matrix is investigated for X-ray imaging applications. The nanocrystalline glass-ceramic scintillator was prepared by a melt-quench method followed by an anneal. The GdF3:Tb nanocrystals precipitated within the oxide glass matrix during the processing and their luminescence and scintillation properties were investigated. In this nanocomposite scintillator system, the incorporation of high atomic number Gd compound into the glass matrix increases the X-ray stopping power of the glass scintillator, and effective energy transfer between Gd3+ and Tb3+ ions in the nanocrystals enhances the scintillation efficiency. PMID:24610960

  11. Evaluation of local site effect in the western side of the Suez Canal area by applying H/V and MASW techniques

    NASA Astrophysics Data System (ADS)

    Mohamed, Emad K.; Shokry, M. M. F.; Hassoup, Awad; Helal, A. M. A.

    2016-11-01

    The soft sediments are one of the most important factors responsible for the amplification of the seismic ground motion in an area of study. Three components, single-station microtremor measurements were performed at 61 sites along the Suez Canal to estimate the fundamental frequencies of the soil and corresponding H/V amplitude ratios by using the horizontal-to-vertical spectral ratio (HVSR) method. We have applied the investigations of the shear wave velocity for supplementing the existing seismic microzonation of the Suez Canal. The multichannel analysis of surface wave (MASW) tests were done along the Suez Canal in the three cities, Suez, Ismailia, and Port Said using 24 channels digital engineering seismograph with 4.5 Hz geophones from September 2014 to January 2015 to get the shear wave velocity VS30. The SeisImager/SW software was used for analyzing the data, and 1D-shear wave velocity model have achieved for each site. The HVSR curves show that the fundamental frequency values are ranging from 0.57 to 1.08 Hz, and H/V amplitude ratios are ranging from 4.05 to 6.46. The average values of VS30 are (548, 301), (241, 319), (194, 110, 238) for Suez, Ismailia, and Port Said respectively. The average of shear wave velocity up to 30 m depth is estimated and used for site classification based on the National Earthquake Hazard Reduction Program (NEHRP) classification. The majority of the sites was classified as Class D (stiff soil) except one site at Port Said city is classified as Class E (soft soils), and another site in the Suez city is classified as Class C (hard rock).

  12. Master's and doctoral theses in family medicine and their publication output, Suez Canal University, Egypt.

    PubMed

    Nour-Eldein, Hebatallah; Mansour, Nadia M; Abdulmajeed, Abdulmajeed A

    2015-01-01

    The completion of a thesis is a significant requirement for both a Master's and a doctorate degree in general practice/family medicine (GP/FM). A postgraduate thesis is a well-planned, time-intensive activity carried out over several years. The quality of the theses can be judged by the proportion of published papers. This study aimed to describe Master's and doctoral theses in family medicine and their publications between 1982 and 2014. GP/FM degree theses were reviewed at the Faculty of Medicine and central Suez Canal libraries. Several characteristics were extracted from each thesis relating to the main researcher, supervisors, themes, and study methods according to predefined criteria. Publications from the theses were described. Over 33 years, 208 theses were completed by 173 GP/FM researchers. The majority of the theses were for Master's degrees (84.1%). Regarding the study design, most of the degree theses were cross-sectional studies (76.9%). The adult population was targeted in 33.7% of research theses. Nonprobability sampling was used in 51%. Rural communities were the setting of research in 43.8%, and primary health center (PHC)-based studies in 59.1%. The "Patient" category exceeded the other categories (28.4%). Publication from theses started in the second decade of research production. Of the degree theses, 21.6% original articles were published. Only 13.3% of articles from theses were published in PubMed-indexed journals. The researcher was first author in 62.2% of published articles. The production of GP/FM theses and their publications are going to increase. Continuous assessment and planning for GP/FM studies are recommended.

  13. Master's and doctoral theses in family medicine and their publication output, Suez Canal University, Egypt

    PubMed Central

    Nour-Eldein, Hebatallah; Mansour, Nadia M.; Abdulmajeed, Abdulmajeed A.

    2015-01-01

    Background: The completion of a thesis is a significant requirement for both a Master's and a doctorate degree in general practice/family medicine (GP/FM). A postgraduate thesis is a well-planned, time-intensive activity carried out over several years. The quality of the theses can be judged by the proportion of published papers. Objective: This study aimed to describe Master's and doctoral theses in family medicine and their publications between 1982 and 2014. Materials and Methods: GP/FM degree theses were reviewed at the Faculty of Medicine and central Suez Canal libraries. Several characteristics were extracted from each thesis relating to the main researcher, supervisors, themes, and study methods according to predefined criteria. Publications from the theses were described. Results: Over 33 years, 208 theses were completed by 173 GP/FM researchers. The majority of the theses were for Master's degrees (84.1%). Regarding the study design, most of the degree theses were cross-sectional studies (76.9%). The adult population was targeted in 33.7% of research theses. Nonprobability sampling was used in 51%. Rural communities were the setting of research in 43.8%, and primary health center (PHC)-based studies in 59.1%. The “Patient” category exceeded the other categories (28.4%). Publication from theses started in the second decade of research production. Of the degree theses, 21.6% original articles were published. Only 13.3% of articles from theses were published in PubMed-indexed journals. The researcher was first author in 62.2% of published articles. Conclusion: The production of GP/FM theses and their publications are going to increase. Continuous assessment and planning for GP/FM studies are recommended. PMID:25949959

  14. Syn-rift carbonate depositional patterns: Miocene, Gulf of Suez, Egypt

    SciTech Connect

    Hurst, J.M.

    1987-05-01

    The Suez rift, initiated in the Miocene, consists of asymmetric fault blocks, separated by transfer zones. Syn-rift Miocene carbonates developed on highs; the intricate relations are illustrated at Gebel Gharamul and Esh El Mellaha. Gebel Gharamul is a rollover, cut by antithetic faults, located on a transfer zone. Small coralgal rimmed shelves initially developed over the eroded footwall nick of an early western antithetic. Steepening depositional dips reflect increasing graben subsidence. Subsequently, the main easterly antithetic regionally lowered the rollover, promoting stacked coral rimmed shelf sequences with increasing dip filling the graben, with the back reef onlapping the main rollover crest. Simultaneously, a low-angle flexure (2/sup 0/-3/sup 0/) developed along the northern rollover margin. Low-angle (5/sup 0/) biostromal rimmed shelves, exhibiting sigmoidal clinoforms rapidly accreted laterally, as reflected in flat-based sequences. Depositional pattern eventually merged over the rollover to produce laterally complex rimmed shelf sequences. Esh El Mellaha is a footwall to a major extensional fault. In a southerly extensional cusp (20 km), the fault throw decreases from kilometers to flexural (2-3/sup 0/) displacement. Coralgal rimmed shelves and escarpment fringing reefs mantle the footwall. Initial, thick, and most laterally extensive sequences develop over the flexure. Accretion is primarily subvertical, reflecting continuous flexural subsidence. Where the fault cusp has less than a 30/sup 0/ inclination, carbonate sequences exhibiting oblique and oblique sigmoid clinoforms (40/sup 0/) prograded over and heeled the fault during periods of fault inactivity. With a fault plane inclination over 40/sup 0/, slope progradation was precluded and thin vertically accreting escarpment sequences developed.

  15. Marine molluscs as biomonitors for heavy metal levels in the Gulf of Suez, Red Sea

    NASA Astrophysics Data System (ADS)

    Hamed, Mohamed A.; Emara, Ahmed M.

    2006-05-01

    Levels of the heavy metals Copper (Cu), Zinc (Zn), Lead (Pb), Cadmium (Cd), Chromium (Cr), Nickel (Ni), Iron (Fe) and Manganese (Mn) were determined in coastal water, sediments and soft tissues of the gastropod limpet, Patella caerulea, and the bivalve, Barbatus barbatus, from seven different stations in the western coast of the Gulf of Suez. The concentrations of heavy metals in water ranged between 3.37-4.78, 18.83-21.46, 2.75-3.17, 0.22-0.27, 0.99-1.21, 2.69-3.65, 3.75-4.56 μg L - 1 and 23.82-32.78 mg g - 1 for Cu, Zn, Pb, Cd, Cr, Ni, Mn and Fe, respectively. The corresponding concentration values in the sediments were 8.65-12.16, 51.78-58.06, 36.52-42.15, 3.23-3.98, 9.03-12.75, 34.31-49.63, 3.28-4.56 and 64.20-70.22 μg g - 1 for Cu, Zn, Pb, Cd, Cr, Ni, Mn and Fe, respectively. The highest accumulated metals were Fe, Zn and Mn in both P. caerulea and B. barbatus, while the lowest one was Cd. The accumulation of metals was more pronounced in P. caerulea than B. barbatus. The highest concentrations of all metals in water, sediments and mollusca were recorded at Adabiya harbour north of the Gulf, while the lowest concentrations were recorded at Gabal El-Zeit and Hurghada. Land based activities and ships awaiting berth are the main source of metal pollution in the northern part of the Gulf.

  16. Kinematics of the Suez-Sinai area from an updated combined GPS velocity field

    NASA Astrophysics Data System (ADS)

    Pietrantonio, Grazia; Devoti, Roberto; Mahmoud, Salah; Riguzzi, Federica

    2017-04-01

    Many studies based on GPS data, have been carried out to shed light on the current kinematics of the Suez-Sinai area, where the interaction of the African and Arabian plates is active. A combined GPS velocity solution covering a wide area from Egypt to Middle East allowed us to infer the current rates across the plate margins. We have estimated 126 velocities from time series of 90 permanent and 36 non permanent GPS sites located in Africa (Egypt), Eurasia and Arabia plates in the time span 1996-2015, the largest available for the Egyptian sites. We have combined our velocity solution in a least-squares sense with two other recent velocity solutions of networks located around the eastern Mediterranean, obtaining a final IGb08 velocity field of about 450 sites. Then, we have estimated the IGb08 Euler poles of Africa, Sinai and Arabia, analyzing the kinematics of the Sinai area, particular velocity profiles, and estimating the 2D strain rate field. We show that it is possible to reliably model the rigid motion of Sinai block only including some GPS sites located south of the Carmel Fault. The estimated relative motion with respect to Africa is of the order of 2-3 mm/yr, however there is a clear mismatch between the modeled and the observed velocities in the southern Sinai sites. We have also assessed the NNE left shear motion along the Dead Sea Transform Fault, estimating a relative motion between Arabia and Africa of about 6 mm/yr in the direction of the Red Sea opening.

  17. Loss of GDF10/BMP3b as a prognostic marker collaborates with TGFBR3 to enhance chemotherapy resistance and epithelial-mesenchymal transition in oral squamous cell carcinoma.

    PubMed

    Cheng, Chieh-Wen; Hsiao, Jenn-Ren; Fan, Chi-Chen; Lo, Yu-Kang; Tzen, Chi-Yuan; Wu, Li-Wha; Fang, Wei-Yu; Cheng, Ann-Joy; Chen, Chung-Hsing; Chang, I-Shou; Jiang, Shih Sheng; Chang, Jang-Yang; Lee, Alan Yueh-Luen

    2016-05-01

    Growth differentiation factor-10 (GDF10), commonly referred as BMP3b, is a member of the transforming growth factor-β (TGF-β) superfamily. GDF10/BMP3b has been considered as a tumor suppressor, however, little is known about the molecular mechanism of its roles in tumor suppression in oral cancer. Clinical significance of GDF10 downregulation in oral squamous cell carcinoma (OSCC) was evaluated using three independent cohorts of OSCC patients. The molecular mechanisms of GDF10 in the suppression of cell survival, cell migration/invasion and epithelial-mesenchymal transition (EMT) were investigated by using oral cancer cell lines. The present study shows that GDF10 is downregulated during oral carcinogenesis, and GDF10 expression is also an independent risk factor for overall survival of OSCC patients. Overexpression of GDF10 attenuates cell proliferation, transformation, migration/invasion, and EMT. GDF10-inhibited EMT is mediated by ERK signaling but not by typical TGF-β signaling. In addition, overexpression of GDF10 promotes DNA damage-induced apoptosis and sensitizes the response to all-trans retinoic acid (ATRA) and camptothecin (CPT). Intriguingly, the expression of GDF10 is induced by type III TGF-β receptor (TGFBR3) through TGF-β-SMAD2/3 signaling. Our findings suggest that TGFBR3 is an upstream activator of GDF10 expression and they share the same signaling to inhibit EMT and migration/invasion. These results support that GDF10 acts as a hinge to collaborate with TGFBR3 in the transition of EMT-MET program. Taken together, we illustrated the clinical significance and the molecular mechanisms of tumor-suppressive GDF10 in OSCC.

  18. The Identification of Trans-acting Factors That Regulate the Expression of GDF5 via the Osteoarthritis Susceptibility SNP rs143383

    PubMed Central

    Syddall, Catherine M.; Reynard, Louise N.; Young, David A.; Loughlin, John

    2013-01-01

    rs143383 is a C to T transition SNP located in the 5′untranslated region (5′UTR) of the growth differentiation factor 5 gene GDF5. The T allele of the SNP is associated with increased risk of osteoarthritis (OA) in Europeans and in Asians. This susceptibility is mediated by the T allele producing less GDF5 transcript relative to the C allele, a phenomenon known as differential allelic expression (DAE). The aim of this study was to identify trans-acting factors that bind to rs143383 and which regulate this GDF5 DAE. Protein binding to the gene was investigated by two experimental approaches: 1) competition and supershift electrophoretic mobility shift assays (EMSAs) and 2) an oligonucleotide pull down assay followed by quantitative mass spectrometry. Binding was then confirmed in vivo by chromatin immunoprecipitation (ChIP), and the functional effects of candidate proteins investigated by RNA interference (RNAi) and over expression. Using these approaches the trans-acting factors Sp1, Sp3, P15, and DEAF-1 were identified as interacting with the GDF5 5′UTR. Knockdown and over expression of the factors demonstrated that Sp1, Sp3, and DEAF-1 are repressors of GDF5 expression. Depletion of DEAF-1 modulated the DAE of GDF5 and this differential allelic effect was confirmed following over expression, with the rs143383 T allele being repressed to a significantly greater extent than the rs143383 C allele. In combination, Sp1 and DEAF-1 had the greatest repressive activity. In conclusion, we have identified four trans-acting factors that are binding to GDF5, three of which are modulating GDF5 expression via the OA susceptibility locus rs143383. PMID:23825960

  19. GDF15 contributes to radioresistance and cancer stemness of head and neck cancer by regulating cellular reactive oxygen species via a SMAD-associated signaling pathway

    PubMed Central

    Lee, Li-Yu; Fan, Kang-Hsing; Lu, Ya-Ching; Li, Yi-Chen; Chiang, Chang-Hsu; You, Guo-Rung; Chen, Hsin-Ying; Cheng, Ann-Joy

    2017-01-01

    Radiotherapy is an integral part for the treatment of head and neck cancer (HNC), while radioresistance is a major cause leads to treatment failure. GDF15, a member of the TGF-β superfamily, is hypothesized to participate in various types of homeostasis. However, the potential role of this molecule in regulation of radiosensitivity remains unclear. In this study, we demonstrated that GDF15 contributed to radioresistance of HNC, as determined by both gain- and lost-of-functional experiments. These results were achieved by the induction of mitochondrial membrane potential and suppression of intracellular reactive oxygen species (ROS). We further showed that GDF15 facilitated the conversion of cancer stemness, as assessed by the promotion of CD44+ and ALDH1+ cell populations and spheroid cell formation. At molecular level, GDF15 conferred to these cellular functions was through phosphorylated SMAD1 proteins to elite downstream signaling molecules. These cellular results were further confirmed in a tumor xenograft mouse study. Taken together, our results demonstrated that GDF15 contributed to radioresistance and cancer stemness by regulating cellular ROS levels via a SMAD-associated signaling pathway. GDF15 may serve as a prediction marker of radioresistance and a therapeutic target for the development of radio-sensitizing agents for the treatment of refractory HNC. PMID:27903972

  20. GDF15 contributes to radioresistance and cancer stemness of head and neck cancer by regulating cellular reactive oxygen species via a SMAD-associated signaling pathway.

    PubMed

    Li, Yan-Liang; Chang, Joseph T; Lee, Li-Yu; Fan, Kang-Hsing; Lu, Ya-Ching; Li, Yi-Chen; Chiang, Chang-Hsu; You, Guo-Rung; Chen, Hsin-Ying; Cheng, Ann-Joy

    2017-01-03

    Radiotherapy is an integral part for the treatment of head and neck cancer (HNC), while radioresistance is a major cause leads to treatment failure. GDF15, a member of the TGF-β superfamily, is hypothesized to participate in various types of homeostasis. However, the potential role of this molecule in regulation of radiosensitivity remains unclear. In this study, we demonstrated that GDF15 contributed to radioresistance of HNC, as determined by both gain- and lost-of-functional experiments. These results were achieved by the induction of mitochondrial membrane potential and suppression of intracellular reactive oxygen species (ROS). We further showed that GDF15 facilitated the conversion of cancer stemness, as assessed by the promotion of CD44+ and ALDH1+ cell populations and spheroid cell formation. At molecular level, GDF15 conferred to these cellular functions was through phosphorylated SMAD1 proteins to elite downstream signaling molecules. These cellular results were further confirmed in a tumor xenograft mouse study. Taken together, our results demonstrated that GDF15 contributed to radioresistance and cancer stemness by regulating cellular ROS levels via a SMAD-associated signaling pathway. GDF15 may serve as a prediction marker of radioresistance and a therapeutic target for the development of radio-sensitizing agents for the treatment of refractory HNC.

  1. Reconstitution of TGFBR2-Mediated Signaling Causes Upregulation of GDF-15 in HCT116 Colorectal Cancer Cells.

    PubMed

    Lee, Jennifer; Fricke, Fabia; Warnken, Uwe; Schnölzer, Martina; Kopitz, Jürgen; Gebert, Johannes

    2015-01-01

    Although inactivating frameshift mutations in the Transforming growth factor beta receptor type 2 (TGFBR2) gene are considered as drivers of microsatellite unstable (MSI) colorectal tumorigenesis, consequential alterations of the downstream target proteome are not resolved completely. Applying a click-it chemistry protein labeling approach combined with mass spectrometry in a MSI colorectal cancer model cell line, we identified 21 de novo synthesized proteins differentially expressed upon reconstituted TGFBR2 expression. One candidate gene, the TGF-ß family member Growth differentiation factor-15 (GDF-15), exhibited TGFBR2-dependent transcriptional upregulation causing increased intracellular and extracellular protein levels. As a new TGFBR2 target gene it may provide a link between the TGF-ß branch and the BMP/GDF branch of SMAD-mediated signaling.

  2. Multiphase flowmeter successfully measures three-phase flow at extremely high gas-volume fractions -- Gulf of Suez, Egypt

    SciTech Connect

    Leggett, R.B.; Borling, D.C.; Powers, B.S.; Shehata, K.; Halvorsen, M.

    1998-02-01

    A multiphase flowmeter (MPFM) installed in offshore Egypt has accurately measured three-phase flow in extremely gassy flow conditions. The meter is completely nonintrusive, with no moving parts, requires no flow mixing before measurement, and has no bypass loop to remove gas before multiphase measurement. Flow regimes observed during the field test of this meter ranged from severe slugging to annular flow caused by the dynamics of gas-lift gas in the production stream. Average gas-volume fraction ranged from 93 to 98% during tests conducted on seven wells. The meter was installed in the Gulf of Suez on a well protector platform in the Gulf of Suez Petroleum Co. (Gupco) October field, and was placed in series with a test separator located on a nearby production platform. Wells were individually tested with flow conditions ranging from 1,300 to 4,700 B/D fluid, 2.4 to 3.9 MMscf/D of gas, and water cuts from 1 to 52%. The meter is capable of measuring water cuts up to 100%. Production was routed through both the MPFM and the test separator simultaneously as wells flowed with the assistance of gas-lift gas. The MPFM measured gas and liquid rates to within {+-} 10% of test-separator reference measurement flow rates, and accomplished this at gas-volume fractions from 93 to 96%. At higher gas-volume fractions up to 98%, accuracy deteriorated but the meter continued to provide repeatable results.

  3. Spatial distribution of radioisotopes in the coast of Suez Gulf, southwestern Sinai and the impact of hot springs.

    PubMed

    Ramadan, Kh A; Seddeek, M K; Elnimr, T; Sharshar, T; Badran, H M

    2011-06-01

    This work describes the concentrations of radioisotopes in soil, sediment, wild plants and groundwater in southwestern Sinai. The study area extends from Suez to Abu Rudies along the eastern part of the Suez Gulf. It included two hot springs: Ayun Musa and Hammam Faraoun. No dependence of ¹³⁷Cs concentrations on any of the measured sand characteristics was found, including calcium carbonate. The enrichment of ²²⁶Ra in Hammam Faraoun hot spring was the most prominent feature. The ²²⁶Ra concentration in hot springs of Ayun Musa and Hammam Faraoun were 68 and 2377 Bq kg⁻¹ for sediments, 3.5 and 54.0 Bq kg⁻¹ for wild plants and 205 and 1945 mBq l⁻¹ for the groundwater, respectively. In addition, ²²⁶Ra activity concentration in local sand in the area of Hammam Faraoun was ∼14 times that of Ayun Musa. On the other hand, the ²³²Th concentrations were comparable in the two hot springs, while ¹³⁷Cs concentrations were relatively higher in Ayun Musa. The characteristics and radioelements studies support possible suggestions that the waters in the two hot springs have different contributions of sea and groundwaters crossing different geological layers where the water-rock interaction takes place.

  4. Reproductive biology of the Suez Canal spider crab Schizophrys aspera (H. Milne Edwards, 1834: Crustacea: Brachyura: Majidae)

    PubMed Central

    El-Serehy, Hamed A.; Al-Rasheid, Khaled A.; Ibrahim, Nesreen K.; Al-Misned, Fahad A.

    2015-01-01

    A reproductive biology study of the spider crab Schizophrys aspera (H. Milne Edwards, 1834) was conducted in the Suez Canal from July 2012 to June 2013. The annual sex ratio (Male:Female) of S. aspera was female biased with values of 1:1.25. Out of the four ovarian development stages of this crab, two stages were observed in the Suez Canal throughout the whole year. The ovigerous crab’s carapace width varied from 28 to 52 mm. This crab species can spawn during most of the year in the canal water, with a peak during late spring and early winter. The fecundity of ovigerous females ranged between 2349 and 13600 eggs with a mean of 5494 ± 1486 eggs. Female crabs that reached sexual maturity exhibited a minimum carapace width varying between 22 and 46 mm, and fifty percentage of all ovigerous females showed a carapace width of 36 mm. PMID:26587008

  5. Absolute quantification of DcR3 and GDF15 from human serum by LC-ESI MS

    PubMed Central

    Lancrajan, Ioana; Schneider-Stock, Regine; Naschberger, Elisabeth; Schellerer, Vera S; Stürzl, Michael; Enz, Ralf

    2015-01-01

    Biomarkers are widely used in clinical diagnosis, prognosis and therapy monitoring. Here, we developed a protocol for the efficient and selective enrichment of small and low concentrated biomarkers from human serum, involving a 95% effective depletion of high-abundant serum proteins by partial denaturation and enrichment of low-abundant biomarkers by size exclusion chromatography. The recovery of low-abundance biomarkers was above 97%. Using this protocol, we quantified the tumour markers DcR3 and growth/differentiation factor (GDF)15 from 100 μl human serum by isotope dilution mass spectrometry, using 15N metabolically labelled and concatamerized fingerprint peptides for the both proteins. Analysis of three different fingerprint peptides for each protein by liquid chromatography electrospray ionization mass spectrometry resulted in comparable concentrations in three healthy human serum samples (DcR3: 27.23 ± 2.49 fmol/ml; GDF15: 98.11 ± 0.49 fmol/ml). In contrast, serum levels were significantly elevated in tumour patients for DcR3 (116.94 ± 57.37 fmol/ml) and GDF15 (164.44 ± 79.31 fmol/ml). Obtained data were in good agreement with ELISA and qPCR measurements, as well as with literature data. In summary, our protocol allows the reliable quantification of biomarkers, shows a higher resolution at low biomarker concentrations than antibody-based strategies, and offers the possibility of multiplexing. Our proof-of-principle studies in patient sera encourage the future analysis of the prognostic value of DcR3 and GDF15 for colon cancer patients in larger patient cohorts. PMID:25823874

  6. Absolute quantification of DcR3 and GDF15 from human serum by LC-ESI MS.

    PubMed

    Lancrajan, Ioana; Schneider-Stock, Regine; Naschberger, Elisabeth; Schellerer, Vera S; Stürzl, Michael; Enz, Ralf

    2015-07-01

    Biomarkers are widely used in clinical diagnosis, prognosis and therapy monitoring. Here, we developed a protocol for the efficient and selective enrichment of small and low concentrated biomarkers from human serum, involving a 95% effective depletion of high-abundant serum proteins by partial denaturation and enrichment of low-abundant biomarkers by size exclusion chromatography. The recovery of low-abundance biomarkers was above 97%. Using this protocol, we quantified the tumour markers DcR3 and growth/differentiation factor (GDF)15 from 100 μl human serum by isotope dilution mass spectrometry, using (15) N metabolically labelled and concatamerized fingerprint peptides for the both proteins. Analysis of three different fingerprint peptides for each protein by liquid chromatography electrospray ionization mass spectrometry resulted in comparable concentrations in three healthy human serum samples (DcR3: 27.23 ± 2.49 fmol/ml; GDF15: 98.11 ± 0.49 fmol/ml). In contrast, serum levels were significantly elevated in tumour patients for DcR3 (116.94 ± 57.37 fmol/ml) and GDF15 (164.44 ± 79.31 fmol/ml). Obtained data were in good agreement with ELISA and qPCR measurements, as well as with literature data. In summary, our protocol allows the reliable quantification of biomarkers, shows a higher resolution at low biomarker concentrations than antibody-based strategies, and offers the possibility of multiplexing. Our proof-of-principle studies in patient sera encourage the future analysis of the prognostic value of DcR3 and GDF15 for colon cancer patients in larger patient cohorts. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  7. Structure and luminescence properties of Eu/Tb codoped oxyfluoride glass ceramics containing Sr 2GdF 7 nanocrystals

    NASA Astrophysics Data System (ADS)

    Xin, Fengxia; Zhao, Shilong; Xu, Shiqing; Huang, Lihui; Jia, Guohua; Deng, Degang; Wang, Huanping

    2011-11-01

    Eu/Tb codoped transparent oxyfluoride borosilicate glass ceramics containing Sr 2GdF 7 nanocrystals were fabricated under a reductive atmosphere and the conversion of Eu 3+ ions to Eu 2+ ions was observed. The Sr 2GdF 7 nanocrystals with an average size of 32 nm were homogeneously precipitated in the oxyfluoride borosilicate glass matrix, which could be evidenced by X-ray diffraction (XRD), transmission electron microscopy (TEM) and energy-dispersive X-ray (EDX) spectroscopy. The enhancement of photoluminescence emission intensity, reduction of the relative emission intensities between 5D 0 → 7F 2 and 5D 0 → 7F 1, and long fluorescence lifetimes of Eu 2+, Eu 3+, and Tb 3+ ions revealed that more rare earth ions were partitioned into the low phonon energy environment Sr 2GdF 7 nanocrystals. Under ultraviolet excitation, pure and bright white light emission was obtained in the oxyfluoride borosilicate glass ceramic, which may be a potential blue, green and red-emitting phosphor for white LEDs.

  8. Recurrent missense mutation of GDF5 (p.R438L) causes proximal symphalangism in a British family

    PubMed Central

    Leonidou, Andreas; Irving, Melita; Holden, Simon; Katchburian, Marcos

    2016-01-01

    Proximal symphalangism (SYM1B) (OMIM 615298) is an autosomal dominant developmental disorder affecting joint fusion. It is characterized by variable fusions of the proximal interphalangeal joints of the hands, typically of the ring and little finger, with the thumb typically being spared. SYM1 is frequently associated with coalition of tarsal bones and conductive hearing loss. Molecular studies have identified two possible genetic aetiologies for this syndrome, NOG and GDF5. We herein present a British caucasian family with SYM1B caused by a mutation of the GDF5 gene. A mother and her three children presented to the orthopaedic outpatient department predominantly for feet related problems. All patients had multiple tarsal coalitions and hand involvement in the form of either brachydactyly or symphalangism of the proximal and middle phalanx of the little fingers. Genetic testing in the eldest child and his mother identified a heterozygous missense mutation in GDF5 c.1313G>T (p.R438L), thereby establishing SYM1B as the cause of the orthopaedic problems in this family. There were no mutations identified in the NOG gene. This report highlights the importance of thorough history taking, including a three generation family history, and detailed clinical examination of children with fixed planovalgus feet and other family members to detect rare skeletal dysplasia conditions causing pain and deformity, and provides details of the spectrum of problems associated with SYM1B. PMID:28032038

  9. Electronic spectra of GdF reanalyzed by decomposing state functions according to f-shell angular momentum

    NASA Astrophysics Data System (ADS)

    Yamamoto, Shigeyoshi; Tatewaki, Hiroshi

    2011-04-01

    The electronic structure of the GdF molecule was studied by means of four-component relativistic configuration interaction (CI) calculations [S. Yamamoto, H. Tatewaki, and T. Saue, J. Chem. Phys. 129, 244505 (2008), 10.1063/1.3039794]. To analyze the electronic spectra more accurately, the CI wave function is decomposed according to the angular momentum (Ωf) generated from the (4f)7 electrons. The weight of a specified Ωf is referred to as the "f-shell Omega component weight." This Ωf plays a crucial role in classifying the strong electronic transitions from the upper states (0.7 eV-3.0 eV) to the lower states (˜0.55 eV). For these transitions, the upper and lower states have almost identical Ωf weights. This appears to be a necessary condition for a transition to be strong. The same condition is expected to hold for other lanthanide linear molecules. A point charge model is also studied, acting as a simplified model of GdF; it successfully reproduces the spectra of GdF, justifying studies based on ligand field theory.

  10. Dipole allowed transitions in GdF: A four-component relativistic general open-shell configuration interaction study

    NASA Astrophysics Data System (ADS)

    Yamamoto, Shigeyoshi; Tatewaki, Hiroshi; Saue, Trond

    2008-12-01

    A four-component relativistic study of electronic transitions in the gadolinium monofluoride molecule (GdF) is presented. The electronic spectra of GdF have been investigated with a general open-shell configuration interaction method, where active electrons are distributed among molecular spinors mainly consisting of the Gd 4f, 5d, and 6s atomic spinors. The near-degeneracy effects of these spinors on the molecular electronic structure are considered by the valence full-CI-like approach. By the magnitudes of calculated transition dipole moments, the candidates for the observable transitions were selected. The present result is complementary to our previous study based on multireference configuration interaction singles and doubles calculations, which identified the electronic excited states of GdF by comparing the calculated excitation energies and angular momenta with those given by the laser spectroscopy. The spectra of the excited states less than 3.0 eV have been refined with the help of the calculated transition probabilities. The transitions between the excited states are newly analyzed and a rearrangement is proposed.

  11. Structural evolution and Cenozoic tectonostratigraphy of the Cairo-Suez district, north Eastern Desert of Egypt: Field-structural data from Gebel Qattamiya-Gebel Um Reheiat area

    NASA Astrophysics Data System (ADS)

    Hagag, Wael

    2016-06-01

    Detailed field mapping reveals that continental rifting is strongly deforming the Gebel Qattamiya-Gebel Um Reheiat area and the entire Cairo-Suez district, in north Eastern Desert of Egypt. Rift-related structures are predominantly represented by E to WNW, NNW and NW oriented faults. The E to WNW oriented faults are small and build up the Gebel Qattamiya en echelon fault belt, whereas the faults trending NNW and NW establish a pervasive horst and graben structural style involving some rhomb-shape horsts as Gebel Qattamiya (GQRH), Gebel Um Reheiat (GURRH) and south Gebel Um Reheiat (SGURRH). Rock units of the Eocene succession and Oligocene sediments are well exposed and highly controlled by rift-related structures. Rifting was developed through two rift-phases; initial and major ones. The initial phase (a newly recognized phase in this contribution) has been occurred in Late Eocene (Priabonian), while the main phase was prevailing during Late Oligocene-Early Miocene time and is characterized by hydrothermal veins and basaltic eruptions. Continental transtension in the Cairo-Suez district, including the study area, was probably synchronous with a major tectonic stage (Pyrenean-Atlasic movement) of continental collision between African-Arabian and Eurasian plates in Late Eocene-Oligocene time. Field investigation suggests that the transfer of displacement (slip) from the Gulf of Suez proto-rift into the E-W oriented faults ''relays'' is an important mechanism, which helps to explain the current structural framework and tectonic evolution of the Cairo-Suez district. Reactivation of such faults with right-lateral divergent wrenching with NE-SW oriented extension deformed the Cairo-Suez district with several E-W oriented en echelon fault belts (e.g. Gebel Qattamiya fault belt in the study area). Thus the Cairo-Suez district represents an accommodation or transfer zone in northeastern Egypt, intercepting the ''far-field stresses'' from the Arabian-Nubian Shield, the Red

  12. GC estimation of organic hydrocarbons that threaten shallow Quaternary sandy aquifer Northwestern Gulf of Suez, Egypt.

    PubMed

    Zawrah, M F; Ebiad, M A; Rashad, A M; El-Sayed, E; Snousy, Moustafa Gamal; Tantawy, M A

    2014-11-01

    Soil and groundwater contamination is one of the important environmental problems at petroleum-related sites, which causes critical environmental and health defects. Severe petroleum hydrocarbon contamination from coastal refinery plant was detected in a shallow Quaternary sandy aquifer is bordered by Gulf in the Northwestern Gulf of Suez, Egypt. The overall objective of this investigation is to estimate the organic hydrocarbons in shallow sandy aquifers, released from continuous major point-source of pollution over a long period of time (91 years ago). This oil refinery contamination resulted mainly in the improper disposal of hydrocarbons and produced water releases caused by equipment failures, vandalism, and accidents that caused direct groundwater pollution or discharge into the gulf. In order to determine the fate of hydrocarbons, detailed field investigations were made to provide intensive deep profile information. Eight composite randomly sediment samples from a test plot were selected for demonstration. The tested plot was 50 m long × 50 m wide × 70 cm deep. Sediment samples were collected using an American auger around the point 29° 57' 33″ N and 32° 30' 40″ E in 2012 and covered an area of 2,500 m(2) which represents nearly 1/15 of total plant area (the total area of the plant is approximately 3.250 km(2)). The detected total petroleum hydrocarbons (TPHs) were 2.44, 2.62, 4.54, 4.78, 2.83, 3.22, 2.56, and 3.13 wt%, respectively. TPH was calculated by differences in weight and subjected to gas chromatography (GC). Hydrocarbons were analyzed on Hewlett-Packard (HP-7890 plus) gas chromatograph equipped with a flame ionization detector (FID). The percentage of paraffine of the investigated TPH samples was 7.33, 7.24, 7.58, 8.25, 10.25, 9.89, 14.77, and 17.53 wt%, respectively.

  13. Lifelong exercise, but not short-term high-intensity interval training, increases GDF11, a marker of successful aging: a preliminary investigation.

    PubMed

    Elliott, Bradley T; Herbert, Peter; Sculthorpe, Nicholas; Grace, Fergal M; Stratton, Daniel; Hayes, Lawrence D

    2017-07-01

    Lifelong exercise is associated with regulation of skeletal mass and function, reductions in frailty, and successful aging. Yet, the influence of exercise on myostatin and myostatin-interacting factors is relatively under examined in older males. Therefore, we investigated whether serum total myostatin, free myostatin, follistatin, and growth and differentiation factor 11 (GDF11) were altered following high-intensity interval training (HIIT) in a group of 13 lifelong sedentary (SED; 64 [6] years) and 11 lifelong exercising (LEX; 62 [6] years) older males. SED follistatin was moderately greater than LEX pre-HIIT (Cohen's d = 0.66), and was largely greater post-HIIT (Cohen's d = 1.22). The HIIT-induced increase in follistatin was large in SED (Cohen's d = 0.82) and absent in LEX (Cohen's d = 0.03). GDF11 was higher in LEX pre-HIIT (Cohen's d = 0.49) and post-HIIT (Cohen's d = 0.63) compared to SED HIIT resulted in no change to GDF11 in LEX or SED (Cohen's d = 0.00-0.03). Peak power output and GDF11 were correlated (r = 0.603), independent of grouping. Differences in GDF11 with lifelong exercise training, paired with the correlation between GDF11 and peak power output, suggested that GDF11 may be a relevant myostatin-interacting peptide to successful aging in humans, and strategies to maintain this need to be further explored. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  14. Bone architecture and disc degeneration in the lumbar spine of mice lacking GDF-8 (myostatin).

    PubMed

    Hamrick, Mark W; Pennington, Catherine; Byron, Craig D

    2003-11-01

    GDF-8, also known as myostatin, is a member of the transforming growth factor-beta superfamily of secreted growth and differentiation factors that is expressed in vertebrate skeletal muscle. Myostatin functions as a negative regulator of skeletal muscle growth and myostatin null mice show a doubling of muscle mass compared to normal mice. We describe here morphology of the lumbar spine in myostatin knockout (Mstn(-/-)) mice using histological and densitometric techniques. The Mstn(-/-) mice examined in this study weigh approximately 10% more than controls (p<0.001) but the iliopsoas muscle is over 50% larger in the knockout mice than in wild-type mice (p<0.001). Peripheral quantitative computed tomography (pQCT) data from the fifth lumbar vertebra show that mice lacking myostatin have approximately 50% greater trabecular bone mineral density (p=0.001) and significantly greater cortical bone mineral content than normal mice. Toluidine blue staining of the intervertebral disc between L4-L5 reveals loss of proteoglycan staining in the hyaline end plates and inner annulus fibrosus of the knockout mice. Loss of cartilage staining in the caudal end plate of L4 is due to ossification of the end plate in the myostatin-deficient animals. Results from this study suggest that increased muscle mass in mice lacking myostatin is associated with increased bone mass as well as degenerative changes in the intervertebral disc.

  15. gdf6a Is Required for Cone Photoreceptor Subtype Differentiation and for the Actions of tbx2b in Determining Rod Versus Cone Photoreceptor Fate

    PubMed Central

    DuVal, Michèle G.; Oel, A. Phillip; Allison, W. Ted

    2014-01-01

    Functional vision restoration is within reach via stem cell therapy, but one of the largest obstacles is the derivation of colour-sensitive cone photoreceptors that are required for high-acuity daytime vision. To enhance progress made using nocturnal murine models, we instead utilize cone-rich zebrafish and herein investigate relationships between gdf6a and tbx2b in cone photoreceptor development. Growth/differentiation factor 6a (gdf6a), a bone morphogenetic protein family ligand, is an emerging factor in photoreceptor degenerative diseases. The T-box transcription factor tbx2b is required to specify UV cone photoreceptor fate instead of rod photoreceptor fate. Interactions between these factors in cone development would be unanticipated, considering the discrete phenotypes in their respective mutants. However, gdf6a positively modulates the abundance of tbx2b transcript during early eye morphogenesis, and we extended this conclusion to later stages of retinal development comprising the times when photoreceptors differentiate. Despite this, gdf6a−/− larvae possess a normal relative number of UV cones and instead present with a low abundance of blue cone photoreceptors, approximately half that of siblings (p<0.001), supporting a differential role for gdf6a amongst the spectral subtypes of cone photoreceptors. Further, gdf6a−/− larvae from breeding of compound heterozygous gdf6a+/−;tbx2b+/− mutants exhibit the recessive lots-of-rods phenotype (which also shows a paucity of UV cones) at significantly elevated rates (44% or 48% for each of two tbx2b alleles, χ2 p≤0.007 for each compared to expected Mendelian 25%). Thus the gdf6a−/− background sensitizes fish such that the recessive lots-of-rods phenotype can appear in heterozygous tbx2b+/− fish. Overall, this work establishes a novel link between tbx2b and gdf6a in determining photoreceptor fates, defining the nexus of an intricate pathway influencing the abundance of cone spectral subtypes and

  16. gdf6a is required for cone photoreceptor subtype differentiation and for the actions of tbx2b in determining rod versus cone photoreceptor fate.

    PubMed

    Duval, Michèle G; Oel, A Phillip; Allison, W Ted

    2014-01-01

    Functional vision restoration is within reach via stem cell therapy, but one of the largest obstacles is the derivation of colour-sensitive cone photoreceptors that are required for high-acuity daytime vision. To enhance progress made using nocturnal murine models, we instead utilize cone-rich zebrafish and herein investigate relationships between gdf6a and tbx2b in cone photoreceptor development. Growth/differentiation factor 6a (gdf6a), a bone morphogenetic protein family ligand, is an emerging factor in photoreceptor degenerative diseases. The T-box transcription factor tbx2b is required to specify UV cone photoreceptor fate instead of rod photoreceptor fate. Interactions between these factors in cone development would be unanticipated, considering the discrete phenotypes in their respective mutants. However, gdf6a positively modulates the abundance of tbx2b transcript during early eye morphogenesis, and we extended this conclusion to later stages of retinal development comprising the times when photoreceptors differentiate. Despite this, gdf6a-/- larvae possess a normal relative number of UV cones and instead present with a low abundance of blue cone photoreceptors, approximately half that of siblings (p<0.001), supporting a differential role for gdf6a amongst the spectral subtypes of cone photoreceptors. Further, gdf6a-/- larvae from breeding of compound heterozygous gdf6a+/-;tbx2b+/- mutants exhibit the recessive lots-of-rods phenotype (which also shows a paucity of UV cones) at significantly elevated rates (44% or 48% for each of two tbx2b alleles, χ2 p≤0.007 for each compared to expected Mendelian 25%). Thus the gdf6a-/- background sensitizes fish such that the recessive lots-of-rods phenotype can appear in heterozygous tbx2b+/- fish. Overall, this work establishes a novel link between tbx2b and gdf6a in determining photoreceptor fates, defining the nexus of an intricate pathway influencing the abundance of cone spectral subtypes and specifying rod vs

  17. GDF11/BMP11 activates both smad1/5/8 and smad2/3 signals but shows no significant effect on proliferation and migration of human umbilical vein endothelial cells

    PubMed Central

    Zhang, Yong-Hui; Cheng, Feng; Du, Xue-Ting; Gao, Jin-Lai; Xiao, Xiao-Lin; Li, Na; Li, Shan-Liang; Dong, De-Li

    2016-01-01

    GDF11/BMP11, a member of TGF-β superfamily, was reported to rejuvenate heart, skeletal muscle and blood vessel architecture in aged mice. However, the rejuvenative effects of GDF11 were questioned recently. Here, we investigated the effects of GDF11 on smad and non-smad signals in human umbilical vein endothelial cells (HUVECs) and the effects of GDF11 on proliferation and migration of HUVECs and primary rat aortic endothelial cells (RAECs). GDF11 factor purchased from two different companies (PeproTech and R&D Systems) was comparatively studied. Western blot was used to detect the protein expressions. The cell viability and migration were examined by using MTT and wound healing assays. Results showed that GDF11 activated both smad1/5/8 and smad2/3 signals in HUVECs. GDF11 increased protein expression of NADPH oxidase 4(NOX4) in HUVECs. GDF11 showed no significant effect on the protein level of p38, p-p38, ERK, p-ERK, Akt, p-Akt (Ser473) and p-Akt(Thr308), but increased the protein level of p-JNK and p-AMPK in HUVECs, and these increases were inhibited by antioxidant mitoTEMPO treatment. GDF11 slightly increased cell viability after short-term treatment and slightly decreased cell viability after long-term treatment. GDF11 showed no significant effect on cell proliferation and migration. These data indicated that the notion of GDF11 as a rejuvenation-related factor for endothelial cells needs to be cautious. PMID:26919250

  18. GDF11/BMP11 activates both smad1/5/8 and smad2/3 signals but shows no significant effect on proliferation and migration of human umbilical vein endothelial cells.

    PubMed

    Zhang, Yong-Hui; Cheng, Feng; Du, Xue-Ting; Gao, Jin-Lai; Xiao, Xiao-Lin; Li, Na; Li, Shan-Liang; Dong, De Li

    2016-03-15

    GDF11/BMP11, a member of TGF-β superfamily, was reported to rejuvenate heart, skeletal muscle and blood vessel architecture in aged mice. However, the rejuvenative effects of GDF11 were questioned recently. Here, we investigated the effects of GDF11 on smad and non-smad signals in human umbilical vein endothelial cells (HUVECs) and the effects of GDF11 on proliferation and migration of HUVECs and primary rat aortic endothelial cells (RAECs). GDF11 factor purchased from two different companies (PeproTech and R&D Systems) was comparatively studied. Western blot was used to detect the protein expressions. The cell viability and migration were examined by using MTT and wound healing assays. Results showed that GDF11 activated both smad1/5/8 and smad2/3 signals in HUVECs. GDF11 increased protein expression of NADPH oxidase 4(NOX4) in HUVECs. GDF11 showed no significant effect on the protein level of p38, p-p38, ERK, p-ERK, Akt, p-Akt (Ser473) and p-Akt(Thr308), but increased the protein level of p-JNK and p-AMPK in HUVECs, and these increases were inhibited by antioxidant mitoTEMPO treatment. GDF11 slightly increased cell viability after short-term treatment and slightly decreased cell viability after long-term treatment. GDF11 showed no significant effect on cell proliferation and migration. These data indicated that the notion of GDF11 as a rejuvenation-related factor for endothelial cells needs to be cautious.

  19. Structural interpretation of seismic data of Abu Rudeis-Sidri area, Northern Central Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Zahra, Hesham Shaker; Nakhla, Adel Mokhles

    2016-12-01

    The 2D and 3D seismic data are interpreted to evaluate the subsurface geologic structures in the Abu Rudeis-Sidri area that occupy the northern central part of the Gulf of Suez. The 2D seismic data are used for determination of the structural configurations and the tectonic features which is analyzed through the study of interpretation with the available geologic data, in which the geo-seismic depth maps for the main interesting tops (Kareem, Nukhul, Matulla, Raha and Nubia Formations) are represented. Such maps reflect that, the Miocene structure of Abu Rudeis-Sidri area is an asymmetrical NW-SE trending anticlinal feature dissected by a set of NW-SE fault system (clysmic). Added, the Pre-Miocene structure of the studied area is very complex, where the area is of NE dip and affected by severe faulting through varying stratigraphic levels.

  20. Low-angle normal faulting and isostatic response in the Gulf of Suez: Evidence from seismic interpretation and geometric reconstruction

    NASA Technical Reports Server (NTRS)

    Perry, S. K.; Schamel, S.

    1985-01-01

    Tectonic extension within continental crust creates a variety of major features best classed as extensional orogens. These features have come under increasing attention in recent years, with the welding of field observation and theoretical concepts. Most recent advances have come from the Basin and Range Province of the southwestern United States and from the North Sea. Application of these geometric and isostatic concepts, in combination with seismic interpretation, to the southern Gulf of Suez, an active extensional orogen, allows generation of detailed structural maps and geometrically balanced sections which suggest a regional structural model. Geometric models which should prove to be a valuable adjunct to numerical and thermal models for the rifting process are discussed.

  1. Band structure and near infrared quantum cutting investigation of GdF3:Yb3+, Ln3+ (Ln = Ho, Tm, Er, Pr, Tb) nanoparticles.

    PubMed

    Guo, Linna; Wang, Yuhua; Zeng, Wei; Zhao, Lei; Han, Lili

    2013-09-14

    A series of GdF3:Yb(3+), Ln(3+) (Ln = Ho, Tm, Er, Pr, Tb) nanoparticles were prepared by a simple and green hydrothermal method without any additives, which exhibited an ellipse-like shape with a diameter of 63 nm and a length of 101 nm on average. To prove the existence (or not) of near infrared quantum cutting for various lanthanide ion couples (Yb/Ho; Yb/Tm; Yb/Er; Yb/Pr; Yb/Tb) in one host lattice (GdF3), the measured luminescence spectra and decay lifetimes of these samples were analysed. Furthermore, the band structures and densities of state of GdF3 were also studied with the help of first-principles calculations, and the direct band gap of GdF3 was estimated to be 7.443 eV wide. Based on this, detailed processes and possible mechanisms of the luminescence phenomena are discussed. GdF3:Yb(3+), Ln(3+) nanoparticles may have potential applications in modifying the solar spectrum to enhance the efficiency of silicon solar cells.

  2. Antagonism between Gdf6a and retinoic acid pathways controls timing of retinal neurogenesis and growth of the eye in zebrafish.

    PubMed

    Valdivia, Leonardo E; Lamb, Dayna B; Horner, Wilson; Wierzbicki, Claudia; Tafessu, Amanuel; Williams, Audrey M; Gestri, Gaia; Krasnow, Anna M; Vleeshouwer-Neumann, Terra S; Givens, McKenzie; Young, Rodrigo M; Lawrence, Lisa M; Stickney, Heather L; Hawkins, Thomas A; Schwarz, Quenten P; Cavodeassi, Florencia; Wilson, Stephen W; Cerveny, Kara L

    2016-04-01

    Maintaining neurogenesis in growing tissues requires a tight balance between progenitor cell proliferation and differentiation. In the zebrafish retina, neuronal differentiation proceeds in two stages with embryonic retinal progenitor cells (RPCs) of the central retina accounting for the first rounds of differentiation, and stem cells from the ciliary marginal zone (CMZ) being responsible for late neurogenesis and growth of the eye. In this study, we analyse two mutants with small eyes that display defects during both early and late phases of retinal neurogenesis. These mutants carry lesions in gdf6a, a gene encoding a BMP family member previously implicated in dorsoventral patterning of the eye. We show that gdf6a mutant eyes exhibit expanded retinoic acid (RA) signalling and demonstrate that exogenous activation of this pathway in wild-type eyes inhibits retinal growth, generating small eyes with a reduced CMZ and fewer proliferating progenitors, similar to gdf6a mutants. We provide evidence that RA regulates the timing of RPC differentiation by promoting cell cycle exit. Furthermore, reducing RA signalling in gdf6a mutants re-establishes appropriate timing of embryonic retinal neurogenesis and restores putative stem and progenitor cell populations in the CMZ. Together, our results support a model in which dorsally expressed gdf6a limits RA pathway activity to control the transition from proliferation to differentiation in the growing eye.

  3. Antagonism between Gdf6a and retinoic acid pathways controls timing of retinal neurogenesis and growth of the eye in zebrafish

    PubMed Central

    Valdivia, Leonardo E.; Lamb, Dayna B.; Horner, Wilson; Wierzbicki, Claudia; Tafessu, Amanuel; Williams, Audrey M.; Gestri, Gaia; Krasnow, Anna M.; Vleeshouwer-Neumann, Terra S.; Givens, McKenzie; Young, Rodrigo M.; Lawrence, Lisa M.; Stickney, Heather L.; Hawkins, Thomas A.; Schwarz, Quenten P.; Cavodeassi, Florencia; Wilson, Stephen W.; Cerveny, Kara L.

    2016-01-01

    Maintaining neurogenesis in growing tissues requires a tight balance between progenitor cell proliferation and differentiation. In the zebrafish retina, neuronal differentiation proceeds in two stages with embryonic retinal progenitor cells (RPCs) of the central retina accounting for the first rounds of differentiation, and stem cells from the ciliary marginal zone (CMZ) being responsible for late neurogenesis and growth of the eye. In this study, we analyse two mutants with small eyes that display defects during both early and late phases of retinal neurogenesis. These mutants carry lesions in gdf6a, a gene encoding a BMP family member previously implicated in dorsoventral patterning of the eye. We show that gdf6a mutant eyes exhibit expanded retinoic acid (RA) signalling and demonstrate that exogenous activation of this pathway in wild-type eyes inhibits retinal growth, generating small eyes with a reduced CMZ and fewer proliferating progenitors, similar to gdf6a mutants. We provide evidence that RA regulates the timing of RPC differentiation by promoting cell cycle exit. Furthermore, reducing RA signalling in gdf6a mutants re-establishes appropriate timing of embryonic retinal neurogenesis and restores putative stem and progenitor cell populations in the CMZ. Together, our results support a model in which dorsally expressed gdf6a limits RA pathway activity to control the transition from proliferation to differentiation in the growing eye. PMID:26893342

  4. Rift-related active fault-system and a direction of maximum horizontal stress in the Cairo-Suez district, northeastern Egypt: A new approach from EMR-Technique and Cerescope data

    NASA Astrophysics Data System (ADS)

    Hagag, Wael; Obermeyer, Hennes

    2016-09-01

    An active fault system has been detected along the Cairo-Suez district in northeastern Egypt, applying the EMR-Technique using Cerescope. The E-W (old Mediterranean) and NW-SE (Red Sea-Gulf of Suez) fault-trends are estimated to have ongoing activity. Horizontal EMR-measurements indicate a NW to NNW orientation as a maximum horizontal stress direction (σ1), whereas an E-W orientation to has a secondary tendency. A simplified stress map for the Cairo-Suez district is constructed from the horizontal stress data measured at about 20 locations within the district. The mapped stresses will contribute to the stress data of the Cairo-Suez region on the world stress map (WSM). The present study results indicate rejuvenation of the inherited Mesozoic E-W oriented and Oligocene-Miocene rift-related NW-SE oriented faults. The transfer of rift-related deformation from Red Sea-Gulf of Suez region, which is currently undergoing an extensional stress regime in NE to NNE direction, would explain a seismotectonic activity of the Cairo-Suez district. These results are consistent with a present day NNW oriented compressional stresses attributed to a convergence between the African and Eurasian plates.

  5. Surface Modification of Titanium with BMP-2/GDF-5 by a Heparin Linker and Its Efficacy as a Dental Implant

    PubMed Central

    Yang, Dae Hyeok; Moon, Sang Woong; Lee, Deok-Won

    2017-01-01

    In this study, we prepared human bone morphogenetic protein-2 (hBMP-2)/human growth and differentiation factor-5 (hGDF-5)-coated titanium (Ti) disc and screw types for controlled release of the growth factors (GFs). The two growth factors were coated onto Ti with a smooth surface using their specific interaction with heparin, because they have heparin binding sites in their molecular structures. Efficacy of the two growth factor-coated Ti for enhancement of bone formation and osseointegration was compared to pristine Ti, and hBMP-2- and hGDF-5-coated Ti in vivo. The surface chemical composition, surface morphology, and wettability characteristics of the metal samples were determined by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and contact angle measurement, respectively. The initial burst of hBMP-2, hGDF-5, and their combination, occurred within one day of the release study, resulting in 12.5%, 4.5%, and 13.5%/3.2%, and then there was a sustained, even release of these two growth factors from the coated metal for 30 days. In vitro tests revealed that MC3T3-E1 cells cultured on the two growth factor-coated Ti had a higher proliferation rate and a higher activity for alkaline phosphatase (ALP), which led to a larger amount of calcium deposition and larger expressions of type I collagen (COL 1), ALP, and osteocalcin (OCN) mRNAs. In vivo animal tests using ten white New Zealand rabbits showed that the two growth factor-coated Ti enhanced bone formation and osseointegration at the interface between the implants and host bone. In addition, histological evaluation showed that bone remodeling, including bone formation by osteoblasts and bone resorption by osteoclasts, actively occurred between the two growth factor-coated Ti and host bone. Consequently, it is suggested that Ti surface modification with the combination of hBMP-2 and hGDF-5 for the two growth factor-coated Ti implants can improve the clinical properties of implants for

  6. GDF-15 secreted from human umbilical cord blood mesenchymal stem cells delivered through the cerebrospinal fluid promotes hippocampal neurogenesis and synaptic activity in an Alzheimer's disease model.

    PubMed

    Kim, Dong Hyun; Lee, Dahm; Chang, Eun Hyuk; Kim, Ji Hyun; Hwang, Jung Won; Kim, Ju-Yeon; Kyung, Jae Won; Kim, Sung Hyun; Oh, Jeong Su; Shim, Sang Mi; Na, Duk Lyul; Oh, Wonil; Chang, Jong Wook

    2015-10-15

    Our previous studies demonstrated that transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the hippocampus of a transgenic mouse model of Alzheimer's disease (AD) reduced amyloid-β (Aβ) plaques and enhanced cognitive function through paracrine action. Due to the limited life span of hUCB-MSCs after their transplantation, the extension of hUCB-MSC efficacy was essential for AD treatment. In this study, we show that repeated cisterna magna injections of hUCB-MSCs activated endogenous hippocampal neurogenesis and significantly reduced Aβ42 levels. To identify the paracrine factors released from the hUCB-MSCs that stimulated endogenous hippocampal neurogenesis in the dentate gyrus, we cocultured adult mouse neural stem cells (NSCs) with hUCB-MSCs and analyzed the cocultured media with cytokine arrays. Growth differentiation factor-15 (GDF-15) levels were significantly increased in the media. GDF-15 suppression in hUCB-MSCs with GDF-15 small interfering RNA reduced the proliferation of NSCs in cocultures. Conversely, recombinant GDF-15 treatment in both in vitro and in vivo enhanced hippocampal NSC proliferation and neuronal differentiation. Repeated administration of hUBC-MSCs markedly promoted the expression of synaptic vesicle markers, including synaptophysin, which are downregulated in patients with AD. In addition, in vitro synaptic activity through GDF-15 was promoted. Taken together, these results indicated that repeated cisterna magna administration of hUCB-MSCs enhanced endogenous adult hippocampal neurogenesis and synaptic activity through a paracrine factor of GDF-15, suggesting a possible role of hUCB-MSCs in future treatment strategies for AD.

  7. Marine integrons containing novel integrase genes, attachment sites, attI, and associated gene cassettes in polluted sediments from Suez and Tokyo Bays.

    PubMed

    Elsaied, Hosam; Stokes, Hatch W; Kitamura, Keiko; Kurusu, Yasurou; Kamagata, Yoichi; Maruyama, Akihiko

    2011-07-01

    In order to understand the structure and biological significance of integrons and associated gene cassettes in marine polluted sediments, metagenomic DNAs were extracted from sites at Suez and Tokyo Bays. PCR amplicons containing new integrase genes, intI, linked with novel gene cassettes, were recovered and had sizes from 1.8 to 2.5 kb. This approach uncovered, for the first time, the structure and diversity of both marine integron attachment site, attI, and the first gene cassette, the most efficiently expressed integron-associated gene cassette. The recovered 13 and 20 intI phylotypes, from Suez and Tokyo Bay samples, respectively, showed a highly divergence, suggesting a difference in integron composition between the sampling sites. Some intI phylotypes showed similarity with that from Geobacter metallireducens, belonging to Deltaproteobacteria, the dominant class in both sampling sites, as determined by 16S rRNA gene analysis. Thirty distinct families of putative attI site, as determined by the presence of an attI-like simple site, were recovered. A total of 146 and 68 gene cassettes represented Suez and Tokyo Bay unsaturated cassette pools, respectively. Gene cassettes, including a first cassette, from both sampling sites encoded two novel families of glyoxalase/bleomycin antibiotic-resistance protein. Gene cassettes from Suez Bay encoded proteins similar to haloacid dehalogenases, protein disulfide isomerases and death-on-curing and plasmid maintenance system killer proteins. First gene cassettes from Tokyo Bay encoded a xenobiotic-degrading protein, cardiolipin synthetase, esterase and WD40-like β propeller protein. Many of the first gene cassettes encoded proteins with no ascribable function but some of them were duplicated and possessed signal functional sites, suggesting efficient adaptive functions to their bacterial sources. Thus, each sampling site had a specific profile of integrons and cassette types consistent with the hypothesis that the

  8. Controls on the development and evolution of transfer zones: the influence of basement structure and sedimentary thickness in the Suez rift and Red Sea

    NASA Astrophysics Data System (ADS)

    Moustafa, Adel R.

    1997-06-01

    Detailed field mapping of the northern part of the Gebel Um Hammad-Gebel Duwi area on the western margin of the Red Sea indicates oppositely dipping rift blocks separated by a 60-km long, WNW-ESE-oriented, reactivated pre-rift fault of Late Precambrian age parallel to the Najd fault system of the Arabian-Nubian Shield. This fault forms the Sudmain transfer zone between the oppositely tilted half-grabens in the northwestern Red Sea region and is associated by a SE-plunging syncline. This pre-rift fault was reactivated by dextral transtension during the Late Oligocene rift opening. Compared to the transfer zones of the Suez rift, the Sudmain transfer zone is narrower. The Gebel Sufr El Dara transfer zone (between the southern and central half-grabens of the Suez rift) is 20 km wide and is also controlled by pre-rift faults oriented ENE-WSW. The latter were reactivated by left-lateral slip during the rift opening. On the other hand, the Gharandal transfer zone (northern part of the Suez rift) is 40-60 km wide and is not affected by the pre-rift faults in the Precambrian basement, perhaps owing to the large thickness of pre-rift sedimentary rocks in this area. The location of the Gharandal transfer zone was controlled by a NE-SW-oriented 'Syrian arc' fold. This study suggests that the northward increase in the width of transfer zones as well as the northward decrease in the length of half-grabens in the Suez-northern Red Sea rift system are related to the corresponding increase in the thickness of pre-rift Phanerozoic sedimentary section from about 400 m in the south to about 1800 m in the north.

  9. Modulation of stress related protein genes in the bass (Epinephelus guaza) caught from the Gulf of Suez, the Red Sea, Egypt.

    PubMed

    Abdel-Gawad, Fagr Kh; Khalil, Wagdy K B

    2013-10-01

    Impact of chemical pollution on expression of stress protein genes in the bass Epinephelus guaga collected from several locations including Suez Oil Production Port (Floating port), Atakah Fishing Port, Adabiya Port and Tawfik Port in Suez Governorate, Egypt, was investigated. In the current study, levels of polycyclic aromatic hydrocarbons (PAHs) in water and fish samples collected from Suez Gulf were assessed. In addition, gills and liver tissues of caught bass fish were used to address the interaction between pollution status and the expression of stress-related genes (Hsp70a, Hsp70b, Hsp47, MT and CYP1A). Our analysis demonstrated that levels of PAHs in Floating and Tawfik ports were higher than those found in the Atakah Fishing Port and the Adabiya Port. In addition, MDA and PC contents were significantly higher in gills and liver tissues collected from Floating and Tawfik ports than those collected from Adabiya and Atakah ports. In correlation to the above results, all fish collected from the Floating and Tawfik ports presented a significant increase in Hsp-, MT- and CYP1A-mRNAs. On the other hand, fish samples collected from the Atakah Fishing and Adabiya ports showed no induction of the stress-related genes transcription in such tissues. In conclusion, the current research demonstrates that remarkable increase in PAH contaminants levels in Floating and Tawfik ports are correlated with the levels stress protein-related genes transcription in E. guaga gills and liver tissues. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Macrophage PPARγ, a Lipid Activated Transcription Factor Controls the Growth Factor GDF3 and Skeletal Muscle Regeneration.

    PubMed

    Varga, Tamas; Mounier, Rémi; Patsalos, Andreas; Gogolák, Péter; Peloquin, Matthew; Horvath, Attila; Pap, Attila; Daniel, Bence; Nagy, Gergely; Pintye, Eva; Póliska, Szilárd; Cuvellier, Sylvain; Larbi, Sabrina Ben; Sansbury, Brian E; Spite, Matthew; Brown, Chester W; Chazaud, Bénédicte; Nagy, Laszlo

    2016-11-15

    Tissue regeneration requires inflammatory and reparatory activity of macrophages. Macrophages detect and eliminate the damaged tissue and subsequently promote regeneration. This dichotomy requires the switch of effector functions of macrophages coordinated with other cell types inside the injured tissue. The gene regulatory events supporting the sensory and effector functions of macrophages involved in tissue repair are not well understood. Here we show that the lipid activated transcription factor, PPARγ, is required for proper skeletal muscle regeneration, acting in repair macrophages. PPARγ controls the expression of the transforming growth factor-β (TGF-β) family member, GDF3, which in turn regulates the restoration of skeletal muscle integrity by promoting muscle progenitor cell fusion. This work establishes PPARγ as a required metabolic sensor and transcriptional regulator of repair macrophages. Moreover, this work also establishes GDF3 as a secreted extrinsic effector protein acting on myoblasts and serving as an exclusively macrophage-derived regeneration factor in tissue repair. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. WHITE UPCONVERSION LUMINESCENCE FROM (Yb3+/Tm3+/Ho3+) TRIDOPED GdF3 NANORODS AFTER HEAT TREATMENT

    NASA Astrophysics Data System (ADS)

    Guo, Linna; Wang, Yuhua; Zhang, Jia; Wang, Yanzhao; Dong, Pengyu

    2012-09-01

    A series of Ho3+/Yb3+/Tm3+ tridoped GdF3 nanorods with different dopant concentrations were synthesized by a hydrothermal method. Transmission electron microscope (TEM) images indicate that the length and diameter of the nanorods is about 90 nm and 31 nm, respectively on average. No bright white upconversion light was observed from the samples with different Yb3+, Ho3+ or Tm3+ concentrations. Unexpectedly, the emission color coordinates of the samples after heat treatment move toward the central white region of the chromaticity diagram, and among these samples, the color coordinate (0.349, 0.329) of GdF3:15% Yb3+, 0.1% Ho3+, 0.8% Tm3+ is the most close to the standard white light (0.333, 0.333). This is unlike previous reports in which white light was achieved via tuning dopant concentration or excitation power. The reasons for the above phenomenon are presented by means of FT-IR spectra and the energy level diagram of dopants.

  12. Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

    PubMed

    Palles, Claire; Chegwidden, Laura; Li, Xinzhong; Findlay, John M; Farnham, Garry; Castro Giner, Francesc; Peppelenbosch, Maikel P; Kovac, Michal; Adams, Claire L; Prenen, Hans; Briggs, Sarah; Harrison, Rebecca; Sanders, Scott; MacDonald, David; Haigh, Chris; Tucker, Art; Love, Sharon; Nanji, Manoj; deCaestecker, John; Ferry, David; Rathbone, Barrie; Hapeshi, Julie; Barr, Hugh; Moayyedi, Paul; Watson, Peter; Zietek, Barbara; Maroo, Neera; Gay, Laura; Underwood, Tim; Boulter, Lisa; McMurtry, Hugh; Monk, David; Patel, Praful; Ragunath, Krish; Al Dulaimi, David; Murray, Iain; Koss, Konrad; Veitch, Andrew; Trudgill, Nigel; Nwokolo, Chuka; Rembacken, Bjorn; Atherfold, Paul; Green, Elaine; Ang, Yeng; Kuipers, Ernst J; Chow, Wu; Paterson, Stuart; Kadri, Sudarshan; Beales, Ian; Grimley, Charles; Mullins, Paul; Beckett, Conrad; Farrant, Mark; Dixon, Andrew; Kelly, Sean; Johnson, Matthew; Wajed, Shahjehan; Dhar, Anjan; Sawyer, Elinor; Roylance, Rebecca; Onstad, Lynn; Gammon, Marilie D; Corley, Douglas A; Shaheen, Nicholas J; Bird, Nigel C; Hardie, Laura J; Reid, Brian J; Ye, Weimin; Liu, Geoffrey; Romero, Yvonne; Bernstein, Leslie; Wu, Anna H; Casson, Alan G; Fitzgerald, Rebecca; Whiteman, David C; Risch, Harvey A; Levine, David M; Vaughan, Tom L; Verhaar, Auke P; van den Brande, Jan; Toxopeus, Eelke L; Spaander, Manon C; Wijnhoven, Bas P L; van der Laan, Luc J W; Krishnadath, Kausilia; Wijmenga, Cisca; Trynka, Gosia; McManus, Ross; Reynolds, John V; O'Sullivan, Jacintha; MacMathuna, Padraic; McGarrigle, Sarah A; Kelleher, Dermot; Vermeire, Severine; Cleynen, Isabelle; Bisschops, Raf; Tomlinson, Ian; Jankowski, Janusz

    2015-02-01

    Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. Granulosa cell tumor mutant FOXL2C134W suppresses GDF-9 and activin A-induced follistatin transcription in primary granulosa cells

    PubMed Central

    McTavish, Kirsten J.; Nonis, David; Hoang, Yvonne D.; Shimasaki, Shunichi

    2013-01-01

    A single somatic FOXL2 mutation (FOXL2C134W) was identified in almost all granulosa cell tumor (GCT) patients. In the pituitary, FOXL2 and Smad3 coordinately regulate activin stimulation of follistatin transcription. We explored whether a similar regulation occurs in the ovary, and whether FOXL2C134W has altered activity. We show that in primary granulosa cells, GDF-9 and activin increase Smad3-mediated follistatin transcription. In contrast to findings in the pituitary, FOXL2 negatively regulates GDF-9 and activin-stimulated follistatin transcription in the ovary. Knockdown of endogenous FOXL2 confirmed this inhibitory role. FOXL2C134W displayed enhanced inhibitory activity, completely ablating GDF-9 and activin-induced follistatin transcription. GDF-9 and activin activity was lost when either the smad binding element or the forkhead binding element were mutated, indicating that both sites are required for Smad3 actions. This study highlights that FOXL2 negatively regulates follistatin expression within the ovary, and that the pathogenesis of FOXL2C134W may involve an altered interaction with Smad3. PMID:23567549

  14. A New Subtype of Multiple Synostoses Syndrome Is Caused by a Mutation in GDF6 That Decreases Its Sensitivity to Noggin and Enhances Its Potency as a BMP Signal

    PubMed Central

    Wang, Jian; Yu, Tingting; Wang, Zhigang; Ohte, Satoshi; Yao, Ru-en; Zheng, Zhaojing; Geng, Juan; Cai, Haiqing; Ge, Yihua; Li, Yuchan; Xu, Yunlan; Zhang, Qinghua; Gusella, James F; Fu, Qihua; Pregizer, Steven; Rosen, Vicki; Shen, Yiping

    2017-01-01

    Growth and differentiation factors (GDFs) are secreted signaling molecules within the BMP family that have critical roles in joint morphogenesis during skeletal development in mice and humans. Using genetic data obtained from a six-generation Chinese family, we identified a missense variant in GDF6 (NP_001001557.1; p.Y444N) that fully segregates with a novel autosomal dominant synostoses (SYNS) phenotype, which we designate as SYNS4. Affected individuals display bilateral wrist and ankle deformities at birth and progressive conductive deafness after age 40 years. We find that the Y444N variant affects a highly conserved residue of GDF6 in a region critical for binding of GDF6 to its receptor(s) and to the BMP antagonist NOG, and show that this mutant GDF6 is a more potent stimulator of the canonical BMP signaling pathway compared with wild-type GDF6. Further, we determine that the enhanced BMP activity exhibited by mutant GDF6 is attributable to resistance to NOG-mediated antagonism. Collectively, our findings indicate that increased BMP signaling owing to a GDF6 gain-of-function mutation is responsible for loss of joint formation and profound functional impairment in patients with SYNS4. More broadly, our study highlights the delicate balance of BMP signaling required for proper joint morphogenesis and reinforces the critical role of BMP signaling in skeletal development. PMID:26643732

  15. Caprellidae (Crustacea: Peracarida: Amphipoda) from the Red Sea and Suez Canal, with the redescription of Metaprotella africana and Paradeutella multispinosa.

    PubMed

    Zeina, Amr F; Guerra-García, José M

    2016-04-06

    The Caprellidae from the Red Sea are reviewed based on the literature data and new collections from the Hurghada coasts. So far, only six valid species has been reported from the Red Sea and Suez Canal: Caprella equilibra Say, 1818, Hemiaegina minuta Mayer, 1890, Metaprotella africana Mayer, 1903, Paracaprella pusilla Mayer, 1890 and Paradeutella multispinosa Schellenberg, 1928 and Pseudocaprellina pambanensis Sundara Raj, 1927. The type material of M. africana (deposited in the Muséum nacional d'Histoire naturelle, Paris) and Paradeutella multispinosa (deposited in the Museum für Naturkunde, Berlin) are redescribed and illustrated in detail. P. pambanensis and H. minuta were the most abundant species in the collections along the northern coast. Most of the sampling effort has been focused on algae from shallow waters; additional substrates such as sediments, hydroids and coral rubble, especially from areas deeper than 15 meters should be explored. The number of caprellid species in the Red Sea is low compared to adjacent waters, as the Mediterranean Sea. However, further research and more extensive caprellid collections should be conducted along the coasts of Saudi Arabia, Yemen, Sudan and Eritrea, which are still unexplored.

  16. Evolution of Miocene footwall-derived coarse-grained deltas, Gulf of Suez, Egypt: Implications for exploration

    SciTech Connect

    Gawthorpe, R.L. ); Hurst, J.M.; Sladen, C.P. )

    1990-07-01

    The Miocene Abu Alaqa Group, exposed on the eastern side of the Gulf of Suez, contains a series of coarse-grained delta deposits located in the hanging wall of the northwest-trending East Margin fault zone. Seven major fan sequences have been identified. The first three fan sequences are aggradational and cover an area of less than 2 km{sup 2}. The sequences are dominated by pebble/boulder conglomerates, with predominantly sigmoidal, high-angle clinoforms (between 15 and 25{degree}) as much as 150 m high. These fan sequences represent talus cones and fan deltas, which were probably deposited during activity on the fault zone and are situated at transfer segments. The other four fan sequences are predominantly progradational, consisting of mixed carbonate-siliciclastic braid deltas with local reefs. They are less than 30 m high, have low-angle clinoforms (< 15{degree}), and cover an area as large as 30 km{sup 2}. These fan sequences were deposited during a phase of tectonic quiescence when sedimentary and eustatic mechanisms determined sand-body geometry. These fan deltas and braid deltas may form hydrocarbon traps in the subsurface and create localized reservoirs. The rapid facies change into basinal fines creates an excellent lateral stratigraphic seal, but vertical and lateral seals across the fault zone generally are not well developed. 8 figs.

  17. The contribution of gravity method in geothermal exploration of southern part of the Gulf of Suez-Sinai region, Egypt

    NASA Astrophysics Data System (ADS)

    Atef, H.; Abd El-Gawad, A. M. S.; Abdel Zaher, M.; Farag, K. S. I.

    2016-06-01

    The Gulf of Suez region represents the most promising area in Egypt for geothermal exploration which is characterized by superficial thermal manifestations represented by a cluster of hot springs with varying temperatures from 35 to 72 °C. The main purpose of the present study was to shed the light on the integration between gravity work and geothermal data in detecting the main subsurface structures in addition to expecting the geothermal sources in the area under consideration. Correction was applied on the bottom hole temperature data to obtain the true formation equilibrium temperatures that can provide useful information about the subsurface thermal regime. Based on these logging data, temperature gradient and heat flow values were computed at each well, and it is found that the mean geothermal gradient of the study area is 32 °C/km; nevertheless, some local geothermal potential fields were located with more than 40 °C/km. Also, heat flow values are ranging from 45 to 115 mW/m2. The Bouguer anomaly map of the study area was used for delineating the subsurface structures and tectonic trends that have resulted in a potential heat source. The gravity inversion revealed a good correlation between areas of high temperature gradients, high heat flow and positive gravity anomalies. The high temperature gradient and heat flow values suggested being associated with a noticeable hydrothermal source of heat anomaly located at relatively shallow depths which is expected to be due to the uplift of the basement in the area.

  18. Maastrichtian-Early Eocene litho-biostratigraphy and palægeography of the northern Gulf of Suez region, Egypt

    NASA Astrophysics Data System (ADS)

    Scheibner, C.; Marzouk, A. M.; Kuss, J.

    2001-02-01

    The Maastrichtian-Lower Eocene sediments on both sides of the northern Gulf of Suez can be subdivided into eight formal formations (including one group) and one informal formation that are described in detail. These lithostratigraphic units reflect three different environmental regimes of deposition or non-deposition. The first regime is characterised by uplift and erosion or non-deposition resulting mostly from the uplift of the Northern Galala/Wadi Araba structure, a branch of the Syrian Arc Foldbelt. The shallow water carbonate platform and slope deposits of the Late Campanian-Maastrichtian St Anthony Formation and the Paleocene-Lower Eocene Southern Galala and Garra Formations represent the second regime and are found north and south of the Northern Galala/Wadi Araba High. The third regime is represented by basinal chalks, marls and shales of the Maastrichtian Sudr Formation and of the Paleocene-Eocene Dakhla, Tarawan and Esna Formations, the Dakhla/Tarawan/Esna informal formation and the Thebes Group. The distribution and lateral interfingering of the above mentioned environmental regimes reflect different vertical movements, changing basin morphology, sea level changes and progradation of shallow water sediments and is illustrated on 11 palæogeographic maps.

  19. Reservoir zonation based on statistical analyses: A case study of the Nubian sandstone, Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    El Sharawy, Mohamed S.; Gaafar, Gamal R.

    2016-12-01

    Both reservoir engineers and petrophysicists have been concerned about dividing a reservoir into zones for engineering and petrophysics purposes. Through decades, several techniques and approaches were introduced. Out of them, statistical reservoir zonation, stratigraphic modified Lorenz (SML) plot and the principal component and clustering analyses techniques were chosen to apply on the Nubian sandstone reservoir of Palaeozoic - Lower Cretaceous age, Gulf of Suez, Egypt, by using five adjacent wells. The studied reservoir consists mainly of sandstone with some intercalation of shale layers with varying thickness from one well to another. The permeability ranged from less than 1 md to more than 1000 md. The statistical reservoir zonation technique, depending on core permeability, indicated that the cored interval of the studied reservoir can be divided into two zones. Using reservoir properties such as porosity, bulk density, acoustic impedance and interval transit time indicated also two zones with an obvious variation in separation depth and zones continuity. The stratigraphic modified Lorenz (SML) plot indicated the presence of more than 9 flow units in the cored interval as well as a high degree of microscopic heterogeneity. On the other hand, principal component and cluster analyses, depending on well logging data (gamma ray, sonic, density and neutron), indicated that the whole reservoir can be divided at least into four electrofacies having a noticeable variation in reservoir quality, as correlated with the measured permeability. Furthermore, continuity or discontinuity of the reservoir zones can be determined using this analysis.

  20. Trace metals in water, sediments and marine organisms from the northern part of the Gulf of Suez, Red Sea

    NASA Astrophysics Data System (ADS)

    El-Moselhy, Khalid Mohamed; Gabal, Mahmoud Nageib

    2004-05-01

    Concentrations of Cd, Pb, Cu and Zn were determined in water, sediments, gastropod ( Bulla umpulla) and green algae ( Ulva lactuca) collected from five stations in the western side of the northern part of the Gulf of Suez during the period February 1993-January 1994. Sediments recorded the highest concentrations of Cd (2.26-4.40 μg/g) and Pb (13.90-28.34 μg/g), While the highest concentrations of the essential metals Cu and Zn were found in B. umpulla (28.19-72.04 and 60.24-108.74 μg/g, respectively). Water and sediments showed similar spatial distribution patterns for the highest mean values of the different metals. Highest values of the studied metals were found at stations influenced by various pollution sources such as harbours, and sewage and industrial drains. In contrast, the lowest concentrations were observed faraway from any pollution source. Calculations of concentration factors (C.F.) for gastropod and algae showed highest C.F. of Cd (4312.5-8705.9) and Pb (2103.3-8317.9) in algae, and highest C.F. of Cu (5288.9-42376.5) and Zn (3686.7-9631.5) in gastropod.

  1. Definition of soil characteristics and ground response at the northwestern part of the Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Adel, M. E. Mohamed; Deif, A.; El-Hadidy, S.; Moustafa Sayed, S. R.; El Werr, A.

    2008-12-01

    The area of interest represents the industrial part of Ain El-Sokhna new port, located in the northwestern part of the seismically active Gulf of Suez zone. The main objective of the current study is to estimate the site characteristics of the area of interest in terms of the fundamental frequency and the corresponding peak amplitude using noise measurements. The microtremor measurements were performed at 44 sites distributed over the study area in order to calculate the horizontal-to-vertical (H/V) spectral ratio. The standard spectral ratio (SSR) is used in addition to the numerical modelling of horizontal shear (SH) waves in soil at selected sites in order to have a comparison with the H/V spectral ratio. The required 1D soil models for the numerical modelling of SH-waves were derived from 220 P-wave shallow seismic refraction profiles in addition to 30 SH-wave profiles. Maps of the fundamental frequency (f0) and its corresponding H/V peak amplitude (A0) were provided, and a range of site conditions in the area were shown. The amplification factor results derived from the SSR technique are very similar to those derived from the H/V spectral ratio. In most cases, the H/V spectral ratio proved to be suitable for calculating the fundamental resonance. Results were found to be compatible with the surface geology of the area of interest.

  2. Extension-related buttress-like folds, the western side of the Gulf of Suez rift, Egypt

    NASA Astrophysics Data System (ADS)

    Abu Sharib, A. S. A. A.; Abdel-Fattah, M. M.; Salama, Y. F.; Abdel-Gawad, G. I.

    2017-02-01

    The wedge-shaped St. Paul block, western side of the Gulf of Suez rift, exposes Late Cretaceous beds that are folded into transverse folds. The block is bounded from the east and west by east- and southeast-dipping rift-related normal faults, respectively. This study reveals that the transverse folds are extension-related, and formed due to the buttress-like effect that was created during the movement along the rift-related normal faults. The more competent Eocene hanging-wall block of the N-S-striking fault buttressed against the moving less competent Cretaceous hanging-wall block of the NE-SW-striking fault. A localized zone of shortening developed between the two fault trends causing the intervening wedge-shaped block to be crumpled and folded into a series of kilometer-scale, gentle SSE-plunging folds. The buttressing, within block internal localized strain caused by the zigzag geometry of the NE-SW-striking fault, and the effect of the minor cross fault explain the SSE-to-ESE plunges of the mesoscopic folds. This study turns the attention to the buttress-like effect as one of the mechanisms of extension-related folds during rifting.

  3. Q-values for P and S waves in Southern Sinai and Southern Gulf of Suez Region, Egypt

    NASA Astrophysics Data System (ADS)

    Mohamed, Gad-Elkareem A.

    2014-05-01

    The quality factor Q has been estimated using spectral amplitudes of P and S waves from earthquakes recorded by the seismic network of the Egyptian National Seismological Network (ENSN) in southern Sinai and southern Gulf of Suez region. The earthquakes recorded at nine stations - DHA, NUB, TR1, TR2, KAT, SH2, GRB, HRG and SFG have been used in this study. The spectral amplitude ratios have been calculated between 2 - 20 Hz and single station spectral ratio method has been applied for this purpose. The results show that the quality factors for both P and S waves (Qp and Qs) increase as a function of frequency according to law the Q = Q0fn. By averaging the estimated Q- Value obtained at all stations we calculated the average attenuation laws: Qp = (13.15± 0.76) f0.95± 0.19 and Qs = (20.05± 0.79) f1.03±0.04 for P and S waves respectively. These relations are useful for the estimation of source parameters of earthquakes and simulation of earthquake strong ground motions. The QS /QP ratio for KAT station is less than 1 at lower frequencies, whereas at HRG and SH2 stations QS /QP ratio is are greater than 1.

  4. Research Publications in Medical Journals (1992-2013) by Family Medicine Authors - Suez Canal University-Egypt

    PubMed Central

    Abdulmajeed, Abdulmajeed A.; Ismail, Mosleh A.; Nour-Eldein, Hebatallah

    2014-01-01

    Background: Research in family medicine (FM) provides an important contribution to its discipline. Family medicine research can contribute to many areas of primary care, ranging from the early diagnosis to equitable health care. Publication productivity is important in academic settings as a marker for career advancement. Objective: To describe the publications by family medicine researcher authors between 1992 and 2013. Materials and Methods: All full text, original articles published by family medicine researcher; author with affiliation to the Suez Canal University were collected using the internet and hand search. The journals that published for family medicine researcher authors were identified. Author characteristics were described. The trend of publications was described. All articles were analyzed for their characteristics, including the themes and study designs according to predefined criteria. Results: Along 22 years, 149 research articles were published by 48 family medicine authors in 39 medical journals. The largest category in publications was related to Family physician/Health service (FP-HS, n = 52 articles), followed by ‘Patient’ category (n = 42). All the studies were quantitative; the largest group was represented by cross-sectional studies (76.5%). Conclusions: The publication productivity by family medicine researchers are going to be increased. FP-HS and patient topics were mostly addressed in publications. Cross-sectional studies exceeded any other designs. There is need to put more emphasis on intervention studies. Continuous assessment and improvement of FM research production and publication is recommended. PMID:25657945

  5. Regulation of α5 and αV Integrin Expression by GDF-5 and BMP-7 in Chondrocyte Differentiation and Osteoarthritis

    PubMed Central

    Garciadiego-Cázares, David; Aguirre-Sánchez, Hilda I.; Abarca-Buis, René F.; Kouri, Juan B.; Velasquillo, Cristina; Ibarra, Clemente

    2015-01-01

    The Integrin β1 family is the major receptors of the Extracellular matrix (ECM), and the synthesis and degradation balance of ECM is seriously disrupted during Osteoarthritis (OA). In this scenario, integrins modify their pattern expression and regulate chondrocyte differen-tiation in the articular cartilage. Members of the Transforming growth factor beta (Tgf-β) Su-perfamily, such as Growth differentiation factor 5 (Gdf-5) and Bone morphogenetic protein 7 (Bmp-7), play a key role in joint formation and could regulate the integrin expression during chondrocyte differentiation and osteoarthritis progression in an experimental OA rat model. Decrease of α5 integrin expression in articular cartilage was related with chondrocyte dedif-ferentiation during OA progression, while increase of α1, α2, and α3 integrin expression was related with fibrous areas in articular cartilage during OA. Hypertrophic chondrocytes expressedαV integrin and was increased in the articular cartilage of rats with OA. Integrin expression during chondrocyte differentiation was also analyzed in a micromass culture system of mouse embryo mesenchymal cells, micromass cultures was treated with Gdf-5 or Bmp-7 for 4 and 6 days, respectively. Gdf-5 induced the expression of theα5 sub-unit, while Bmp-7 induced the expression of the αV sub-unit. This suggests a switch in signaling for prehypertrophic chondrocyte differentiation towards hypertrophy, where Gdf-5 could maintain the articular chondrocyte phenotype and Bmp-7 would induce hypertrophy. Decrease of Ihh expression during late stages of OA in rat model suggest that the ossification in OA rat knees and endochondral ossification could be activated by Bmp-7 and αV integrin in absence of Ihh. Thus, chondrocyte phenotype in articular cartilage is similar to prehypetrophic chondrocyte in growth plate, and is preserved due to the presence of Indian hedgehog (Ihh), Gdf-5 and α5 integrin to maintain articular cartilage and prevent hy

  6. Regulation of α5 and αV Integrin Expression by GDF-5 and BMP-7 in Chondrocyte Differentiation and Osteoarthritis.

    PubMed

    Garciadiego-Cázares, David; Aguirre-Sánchez, Hilda I; Abarca-Buis, René F; Kouri, Juan B; Velasquillo, Cristina; Ibarra, Clemente

    2015-01-01

    The Integrin β1 family is the major receptors of the Extracellular matrix (ECM), and the synthesis and degradation balance of ECM is seriously disrupted during Osteoarthritis (OA). In this scenario, integrins modify their pattern expression and regulate chondrocyte differentiation in the articular cartilage. Members of the Transforming growth factor beta (Tgf-β) Superfamily, such as Growth differentiation factor 5 (Gdf-5) and Bone morphogenetic protein 7 (Bmp-7), play a key role in joint formation and could regulate the integrin expression during chondrocyte differentiation and osteoarthritis progression in an experimental OA rat model. Decrease of α5 integrin expression in articular cartilage was related with chondrocyte dedifferentiation during OA progression, while increase of α1, α2, and α3 integrin expression was related with fibrous areas in articular cartilage during OA. Hypertrophic chondrocytes expressed αV integrin and was increased in the articular cartilage of rats with OA. Integrin expression during chondrocyte differentiation was also analyzed in a micromass culture system of mouse embryo mesenchymal cells, micromass cultures was treated with Gdf-5 or Bmp-7 for 4 and 6 days, respectively. Gdf-5 induced the expression of the α5 sub-unit, while Bmp-7 induced the expression of the αV sub-unit. This suggests a switch in signaling for prehypertrophic chondrocyte differentiation towards hypertrophy, where Gdf-5 could maintain the articular chondrocyte phenotype and Bmp-7 would induce hypertrophy. Decrease of Ihh expression during late stages of OA in rat model suggest that the ossification in OA rat knees and endochondral ossification could be activated by Bmp-7 and αV integrin in absence of Ihh. Thus, chondrocyte phenotype in articular cartilage is similar to prehypetrophic chondrocyte in growth plate, and is preserved due to the presence of Indian hedgehog (Ihh), Gdf-5 and α5 integrin to maintain articular cartilage and prevent hypertrophy.

  7. Large-Scale Analysis of Association Between GDF5 and FRZB Variants and Osteoarthritis of the Hip, Knee, and Hand

    PubMed Central

    Evangelou, Evangelos; Chapman, Kay; Meulenbelt, Ingrid; Karassa, Fotini B.; Loughlin, John; Carr, Andrew; Doherty, Michael; Doherty, Sally; Gómez-Reino, Juan J.; Gonzalez, Antonio; Halldorsson, Bjarni V.; Hauksson, Valdimar B.; Hofman, Albert; Hart, Deborah J.; Ikegawa, Shiro; Ingvarsson, Thorvaldur; Jiang, Qing; Jonsdottir, Ingileif; Jonsson, Helgi; Kerkhof, Hanneke J. M.; Kloppenburg, Margreet; Lane, Nancy E.; Li, Jia; Lories, Rik J.; van Meurs, Joyce B. J.; Näkki, Annu; Nevitt, Michael C.; Rodriguez-Lopez, Julio; Shi, Dongquan; Slagboom, P. Eline; Stefansson, Kari; Tsezou, Aspasia; Wallis, Gillian A.; Watson, Christopher M.; Spector, Tim D.; Uitterlinden, Andre G.; Valdes, Ana M.; Ioannidis, John P. A.

    2015-01-01

    Objective GDF5 and FRZB have been proposed as genetic loci conferring susceptibility to osteoarthritis (OA); however, the results of several studies investigating the association of OA with the rs143383 polymorphism of the GDF5 gene or the rs7775 and rs288326 polymorphisms of the FRZB gene have been conflicting or inconclusive. To examine these associations, we performed a large-scale meta-analysis of individual-level data. Methods Fourteen teams contributed data on polymorphisms and knee, hip, and hand OA. For rs143383, the total number of cases and controls, respectively, was 5,789 and 7,850 for hip OA, 5,085 and 8,135 for knee OA, and 4,040 and 4,792 for hand OA. For rs7775, the respective sample sizes were 4,352 and 10,843 for hip OA, 3,545 and 6,085 for knee OA, and 4,010 and 5,151 for hand OA, and for rs288326, they were 4,346 and 8,034 for hip OA, 3,595 and 6,106 for knee OA, and 3,982 and 5,152 for hand OA. For each individual study, sex-specific odds ratios (ORs) were calculated for each OA phenotype that had been investigated. The ORs for each phenotype were synthesized using both fixed-effects and random-effects models for allele-based effects, and also for haplotype effects for FRZB. Results A significant random-effects summary OR for knee OA was demonstrated for rs143383 (1.15 [95% confidence interval 1.09–1.22]) (P = 9.4 × 10−7), with no significant between-study heterogeneity. Estimates of effect sizes for hip and hand OA were similar, but a large between-study heterogeneity was observed, and statistical significance was borderline (for OA of the hip [P = 0.016]) or absent (for OA of the hand [P = 0.19]). Analyses for FRZB polymorphisms and haplotypes did not reveal any statistically significant signals, except for a borderline association of rs288326 with hip OA (P = 0.019). Conclusion Evidence of an association between the GDF5 rs143383 polymorphism and OA is substantially strong, but the genetic effects are consistent across different

  8. Analysis of the similar epicenter earthquakes on 22 January 2013 and 01 June 2013, Central Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Toni, Mostafa; Barth, Andreas; Ali, Sherif M.; Wenzel, Friedemann

    2016-09-01

    On 22 January 2013 an earthquake with local magnitude ML 4.1 occurred in the central part of the Gulf of Suez. Six months later on 1 June 2013 another earthquake with local magnitude ML 5.1 took place at the same epicenter and different depths. These two perceptible events were recorded and localized by the Egyptian National Seismological Network (ENSN) and additional networks in the region. The purpose of this study is to determine focal mechanisms and source parameters of both earthquakes to analyze their tectonic relation. We determine the focal mechanisms by applying moment tensor inversion and first motion analysis of P- and S-waves. Both sources reveal oblique focal mechanisms with normal faulting and strike-slip components on differently oriented faults. The source mechanism of the larger event on 1 June in combination with the location of aftershock sequence indicates a left-lateral slip on N-S striking fault structure in 21 km depth that is in conformity with the NE-SW extensional Shmin (orientation of minimum horizontal compressional stress) and the local fault pattern. On the other hand, the smaller earthquake on 22 January with a shallower hypocenter in 16 km depth seems to have happened on a NE-SW striking fault plane sub-parallel to Shmin. Thus, here an energy release on a transfer fault connecting dominant rift-parallel structures might have resulted in a stress transfer, triggering the later ML 5.1 earthquake. Following Brune's model and using displacement spectra, we calculate the dynamic source parameters for the two events. The estimated source parameters for the 22 January 2013 and 1 June 2013 earthquakes are fault length (470 and 830 m), stress drop (1.40 and 2.13 MPa), and seismic moment (5.47E+21 and 6.30E+22 dyn cm) corresponding to moment magnitudes of MW 3.8 and 4.6, respectively.

  9. Provenance, diagenesis, tectonic setting and reservoir quality of the sandstones of the Kareem Formation, Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Zaid, Samir M.

    2013-09-01

    The Middle Miocene Kareem sandstones are important oil reservoirs in the southwestern part of the Gulf of Suez basin, Egypt. However, their diagenesis and provenance and their impact on reservoir quality, are virtually unknown. Samples from the Zeit Bay Oil Field, and the East Zeit Oil Field represent the Lower Kareem (Rahmi Member) and the Upper Kareem (Shagar Member), were studied using a combination of petrographic, mineralogical and geochemical techniques. The Lower Rahmi sandstones have an average framework composition of Q95F3.4R1.6, and 90% of the quartz grains are monocrystalline. By contrast, the Upper Shagar sandstones are only slightly less quartzose with an average framework composition of Q76F21R3 and 82% of the quartz grains are monocrystalline. The Kareem sandstones are mostly quartzarenite with subordinate subarkose and arkose. Petrographical and geochemical data of sandstones indicate that they were derived from granitic and metamorphic terrains as the main source rock with a subordinate quartzose recycled sedimentary rocks and deposited in a passive continental margin of a syn rift basin. The sandstones of the Kareem Formation show upward decrease in maturity. Petrographic study revealed that dolomite is the dominant cement and generally occurs as fine to medium rhombs pore occluding phase and locally as a grain replacive phase. Authigenic quartz occurs as small euhedral crystals, locally as large pyramidal crystals in the primary pores. Authigenic anhydrites typically occur as poikilotopic rhombs or elongate laths infilling pores but also as vein filling cement. The kaolinite is a by-product of feldspar leaching in the presence of acidic fluid produced during the maturation of organic matter in the adjacent Miocene rocks. Diagenetic features include compaction; dolomite, silica and anhydrite cementation with minor iron-oxide, illite, kaolinite and pyrite cements; dissolution of feldspars, rock fragments. Silica dissolution, grain replacement and

  10. Facies and geologic history of an exposed Miocene rift-margin carbonate platform: Gulf of Suez, Egypt

    SciTech Connect

    James, N.P.; Coniglio, M.; Aissaoui, D.M.; Purser, B.H.

    1988-05-01

    Abu Shaar is a small exhumed carbonate platform of lower to middle Miocene age on a horst of Precambrian crystalline rock along the western side of the Gulf of Suez. The reef-rimmed complex is entirely dolomite but with exquisitely preserved primary and diagenetic microfabrics. Similar platforms, some of which contain hydrocarbons, are buried beneath evaporites in the Gulf. The platform developed in three stages, defined as local members of the Rudeis Formation. The first stage records deposition during progressive marine onlap as aprons of mixed terrigenous-carbonate sediments evolved into a wide reef-rimmed platform. Synsedimentary platform-margin collapse subsequently removed the most seaward portions of the reefs along the eastern Gulf-facing margin. These truncation surfaces were then covered by a second phase of reef growth and deposition of fore-reef carbonates. The third and final stage, deposited following a sea level drop and subaerial exposure, is a series of well-bedded peritidal carbonates that become progressively more evaporitic upward. Fore-reef facies are again truncated by synsedimentary slope failure. Former evaporites are now recorded as collapse breccias, contorted bedding, black chert nodules, and evaporite molds. Porosity is mainly secondary as vugs and molds and is highest in platform interior facies. These more porous sediments contained more aragonitic components originally and were less affected by submarine cementation. In contrast, the higher degree of synsedimentary lithification of platform-margin reef and fore-reef sediments is comparable with what is commonly observed in modern reef-dominated platform margins. 15 figures, 1 tables.

  11. Oil pollution in the Red Sea — Environmental monitoring of an oilfield in a coral area, Gulf of Suez

    NASA Astrophysics Data System (ADS)

    Dicks, Brian

    The Red Sea is rapidly developing as one of the world's largest offshore oil production areas. It also comprises a wide range of tropical marine habitats, many of which are internationally recognised for their conservation, scientific, economic or recreational value. Past oil production, refining and transport have resulted in chronic pollution of some areas, and environmental programmes to protect new areas of development from pollution damage are assuming increasing importance. At the initiative of an Egyptian oil company operating in the Gulf of Suez, an environmental protection and management scheme has been prepared for a new offshore oilfield and marine terminal at Ras Budran. This paper describes the form of the scheme and the results of its component environmental surveys. The development area comprises rich and diverse marine communities of fringing coral reefs, nearshore lagoons, seagrass beds, sandy beaches and fine sediments offshore. A baseline survey was designed following detailed discussion of the scope of the development with the company and a preliminary site visit, and the fieldwork was completed in October 1980. On the basis of the findings of the survey, a series of recommendations was made to the company, aimed at reducing environmental impacts during construction and operation to a minimum and acceptable level. These were subsequently implemented and the results of a post-construction survey in February 1983 are reported which show that environmental damage to the nearshore habitats during the construction phase had been relatively small and localised. Recently, the biological information obtained from the two surveys has also been incorporated into oil spill contingency plans.

  12. Provenance, diagenesis, tectonic setting and geochemistry of Rudies sandstone (Lower Miocene), Warda Field, Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Zaid, Samir M.

    2012-05-01

    The Lower Miocene Rudies sandstones are important oil reservoirs in the southeastern part, Gulf of Suez basin, Egypt. However, their provenance and diagenesis and their impact in reservoir quality, are virtually unknown. Samples from the Warda field, representing the Lower and Middle Rudies, were studied using a combination of petrographic, mineralogical and geochemical techniques. The Lower Rudies sandstones have an average framework composition of Q85F7.2R7.8, and 83% of the quartz grains are monocrystalline. By contrast, the Middle Rudies sandstones are only slightly more quartzose with an average framework composition of Q90F7R3 and 86% of the quartz grains are monocrystalline. Rudies sandstones are mostly quartz arenite with subordinate subarkose and sublithic arenites and their bulk-rock geochemistry support the petrographic results. The modal analysis data of studied samples suggest influence of granitic and metamorphic terrains as the main source rock with a subordinate quartzose recycled sedimentary rocks. The geochemical data interpretation on the basis of discriminate function diagrams reveal the source material was deposited on a passive margin. Textural attributes possibly suggest long-distance transport of grains from the source region and indicates a cratonic or a recycled source. Tectonic setting of Rudies Formation reveals that the lower Rudies sandstones are typically rift sandstone and their deposition constrained the beginning of the faulting, while the middle Rudies sandstones were transported from the far along the rift. Diagenetic features include compaction; dolomite, silica and anhydrite cementation with minor iron-oxide, illite, kaolinite and pyrite cements; dissolution of feldspars, rock fragments. Silica dissolution, grain replacement and carbonate dissolution greatly enhance the petrophysical properties of many sandstone samples.

  13. Molecular characterisation of growth differentiation factor 9 (gdf9) and bone morphogenetic protein 15 (bmp15) and their patterns of gene expression during the ovarian reproductive cycle in the European sea bass.

    PubMed

    Halm, S; Ibañez, A J; Tyler, C R; Prat, F

    2008-09-10

    Members of the transforming growth factor-beta superfamily, growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), have crucial roles in primary follicle growth in mammals. To initiate investigations into their significance in teleost oogenesis, we set out to clone and characterise the cDNAs of gdf9 and bmp15 and analysed their patterns of gene expression during the ovarian reproductive cycle in the European sea bass (Dicentrachus labrax). Sea bass gdf9 and bmp15 cDNAs were 2200 and 2049 bp long, coding for 438 and 459 amino acids (aas), respectively, and were most similar to zebrafish gdf9 and bmp15 (64.4 and 56.1%, respectively). By Northern analysis, sea bass gdf9 and bmp15 mRNA transcripts were detected in the ovary only of the tissues analysed and their sizes were 2.2 and 2.1 kb, respectively. Dot-blot analysis revealed high levels of gdf9 and bmp15 expression in the ovary during primary oocyte growth and previtellogenesis (July to October), with a significant decline at the onset of vitellogenesis (November) and remaining low until the beginning of new oocyte growth (April/May). There was a highly significant positive correlation (r=0.939) between gdf9 and bmp15 gene expression in individual samples. The high levels of gdf9 and bmp15 mRNA transcripts in the ovary, especially during the previtellogenic growth period suggest an important role for these factors in early primary oocyte growth in the European sea bass.

  14. Spectroscopic properties Eu 3+ doped and Tm 3+/Yb 3+ codoped oxyfluoride glass ceramics containing Ba 2GdF 7 nanocrystals

    NASA Astrophysics Data System (ADS)

    Zhao, Shilong; Xu, Shiqing; Deng, Degang; Wang, Huanping; Huang, Lihui; Fan, Xianping

    2010-07-01

    Transparent Eu 3+ doped and Tm 3+/Yb 3+ codoped oxyfluoride glass ceramics were prepared and spectroscopic properties were investigated. The XRD and TEM results demonstrated the formation of Ba 2GdF 7 nanocrystals, and the reduction of the ratio β between 5D0→7F2 and 5D0→7F1 transitions of Eu 3+ ions evidenced rare-earth ions incorporation into Ba 2GdF 7 nanocrystals. For Tm 3+/Yb 3+ codoped glass ceramic, unusual ultraviolet upconversion emissions from 6PJ→8S transition of Gd 3+ at 308 nm and 1D2→3H6, 1D2→3F4 and 1G4→3H6 transitions of Tm 3+ at 359 nm, 449 nm and 476 nm were observed under 980 nm excitation, respectively. And upconversion mechanism of Tm 3+-Yb 3-Gd 3++ system was analyzed.

  15. PEG-capped, lanthanide doped GdF3 nanoparticles: luminescent and T2 contrast agents for optical and MRI multimodal imaging

    NASA Astrophysics Data System (ADS)

    Passuello, Tiziana; Pedroni, Marco; Piccinelli, Fabio; Polizzi, Stefano; Marzola, Pasquina; Tambalo, Stefano; Conti, Giamaica; Benati, Donatella; Vetrone, Fiorenzo; Bettinelli, Marco; Speghini, Adolfo

    2012-11-01

    A facile method for the synthesis of water dispersible Er3+/Yb3+ and Tm3+/Yb3+ doped upconverting GdF3 nanoparticles is reported. Strong upconversion emissions are observed in the red (for Er/Yb doped) and near-infrared (for Tm/Yb doped) regions upon laser excitation at 980 nm. The PEG coating ensures a good dispersion of the system in water and reduces the radiationless de-excitation of the excited states of the Er3+ and Tm3+ ions by water molecules. The r2 relaxivity values are quite high with respect to the common T2-relaxing agents (22.6 +/- 3.4 mM-1 s-1 and 15.8 +/- 3.4 mM-1 s-1 for the Tm/Yb and Er/Yb doped samples, respectively), suggesting that the present NPs can be interesting as T2 weighted contrast agents for proton MRI purpose. Preliminary experiments conducted in vitro, in stem cell cultures, and in vivo, after subcutaneous injection of the lanthanide-doped GdF3 NPs, indicate scarce toxic effects. After an intravenous injection in mice, the GdF3 NPs localize mainly in the liver. The present results indicate that the present Er3+/Yb3+ and Tm3+/Yb3+ doped GdF3 NPs are suitable candidates to be efficiently used as bimodal probes for both in vitro and in vivo optical and magnetic resonance imaging.A facile method for the synthesis of water dispersible Er3+/Yb3+ and Tm3+/Yb3+ doped upconverting GdF3 nanoparticles is reported. Strong upconversion emissions are observed in the red (for Er/Yb doped) and near-infrared (for Tm/Yb doped) regions upon laser excitation at 980 nm. The PEG coating ensures a good dispersion of the system in water and reduces the radiationless de-excitation of the excited states of the Er3+ and Tm3+ ions by water molecules. The r2 relaxivity values are quite high with respect to the common T2-relaxing agents (22.6 +/- 3.4 mM-1 s-1 and 15.8 +/- 3.4 mM-1 s-1 for the Tm/Yb and Er/Yb doped samples, respectively), suggesting that the present NPs can be interesting as T2 weighted contrast agents for proton MRI purpose. Preliminary

  16. Ror2 signaling is required for local upregulation of GDF6 and activation of BMP signaling at the neural plate border.

    PubMed

    Schille, Carolin; Bayerlová, Michaela; Bleckmann, Annalen; Schambony, Alexandra

    2016-09-01

    The receptor tyrosine kinase Ror2 is a major Wnt receptor that activates β-catenin-independent signaling and plays a conserved role in the regulation of convergent extension movements and planar cell polarity in vertebrates. Mutations in the ROR2 gene cause recessive Robinow syndrome in humans, a short-limbed dwarfism associated with craniofacial malformations. Here, we show that Ror2 is required for local upregulation of gdf6 at the neural plate border in Xenopus embryos. Ror2 morphant embryos fail to upregulate neural plate border genes and show defects in the induction of neural crest cell fate. These embryos lack the spatially restricted activation of BMP signaling at the neural plate border at early neurula stages, which is required for neural crest induction. Ror2-dependent planar cell polarity signaling is required in the dorsolateral marginal zone during gastrulation indirectly to upregulate the BMP ligand Gdf6 at the neural plate border and Gdf6 is sufficient to rescue neural plate border specification in Ror2 morphant embryos. Thereby, Ror2 links Wnt/planar cell polarity signaling to BMP signaling in neural plate border specification and neural crest induction.

  17. Study on up-conversion emissions of Yb 3+/Tm 3+ co-doped GdF 3 and NaGdF 4

    NASA Astrophysics Data System (ADS)

    Cao, Chunyan; Qin, Weiping; Zhang, Jisen

    2010-02-01

    The Yb 3+/Tm 3+ co-doped GdF 3 and NaGdF 4 samples were synthesized through a combination method of a co-precipitation and an argon atmosphere annealing procedures. X-ray diffraction analysis indicated that the Yb 3+/Tm 3+ co-doped GdF 3 sample crystallized well and was orthorhombic phase, and the Yb 3+/Tm 3+ co-doped NaGdF 4 sample was hexagonal phase. With a 980-nm semiconductor continuous wave laser diode as the excitation source, the up-conversion emission spectra of the two samples in the wavelength range of 240-510 nm were recorded. In the up-conversion emissions of the samples, Yb 3+ transferred energies to Tm 3+ resulting in their ultraviolet, violet, and blue up-conversion emissions. And, Tm 3+ simultaneously transferred energies to Gd 3+, which finally resulted in ultraviolet up-conversion emissions of Gd 3+. The study on the excitation power dependence of up-conversion fluorescence intensity indicated that there were multi-photon (three-, four-, five-, and six-) processes in the up-conversion emissions of the samples. And the up-conversion emissions of Gd 3+ and Tm 3+ in the Yb 3+/Tm 3+ co-doped GdF 3 and NaGdF 4 samples were compared studied, too.

  18. GDF15(MIC1) H6D Polymorphism Does Not Influence Cardiovascular Disease in a Latin American Population with Rheumatoid Arthritis

    PubMed Central

    Amaya-Amaya, Jenny; Rojas-Villarraga, Adriana; Molano-Gonzalez, Nicolas; Montoya-Sánchez, Laura; Nath, Swapan K.; Anaya, Juan-Manuel

    2015-01-01

    Objective. Rheumatoid arthritis (RA) is the most common autoimmune arthropathy worldwide. The increased prevalence of cardiovascular disease (CVD) in RA is not fully explained by classic risk factors. The aim of this study was to determine the influence of rs1058587 SNP within GDF15(MIC1) gene on the risk of CVD in a Colombian RA population. Methods. This was a cross-sectional analytical study in which 310 consecutive Colombian patients with RA and 228 age- and sex-matched controls were included and assessed for variables associated with CVD. The mixed cluster methodology based on multivariate descriptive methods such as principal components analysis and multiple correspondence analyses and regression tree (CART) predictive model were performed. Results. Of the 310 patients, 87.4% were women and CVD was reported in 69.5%. Significant differences concerning GDF15 polymorphism were not observed between patients and controls. Mean arterial pressure, current smoking, and some clusters were significantly associated with CVD. Conclusion. GDF15 (rs1058587) does not influence the development of CVD in the population studied. PMID:26090487

  19. Anorexia-cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15.

    PubMed

    Tsai, V W W; Lin, S; Brown, D A; Salis, A; Breit, S N

    2016-02-01

    Anorexia-cachexia associated with cancer and other diseases is a common and often fatal condition representing a large area of unmet medical need. It occurs most commonly in advanced cancer and is probably a consequence of molecules released by tumour cells, or tumour-associated interstitial or immune cells. These may then act directly on muscle to cause atrophy and/or may cause anorexia, which then leads to loss of both fat and lean mass. Although the aetiological triggers for this syndrome are not well characterized, recent data suggest that MIC-1/GDF15, a transforming growth factor-beta superfamily cytokine produced in large amounts by cancer cells and as a part of other disease processes, may be an important trigger. This cytokine acts on feeding centres in the hypothalamus and brainstem to cause anorexia leading to loss of lean and fat mass and eventually cachexia. In animal studies, the circulating concentrations of MIC-1/GDF15 required to cause this syndrome are similar to those seen in patients with advanced cancer, and at least some epidemiological studies support an association between MIC-1/GDF15 serum levels and measures of nutrition. This article will discuss its mechanisms of central appetite regulation, and the available data linking this action to anorexia-cachexia syndromes that suggest it is a potential target for therapy of cancer anorexia-cachexia and conversely may also be useful for the treatment of severe obesity.

  20. Rac1 modulates the formation of primordial follicles by facilitating STAT3-directed Jagged1, GDF9 and BMP15 transcription in mice

    PubMed Central

    Zhao, Lihua; Du, Xinhua; Huang, Kun; Zhang, Tuo; Teng, Zhen; Niu, Wanbao; Wang, Chao; Xia, Guoliang

    2016-01-01

    The size of the primordial follicle pool determines the reproductive potential of mammalian females, and establishment of the pool is highly dependent on specific genes expression. However, the molecular mechanisms by which the essential genes are regulated coordinately to ensure primordial follicle assembly remain a mystery. Here, we show that the small GTPase Rac1 plays an indispensable role in controlling the formation of primordial follicles in mouse ovary. Employing fetal mouse ovary organ culture system, we demonstrate that disruption of Rac1 retarded the breakdown of germline cell cysts while Rac1 overexpression accelerated the formation of primordial follicles. In addition, in vivo inhibitor injection resulted in the formation of multi-oocyte follicles. Subsequent investigation showed that Rac1 induced nuclear import of STAT3 by physical binding. In turn, nuclear STAT3 directly activated the transcription of essential oocyte-specific genes, including Jagged1, GDF9, BMP15 and Nobox. Further, GDF9 and BMP15 regulated the translation of Notch2 via mTORC1 activation in pregranulosa cells. Overexression or addition of Jagged1, GDF9 and BMP15 not only reversed the effect of Rac1 disruption, but also accelerated primordial follicle formation via Notch2 signaling activation. Collectively, these results indicate that Rac1 plays important roles as a key regulator in follicular assembly. PMID:27050391

  1. Rac1 modulates the formation of primordial follicles by facilitating STAT3-directed Jagged1, GDF9 and BMP15 transcription in mice.

    PubMed

    Zhao, Lihua; Du, Xinhua; Huang, Kun; Zhang, Tuo; Teng, Zhen; Niu, Wanbao; Wang, Chao; Xia, Guoliang

    2016-04-06

    The size of the primordial follicle pool determines the reproductive potential of mammalian females, and establishment of the pool is highly dependent on specific genes expression. However, the molecular mechanisms by which the essential genes are regulated coordinately to ensure primordial follicle assembly remain a mystery. Here, we show that the small GTPase Rac1 plays an indispensable role in controlling the formation of primordial follicles in mouse ovary. Employing fetal mouse ovary organ culture system, we demonstrate that disruption of Rac1 retarded the breakdown of germline cell cysts while Rac1 overexpression accelerated the formation of primordial follicles. In addition, in vivo inhibitor injection resulted in the formation of multi-oocyte follicles. Subsequent investigation showed that Rac1 induced nuclear import of STAT3 by physical binding. In turn, nuclear STAT3 directly activated the transcription of essential oocyte-specific genes, including Jagged1, GDF9, BMP15 and Nobox. Further, GDF9 and BMP15 regulated the translation of Notch2 via mTORC1 activation in pregranulosa cells. Overexression or addition of Jagged1, GDF9 and BMP15 not only reversed the effect of Rac1 disruption, but also accelerated primordial follicle formation via Notch2 signaling activation. Collectively, these results indicate that Rac1 plays important roles as a key regulator in follicular assembly.

  2. Sedimentology of rift climax deep water systems; Lower Rudeis Formation, Hammam Faraun Fault Block, Suez Rift, Egypt

    NASA Astrophysics Data System (ADS)

    Leppard, Christopher W.; Gawthorpe, Rob L.

    2006-09-01

    In most marine rift basins, subsidence outpaces sedimentation during rift climax times. Typically this results in sediment-starved hangingwall depocentres dominated by deep-marine mudstones, with subordinate local development of coarser clastics in the immediate hangingwall derived from restricted catchments on the immediate footwall scarp. To highlight the spatial variability of rift climax facies and the controls upon them, we have investigated the detailed three-dimensional geometry and facies relationships of the extremely well exposed Miocene, rift climax Lower Rudeis Formation in the immediate hangingwall to the Thal Fault Zone, Suez Rift, Egypt. Detailed sedimentological analyses allows the Lower Rudeis Formation to be divided into two contemporaneous depositional systems, (1) a laterally continuous slope system comprising, hangingwall restricted (< 250 m wide) slope apron, slope slumps, fault scarp degradation complex and laterally extensive lower slope-to-basinal siltstones, and (2) a localized submarine fan complex up to 1 km wide and extending at least 2 km basinward of the fault zone. Interpretation of individual facies, facies relationships and their spatial variability indicate that deposition in the immediate hangingwall to the Thal Fault occurred via a range of submarine concentrated density flows, surge-like turbidity flows, mass wasting and hemipelagic processes. Major controls on the spatial variability and stratigraphic architecture of the depositional systems identified reflect the influence of the steep footwall physiography, accommodation and drainage evolution associated with the growth of the Thal Fault. The under-filled nature of the hangingwall depocentre combined with the steep footwall gradient result in a steep fault-controlled basin margin characterised by either slope bypass or erosion, with limited coastal plain or shelf area. Sediment supply to the slope apron deposits is controlled in part by the evolution and size of small

  3. Preparation and optimization of ceramic neutron image plates based on BaFBr : Eu2+ and GdF3

    NASA Astrophysics Data System (ADS)

    Kolb, R.; Zimmermann, J.; Schlapp, M.; Hesse, S.; von Seggern, H.

    2005-09-01

    Commercially available neutron image plates (NIPs) consist of a mixture of a powdered x-ray storage phosphor and a neutron converter, both embedded in an organic binder supported on a polymer sheet. The initiation of the storage mechanism in the phosphor is caused by conversion electrons generated in the neutron converter due to neutron absorption and activation and its subsequent decay. The organic binder phase just provides mechanical stability to the NIP but reduces its efficiency through two effects: first by the absorption of low energy electrons and second by introducing an inactive volume fraction to the layer. Avoiding the organic fraction, for example by preparing a ceramic NIP without binder, could increase the efficiency and spatial resolution without a loss in mechanical stability. In the following, two processes for preparation of ceramic NIPs are reported, both delivering ceramic NIPs consisting solely of GdF3, as the neutron converter and BaFBr : Eu2+, as the storage phosphor. The correlation between the sintering parameters and volume fraction of the neutron converter is investigated with respect to high efficiency and high spatial resolution. The generally observed antidromic behaviour between these two quantities was observed in this study also.

  4. Frequent sequence variation in the human myostatin (GDF8) gene as a marker for analysis of muscle-related phenotypes.

    PubMed

    Ferrell, R E; Conte, V; Lawrence, E C; Roth, S M; Hagberg, J M; Hurley, B F

    1999-12-01

    Myostatin is a recently identified member of the transforming growth factor-beta family of regulatory factors, also known as growth and differentiation factor 8 (GDF8). The nucleotide sequence of human myostatin was determined in 40 individuals. The invariant promoter contains a consensus MyoD binding site, and the coding sequence contains five missense substitutions in conserved amino acid residues (A55T, K153R, E164K, P198A, and I225T). Two of these, A55T in exon 1 and K153R in exon 2, are polymorphic in the general population with significantly different allele frequencies in Caucasians and African Americans (P < 0.001). Neither of the common polymorphisms had a significant impact on muscle mass response to strength training in either Caucasians or African Americans, although skewed allele frequencies preclude detection of small effects. These allelic variants provide markers for examining association between the myostatin gene and interindividual variation in muscle mass and differences in loss of muscle mass with aging.

  5. Deducing the subsurface geological conditions and structural framework of the NE Gulf of Suez area, using 2-D and 3-D seismic data

    NASA Astrophysics Data System (ADS)

    Zahra, Hesham Shaker; Nakhla, Adel Mokhles

    2015-06-01

    An interpretation of the seismic data of Ras Budran and Abu Zenima oil fields, northern central Gulf of Suez, is carried out to evaluate its subsurface tectonic setting. The structural configuration, as well as the tectonic features of the concerned area is criticized through the study of 2D and 3D seismic data interpretation with the available geological data, in which the geo-seismic depth maps for the main interesting levels (Kareem, Nukhul, Matulla, Raha and Nubia Formations) are depicted. Such maps reflect that, the Miocene structure of Ras Budran area is a nearly NE-SW trending anticlinal feature, which broken into several panels by a set of NWSE and NE-SW trending faults. The Pre-Miocene structure of the studied area is very complex, where Ras Budran area consists of step faults down stepping to the south and southwest, which have been subjected to cross faults of NE-SW trend with lateral and vertical displacements.

  6. Assessment of genetic diversity and relationships among Egyptian mango (Mangifera indica L.) cultivers grown in Suez Canal and Sinai region using RAPD markers.

    PubMed

    Mansour, Hassan; Mekki, Laila E; Hussein, Mohammed A

    2014-01-01

    DNA-based RAPD (Random Amplification of Polymorphic DNA) markers have been used extensively to study genetic diversity and relationships in a number of fruit crops. In this study, 10 (7 commercial mango cultivars and 3 accessions) mango genotypes traditionally grown in Suez Canal and Sinai region of Egypt, were selected to assess genetic diversity and relatedness. Total genomic DNA was extracted and subjected to RAPD analysis using 30 arbitrary 10-mer primers. Of these, eleven primers were selected which gave 92 clear and bright fragments. A total of 72 polymorphic RAPD bands were detected out of 92 bands, generating 78% polymorphisms. The mean PIC values scores for all loci were of 0.85. This reflects a high level of discriminatory power of a marker and most of these primers produced unique band pattern for each cultivar. A dendrogram based on Nei's Genetic distance co-efficient implied a moderate degree of genetic diversity among the cultivars used for experimentation, with some differences. The hybrid which had derived from cultivar as female parent was placed together. In the cluster, the cultivars and accessions formed separate groups according to bearing habit and type of embryo and the members in each group were very closely linked. Cluster analysis clearly showed two main groups, the first consisting of indigenous to the Delta of Egypt cultivars and the second consisting of indigenous to the Suez Canal and Sinai region. From the analysis of results, it appears the majority of mango cultivars originated from a local mango genepool and were domesticated later. The results indicated the potential of RAPD markers for the identification and management of mango germplasm for breeding purposes.

  7. Late Quaternary reorientation of stress field and extension direction in the southern Gulf of Suez, Egypt: Evidence from uplifted coral terraces, mesoscopic fault arrays, and borehold breakouts

    NASA Astrophysics Data System (ADS)

    Bosworth, William; Taviani, Marco

    1996-08-01

    Uplifted Pleistocene coral terraces and modern earthquakes show that several large normal faults are presently active in the southern Gulf of Suez rift basin. The footwall of one of these faults is exposed at Gebel el Zeit, where terraces at elevations of +10-18 and +42 m have been radiometrically dated as 125 ka and 426 ka, respectively. After correcting for eustatic sea-level changes, this results in net tectonic uplift rates of about 0.1 m/kyr. Published interpretations and our own observations indicate that the average extension direction during the Miocene to Pliocene synrift history was 055°. Analysis of borehole breakouts and published earthquake fault plane solutions, however, suggests that the present-day stress field in the southern Gulf has a 010°-020° Shmin orientation. Detailed structural observations show that a change in extension direction occurred in the late Pleistocene, with rotation of the stress field beginning prior to formation of the 125 ka terraces but after formation of older Pleistocene terraces whose ages are less tightly constrained. Using a horizontal slip direction of 015° and our observed net footwall uplift rate, we calculate a separation velocity between Sinai and Africa of 0.8-1.2 m/kyr. The proposed Pleistocene change in extension direction in the Gulf of Suez corresponds closely with the post-500 ka change in extension direction documented in the Kenyan rift system and a similar change in extension direction recorded in the central Red Sea. These regional similarities in tectonic history suggest that the underlying causes of these events may be a plate-scale phenomenon affecting the entire Afro-Arabian rift system, rather than local changes in the Quaternary stress field.

  8. Flawed Policy: Suez 1956

    DTIC Science & Technology

    1990-03-30

    nationalized canal under full Egyptian control as a threat to the flow of oil from Iran and the Gulf States. England saw herself cut off from Asia...were similarly arganized , with each service under British command with a French deputy.(11) By 5 August the joint staff was working in the old Second

  9. Characterization of an acromesomelic dysplasia, Grebe type case: novel mutation affecting the recognition motif at the processing site of GDF5.

    PubMed

    Martinez-Garcia, Monica; Garcia-Canto, Eva; Fenollar-Cortes, Maria; Aytes, Antonio Perez; Trujillo-Tiebas, María José

    2016-09-01

    Acromesomelic dysplasia, Grebe type is a very rare skeletal dysplasia characterized by severe dwarfism with marked micromelia and deformation of the upper and lower limbs, with a proximodistal gradient of severity. CDMP1 gene mutations have been associated with Grebe syndrome, Hunter-Thompson syndrome, Du Pan syndrome and brachydactyly type C. The proband is a 4-year-old boy, born of consanguineous Pakistani parents. Radiographic imaging revealed features typical of Grebe syndrome: severe shortening of the forearms with an acromesomelic pattern following a proximodistal gradient, with distal parts more severely affected than medial parts; hypoplastic hands, with the phalangeal zone more affected than the metacarpal zone; and severe hypoplastic tibial/femoral zones in both limbs. After molecular analyses, the p.Arg377Trp variant in a homozygous pattern was identified in the CDMP1 gene in the affected child. In silico and structural analyses predicted the p.Arg377Trp amino acid change to be pathogenic. Of the 34 mutations described in the CDMP1 gene, four different missense mutations have been associated with Grebe syndrome. The CDMP1 gene encodes growth differentiation factor 5 (GDF5), which plays a role in regulation of limb patterning, joint formation and distal bone growth. Homozygous mutations in the mature domain of GDF5 result in severe limb malformations such as the Grebe type or the Hunter-Thompson type of acromesomelic chondrodysplasia. The p.Arg377Trp mutation is located within the recognition motif at the processing site of GDF5 where the sequence RRKRR changes to WRKRR. The genotype-phenotype correlation allowed not only confirmation of the clinical diagnosis but also appropriate genetic counselling to be offered to this family.

  10. A Surprise Out of Zion? Case Studies in Israel’s Decisions on Whether to Alert the United States to Preemptive and Preventive Strikes, from Suez to the Syrian Nuclear Reactor

    DTIC Science & Technology

    2015-01-01

    Case I: The Suez War, 1956 11 ance between Egypt, Jordan and Syria,” and Iraq’s own mobilization of troops along its frontier with Jordan .13...to Ben-Gurion, warning Israel against a military operation”—although the president still thought Israel had Jordan in its gunsights, not Egypt. Ben...blasted Giscard d’Estaing’s proliferation policies, that an additional shipment of highly enriched uranium would let Iraq enter the nuclear club. “If I

  11. qPCR and HRM-based diagnosis of SNPs on growth differentiation factor 9 (GDF9), a gene associated with sheep (Ovis aries) prolificacy.

    PubMed

    Escobar-Chaparro, Raquel Anahí; Guillén, Gabriel; Espejo-Galicia, Luis Uribe; Meza-Villalvazo, Víctor Manuel; Peña-Castro, Julián Mario; Abad-Zavaleta, José

    2017-07-01

    Prolificacy is a desirable trait for genetic improvement of sheep flocks, since it holds the potential to improve productivity. Animals carrying single-nucleotide polymorphisms (SNPs) in genes associated with this trait can be identified and employed to increase prolificacy in flocks. In this study, we report a diagnostic method based on quantitative PCR and high-resolution melting curves to detect different SNPs in the prolificacy-associated gene growth differentiation factor 9 (GDF9). The diagnostic method was validated using artificial sequences representing known SNPs in GDF9, then applied to a real flock comprising four breeds and admixed animals (n = 306). Five different SNPs were identified in this flock, as was a low or null frequency of occurrence of SNPs positively associated with prolificacy. This indicates a need to implement a breeding strategy for recovering or reintroducing such SNPs. Our method provides a genotyping strategy for identifying individuals with SNPs of interest for prolificacy, which will help producers plan a breeding strategy for this trait. This method can be adapted and expanded for the diagnosis of other traits of interest.

  12. Analysis of association between IL-1β, CASP-9, and GDF5 variants and low-back pain in Chinese male soldier: clinical article.

    PubMed

    Mu, Jihong; Ge, Weiming; Zuo, Xincheng; Chen, Yuxuan; Huang, Changlin

    2013-08-01

    Recent studies have suggested that genetic risk factors play an important role in the occurrence of low-back pain (LBP) and lumbar disc disease. The authors' study aimed to assess the association between 3 single-nucleotide polymorphisms (SNPs) and susceptibility to LBP related to military training. In this case-control study, data from 892 Chinese male soldiers were retrospectively reviewed. The case group was made up of 305 soldiers with LBP related to military training and a control group of 587 soldiers without constant LBP for more than 2 weeks. Genomic DNA was extracted from peripheral blood leukocytes of all subjects and polymerase chain reaction products were genotyped. No association was found between the SNP of interleukin-1β (IL-1β; +3954C/T) and LBP at both the genotypic (p = 0.104) and the allelic (p = 0.098) level. However, the G allele of caspase-9 (CASP-9) and the T allele of growth differentiation factor 5 (GDF5) were more common in patients with LBP than in patients without LBP (p < 0.001). The findings in a Chinese military cohort indicated that CASP-9 (-1263A/G) and GDF5 (+104T/C) polymorphisms are associated with a susceptibility to LBP related to military training.

  13. The influence of surface coatings of dicalcium phosphate (DCPD) and growth and differentiation factor-5 (GDF-5) on the stability of titanium implants in vivo.

    PubMed

    Simank, Hans-Georg; Stuber, Marco; Frahm, Ronny; Helbig, Lars; van Lenthe, Harry; Müller, Ralph

    2006-07-01

    Mechanical stability of implants is usually tested by pull out or push out tests which destroy the interface between the implant and bone. Pull out tests do not ideally reflect the clinical situation. In contrast, applying submaximal load leads to more physiologic micro-displacement between implant and bone. The aim of this study was to evaluate a new non-destructive mechanical testing device on different modifications of titanium implants. In 18 rabbits we investigated the influence of a dicalcium phosphate (DCPD) coating, or of a growth and differentiation factor-5 (GDF-5) coating, or a combination of both on the stability of titanium implants. The stability of implant was assessed by a non-destructive micro-measurement. In the same specimens the interface was investigated by micro-CT and histological evaluation. Surface modifications had a positive effect on the implant stability regarding displacement (p=0.001). Mechanical stability correlated with the quality of peri-implant tissue. Micro-displacement correlated negatively with the bone formation around the implants in histomorphometric evaluation (p=0.02). Amount of peri-prosthetic soft tissue showed a positive correlation with micro-displacement (p=0.01). Our findings indicate the positive effect of DCPD and GDF-5 coatings on stability of titanium implants. Results demonstrate the non-destructive testing to be an effective method to evaluate mechanical stability of implants.

  14. Polymorphisms Near TBX5 and GDF7 Are Associated With Increased Risk for Barrett’s Esophagus

    PubMed Central

    Palles, Claire; Chegwidden, Laura; Li, Xinzhong; Findlay, John M.; Farnham, Garry; Castro Giner, Francesc; Peppelenbosch, Maikel P.; Kovac, Michal; Adams, Claire L.; Prenen, Hans; Briggs, Sarah; Harrison, Rebecca; Sanders, Scott; MacDonald, David; Haigh, Chris; Tucker, Art; Love, Sharon; Nanji, Manoj; deCaestecker, John; Ferry, David; Rathbone, Barrie; Hapeshi, Julie; Barr, Hugh; Moayyedi, Paul; Watson, Peter; Zietek, Barbara; Maroo, Neera; Gay, Laura; Underwood, Tim; Boulter, Lisa; McMurtry, Hugh; Monk, David; Patel, Praful; Ragunath, Krish; Al Dulaimi, David; Murray, Iain; Koss, Konrad; Veitch, Andrew; Trudgill, Nigel; Nwokolo, Chuka; Rembacken, Bjorn; Atherfold, Paul; Green, Elaine; Ang, Yeng; Kuipers, Ernst J.; Chow, Wu; Paterson, Stuart; Kadri, Sudarshan; Beales, Ian; Grimley, Charles; Mullins, Paul; Beckett, Conrad; Farrant, Mark; Dixon, Andrew; Kelly, Sean; Johnson, Matthew; Wajed, Shahjehan; Dhar, Anjan; Sawyer, Elinor; Roylance, Rebecca; Onstad, Lynn; Gammon, Marilie D.; Corley, Douglas A.; Shaheen, Nicholas J.; Bird, Nigel C.; Hardie, Laura J.; Reid, Brian J.; Ye, Weimin; Liu, Geoffrey; Romero, Yvonne; Bernstein, Leslie; Wu, Anna H.; Casson, Alan G.; Fitzgerald, Rebecca; Whiteman, David C.; Risch, Harvey A.; Levine, David M.; Vaughan, Tom L.; Verhaar, Auke P.; van den Brande, Jan; Toxopeus, Eelke L.; Spaander, Manon C.; Wijnhoven, Bas P.L.; van der Laan, Luc J.W.; Krishnadath, Kausilia; Wijmenga, Cisca; Trynka, Gosia; McManus, Ross; Reynolds, John V.; O’Sullivan, Jacintha; MacMathuna, Padraic; McGarrigle, Sarah A.; Kelleher, Dermot; Vermeire, Severine; Cleynen, Isabelle; Bisschops, Raf; Tomlinson, Ian; Jankowski, Janusz

    2015-01-01

    Background & Aims Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. Methods We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. Results We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09–1.18; P = 1.8 × 10−11) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86–0.93; P = 7.5 × 10−9). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87–0.93; P = 3.72 × 10−9). Conclusions We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response. PMID:25447851

  15. 77 FR 60978 - Combined Notice of Filings #1

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-05

    ... Limited Partnership, IPR-GDF SUEZ Energy Marketing North America, Inc., Hopewell Cogeneration Ltd Partnership, Hot Spring Power Company, LLC, Northeastern Power Company, Syracuse Energy Corporation, Northeast Energy Associates, A Limited Partnership, North Jersey Energy Associates, A Limited Partnership, Astoria...

  16. Aqaba-Levant transform-related faults in the Gulf of Suez rift: The Durba-Araba fault, Sinai Peninsula, Egypt

    NASA Astrophysics Data System (ADS)

    Abdeen, Mamdouh M.; Abdelmaksoud, Ashraf S.

    2014-09-01

    The Gulf of Suez rift is dominated by NNW- to NW-striking “Clysmic” faults trending parallel to the rift. In addition there are NNE- and WNW-striking (oblique) faults that trend at an angle to the rift. The Durba-Araba fault (DAF) in southwestern Sinai represents one of several NNE-striking faults. It separates the Durba fault block on its NW from the Araba fault block on its SE. Detailed (1:20,000 scale) field mapping and structural studies of the DAF and the onshore area to the east of Belayim Bay (eastern margin of the central Gulf of Suez rift), indicate that the exposed part of the DAF extends for 7.5 km NNE from the mouth of Wadi Araba, at which point it bends and splays into three N- to NNW striking faults, forming a horse tail structure. The fault shows 4 km of pure sinistral strike-slip displacement. Northerly plunging fault propagation folds in the Phanerozoic rocks adjacent to the DAF accommodated the sinistral displacement. These folds are cut and displaced by the splay faults. Near its northern end, the middle splay fault affects the Pliocene El Qa'a Formation. At Gebel Qabeliat a group of en echelon left-stepping NNE- to N-striking faults overlaps the DAF generating a pull-apart (rhomb) graben, in which Pliocene and Quaternary sediments are downthrown against the Upper Miocene rocks. Kinematic indicators on most of these faults show major sinistral strike-slip movement. Palaeostress analysis of slip striae indicates sub-horizontal ENE to NNE extension, comparable to the present day stress regime. Cross-cutting relationships indicate that the NNE- to N-striking oblique faults are younger than the NW-striking Clysmic faults. These faults are probably presently active since they affect Pliocene and Quaternary sediments. It is proposed that these faults are related to the Aqaba-Levant transform that has been active since the Middle Miocene.

  17. Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries).

    PubMed

    Hanrahan, James P; Gregan, Scott M; Mulsant, Philippe; Mullen, Michael; Davis, George H; Powell, Richard; Galloway, Susan M

    2004-04-01

    Belclare and Cambridge are prolific sheep breeds, the origins of which involved selecting ewes with exceptionally high litter size records from commercial flocks. The variation in ovulation rate in both breeds is consistent with segregation of a gene (or genes) with a large effect on this trait. Sterile ewes, due to a failure of normal ovarian follicle development, occur in both breeds. New naturally occurring mutations in genes for the oocyte-derived growth factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are described. These mutations are associated with increased ovulation rate in heterozygous carriers and sterility in homozygous carriers in both breeds. This is the first time that a mutation in the gene for GDF9 has been found that causes increased ovulation rate and infertility in a manner similar to inactivating mutations in BMP15, and shows that GDF9 is essential for normal folliculogenesis in sheep. Furthermore, it is shown, for the first time in any species, that individuals with mutations in both GDF9 and BMP15 have a greater ovulation rate than sheep with either of the mutations separately.

  18. Investigating the complex structural integrity of the Zeit Bay Field, Gulf of Suez, Egypt, using interpretation of 3D seismic reflection data

    NASA Astrophysics Data System (ADS)

    Afife, M.; Salem, M.; Aziz, M. Abdel

    2017-07-01

    Zeit Bay Field is one of the most important oil-bearing fields in the Gulf of Suez, Egypt, producing oil from the fractured basement rocks. Due to the complex structural setting of the area and the classical exploration concept that was based mainly on 2D seismic survey data, the area suffered from limited hydrocarbon interest for several years. During this time, most of the drilled wells hit structural highs and resulted in several dry holes. The present study is based on the interpretation of more recently acquired 3D seismic survey data as, matched with the available well logs, used to understand the complex structural setting of the Zeit Bay Field and provide insight into the entrapment style of the implied hydrocarbons. Several selected seismic cross sections were constructed, to extract subsurface geologic information, using available seismic profiles and wells. In addition, structure contour maps (isochronous maps, converted to depth maps) were constructed for the peaks of the basement, Nubian Sandstone, Kareem and Belayim Formations. Folds (anticlines and synclines) and faults (dip-slip) are identified on these maps, both individually and in groups, giving rise to step-like belts, as well as graben and horst blocks.

  19. Palynology, palynofacies and petroleum potential of the Upper Cretaceous-Eocene Matulla, Brown Limestone and Thebes formations, Belayim oilfields, central Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    El Diasty, W. Sh.; El Beialy, S. Y.; Abo Ghonaim, A. A.; Mostafa, A. R.; El Atfy, H.

    2014-07-01

    Palynological, palynofacies and organic geochemical results of 46 samples retrieved from the Upper Cretaceous - Eocene Matulla, Brown Limestone and Thebes formations, Belayim oilfields, central Gulf of Suez, Egypt are presented. The two latter formations are not dated palynologically as their lithology is not promising for palynological yield. However the Matulla Formation is dated as Turonian-Santonian age, based on the combined evidence of pollen and dinocysts. Palynofacies analysis carried out under both transmitted and fluorescent microscopy indicated that both the Thebes and Brown Limestone formations are deposited under a distal suboxic-anoxic environment. On the other hand, the Turonian-Santonian Matulla Formation supported the existence of a marginal marine deposition under dysoxic-anoxic basin to proximal suboxic-anoxic shelf environments. Rock-Eval pyrolysis and TOC results indicated that most of the studied formations are thermally immature to marginally mature and have a good petroleum potential. They are organically-rich in both oil- and gas-prone kerogen Type-II and II/III, deposited under marine reducing conditions favorable for hydrocarbon generation and expulsion.

  20. Potential migration of buoyant LNAPL from Intermediate Level Waste (ILW) emplaced in a geological disposal facility (GDF) for UK radioactive waste

    NASA Astrophysics Data System (ADS)

    Benbow, Steven J.; Rivett, Michael O.; Chittenden, Neil; Herbert, Alan W.; Watson, Sarah; Williams, Steve J.; Norris, Simon

    2014-10-01

    A safety case for the disposal of Intermediate Level (radioactive) Waste (ILW) in a deep geological disposal facility (GDF) requires consideration of the potential for waste-derived light non-aqueous phase liquid (LNAPL) to migrate under positive buoyancy from disposed waste packages. Were entrainment of waste-derived radionuclides in LNAPL to occur, such migration could result in a shorter overall travel time to environmental or human receptors than radionuclide migration solely associated with the movement of groundwater. This paper provides a contribution to the assessment of this issue through multiphase-flow numerical modelling underpinned by a review of the UK's ILW inventory and literature to define the nature of the associated ILW LNAPL source term. Examination has been at the waste package-local GDF environment scale to determine whether proposed disposal of ILW would lead to significant likelihood of LNAPL migration, both from waste packages and from a GDF vault into the local host rock. Our review and numerical modelling support the proposition that the release of a discrete free phase LNAPL from ILW would not present a significant challenge to the safety case even with conservative approximations. 'As-disposed' LNAPL emplaced with the waste is not expected to pose a significant issue. 'Secondary LNAPL' generated in situ within the disposed ILW, arising from the decomposition of plastics, in particular PVC (polyvinyl chloride), could form the predominant LNAPL source term. Released high molecular weight phthalate plasticizers are judged to be the primary LNAPL potentially generated. These are expected to have low buoyancy-based mobility due to their very low density contrast with water and high viscosity. Due to the inherent uncertainties, significant conservatisms were adopted within the numerical modelling approach, including: the simulation of a deliberately high organic material - PVC content wastestream (2D03) within an annular grouted waste package

  1. Potential migration of buoyant LNAPL from intermediate level waste (ILW) emplaced in a geological disposal facility (GDF) for U.K. radioactive waste.

    PubMed

    Benbow, Steven J; Rivett, Michael O; Chittenden, Neil; Herbert, Alan W; Watson, Sarah; Williams, Steve J; Norris, Simon

    2014-10-15

    A safety case for the disposal of Intermediate Level (radioactive) Waste (ILW) in a deep geological disposal facility (GDF) requires consideration of the potential for waste-derived light non-aqueous phase liquid (LNAPL) to migrate under positive buoyancy from disposed waste packages. Were entrainment of waste-derived radionuclides in LNAPL to occur, such migration could result in a shorter overall travel time to environmental or human receptors than radionuclide migration solely associated with the movement of groundwater. This paper provides a contribution to the assessment of this issue through multiphase-flow numerical modelling underpinned by a review of the UK's ILW inventory and literature to define the nature of the associated ILW LNAPL source term. Examination has been at the waste package-local GDF environment scale to determine whether proposed disposal of ILW would lead to significant likelihood of LNAPL migration, both from waste packages and from a GDF vault into the local host rock. Our review and numerical modelling support the proposition that the release of a discrete free phase LNAPL from ILW would not present a significant challenge to the safety case even with conservative approximations. 'As-disposed' LNAPL emplaced with the waste is not expected to pose a significant issue. 'Secondary LNAPL' generated in situ within the disposed ILW, arising from the decomposition of plastics, in particular PVC (polyvinyl chloride), could form the predominant LNAPL source term. Released high molecular weight phthalate plasticizers are judged to be the primary LNAPL potentially generated. These are expected to have low buoyancy-based mobility due to their very low density contrast with water and high viscosity. Due to the inherent uncertainties, significant conservatisms were adopted within the numerical modelling approach, including: the simulation of a deliberately high organic material--PVC content wastestream (2D03) within an annular grouted waste package

  2. Statistical methods and errors in family medicine articles between 2010 and 2014-Suez Canal University, Egypt: A cross-sectional study.

    PubMed

    Nour-Eldein, Hebatallah

    2016-01-01

    With limited statistical knowledge of most physicians it is not uncommon to find statistical errors in research articles. To determine the statistical methods and to assess the statistical errors in family medicine (FM) research articles that were published between 2010 and 2014. This was a cross-sectional study. All 66 FM research articles that were published over 5 years by FM authors with affiliation to Suez Canal University were screened by the researcher between May and August 2015. Types and frequencies of statistical methods were reviewed in all 66 FM articles. All 60 articles with identified inferential statistics were examined for statistical errors and deficiencies. A comprehensive 58-item checklist based on statistical guidelines was used to evaluate the statistical quality of FM articles. Inferential methods were recorded in 62/66 (93.9%) of FM articles. Advanced analyses were used in 29/66 (43.9%). Contingency tables 38/66 (57.6%), regression (logistic, linear) 26/66 (39.4%), and t-test 17/66 (25.8%) were the most commonly used inferential tests. Within 60 FM articles with identified inferential statistics, no prior sample size 19/60 (31.7%), application of wrong statistical tests 17/60 (28.3%), incomplete documentation of statistics 59/60 (98.3%), reporting P value without test statistics 32/60 (53.3%), no reporting confidence interval with effect size measures 12/60 (20.0%), use of mean (standard deviation) to describe ordinal/nonnormal data 8/60 (13.3%), and errors related to interpretation were mainly for conclusions without support by the study data 5/60 (8.3%). Inferential statistics were used in the majority of FM articles. Data analysis and reporting statistics are areas for improvement in FM research articles.

  3. Geometry and architecture of faults in a syn-rift normal fault array: The Nukhul half-graben, Suez rift, Egypt

    NASA Astrophysics Data System (ADS)

    Wilson, Paul; Gawthorpe, Rob L.; Hodgetts, David; Rarity, Franklin; Sharp, Ian R.

    2009-08-01

    The geometry and architecture of a well exposed syn-rift normal fault array in the Suez rift is examined. At pre-rift level, the Nukhul fault consists of a single zone of intense deformation up to 10 m wide, with a significant monocline in the hanging wall and much more limited folding in the footwall. At syn-rift level, the fault zone is characterised by a single discrete fault zone less than 2 m wide, with damage zone faults up to approximately 200 m into the hanging wall, and with no significant monocline developed. The evolution of the fault from a buried structure with associated fault-propagation folding, to a surface-breaking structure with associated surface faulting, has led to enhanced bedding-parallel slip at lower levels that is absent at higher levels. Strain is enhanced at breached relay ramps and bends inherited from pre-existing structures that were reactivated during rifting. Damage zone faults observed within the pre-rift show ramp-flat geometries associated with contrast in competency of the layers cut and commonly contain zones of scaly shale or clay smear. Damage zone faults within the syn-rift are commonly very straight, and may be discrete fault planes with no visible fault rock at the scale of observation, or contain relatively thin and simple zones of scaly shale or gouge. The geometric and architectural evolution of the fault array is interpreted to be the result of (i) the evolution from distributed trishear deformation during upward propagation of buried fault tips to surface faulting after faults breach the surface; (ii) differences in deformation response between lithified pre-rift units that display high competence contrasts during deformation, and unlithified syn-rift units that display low competence contrasts during deformation, and; (iii) the history of segmentation, growth and linkage of the faults that make up the fault array. This has important implications for fluid flow in fault zones.

  4. Statistical methods and errors in family medicine articles between 2010 and 2014-Suez Canal University, Egypt: A cross-sectional study

    PubMed Central

    Nour-Eldein, Hebatallah

    2016-01-01

    Background: With limited statistical knowledge of most physicians it is not uncommon to find statistical errors in research articles. Objectives: To determine the statistical methods and to assess the statistical errors in family medicine (FM) research articles that were published between 2010 and 2014. Methods: This was a cross-sectional study. All 66 FM research articles that were published over 5 years by FM authors with affiliation to Suez Canal University were screened by the researcher between May and August 2015. Types and frequencies of statistical methods were reviewed in all 66 FM articles. All 60 articles with identified inferential statistics were examined for statistical errors and deficiencies. A comprehensive 58-item checklist based on statistical guidelines was used to evaluate the statistical quality of FM articles. Results: Inferential methods were recorded in 62/66 (93.9%) of FM articles. Advanced analyses were used in 29/66 (43.9%). Contingency tables 38/66 (57.6%), regression (logistic, linear) 26/66 (39.4%), and t-test 17/66 (25.8%) were the most commonly used inferential tests. Within 60 FM articles with identified inferential statistics, no prior sample size 19/60 (31.7%), application of wrong statistical tests 17/60 (28.3%), incomplete documentation of statistics 59/60 (98.3%), reporting P value without test statistics 32/60 (53.3%), no reporting confidence interval with effect size measures 12/60 (20.0%), use of mean (standard deviation) to describe ordinal/nonnormal data 8/60 (13.3%), and errors related to interpretation were mainly for conclusions without support by the study data 5/60 (8.3%). Conclusion: Inferential statistics were used in the majority of FM articles. Data analysis and reporting statistics are areas for improvement in FM research articles. PMID:27453839

  5. Structural geology and 4D evolution of a half-graben: New digital outcrop modelling techniques applied to the Nukhul half-graben, Suez rift, Egypt

    NASA Astrophysics Data System (ADS)

    Wilson, Paul; Hodgetts, David; Rarity, Franklin; Gawthorpe, Rob L.; Sharp, Ian R.

    2009-03-01

    LIDAR-based digital outcrop mapping, in conjunction with a new surface modelling approach specifically designed to deal with outcrop datasets, is used to examine the evolution of a half-graben scale normal fault array in the Suez rift. Syn-rift deposition in the Nukhul half-graben was controlled by the graben-bounding Nukhul fault. The fault can be divided into four segments based on the strike of the fault, the morphology of hangingwall strata, and the variation in throw along strike. The segments of the fault became geometrically linked within the first 2.5 m.y. of rifting, as evidenced by the presence of early syn-rift Abu Zenima Formation strata at the segment linkage points. Fault-perpendicular folds in the hangingwall related to along-strike variations in throw associated with precursor fault segments persist for a further 1.8 m.y. after linkage of the segments, suggesting that the fault remains kinematically segmented. We suggest this occurs because of sudden changes in fault strike at the segment linkage points that inhibit earthquake rupture propagation, or because displacement is geometrically inhibited at fault linkage points where the orientation of the intersection line of the segments is significantly different from the orientation of the slip vector on the fault system. Length/throw plots and throw contour patterns for minor faults show that some faults initiated in pre-rift strata, whereas late east-striking faults initiated in the syn-rift basin fill. The late initiating faults are spatially associated with the east-striking Baba-Markha fault, which was active throughout the rift history, but developed as a transfer fault between major block-bounding fault systems around 6-7 Ma after rift initiation.

  6. Pullulan microbeads/Si-HPMC hydrogel injectable system for the sustained delivery of GDF-5 and TGF-β1: new insight into intervertebral disc regenerative medicine.

    PubMed

    Henry, Nina; Clouet, Johann; Fragale, Audrey; Griveau, Louise; Chédeville, Claire; Véziers, Joëlle; Weiss, Pierre; Le Bideau, Jean; Guicheux, Jérôme; Le Visage, Catherine

    2017-11-01

    Discogenic low back pain is considered a major health concern and no etiological treatments are today available to tackle this disease. To clinically address this issue at early stages, there is a rising interest in the stimulation of local cells by in situ injection of growth factors targeting intervertebral disc (IVD) degenerative process. Despite encouraging safety and tolerability results in clinic, growth factors efficacy may be further improved. To this end, the use of a delivery system allowing a sustained release, while protecting growth factors from degradation appears of particular interest. We propose herein the design of a new injectable biphasic system, based on the association of pullulan microbeads (PMBs) into a cellulose-based hydrogel (Si-HPMC), for the TGF-β1 and GDF-5 growth factors sustained delivery. We present for the first time the design and mechanical characterization of both the PMBs and the called biphasic system (PMBs/Si-HPMC). Their loading and release capacities were also studied and we were able to demonstrate a sustained release of both growth factors, for up to 28 days. Noteworthy, the growth factors biological activity on human cells was maintained. Altogether, these data suggest that this PMBs/Si-HPMC biphasic system may be a promising candidate for the development of an innovative bioactive delivery system for IVD regenerative medicine.

  7. The involvement of growth differentiation factor 5 (GDF5) and aggrecan in the epithelial-mesenchymal transition of salivary gland pleomorphic adenoma.

    PubMed

    Enescu, Anca Stefania; Mărgăritescu, C L; Crăiţoiu, Monica Mihaela; Enescu, Aurelia; Crăiţoiu, Ştefania

    2013-01-01

    Pleomorphic adenoma is the most common salivary gland tumor with annual incidence of 2-3.5/100 000 in population. The histogenesis of salivary gland pleomorphic adenoma is still unclear. One concept sustains the existence of an epithelial-mesenchymal transitions (EMT) process in pleomorphic adenomas by which neoplastic epithelial cells transdifferentiate into mesenchymal cells and leading to tissue heterogeneity from this salivary gland neoplasia. Here we investigate by immunohistochemistry the expression of growth differentiation factor 5 (GDF5) and aggrecan in 15 cases of salivary gland pleomorphic adenomas. We found that both markers were present in normal salivary gland, mainly in the cells that line striated and intercalated ducts suggesting their involvement in the morphogenesis of this duct system. A constant positive reactivity for both markers was recorded in transition regions from tubular proliferative units to myxoid areas suggesting the involvement of an EMT process during the tumorigenesis of such salivary gland neoplasia. Also, both markers may be implicated in the transdifferentiation of neoplastic myoepithelial cells from the myxoid zones to lacuna cells of adjacent chondroid areas completing the morphology of this salivary gland tumor.

  8. Integrated petrophysical and sedimentological study of the Middle Miocene Nullipore Formation (Ras Fanar Field, Gulf of Suez, Egypt): An approach to volumetric analysis of reservoirs

    NASA Astrophysics Data System (ADS)

    Afife, Mohamed M.; Sallam, Emad S.; Faris, Mohamed

    2017-10-01

    This study aims to integrate sedimentological, log and core analyses data of the Middle Miocene Nullipore Formation at the Ras Fanar Field (west central Gulf of Suez, Egypt) to evaluate and reconstruct a robust petrophysical model for this reservoir. The Nullipore Formation attains a thickness ranging from 400 to 980 ft and represents a syn-rift succession of the Middle Miocene marine facies. It consists of coralline-algal-reefal limestone, dolomitic limestone and dolostone facies, with few clay and anhydrite intercalations. Petrographically, seven microfacies types (MF1 to MF7) have been recognized and assembled genetically into three related facies associations (FA1 to FA3). These associations accumulated in three depositional environments: 1) peritidal flat, 2) restricted lagoon, and 3) back-shoal environments situated on a shallow inner ramp (homoclinal) setting. The studied rocks have been influenced by different diagenetic processes (dolomitization, cementation, compaction, authigenesis and dissolution), which led to diminishing and/or enhancing the reservoir quality. Three superimposed 3rd-order depositional sequences are included in the Nullipore succession displaying both retrogradational and aggradational packages of facies. Given the hydrocarbon potential of the Nullipore Formation, conventional well logs of six boreholes and core analyses data from one of these wells (RF-B12) are used to identify electrofacies zones of the Nullipore Formation. The Nullipore Formation has been subdivided into three electrofacies zones (the Nullipore-I, Nullipore-II, and Nullipore-III) that are well-correlated with the three depositional sequences. Results of petrographical studies and log analyses data have been employed in volumetric calculations to estimate the amount of hydrocarbon-in-place and then the ultimate recovery of the Nullipore reservoir. The volumetric calculations indicate that the total volume of oil-in-place is 371 MMSTB at 50% probability (P50), whereas

  9. Loss of Myostatin (GDF8) Function Increases Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells but the Osteogenic Effect is Ablated with Unloading

    PubMed Central

    Hamrick, M.; Shi, X.; Zhang, W.; Pennington, C.; Thakore, H.; Haque, M.; Kang, B.; Isales, C.M.; Fulzele, S.; Wenger, K.

    2007-01-01

    Myostatin (GDF8) is a negative regulator of skeletal muscle growth and mice lacking myostatin show a significant increase in muscle mass and bone density compared to normal mice. In order to further define the role of myostatin in regulating bone mass we sought to determine if loss of myostatin function significantly altered the potential for osteogenic differentiation in bone marrow-derived mesenchymal stem cells in vitro and in vivo. We first examined expression of the myostatin receptor, the type IIB activin receptor (AcvrIIB), in bone marrow-derived mesenchymal stem cells (BMSCs) isolated from mouse long bones. This receptor was found to be expressed at high levels in BMSCs, and we were also able to detect AcvrIIB protein in BMSCs in situ using immunofluorescence. BMSCs isolated from myostatin-deficient mice showed increased osteogenic differentiation compared to wild-type mice; however, treatment of BMSCs from myostatin-deficient mice with recombinant myostatin did not attenuate the osteogenic differentiation of these cells. Loading of BMSCs in vitro increased the expression of osteogenic factors such as BMP-2 and IGF-1, but treatment of BMSCs with recombinant myostatin was found to decrease the expression of these factors. We investigated the effects of myostatin loss-of-function on the differentiation of BMSCs in vivo using hindlimb unloading (7 days tail suspension). Unloading caused a greater increase in marrow adipocyte number, and a greater decrease in osteoblast number, in myostatin-deficient mice than in normal mice. These data suggest that the increased osteogenic differentiation of BMSCs from mice lacking myostatin is load-dependent, and that myostatin may alter the mechanosensitivity of BMSCs by suppressing the expression of osteogenic factors during mechanical stimulation. Furthermore, although myostatin deficiency increases muscle mass and bone strength, it does not prevent muscle and bone catabolism with unloading. PMID:17383950

  10. Recombinant Myostatin (GDF-8) Propeptide Enhances the Repair and Regeneration of both Muscle and Bone in a Model of Deep Penetrant Musculoskeletal Injury

    PubMed Central

    Hamrick, Mark W.; Arounleut, Phonepasong; Kellum, Ethan; Cain, Matthew; Immel, David; Liang, Li

    2013-01-01

    Background Myostatin (GDF-8) is known as a potent inhibitor of muscle growth and development, and myostatin is also expressed early in the fracture healing process. The purpose of this study was to test the hypothesis that a new myostatin inhibitor, a recombinant myostatin propeptide, can enhance the repair and regeneration of both muscle and bone in cases of deep penetrant injury. Methods We used a fibula osteotomy model with associated damage to lateral compartment muscles (fibularis longus and brevis) in mice to test the hypothesis that blocking active myostatin with systemic injections of a recombinant myostatin propeptide would improve muscle and bone repair. Mice were assigned to two treatment groups after undergoing a fibula osteotomy: those receiving either vehicle (saline) or recombinant myostatin propeptide (20 mg/kg). Mice received one treatment on the day of surgery, another injection five days following surgery, and a third injection 10 days following surgery. Mice were euthanized 15 days following the osteotomy procedure. Bone repair was assessed using microCT and histological evaluation of the fracture callus. Muscle healing was assessed using Masson trichrome staining of the injury site, and image analysis used to quantify the degree of fibrosis and muscle regeneration. Results Three propeptide injections over a period of 15 days increased body mass by 7% and increased muscle mass by almost 20% (P<.001). MicroCT analysis of the osteotomy site shows that by 15 days post-osteotomy, bony callus tissue was observed bridging the osteotomy gap in 80% of the propeptide- treated mice, but only 40% of the control (vehicle)-treated mice (P<.01). MicroCT quantification shows that bone volume of the fracture callus was increased by approximately 30% (P<.05) with propeptide treatment, and the increase in bone volume was accompanied by a significant increase in cartilage area (P=.01). Propeptide treatment significantly decreased the fraction of fibrous tissue in

  11. Runx2 mediates epigenetic silencing of the bone morphogenetic protein-3B (BMP-3B/GDF10) in lung cancer cells

    PubMed Central

    2012-01-01

    Background The Runt-related transcription factor Runx2 is essential for bone development but is also implicated in progression of several cancers of breast, prostate and bone, where it activates cancer-related genes and promotes invasive properties. The transforming growth factor β (TGF-β) family member bone morphogenetic protein-3B (BMP-3B/GDF10) is regarded as a tumor growth inhibitor and a gene silenced in lung cancers; however the regulatory mechanisms leading to its silencing have not been identified. Results Here we show that Runx2 is highly expressed in lung cancer cells and downregulates BMP-3B. This inverse relationship between Runx2 and BMP-3B expression is further supported by increased expression of BMP-3B in mesenchymal cells from Runx2 deficient mice. The ectopic expression of Runx2, but not DNA binding mutant Runx2, in normal lung fibroblast cells and lung cancer cells resulted in suppression of BMP-3B levels. The chromatin immunoprecipitation studies identified that the mechanism of Runx2-mediated suppression of BMP-3B is due to the recruitment of Runx2 and histone H3K9-specific methyltransferase Suv39h1 to BMP-3B proximal promoter and a concomitant increase in histone methylation (H3K9) status. The knockdown of Runx2 in H1299 cells resulted in decreased histone H3K9 methylation on BMP-3B promoter and increased BMP-3B expression levels. Furthermore, co-immunoprecipitation studies showed a direct interaction of Runx2 and Suv39h1 proteins. Phenotypically, Runx2 overexpression in H1299 cells increased wound healing response to TGFβ treatment. Conclusions Our studies identified BMP-3B as a new Runx2 target gene and revealed a novel function of Runx2 in silencing of BMP-3B in lung cancers. Our results suggest that Runx2 is a potential therapeutic target to block tumor suppressor gene silencing in lung cancer cells. PMID:22537242

  12. The Maternal Maverick/GDF15-like TGF-β Ligand Panda Directs Dorsal-Ventral Axis Formation by Restricting Nodal Expression in the Sea Urchin Embryo.

    PubMed

    Haillot, Emmanuel; Molina, Maria Dolores; Lapraz, François; Lepage, Thierry

    2015-01-01

    Specification of the dorsal-ventral axis in the highly regulative sea urchin embryo critically relies on the zygotic expression of nodal, but whether maternal factors provide the initial spatial cue to orient this axis is not known. Although redox gradients have been proposed to entrain the dorsal-ventral axis by acting upstream of nodal, manipulating the activity of redox gradients only has modest consequences, suggesting that other factors are responsible for orienting nodal expression and defining the dorsal-ventral axis. Here we uncover the function of Panda, a maternally provided transforming growth factor beta (TGF-β) ligand that requires the activin receptor-like kinases (Alk) Alk3/6 and Alk1/2 receptors to break the radial symmetry of the embryo and orient the dorsal-ventral axis by restricting nodal expression. We found that the double inhibition of the bone morphogenetic protein (BMP) type I receptors Alk3/6 and Alk1/2 causes a phenotype dramatically more severe than the BMP2/4 loss-of-function phenotype, leading to extreme ventralization of the embryo through massive ectopic expression of nodal, suggesting that an unidentified signal acting through BMP type I receptors cooperates with BMP2/4 to restrict nodal expression. We identified this ligand as the product of maternal Panda mRNA. Double inactivation of panda and bmp2/4 led to extreme ventralization, mimicking the phenotype caused by inactivation of the two BMP receptors. Inhibition of maternal panda mRNA translation disrupted the early spatial restriction of nodal, leading to persistent massive ectopic expression of nodal on the dorsal side despite the presence of Lefty. Phylogenetic analysis indicates that Panda is not a prototypical BMP ligand but a member of a subfamily of TGF-β distantly related to Inhibins, Lefty, and TGF-β that includes Maverick from Drosophila and GDF15 from vertebrates. Indeed, overexpression of Panda does not appear to directly or strongly activate phosphoSmad1

  13. The Maternal Maverick/GDF15-like TGF-β Ligand Panda Directs Dorsal-Ventral Axis Formation by Restricting Nodal Expression in the Sea Urchin Embryo

    PubMed Central

    Haillot, Emmanuel; Molina, Maria Dolores; Lapraz, François; Lepage, Thierry

    2015-01-01

    Specification of the dorsal-ventral axis in the highly regulative sea urchin embryo critically relies on the zygotic expression of nodal, but whether maternal factors provide the initial spatial cue to orient this axis is not known. Although redox gradients have been proposed to entrain the dorsal-ventral axis by acting upstream of nodal, manipulating the activity of redox gradients only has modest consequences, suggesting that other factors are responsible for orienting nodal expression and defining the dorsal-ventral axis. Here we uncover the function of Panda, a maternally provided transforming growth factor beta (TGF-β) ligand that requires the activin receptor-like kinases (Alk) Alk3/6 and Alk1/2 receptors to break the radial symmetry of the embryo and orient the dorsal-ventral axis by restricting nodal expression. We found that the double inhibition of the bone morphogenetic protein (BMP) type I receptors Alk3/6 and Alk1/2 causes a phenotype dramatically more severe than the BMP2/4 loss-of-function phenotype, leading to extreme ventralization of the embryo through massive ectopic expression of nodal, suggesting that an unidentified signal acting through BMP type I receptors cooperates with BMP2/4 to restrict nodal expression. We identified this ligand as the product of maternal Panda mRNA. Double inactivation of panda and bmp2/4 led to extreme ventralization, mimicking the phenotype caused by inactivation of the two BMP receptors. Inhibition of maternal panda mRNA translation disrupted the early spatial restriction of nodal, leading to persistent massive ectopic expression of nodal on the dorsal side despite the presence of Lefty. Phylogenetic analysis indicates that Panda is not a prototypical BMP ligand but a member of a subfamily of TGF-β distantly related to Inhibins, Lefty, and TGF-β that includes Maverick from Drosophila and GDF15 from vertebrates. Indeed, overexpression of Panda does not appear to directly or strongly activate phosphoSmad1

  14. Sub-10 nm Sr2LuF7:Yb/Er@Sr2GdF7@SrF2 Up-Conversion Nanocrystals for Up-Conversion Luminescence-Magnetic Resonance-Computed Tomography Trimodal Bioimaging.

    PubMed

    Chen, Cailing; Liu, Jianhua; Chen, Ying; Li, Chunguang; Liu, Xiaomin; Huang, He; Liang, Chen; Lou, Yue; Shi, Zhan; Feng, Shouhua

    2017-02-22

    Herein, sub-10 nm core-shell nanocrystals (NCs), which select Sr2LuF7:Yb/Er as core, Sr2GdF7 as middle shell, and SrF2 as an outermost shell, were synthesized by a seed-mediated growth process. The NCs possess good crystallinity, morphology, and up-conversion luminescent properties. After modification by polyethylenimine branched (PEI), in vitro cell up-conversion imaging with low autofluorescence was realized. Due to the presence of Gd(3+) ions, in vivo magnetic resonance (MR) imaging was also achieved with these designed NCs. More significantly, these special core-shell NCs exhibited high contrast in in vivo X-ray computed tomography (CT) imaging because of their good X-ray absorption ability. These results indicate that the core-shell up-conversion NCs can serve as promising contrast agents for up-conversion luminescence-MR-CT trimodal bioimaging.

  15. Two new Myxidium species (Myxosporea: Myxidiidae) infecting the gallbladder of African flying fish, Cheilopogon nigricans and Suez fusilier, Caesio suevicus from the Red Sea, Egypt: a morphological and morphometric study.

    PubMed

    Abdel-Baki, Abdel-Azeem Sh

    2009-08-01

    Myxidium maamouni sp. n. and Myxidium aydai sp. n. were described from the gallbladder of the African flying fish Cheilopogon nigricans and Suez fusilier Caesio suevicus, respectively. Fishes were collected from the Red Sea at Al-Quseir, Egypt. M. maamouni have irregular to mostly rounded polysporous plasmodia with diameter of 27 microm. Spores were sigmoid or S-shaped and sometimes spindle-shaped in the frontal view with smooth valves. They measured 13.5 x 8.0 x 8.2 microm in size. Their polar capsules were equal pyriform and measured 7.0 x 3.2 microm in size with nine to 12 coils. Spores of M. aydai were spindle-shaped in the frontal view with thin smooth valves. They measured 23.0 x 5.6 x 5.5 microm in size. Their polar capsules were pyriform and measured 7.2 x 3.4 microm in size with eight to nine coils.

  16. Volcano-sedimentary characteristics in the Abu Treifiya Basin, Cairo-Suez District, Egypt: Example of dynamics and fluidization over sedimentary and volcaniclastic beds by emplacement of syn-volcanic basaltic rocks

    NASA Astrophysics Data System (ADS)

    Khalaf, E. A.; Abdel Motelib, A.; Hammed, M. S.; El Manawi, A. H.

    2015-12-01

    This paper describes the Neogene lava-sediment mingling from the Abu Treifiya Basin, Cairo-Suez district, Egypt. The lava-sediment interactions as peperites have been identified for the first time at the study area and can be used as paleoenvironmental indicators. The identification of peperite reflects contemporaneous time relationship between volcanism and sedimentation and this finding is of primary importance to address the evolutional reconstruction of the Abu Treifiya Basin. Characterization of the facies architecture and textural framework of peperites was carried out through detailed description and interpretation of their outcrops. The peperites and sedimentary rocks are up to 350 m thick and form a distinct stratigraphic framework of diverse lithology that is widespread over several kilometers at the study area. Lateral and vertical facies of the peperites vary from sediment intercalated with the extrusive/intrusive basaltic rocks forming peperitic breccias to lava-sediment contacts at a large to small scales, respectively. Peperites encompass five main facies types ascribed to: (i) carbonate sediments-hosted fluidal and blocky peperites, (ii) lava flow-hosted blocky peperites, (iii) volcaniclastics-hosted fluidal and blocky peperites, (iv) sandstone/siltstone rocks-hosted blocky peperites, and (iv) debris-flows-hosted blocky peperites. Soft sediment deformation structures, vesiculated sediments, sediments filled-vesicles, and fractures in lava flows indicate that lava flows mingled with unconsolidated wet sediments. All the peperites in this study could be described as blocky or fluidal, but mixtures of different clast shapes occur regardless of the host sediment. The presence of fluidal and blocky juvenile clasts elucidates different eruptive styles, reflecting a ductile and brittle fragmentation. The gradual variation from fluidal to blocky peperite texture, producing the vertical grading is affected by influencing factors, e.g., the viscosity, magma

  17. 77 FR 273 - Combined Notice of Filings #1

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-04

    ... Generation Limited Partnership, Hot Spring Power Company, LLC,GDF SUEZ Energy Marketing NA, Inc., IPA Trading, LLC, Choctaw Gas Generation, LLC, FirstLight Power Resources Management, L, ANP Funding I, LLC..., Brookfield Energy Marketing US LLC, Brookfield Power Piney & Deep Creek LLC, Brookfield Renewable...

  18. 78 FR 21926 - Combined Notice of Filings #1

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-12

    ..., Hopewell Cogeneration Ltd Partnership, GDF SUEZ Energy Marketing NA, Inc., Milford Power Limited Partnership, Mt. Tom Generating Company LLC, Northeastern Power Company, North Jersey Energy Associates, A... Energy Company, LLC, Armstrong Energy Limited Partnership, L., Astoria Energy LLC, Astoria Energy II LLC...

  19. Gene expression analysis suggests bone development-related genes GDF5 and DIO2 are involved in the development of Kashin-Beck disease in children rather than adults.

    PubMed

    Wen, Yan; Zhang, Feng; Li, Chunyan; He, Shulan; Tan, Wuhong; Lei, Yanxia; Zhang, Qiang; Yu, Hanjie; Zheng, Jingjing; Guo, Xiong

    2014-01-01

    To investigate the differences in gene expression between children and adults with Kashin-Beck disease (KBD). 12 children with KBD and 12 healthy children were selected and divided into 4 KBD vs. control pairs matched according to age and gender, with each pair having 3 KBD children and 3 healthy children. Additionally, 15 adults with KBD and 15 healthy adults were selected and divided into 5 KBD vs. control pairs matched according to age and gender, with each pair having 3 KBD adults and 3 healthy adults. Total RNA was isolated from peripheral blood mononuclear cells (PBMCs) respectively. A total of 367 target genes were selected based on previous genome-wide gene expression profile analysis. Expression levels of the 367 genes were evaluated by customized oligonucleotide microarray and the differentially expressed genes were identified. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was conducted to validate the microarray data. A total of 95 (25.9%) genes in KBD children and 158 (43.1%) genes in KBD adults were found to exhibit more than two-fold change in gene expression level relative to healthy controls. By comparing differentially expressed genes identified in KBD children to those of KBD adults, 42 genes were found to be differentially expressed only in KBD children. And 105 genes were found to be differentially expressed only in KBD adults. Further, 16 differentially expressed genes common to both KBD children and adults were found to be asynchronously expressed in KBD children compared to KBD adults. Significant differences in gene expression pattern were identified between KBD children and KBD adults, indicating different molecular mechanisms underlying cartilage lesions of KBD children and KBD adults. In addition, bone development-related genes GDF5 (expression ratio = 2.14±0.02) and DIO2 (expression ratio = 0.11±0.05) may contribute to the development of KBD in children rather than in adults.

  20. Suez Canal Clearance Operation, Task Force 65

    DTIC Science & Technology

    1975-05-01

    and remove the four wrecks from the central region of the canal; DREDGE 23, Tug MONGUED, Dredge KASSER and a Concrete Caisson. All salvage operations...feet BUCKET DREDGE NO. 23 72.00 1600 tons 191 feet TUG MONGUED 81.50 1200 tons 165 feet DIPPER DREDGE KASSER 81.50 1200 tons 125 feet CONCRETE CAISSON...MONGUED, DREDGE KASSER , and DREDGE 23 to wet dump in the Great Bitter Lake. Heavy crane THOR arrived in Port Said after transit from Hamburg, Germany

  1. Investigation of prolific sheep from UK and Ireland for evidence on origin of the mutations in BMP15 (FecX(G), FecX(B)) and GDF9 (FecG(H)) in Belclare and Cambridge sheep.

    PubMed

    Mullen, Michael P; Hanrahan, James P; Howard, Dawn J; Powell, Richard

    2013-01-01

    This paper concerns the likely origin of three mutations with large effects on ovulation rate identified in the Belclare and Cambridge sheep breeds; two in the BMP15 gene (FecX(G) and FecX(B)) and the third (FecG(H)) in GDF9. All three mutations segregate in Belclare sheep while one, FecX(B), has not been found in the Cambridge. Both Belclare and Cambridge breeds are relatively recently developed composites that have common ancestry through the use of genetic material from the Finnish Landrace and Lleyn breeds. The development of both composites also involved major contributions from exceptionally prolific ewes screened from flocks in Ireland (Belclare) and Britain (Cambridge) during the 1960s. The objective of the current study was to establish the likely origin of the mutations (FecX(G), FecX(B) and FecG(H)) through analysis of DNA from Finnish Landrace and Lleyn sheep, and Galway and Texel breeds which contributed to the development of the Belclare breed. Ewes with exceptionally high prolificacy (hyper-prolific ewes) in current flocks on Irish farms were identified to simulate the screening of ewes from Irish flocks in the 1960s. DNA was obtained from: prolific ewes in extant flocks of Lleyn sheep (n = 44) on the Lleyn peninsula in Wales; hyper-prolific ewes (n = 41); prolific Galway (n = 41) ewes; Finnish Landrace (n = 124) and Texel (n = 19) ewes. The FecX(G) mutation was identified in Lleyn but not in Finnish Landrace, Galway or Texel sheep; FecX(B) was only found among the hyper-prolific ewes. The FecG(H) mutation was identified in the sample of Lleyn sheep. It was concluded from these findings that the Lleyn breed was the most likely source of the FecX(G) and FecG(H) mutations in Belclare and Cambridge sheep and that the FecX(B) mutation came from the High Fertility line that was developed using prolific ewes selected from commercial flocks in Ireland in the 1960's and subsequently used in the genesis of the Belclare.

  2. Investigation of Prolific Sheep from UK and Ireland for Evidence on Origin of the Mutations in BMP15 (FecXG, FecXB) and GDF9 (FecGH) in Belclare and Cambridge Sheep

    PubMed Central

    Mullen, Michael P.; Hanrahan, James P.; Howard, Dawn J.

    2013-01-01

    This paper concerns the likely origin of three mutations with large effects on ovulation rate identified in the Belclare and Cambridge sheep breeds; two in the BMP15 gene (FecXG and FecXB) and the third (FecGH) in GDF9. All three mutations segregate in Belclare sheep while one, FecXB, has not been found in the Cambridge. Both Belclare and Cambridge breeds are relatively recently developed composites that have common ancestry through the use of genetic material from the Finnish Landrace and Lleyn breeds. The development of both composites also involved major contributions from exceptionally prolific ewes screened from flocks in Ireland (Belclare) and Britain (Cambridge) during the 1960s. The objective of the current study was to establish the likely origin of the mutations (FecXG, FecXB and FecGH) through analysis of DNA from Finnish Landrace and Lleyn sheep, and Galway and Texel breeds which contributed to the development of the Belclare breed. Ewes with exceptionally high prolificacy (hyper-prolific ewes) in current flocks on Irish farms were identified to simulate the screening of ewes from Irish flocks in the 1960s. DNA was obtained from: prolific ewes in extant flocks of Lleyn sheep (n = 44) on the Lleyn peninsula in Wales; hyper-prolific ewes (n = 41); prolific Galway (n = 41) ewes; Finnish Landrace (n = 124) and Texel (n = 19) ewes. The FecXG mutation was identified in Lleyn but not in Finnish Landrace, Galway or Texel sheep; FecXB was only found among the hyper-prolific ewes. The FecGH mutation was identified in the sample of Lleyn sheep. It was concluded from these findings that the Lleyn breed was the most likely source of the FecXG and FecGH mutations in Belclare and Cambridge sheep and that the FecXB mutation came from the High Fertility line that was developed using prolific ewes selected from commercial flocks in Ireland in the 1960′s and subsequently used in the genesis of the Belclare. PMID:23301039

  3. Basement reservoir in Zeit Bay oil field, Gulf of Suez

    SciTech Connect

    Zahran, I.; Askary, S.

    1988-01-01

    Fractured basement, one of the most important reservoirs of Zeit Bay field, contains nearly one-third of oil in place of the field. The flow rates per well vary from 700 to 9,000 BOPD. Due to its well-established production potential, 60% of the wells for the development of the field were drilled down to basement. The Zeit Bay basement consist of granitic rocks of pegmatitic to coarse porphyritic texture and has equal proportions of alkali feldspars. Dykes of various compositions are present, traversing the granite at different intervals. Dykes include aplite, microsyenite, diabase and lamprophyre. The last two pertain to the post-granitic dykes of later Proterozoic age. The main granitic luton is related to one of the final stages of the tectonic-magmatic cycle of the Arabo-Nubian sheild. The Zeit Bay area was a significant paleohigh until the Miocene, hence its structural picture is very complicated due to the impact of different tectonic movements from the late Precambrian to Cenozoic. The resulting structural elements were carefully investigated and statistically analyzed to decipher the influence of various tectonic events. The presence of high porosity in some intervals and low porosity in others could be tied to the presence of new fractures and the nature of cementing minerals. The relation of mineralized fractures and their depths lead to zonation of porous layers in the granitic pluton. Diagenetic processes on the granitic body and the alternation/resedimentation of the diagenetic products controlled the magnitude and amplitude of the porosity layers.

  4. Basement reservoir in Zeit Bay oil field, Gulf of Suez

    SciTech Connect

    Zahran, I.; Askary, S.

    1988-02-01

    Fractured basement, one of the most important reservoirs of Zeit Bay field, contains nearly one-third of oil in place of the field. The flow rates per well vary from 700 to 9,000 BOPD. Due to its well-established production potential, 60% of the wells for the development of the field were drilled down to basement. The Zeit Bay basement consists of granitic rocks of pegmatitic to coarse porphyritic texture and has equal proportions of alkali feldspars. Dykes of various compositions are present, traversing the granite at different intervals. Dykes include aplite, microsyenite, diabase and lamprophyre. The last two pertain to the post-granitic dykes of late Proterozoic age. The main granitic pluton is related to one of the final stages of the tectonic-magmatic cycle of the Arabo-Nubian shield. The Zeit Bay area was a significant paleohigh until the Miocene, hence its structural picture is very complicated due to the impact of different tectonic movements from the late Precambrian to Cenozoic. The resulting structural elements were carefully investigated and statistically analyzed to decipher the influence of various tectonic events. The presence of high porosity in some intervals and low porosity in others could be tied to the presence of new fractures and the nature of cementing minerals. The relation of mineralized fractures and their depths lead to zonation of porous layers in the granitic pluton. Diagenetic processes on the granitic body and the alteration/resedimentation of the diagenetic products controlled the magnitude and amplitude of the porosity layers. A model has been constructed to illustrate the changes in the primary rock texture and structure with sequential diagenetic processes, taking into consideration the fracture distribution and their opening affinities as related to their depths.

  5. The 1956 Suez Crisis and the United Nations

    DTIC Science & Technology

    2004-06-17

    crossroad since 1945. By 2003, Iraq had violated seventeen UN resolutions, had expelled UN weapons inspectors, and had funded suicide bombings in Israel...Sierra Leone in 1996 and 1997. When these enablers of coercive order left, gangs of armed, drugged-addicted teenagers ravaged the city for two years...allies was that world opinion favored Egypt as a “victim of imperialist bullies .” Selwyn Lloyd wrote that Dwight Eisenhower “had twice let us down and

  6. Interaction between acari ectoparasites and rodents in Suez Governorate, Egypt.

    PubMed

    Younis, T A; Fayad, M E; el Hariry, M A; Morsy, T A

    1995-08-01

    From the medical point of view, the relation between man and rodents comes in the priority. Some rodent populations are wild but others are commensal and live in close association with man. They steal his food and conveying many zoonotic diseases. Their arthropod ectoparasites play an important role in conveying or transmitting these zoonotic diseases. Several disorders and diseases of man are tick borne relapsing fever, Rocky mountain spotted fever, Lyme disease, and many others. Besides numerous species of mites occasionally infest man. They transmit several diseases as Rickettsia tsutsugamushi fever, epidemic haemorrhagic fever, and they cause severe allergic reaction. The results obtained are summarized in the following (1) Six species and subspecies of rodents were detected. In a descending order of abundance, they were (a) Rattus norvegicus, (b) Rattus rattus alexandrinus (c) Rattus rattus frugivorous (d) Acomys cahirinus (e) Gerbillus gerbillus asyutensis (f) Mus m. praetextus. (2) The most common rodent was R. norvegicus and the least common was M. musculus. (3) The collected ticks and mites were 2 genera of tick larvae; Rhipicephalus species and Hyalomma species. The collected mites were Ornithonyssus bacoti and Laelaps nuttali. (4) Most of the tick larvae were collected from wild rodents; Gerbillus g. asyutensis. (5) Most of the mites were collected from commensal rodents particularly R. norvegicus. Descriptive morphology and illustrations were given to the collected rodents and their acari ectoparasites.

  7. Eisenhower and Suez: An Appraisal of Presidential Leadership

    DTIC Science & Technology

    1992-06-05

    the position was still in the 15 Dwight D. Eisenhower Diary, May 14, 1953, Ann Whitman File, Eisenhower Library. See also Robert H. Ferrell ed., The...Wilson’s background and shortcomings, see p. 48. 18 As quoted in Ferrell , The Eisenhower Diaries. p. 237. 20 all of what embarrassment his remarks...Egyptian nationalism and Communism vanished. 23 R. H. Ferrell , ed., The Eisenhower Diaries (New York: W.W. Norton & Company, 1981) pp. 318-319. 24 Ibid., p

  8. Stockage thermique saisonnier par puits geothermiques pour batiments residentiels equipes de panneaux photovoltaiques-thermiques

    NASA Astrophysics Data System (ADS)

    Brischoux, Pauline

    The energy efficiency of a ground-source heat pump system with solar heat injection from photovoltaic-thermal panels is evaluated. The system provides heat to a single-family house located in Montreal. Unlike conventional GSHP systems, the borehole, or boreholes, is equipped with two independent fluid circuits. Thus, it is possible to inject heat from the solar panels and extract energy with the heat pump simultaneously. First, the system is analyzed with a single borehole using numerical simulations within the TRNSYS environment. Results show that the heat injection in the borehole increases the efficiency of the system and limits the reduction in performance caused by unbalanced ground loads. However, part of the heat injected during the summer is lost by thermal diffusion to the ground surrounding the borehole and a single borehole is not appropriate for seasonal thermal energy storage. A study of the same system is performed after replacing the single borehole by a borefield consisting of 15 shallow boreholes. This analysis points out the technical feasibility of seasonal borehole thermal energy storage (BTES) systems for residential applications. Such a system reaches a higher energy efficiency than the system including a single borehole with solar charging but requires a large storage volume. The last part of this thesis presents a preliminary study of an ice storage system. The results are compared to the BTES in terms of energy efficiency and needed configuration. The system with BTES requires a large storage volume but achieves a high overall energy efficiency. The ice storage system involves a much smaller storage volume but does not seem to be able to reach an energy efficiency similar to the BTES, the heat pump inlet temperature being limited by the low storage temperature. However, the overall energy efficiency of this system is similar to conventional GSHP systems, i.e. without solar charging.

  9. Building Maintenance Mechanic. Apprenticeship Training Standards = Mecanicien d'entretien des batiments. Normes de formation en apprentissage.

    ERIC Educational Resources Information Center

    Ontario Ministry of Skills Development, Toronto.

    These training standards for building maintenance mechanics are intended to be used by apprentice/trainees, instructors, and companies in Ontario, Canada, as a blueprint for training or as a prerequisite for accreditation/certification. The training standards identify skills required for this occupation and its related training program. They are…

  10. Simulation d'un systeme de stockage saisonnier de glace pour la climatisation d'un batiment commercial ou institutionnel

    NASA Astrophysics Data System (ADS)

    Giraldo, Raul Alberto

    The principal goal of this study was to evaluate, using numerical simulation, the feasibility of an air conditioning system, supported by a seasonal ice storage system, installed in a commercial or institutional building. In this regard, the effects of changing several elements around the design of two possible scenarios were modeled in TRNSYS using Matlab® as a programming tool. In the first scenario, the air demanded inside the building passes directly through the ice storage system. In a second scenario, a closed loop pipe full of glycol transports the heat between the ice reservoir and an air cooling coil. First of all, the literature review shows some studies and earlier relevant applications, as well as different solving methods for moving boundary problems in a biphasic medium (waterice). Next, the heat load profile for a typical institutional building in Montreal is determined as a reference point using EE4 and three different methods of solving the boundary motion problem are compared for both, ice training and ice melting. Subsequently, the design parameters are presented for each scenario. This is followed by a description of the programming codes in Matlab® and the components that have been implemented in TRNSYS. Finally, the results involving the heat exchanged and the waterice boundary movements, among others, are collected for one year and for three years. The simulations of both scenarios have also included the experimental variation of some parameters such as the construction area for the ice reservoir, the duration of the ice melting period and other related physical variables. A final analysis of results was followed by an economic study, which considered the changes in initial investment and the potential energy savings for each scenario, compared with a traditional air conditioning unit. This showed that, although research is still needed on many improvements in the design of scenarios and whether its application is limited by several macroeconomic factors, a seasonal ice storage system is an appealing option in energy efficiency terms and it could potentially be, technically and ecologically, a good way to obtain energy savings.

  11. L'influence des batiments et de l'inclinaison des forages sur le dimensionnement des systemes geothermiques

    NASA Astrophysics Data System (ADS)

    Giordanengo, Maude

    In new constructions, it often happens that Ground-Loop Heat Exchangers (GLHE) are positioned beneath the building foundation rather than outside. This can be due to a lack of space, for example in urban zones, or a simple choice of conception. At present, the available analytical models do not account for the thermal interaction between the building and the ground. This simplification means that we consider the geothermal system to be located outside of the building, what might bring errors for the sizing of the system. The thermal disturbance created by the building increases the average temperature of the ground beneath it. Our assumption is the following: when the geothermal system is operating in dominant heating mode, the effect of heat transferred from the building will be positive; it will be negative when operating in the dominant cooling mode. The proposed approach is based on the superposition principle in space. It is necessary to begin with a finite element model (FEM) of a building into the ground and by applying the heat equation we quantify the heat transfer of a 3D building into the ground. Afterward, the building thermal model is superposed with the analytical answer of a GLHE. We assume the temperature variations obtained from two models can be added everywhere. It is interesting to observe that factors such as the size of the building, the presence of insulation between the slab and the GLHE, the climate and the inclination of the boreholes interfere with the ground temperature. This works aim at testing the approach on synthetic cases, but also by means of real data. The building model is in steady state, whereas the ground analytical response is in transient state. This study demonstrates that the effect of the building can be favourable or unfavourable according to the heat load profile to the ground. If it is unbalanced in cooling, the effect is negative whereas if the heat loads to the ground are dominant in heating, it' effect is positive. When there is unbalanced loads in cooling, the temperature of the fluid entering the heat pump (EWT) increases in time and aims to reach the superior limit of the heat pump. The addition of the heat generated by the building in that case will increase EWT and will induce a loss of autonomy of the system. However, when the heat loads to the ground are heating dominant, the temperature of the fluid entering the heat pump follows the inverse tendency and decreases in time. The lower limit of the heat pump can be reached. Because the effect of the building is increasing the EWT, it is worthwhile for the autonomy of the system. If the EWT does not reach both limits of the heat pump, the system can be oversized and useless costs would be involved. The length of boreholes is an important factor on the quantity of additional heat which can be gained. For the same dimension of building, the shorter the borehole, the more the effect of the building is important. For 50 meter boreholes positioned beneath the building, we can gain 1.3°C on the average ground temperature in the center of the building. In the tested synthetic cases, the arrangement of boreholes beneath the building allows a 12% maximum additional rise of autonomy in a heating dominant system. The second factor considered in this study is the inclination of the boreholes. The comparison of the performances between vertical or slightly tilted boreholes reveals a beneficial effect of the inclination of borehole as well in heating dominant mode that in cooling dominant mode. The decrease of the interactions between boreholes explains this result. The gains of performance are of the order of those obtained by the building in heating dominant mode. The combination of both strategies leads to a 25% maximum rise of autonomy for short borehole (50 m) slightly tilted. However, in cooling dominant mode, the inclination of boreholes remains beneficial while the effect of the building is disadvantageous to the performance of the system. The net effect of both factors varies according to the characteristics of the load profile. In Quebec, as heating mode is usually dominant, we can assume that the inclination of borehole as well as the effect of the building are worthwhile to be considered in the sizing of GLHE.

  12. Building Maintenance Mechanic. Apprenticeship Training Standards = Mecanicien d'entretien des batiments. Normes de formation en apprentissage.

    ERIC Educational Resources Information Center

    Ontario Ministry of Skills Development, Toronto.

    These training standards for building maintenance mechanics are intended to be used by apprentice/trainees, instructors, and companies in Ontario, Canada, as a blueprint for training or as a prerequisite for accreditation/certification. The training standards identify skills required for this occupation and its related training program. They are…

  13. Investigation of CO2 induced biogeochemical reactions and active microorganisms of two German gas fields

    NASA Astrophysics Data System (ADS)

    Hoth, N.; Kassahun, A.; Seifert, J.; Krüger, M.; Bretschneider, H.; Gniese, C.; Frerichs, J.; Simon, A.; Simon, E.; Muschalle, T.

    2009-04-01

    The BMBF-Geotechnologien project "RECOBIO 2" continues the investigation of the long-term biogeochemical transformation of stored CO2. In addition to the Upper Carboniferous gas reservoir Schneeren (Westphalian C) the almost depleted Altmark gas field (Permian - Upper Rotliegend) is also investigated. Both sandstone reservoirs belong to the North German Basin and are operated by the GDF SUEZ E&P Germany (GDF SUEZ). The reservoirs differ in depth, initial and current fluid pressure as well as reservoir temperature, which is a biogeochemical important parameter. While the uplifted horst structure of Schneeren (approx. depth 2700 m) has a temperature level of 80 - 90 °C, the Altmark gas field (approx. depth 3300 m) shows temperatures around 120 °C. The Altmark site is known to be favourable for underground CO2-storage by enhanced gas recovery (EGR). This EGR process is operated by GDF SUEZ at the small and hydraulic isolated reservoir block "Altensalzwedel". This pilot test is accompanied by the scientific large-scale project CLEAN. In addition the RECOBIO2 project characterises the biogeochemical situation of the both large reservoir blocks of the Altmark gas field - „Salzwedel/ Peckensen" and „Heidberg/ Mellin". The produced formation waters of these reservoir blocks were sampled on different wellheads. The redox potentials are partly very low (Eh up to -300 mV) with slightly acidic pH-values (5,5 to 6). The high saline and (nearly) sulphate free formation waters of Na/Ca-Cl type have very high loads of Zn, Pb, Hg and As. In combination to the analysed DOC levels the talk discusses the importance of metal organic complexes. Also results of fluid geochemical calculations will be presented. Furthermore the diversity of bacteria and archaea of the formation waters as well as the potentials of CH4-, CO2-formation and sulphate reduction will be shown. Therefore the cultivation experiments were carried out with different substrates (H2/CO2, acetate, methanol). It

  14. Kinematics of the Suez-Sinai area from combined GPS velocity field

    NASA Astrophysics Data System (ADS)

    Pietrantonio, G.; Devoti, R.; Mahmoud, S.; Riguzzi, F.

    2016-12-01

    A combined GPS velocity solution covering a wide area from Egypt to Middle East allowed us to infer the current rates across the main, already well known, tectonic features. We have estimated 126 velocities from time series of 90 permanent and 36 non permanent GPS sites located in Africa (Egypt), Eurasia and Arabia plates in the time span 1996-2015, the largest available for the Egyptian sites. We have combined our velocity solution in a least-squares sense with two other recent velocity solutions of networks located around the eastern Mediterranean, obtaining a final IGb08 velocity field of about 450 sites. Then, we have estimated the IGb08 Euler poles of Africa, Sinai and Arabia, analyzing the kinematics of the Sinai area, particular velocity profiles, and estimating the 2D strain rate field. We show that it is possible to reliably model the rigid motion of Sinai block only including some GPS sites located south of the Carmel Fault. The estimated relative motion with respect to Africa is of the order of 2-3 mm/yr, however there is a clear mismatch between the modeled and the observed velocities in the southern Sinai sites. We have also assessed the NNE left shear motion along the Dead Sea Transform Fault, estimating a relative motion between Arabia and Africa of about 6 mm/yr in the direction of the Red Sea opening.

  15. Dynamics of wind setdown at Suez and the Eastern Nile Delta.

    PubMed

    Drews, Carl; Han, Weiqing

    2010-08-30

    Wind setdown is the drop in water level caused by wind stress acting on the surface of a body of water for an extended period of time. As the wind blows, water recedes from the upwind shore and exposes terrain that was formerly underwater. Previous researchers have suggested wind setdown as a possible hydrodynamic explanation for Moses crossing the Red Sea, as described in Exodus 14. This study analyzes the hydrodynamic mechanism proposed by earlier studies, focusing on the time needed to reach a steady-state solution. In addition, the authors investigate a site in the eastern Nile delta, where the ancient Pelusiac branch of the Nile once flowed into a coastal lagoon then known as the Lake of Tanis. We conduct a satellite and modeling survey to analyze this location, using geological evidence of the ancient bathymetry and a historical description of a strong wind event in 1882. A suite of model experiments are performed to demonstrate a new hydrodynamic mechanism that can cause an angular body of water to divide under wind stress, and to test the behavior of our study location and reconstructed topography. Under a uniform 28 m/s easterly wind forcing in the reconstructed model basin, the ocean model produces an area of exposed mud flats where the river mouth opens into the lake. This land bridge is 3-4 km long and 5 km wide, and it remains open for 4 hours. Model results indicate that navigation in shallow-water harbors can be significantly curtailed by wind setdown when strong winds blow offshore.

  16. Comparison of burnout pattern between hospital physicians and family physicians working in Suez Canal University Hospitals

    PubMed Central

    Kotb, Amany Ali; Mohamed, Khalid Abd-Elmoez; Kamel, Mohammed Hbany; Ismail, Mosleh Abdul Rahman; Abdulmajeed, Abdulmajeed Ahmed

    2014-01-01

    Introduction The burnout syndrome is characterized by emotional exhaustion, depersonalization, and low personal accomplishment. It is associated with impaired job performance. Methods This descriptive study examined 171 physicians for the presence of burnout and its related risk factors. The evaluation of burnout was through Maslach Burnout Inventory (MBI). The participant was considered to meet the study criteria for burnout if he or she got a “high“ score on at least 2 of the three dimensions of MBI. Results In the current study, the prevalence of burnout in hospital physicians (53.9%) was significantly higher than family physicians (41.94%) with (p=0.001). Participants who work in the internal medicine department scored the highest prevalence (69.64%) followed by Surgeons (56.50%) and Emergency doctors (39.39%). On the other hand, Pediatricians got the lowest prevalence (18.75%). Working in the teaching hospital and being married are strong predictors for occurrence of burnout. Conclusion There is a significant difference of burnout between hospital physicians and family physicians among the study subjects. Working in the teaching hospital and being married are strong predictors for occurrence of burnout. PMID:25422682

  17. Revolution in Egypt and the Potential for a New Suez Crisis

    DTIC Science & Technology

    2012-12-06

    2011), 109. 75 Wolman, "The Instigators", 9. 76 Blake Hounshell, "February 11: Pharaoh is Dead, Long Live Pharaoh ?" In Revolution in the Arab World...by Marc Lynch, 64-67. N.p.: The FP Group, a division of the Washington Post Company, 2012. Hounshell, Blake. "February 11: Pharaoh is Dead, Long...Live Pharaoh ?" In Revolution in the Arab World: Tunisia, Egypt, and the Unmaking of an Era, by Foreign Policy, edited by Marc Lynch, B Glasser Susan

  18. Family physicians' attitude and practice of infertility management at primary care--Suez Canal University, Egypt.

    PubMed

    Eldein, Hebatallah Nour

    2013-01-01

    The very particular natures of infertility problem and infertility care make them different from other medical problems and services in developing countries. Even after the referral to specialists, the family physicians are expected to provide continuous support for these couples. This place the primary care service at the heart of all issues related to infertility. to improve family physicians' attitude and practice about the approach to infertility management within primary care setting. This study was conducted in the between June and December 2010. The study sample comprised 100 family physician trainees in the family medicine department and working in family practice centers or primary care units. They were asked to fill a questionnaire about their personal characteristics, attitude, and practice towards support, investigations, and treatment of infertile couples. Hundred family physicians were included in the study. They were previously received training in infertility management. Favorable attitude scores were detected among (68%) of physicians and primary care was considered a suitable place for infertility management among (77%) of participants. There was statistically significant difference regarding each of age groups, gender and years of experience with the physicians' attitude. There was statistically significant difference regarding gender, perceiving PHC as an appropriate place to manage infertility and attitude towards processes of infertility management with the physicians' practice. Favorable attitude and practice were determined among the study sample. Supporting the structure of primary care and evidence-based training regarding infertility management are required to improve family physicians' attitude and practice towards infertility management.

  19. Provenance of Gebel El-Zeit sandstones, gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Abdel-Wahab, Antar A.

    1992-01-01

    The Paleozoic elastic succession at Gebel Zeit chiefly consists of fine- to medium-grained quartz arenite, locally containing well-rounded quartz pebbles. The marine Araba Formation (Early Cambrian) was deposited during transgression over a Precambrian granite. The overlying Naqus Formation (Late Cambrian) is fluvial, except for the uppermost few meters. Paleocurrent data for the Araba and Naqus formations indicate derivation from the north-northeast and south-southwest respectively. Quartz typology, other morphologic features of quartz, and mineral inclusions in quartz, as well as the study of heavy minerals were used to determine the provenance of the sandstones. Quartz typology successfully identified a granitic source for the Araba Formation. A combination of parameters indicates that the Naqus Formation was derived chiefly from a metamorphic terrain. Two ratios, polycrystalline/monocrystalline quartz and undulose/non-undulose quartz, successfully distinguish sandstones of the Araba Formation from those of the Naqus Formation. These values are 0.14 and 0.25 for Araba sandstones and 0.26 and 0.46 for Naqus sandstones, respectively. These differences either reflect different source rocks, or have resulted from selective abrasion loss of polycrystalline quartz in the rigorous surf zone during the marine transgression that deposited the Araba Formation.

  20. Dynamics of Wind Setdown at Suez and the Eastern Nile Delta

    PubMed Central

    Drews, Carl; Han, Weiqing

    2010-01-01

    Background Wind setdown is the drop in water level caused by wind stress acting on the surface of a body of water for an extended period of time. As the wind blows, water recedes from the upwind shore and exposes terrain that was formerly underwater. Previous researchers have suggested wind setdown as a possible hydrodynamic explanation for Moses crossing the Red Sea, as described in Exodus 14. Methodology/Principal Findings This study analyzes the hydrodynamic mechanism proposed by earlier studies, focusing on the time needed to reach a steady-state solution. In addition, the authors investigate a site in the eastern Nile delta, where the ancient Pelusiac branch of the Nile once flowed into a coastal lagoon then known as the Lake of Tanis. We conduct a satellite and modeling survey to analyze this location, using geological evidence of the ancient bathymetry and a historical description of a strong wind event in 1882. A suite of model experiments are performed to demonstrate a new hydrodynamic mechanism that can cause an angular body of water to divide under wind stress, and to test the behavior of our study location and reconstructed topography. Conclusions/Significance Under a uniform 28 m/s easterly wind forcing in the reconstructed model basin, the ocean model produces an area of exposed mud flats where the river mouth opens into the lake. This land bridge is 3–4 km long and 5 km wide, and it remains open for 4 hours. Model results indicate that navigation in shallow-water harbors can be significantly curtailed by wind setdown when strong winds blow offshore. PMID:20827299

  1. Sedimentation and early rift development in the northwest Red Sea and Gulf of Suez

    SciTech Connect

    Purser, B.H.; Orszag-Sperber, F.; Plaziat, J.C. )

    1988-08-01

    Late Oligocene and early Miocene strike-slip and vertical displacement created a system of structural depressions and highs which strongly influenced the localization of continental, protorift sediments. Alluvial fans prograded along grabens, generally oriented obliquely to the rift axis. These initial sediments, together with underlying prerift basement, were subsequently deformed, the resulting system of structural highs and lows influencing the mineralogy and geometry of the succeeding lower Miocene marine sediments. Lows oriented obliquely with respect to the rift axis continued to function as depocenters for siliciclastic marine-fan sedimentation. Other half-grabens oriented parallel to the axis trapped detritals, permitting carbonate sedimentation along the seaward side of the adjacent blocks. Carbonates accumulated as reefs concentrated along the margins of small structural platforms and as spectacular talus deposits on nearby flanks. These slope deposits prograded at variable rates which depend on both the angle and its orientation with respect to the onshore paleocurrent direction. The relationship between tectonic blocks and contemporaneous sedimentation, relatively intimate during the early phases, gradually becomes more remote as the carbonate slopes prograde asymmetrically with respect to the initial structural axes.

  2. Strong motion simulation at Abu Zenima city, Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Khalil, Amin Esmail

    2013-06-01

    Earthquake hazard assessments are an important task for the design of earthquake resistant structures and insurance industry. Such assessments get more importance when the site of interest is located near an active earthquake zone. Such situation is present for the location of Abu Zenima city. The city is characterized by the presence of industrial and Maritime platform in addition to other Oil production facilities. These industrial facilities motivated the present work. The simulated earthquake ground motion time histories are conducted using stochastic technique. The magnitude used for simulation is obtained using both probabilistic and deterministic approaches. An analysis using both approaches shows that moderate earthquakes in the vicinity of the site could have the largest effects on the area. Thus an earthquake of magnitude 4.5 at a distance of 21 km is chosen as design earthquake. The simulated ground motions are presented in terms of acceleration, velocity, and displacement time histories. In addition the response spectra are also presented that may be used for engineering purposes.

  3. The Tayiba Red Beds: Transitional marine-continental deposits in the precursor Suez Rift, Sinai, Egypt

    NASA Astrophysics Data System (ADS)

    Refaat, A. A.; Imam, M. M.

    1999-04-01

    The Tayiba Red Beds, exposed in the Abu Zenima area, west-central Sinai, have been intensively studied for their clay mineralogy and charophytes assemblages. Three surface sections exposed at Wadi El-Tayiba and Wadi Nukhul were studied. The Tayiba Formation uncomformably overlies the Middle Eocene Khaboba Formation at Wadi Nukhul and the Late Eocene Tanka Formation at Wadi El-Tayiba and commonly underlies the Early Miocene Nukhul Formation with unconformable relationships. The Tayiba Formation at Wadi Nukhul consists predominantly of continental coarse clastic sediments represented by polymictic conglomerates, alternating with red to pinkish mudstone, ferruginous sandstone and varicoloured mottled siltstone with plant remains. At Wadi El-Tayiba, the Tayiba Formation is represented by marine, yellow mudstone and red siltstone, alternating with greyish and reddish-yellow argillaceous to sandy limestone, highly fossiliferous with reworked Nummulites spp. and molluscan shell fragments. The mineralogical composition of the studied clay size fraction showed that most samples are dominated by illite, together with smectite, kaolinite and illite/smectite mixed layers. The relative proportion of these constituents shows wide variation. Smectite is more abundant than other constituents at Wadi El-Tayiba. The high content of smectite is usually accompanied by a terrigenous influx in the form of kaolinite and illite, reflecting deposition in an inner neritic shallow marine environment. The sediments of Wadi Nukhul are characterised by an appreciable proportion of illite, together with an illite/smectite mixed layer and minor amounts of kaolinite, suggesting deposition in fluviatile environments. The detailed investigation of charophytes (green algae) in the investigated sections showed that Wadi El-Tayiba is nearly barren of these microflorae, except for some benthic foraminifera from a shallow marine environment. In contrast, Wadi Nukhul yielded a high frequency and great diversity of charophytes, where 15 species have been identified, described and illustrated for the first time. The utilisation of the ranges of these species allowed the subdivision of the section into three charophyte zones, which are correlated with other zones recorded in Europe, as well as the standard mammal levels in the world. These biozones strongly assign the Tayiba Formation to the Late Eocene to Late Oligocene (Late Priabonian to Chattian). A depositional model was suggested for the Tayiba Formation in west-central Sinai.

  4. Petrophysical and petrographic evaluation of Sidri Member of Belayim Formation, Badri field, Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Abudeif, A. M.; Attia, M. M.; Radwan, A. E.

    2016-03-01

    Presence of sandstone streaks in Sidri Member within Belayim Formation that lies between two productive zones; Kareem Formation and Hammam Faraun Member, was the main reason to perform this study. It may represent a good hydrocarbon reservoir and will be added to the Egyptian oil production in some wells of Badri field. This Member has high resistivity signature on Electric-logs responses which attracted the attention to investigate its occurrence in the field, to delineate its distribution all-over the area, to evaluate the petrographic and petrophysical characteristics and to evaluate its productivity. Petrographic and petrophysical analyses of these sand zones were undertaken using thin section samples. The electric logs and subsurface geologic data was used to evaluate the main reservoir characteristics of the Sidri sandstone such as lithology, cementation, shale volume, porosity (Φ), effective porosity (Φ eff), estimated permeability (K), fluid saturation, fluid type and Net pay thickness. This study revealed that, Sidri sandstone facies was classified into two mainly sandy facies; blocky sandy facies which located at the northern part of the field and streaky sandy facies at the southern area of the field. These two facies are separated by shaley facies. Some wells were studied to represent the two sandy facies in Sidri Member and these sand intervals have not been tested yet. These sands consist of quartz grains with grey and pink feldspars as accessory minerals, with siliceous and calcareous cementation, with good porosity. Petrophysical evaluation of this sand unit indicated that it is hydrocarbon bearing formation in three wells and water bearing one in other wells. Electrical logs analysis (Resistivity, Density-Neutron, Sonic and Gamma-Ray) revealed that The volume of shale in this sandstone, the effective porosity, the water saturation, the estimated permeability, the hydrocarbon saturation, and the net-pay thickness are varying from 9 to 13%, 19%-22%, 26%-34%, 200 and 600 mD, 66 and 74%, 20-35 feet respectively. The fluid types are oil, gas and water.

  5. Family physicians’ attitude and practice of infertility management at primary care - Suez Canal University, Egypt

    PubMed Central

    Eldein, Hebatallah Nour

    2013-01-01

    Introduction The very particular natures of infertility problem and infertility care make them different from other medical problems and services in developing countries. Even after the referral to specialists, the family physicians are expected to provide continuous support for these couples. This place the primary care service at the heart of all issues related to infertility. The aim of the work: to improve family physicians' attitude and practice about the approach to infertility management within primary care setting. Methods This study was conducted in the between June and December 2010. The study sample comprised 100 family physician trainees in the family medicine department and working in family practice centers or primary care units. They were asked to fill a questionnaire about their personal characteristics, attitude, and practice towards support, investigations, and treatment of infertile couples. Results Hundred family physicians were included in the study. They were previously received training in infertility management. Favorable attitude scores were detected among (68%) of physicians and primary care was considered a suitable place for infertility management among (77%) of participants. There was statistically significant difference regarding each of age groups, gender and years of experience with the physicians′ attitude. There was statistically significant difference regarding gender, perceiving PHC as an appropriate place to manage infertility and attitude towards processes of infertility management with the physicians′ practice. Conclusion Favorable attitude and practice were determined among the study sample. Supporting the structure of primary care and evidence-based training regarding infertility management are required to improve family physicians' attitude and practice towards infertility management. PMID:24244792

  6. Diagenesis of diagenetic quartzarenites, Gebel El-Zeit area, Gulf of Suez, Egypt

    SciTech Connect

    Abdel-Wahab, A.A.; McBridge, E.F. )

    1990-05-01

    At the northern corner of El Zeit Range, 370 m of sandstone overlie Precambrian granite and underlie Cretaceous marine strata. The sandstones include the marine Lower Cambrian Araba Formation and the overlying dominantly fluvial Upper Cambrian( ) Naqus Formation The framework composition of both sandstones is almost entirely quartz with trace amounts of muscovite, K-feldspar, and heavy minerals. Up to 18% oversize pores, some filled with younger cements, attest to extensive dissolution loss of detrital grains. Because the final mineralogical maturation of these quartzarenites was through diagenesis, they are diagenetic quartzarenite. During burial diagenesis, the introduction of 5% quartz cement (unhomogeneously distributed) was followed by locally pore-occluding calcite cement. The sands were then compacted sufficiently to develop slightly sutured quartz grain contacts. These events were followed by extensive dissolution loss of carbonate cement, detrital feldspars, micas, and heavy minerals; by the formation of local patches of kaolinite (average = 6%); and by the formation of extensive iron-oxide cement, including specular hematite. These features suggest extensive invasion of meteoric water and exposure to oxidizing conditions. The time of this event can only be dated as post-Cambrian( ) and pre-Cenomanian. Some outcrop samples contain pore-occluding gypsum cement or mixtures of gypsum and halite cement. Sr{sup 87}/Sr{sup 86} ratios of four samples of gypsum cement have two modes equal to 0.7079 and 0.7085. These values are those of Miocene and slightly younger seawater. They suggest that evaporites were leached by modern meteoric water from nearby exposed Miocene and younger marine evaporite-bearing strata, transported in surface and groundwater to the topographically low terrain where the Cambrian sandstones crop out, and were precipitated by evaporation of surface water.

  7. A GDI/GDF-like system for sorting and shuttling ciliary proteins.

    PubMed

    Ismail, Shehab

    2016-08-03

    Post/co-translational modifications by the addition of lipids take place in a vast number of proteins. Rab and Rho are small G proteins which are prenylated and targeted to membranes in complex with solubilizing factors called guanosine dissociation inhibitors (GDIs). The release of Rab and Rho at the correct destination from their cognate GDI has been proposed to be mediated through GDI displacement factors. However this mechanism is yet to be established and it has been shown that loading of Rab proteins with GTP at the destination can be sufficient for their correct targeting. PDE6D shares structural homology with Rho GDI and solubilises several prenylated proteins and mediate their targeting to different destinations including cilia. In a paper published by Fansa et al, the authors propose that sorting of cargo is dependent on the differential release by bona fide GDFs, Arl2 and Arl3, and the localization of the active Arl3GTP in cilia.

  8. [Prevalence of health problems in the Gazel (EDF-GDF) cohort: regional distribution and disparities].

    PubMed

    Tran, P D; Leclerc, A; Chastang, J F; Goldberg, M

    1994-01-01

    This study deals with regional differences in annual prevalence of 44 declared diseases or clinical disorders in 1989 in GAZEL cohort participants from "Electricité de France-Gaz de France" company. The studied sample consisted of 20,325 people, from 35 to 50 years old, living in France, who answered to a mail questionnaire in 1989. The collected data from one year were analysed. An overall "regional effect" was searched about every listed disease in the questionnaire. For this purpose, a logistic model, controlling for age and sex, was used. For comparing prevalence of a disease in one region with average prevalence, an odds ratio (OR) was calculated: it was defined here as the ratio of disease odd in the region to the average French odd. The regional effect was studied in greater detail for five diseases, making allowance for extra factors of adjustment (tobacco and alcohol consumption, Quetelet index, salary category, number of declared diseases). The regional effect remained significative for four diseases: hypertension with OR from 1.26 to 1.68 in northern regions, and from 0.63 to 0.75 in southeastern ones; osteoarthrosis with OR lower than 1 in western regions (0.60 to 0.79), and larger in the South (1.24 to 1.46); hyperthyroidism, goiter with OR elevated in Midi-Pyrénées (2.91) and Lorraine (1.82) [corrected]; renal stones with OR high in the South (1.85 in Provence Riviera). These results can be compared to known observations about geographical differences in mortality. They also suggest persistence of hazardous areas for some diseases.

  9. Methodologie d'evaluation de la demande de chaleur des groupes de batiments dans le cadre d'une etude de faisabilite du chauffage urbain

    NASA Astrophysics Data System (ADS)

    Quirion-Blais, Olivier

    In the context of energy efficiency improvements to pulp and paper mills, process modifications allow to free low quality steam. This kind of low pressure and temperature steam is often found to be in excess in mills. New opportunities to use this energy could be created by gathering plants along with local communities and other enterprises into eco-industrial clusters. Following this proposition, district heating is an interesting technology that could be developed. It consists in supplying buildings with steam or hot water from one or more central heating plants through a series of canalization, generally underground. The supplied energy is used mostly for space heating but it can also be used with appliances specially designed for this purpose. Under certain conditions, this type of heating is cheaper and more environmentally friendly for several reasons including the facts that one central boiler plant is more efficient and has lower pollutant emissions due to better combustion control. Moreover, it can be adapted to multiple fuels that are locally available such as biomass around some pulp and paper mills. However, to insure that the savings occur, the heat demand must be sufficiently high and concentrated. Therefore, detailed feasibility studies shall be conducted to justify significant investments. Such studies require a lot of time not to mention that they necessitate a lot of data which can be difficult to obtain. The objective of this work is to develop a methodology that can assess the feasibility of district heating quickly and using easily accessible data. It was mainly designed to determine the heat consumption, which is especially critical as to decide whether or not to implement this technology. The focus is primarily directed on residential buildings, but another methodology is also developed to take into account the commercial and institutional buildings demand. An analysis of the sources of data revealed a certain redundancy among them. Therefore, four different computation procedures were developed to obtain the heat consumption of residential buildings: • C1, the first procedure, is the most time consuming one. It is also the one that uses the most specific information from the case: aerial photographs, census data (building year of construction and type (single family detached, single family attached, apartments or mobile homes)) and punctual on-site verification from the target area. National estimates of thermal requirements values are also used. • C2, the second procedure, is less specific than C1, but is much less time consuming to achieve. The local data sources used are: aerial photographs and census data from the case. While the national ones are: estimates of the building heating surfaces and thermal requirements. • C3 and C4, are the easiest procedures. Those two are very similar. The specific data used in these cases are census data from the locations under study. National data used for C3 are building surface estimates and thermal requirements values while C4 only uses thermal requirement values which are slightly different from those of C3. A further analysis revealed later that these two calculations yielded the same results. Therefore, since C3 is slightly more complicated to implement, it was removed from further analysis. Using three procedures thus ensures the stability of the methodology when the three results are the same order of magnitude. An average of the three results gives a good estimation of the consumption. The methodology was then applied to four study cases. One of them has already been the subject of a detailed district heating assessment feasibility study. It is used to validate the results obtained with the new methodology. The three other cases are rather used to test different conditions (number, density, type and year of construction of buildings). The validation results showed that the methodology can determine the heat consumption to about 20% of the baseline value. It also determines the total heating surface to about 5%. The three other study cases, A, B and C, have confirmed that possibility of applying the methodology in various conditions. Case A showed lower gaps between the four procedures when the rate of single family houses is lower. Since this rate is high in the validation case, better results can be expected for cases where the number of single family houses is low, such as in case A. In case B, the global results showed a particularly low gap between the four procedures with a maximum of 5%. However, an analysis of individual dissemination areas showed higher positive and negative gaps, which, when they are summed, compensate for the individual errors. The bigger errors in this case are explained by the fact that the apartments in this city are larger than the national average. Case C presented an additional challenge since no aerial photo was available. It has nevertheless been possible to realize two calculation procedures, C3 and C4, which provided a broad approximation of the consumption. For the commercial sector, a similar methodology to that of the residential sector is developed. However, the lack of global data has prescribed the individual processing of every building. This approach is also justified by the fact that commercial and institutional buildings are less numerous and have higher consumption. Due to the extended duration of this type of approach, only the validation and case Aare realized. The first one confirmed the better results than the ones from the residential sector with a gap of 7% compared to the consumption baseline. The results from case A showed the areas where the heat consumption is higher. Furthermore, it showed that the commercial and institutional demand accounts for 10% to 40% of the total heat demand. The integration of the results obtained into a district heating feasibility study is then discussed. A joint analysis of the residential and the commercial and institutional sectors showed the importance of considering each building's heat consumption for the planning of a district heating network. The profitability of the study cases is considered in relation to the thermal thresholds suggested in the literature.

  10. Controle sismique d'un batiment en acier de 3 etages a l'echelle 1/3 par amortisseurs elastomeres et contreventements en chevron

    NASA Astrophysics Data System (ADS)

    Gauron, Olivier

    This study develops an innovative configuration of seismic natural rubber dampers for multistory low- and medium-rise steel braced frames. The dampers are directly integrated in an horizontal position in the seismic force resisting system of the structure. They are connected in a series with typical chevron brace systems. This control system provides not only additional structural damping to the structure but also a period shift, acting in the same way as a base isolation system. First, the fiber reinforced natural rubber used in the application was tested. It exhibited strong non linear dependance of its equivalent viscoelastic properties related to the shear strain. Then, a 1/3-scale 3-story chevron braced steel frame with and without dampers was considered. The structure was build and placed on the shaking table of the University of Sherbrooke Structures Laboratory. Numerical studies show that the efficiency of the control system reduces strongly the seismic induced forces of the undamped structure without any amplification of displacement or drift. Obtained seismic response reduction levels represent significant safety and economical benefits for the proposed application. Finally, the control system viability is experimentally demonstrated by shaking table tests at different reduced seismic intensities. Non linear behavior of the structure due to non linear behavior of the damping material is highlighted, and the dependance of seismic control performances is shown to be related to seismic intensities. Results allow an extrapolation of the experimental control peformances tending to the numerical results at higher intensities. Key-words : chevron braces, damper, multistory building, natural rubber, seismic control, shaking table.

  11. Success in Opposite Direction: Strategic Culture and the French Experience in Indochina, the Suez, and Algeria, 1945-1962

    DTIC Science & Technology

    2015-05-21

    culture and a lack of institutional learning and adaptability when confronted with changing strategic contexts. An examination of the French...thereby better preparing the United States for future wars. The US Army can learn from these experiences by better understanding how the American...lack of institutional learning and adaptability when confronted with changing strategic contexts. An examination of the French experience in

  12. Studies on rodents role as reservoir hosts of leishmaniasis with specical reference to their ectoparasites in Suez Governorate.

    PubMed

    Shoukry, Nahla M; El-Naggar, Mostafa H; Darwish, Ahmed B; Soliman, Belal A; El-Sawaf, Bahira M

    2006-04-01

    The distribution of rodents was studied in three different habitats. Seven rodent species were identified: Rattus norvegicus, R. alexandrinus, R. frugivorous, Mus musculus, Acomys russatus, Meriones sacramenti and Gerbillus pyramidum. The species distribution varied with the habitat type. The highest density of rodents was in July and August and the lowest one was in January. However, some species were collected all the year round. The rodents were investigated for the endo- and ecto-parasites. No Leishmania parasites were found. The ectoparasites were: Xenopsylla cheopis, Leptopsylla segnis and Ctenocephalides felis, Polyplax spinulos, Hyalomma dromedarii (nymph) and Echinolaelaps echidninus and Hemolaelaps glassgowi. Ecto-parasites were on rodents all year-round in domestic habitat and peridomestic habitats. In wild one, ecto-parasites activity was from March to December. The rodents' role as reservoir for L. major was experimentally studied. Rodents inoculated with L. major together with hamster and BALB-c mice developed cutaneous lesions. The active lesions, the rodents' ecological habitats and the presence of insect-vector may pave the way to an epidemic zoonotic leishmaniasis role.

  13. Sedimentological and palaeoenvironmental studies on the clastic sequence of Gebel El-Zeit area, gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Abdel-Wahab, Antar; Allam, A.; Kholief, M.; Salem, A.

    1992-01-01

    The present work deals with the sedimentological and palaeoenvironmental studies of the Palaeozoic clastic sequence (Cambrian?) of the Gebel El-Zeit area. The sandstones which build up the major part of this sequence are fine to coarse grained moderately to well sorted, mostly of unimodal patterns, strongly fine skewed to near symmetrical and vary from meso- to very lepto-kurtic. The grain-size parameters and their bivariate relations do not give an exact environment of deposition nevertheless, most of them have a fluviatile origin. So, the application of some of the bivariate relations to ancient sediments, which microscopically show mild or no cementation, is still valid if coupled with other parameters, such as sedimentary structures, palaeocurrent analysis and other confirmed data. The palaeocurrent analysis indicates that these sandstones came from two completely different sources. A marine transgression from the north northeast produced the Araba Formation, whereas the Naqus Formation has been interpreted as fluvial. The source is situated to the south southwest. The streams were probably very erratic and intermittent.

  14. Integrated petrophysical and lithofacies studies of lower-middle Miocene reservoirs in Belayim marine oil field, Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Ali Ali, El-Khadragy; Emad El Din Abd Elrazik, Eysa; Shebl Azam, Salah; Ahmed Hassan, Saleh

    2016-05-01

    The reservoir parameters (total gross thickness, shale volume, total porosity, effective porosity, water saturation, bulk pore volume, net pay thickness and oil in place indicator) of Kareem and Belayim formations are studied through nine wells and mapped to show the aerial distribution of these parameters. Interpretation of these maps showed that, the best locations of hydrocarbon accumulation in Belayim marine oil field are middle part, northeast and the south west directions for Kareem formation and southwest and northeast directions for Belayim formation. The petrophysical results of Belayim formation were presented in the form of 3D slicing models to exhibit the variation of these parameters in the different directions. Cross plots of Kareem formation were done using neutron, density and sonic logs which is directly influenced by the matrix composition. By using two or three porosity logs reading we determined the porosity and evaluated the matrix characteristics of Kareem formation as it is considered as a good reservoir for oil and gas and mainly composed of sand stone. Finally, facies maps for Kareem and Belayim formations which established using composite logs indicate that, the environment of deposition of Kareem formation was deep marine in the middle and northern parts and shallow in the southern parts of the study area, meanwhile in Belayim formation the environment of deposition was in lagoonal through the deposition of Baba and Feiran members and shallow to deep during the sedimentation of Sidri and Hammam Faraun members.

  15. Problemes et methodes de la lexicographie quebecoise (Problems and Methods of Quebec Lexicography).

    ERIC Educational Resources Information Center

    Cormier, Monique C., Ed.; Francoeur, Aline, Ed.

    Papers on lexicographic research in Quebec (Canada) include: "Indications semantiques dans les dictionnaires bilingues" ("Semantic Indications in Bilingual Dictionaries) (Johanne Blais, Roda P. Roberts); "Definitions predictionnairiques de 'maison, batiment, et pavillon'" ("Pre-dictionary definitions of 'house,…

  16. The Federal Public Works Infrastructure Strategy Program - Federal Works Infrastructure R&D: A New Perspective

    DTIC Science & Technology

    1993-07-01

    broader context, especially in view of the changing global environment. This more expansive view includes the traditional components and incorporates the...the Centre Scientifique et Technique du Batiment ( CSTB ), the Laboratorie Central des Ponts et Chaussees (LCPC), and the Centre Experimental de...Recherches et d’Etudes du Batiment et Travaux Publics (CEBTP). Focus of French research was defined by the CSTB in 1989, as follows: • Improvement in the

  17. The Diverse Roles of Nonsteroidal Anti-inflammatory Drug Activated Gene (NAG-1/GDF15) in Cancer

    PubMed Central

    Wang, Xingya; Baek, Seung Joon; Eling, Thomas E.

    2013-01-01

    Nonsteroidal anti-inflammatory drug (NSAID) activated gene-1, NAG-1, is a divergent member of the transforming growth factor-beta (TGF-β) superfamily that plays a complex but poorly understood role in several human diseases including cancer. NAG-1 expression is substantially increased during cancer development and progression especially in gastrointestinal, prostate, pancreatic, colorectal, breast, melanoma, and glioblastoma brain tumors. Aberrant increases in the serum levels of secreted NAG-1 correlate with poor prognosis and patient survival rates in some cancers. In contrast, the expression of NAG-1 is up-regulated by several tumor suppressor pathways including p53, GSK-3β, and EGR-1. NAG-1 expression is also induced by many drugs and dietary compounds which are documented to prevent the development and progression of cancer in mouse models. Studies with transgenic mice expressing human NAG-1 demonstrated that the expression of NAG-1 inhibits the development of intestinal tumors and prostate tumors in animal models. Laboratory and clinical evidence suggest that NAG-1, like other TGF-β family members, may have different or pleiotropic functions in the early and late stages of carcinogenesis. Upon understanding the molecular mechanism and function of NAG-1 during carcinogenesis, NAG-1 may serve as a potential biomarker for the diagnosis and prognosis of cancer and a therapeutic target for the inhibition and treatment of cancer development and progression. PMID:23220538

  18. Experimental investigation on heat transfer for two-phase flow under natural convection

    SciTech Connect

    Amizic, Milan; Guyez, Estelle; Seiler, Jean-Marie

    2012-07-01

    In the frame of severe accident research for the second and the third generation of nuclear power plants, some aspects of the concrete cavity ablation during the molten corium - concrete interaction are still remaining issues. The determination of heat transfer along the interfacial region between the molten corium pool and the ablating basemat concrete is crucial for the assessment of concrete ablation progression and eventually the basemat melt-through. For the purpose of experimental investigation of thermal-hydraulics inside a liquid pool agitated by gas bubbles, the CLARA project has been launched jointly by CEA, EDF, IRSN, GDF-Suez and SARNET. The CLARA experiments are performed using simulant materials and they reveal the influence of superficial gas velocity, liquid viscosity and pool geometry on the heat transfer coefficient between the internally heated liquid pool and vertical and horizontal pool walls maintained at uniform temperature. The first test campaign has been conducted with the smallest pool configuration (50 cm x 25 cm x 25 cm). The tests have been performed with liquids covering a wide range of dynamic viscosity from approximately 1 mPa s to 10000 mPa s. This paper presents some preliminary conclusions deduced from the experiments which involve a liquid pool with the gas injection only from the bottom plate. A comparison with existing models for the assessment of heat transfer has also been carried out. (authors)

  19. Large eddy simulation of unsteady wind farm behavior using advanced actuator disk models

    NASA Astrophysics Data System (ADS)

    Moens, Maud; Duponcheel, Matthieu; Winckelmans, Gregoire; Chatelain, Philippe

    2014-11-01

    The present project aims at improving the level of fidelity of unsteady wind farm scale simulations through an effort on the representation and the modeling of the rotors. The chosen tool for the simulations is a Fourth Order Finite Difference code, developed at Universite catholique de Louvain; this solver implements Large Eddy Simulation (LES) approaches. The wind turbines are modeled as advanced actuator disks: these disks are coupled with the Blade Element Momentum method (BEM method) and also take into account the turbine dynamics and controller. A special effort is made here to reproduce the specific wake behaviors. Wake decay and expansion are indeed initially governed by vortex instabilities. This is an information that cannot be obtained from the BEM calculations. We thus aim at achieving this by matching the large scales of the actuator disk flow to high fidelity wake simulations produced using a Vortex Particle-Mesh method. It is obtained by adding a controlled excitation at the disk. We apply this tool to the investigation of atmospheric turbulence effects on the power production and on the wake behavior at a wind farm level. A turbulent velocity field is then used as inflow boundary condition for the simulations. We gratefully acknowledge the support of GDF Suez for the fellowship of Mrs Maud Moens.

  20. Depositional framework and sequence stratigraphic aspects of the Coniacian Santonian mixed siliciclastic/carbonate Matulla sediments in Nezzazat and Ekma blocks, Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    El-Azabi, M. H.; El-Araby, A.

    2007-04-01

    Superb outcrops of mixed siliciclastic/carbonate rocks mark the Coniacian-Santonian Matulla Formation exposed in Nezzazat and Ekma blocks, west central Sinai. They are built up of various lithofacies that reflect minor fluctuations in relative sea-level from lower intertidal to slightly deep subtidal settings. Relying on the facies characteristics and stratal geometries, the siliciclastic rocks are divided into seven depositional facies, including beach foreshore laminated sands, upper shoreface cross-bedded sandstone, lower shoreface massive bioturbated and wave-rippled sandstones, shallow subtidal siltstone and deep subtidal shale/claystone. The carbonate rocks comprise lower intertidal lime-mudstone, floatstone and dolostone, shallow subtidal skeletal shoal of oyster rudstone/bioclastic grainstone, and shoal margin packstone. Oolitic grain-ironstone and ferribands are partially intervened the facies types. Deposition has taken place under varied conditions of restricted, partly open marine circulation, low to high wave energy and normal to raised salinity during alternating periods of abundant and ceased clastic supply. The facies types are arranged into asymmetric upward-shallowing cycles that record multiple small-scale transgressive-regressive events. Lime-mudstone and sandstone normally terminate the regressive events. Four sequence boundaries marking regional relative sea-level falls divide the Matulla Formation into three stratigraphic units. These boundaries are Turonian/Coniacian, intra-Coniacian, Coniacian/Santonian and Santonian/Campanian. They do not fit with those sequence boundaries proposed in Haq et al.'s global eustatic curves (1988) except for the sea-level fall associated with the intra-Coniacian boundary. Other sequence boundaries have resulted from regional tectonic impact of the Syrian Arc Fold System that has been initiated in north Egypt during the Latest Turonian-Coniacian. These boundaries enclose three well-defined 3rd order depositional sequences; their enclosing shallowing-upward cycles (i.e. parasequences) record the 4th order relative sea-level fluctuations. 34 and 20 parasequence sets, in the order of a few meters to tens of meters thick, mark the Matulla sequences in Nezzazat and Ekma blocks respectively. Each sequence shows an initial phase of rapid sea-level rise with retrogradational sets, followed by lowering sea-level and progradation/aggradation of the parasequence sets. The transgressive deposits display predominance of deep subtidal lagoonal facies, while highstand deposits show an increase in siliciclastic and carbonate facies with the progressive decrease of lagoonal facies. The sedimentary patterns and environments suggest that the regional, partly eustatic sea-level (i.e. intra-Coniacian) changes controlled the overall architecture of the sequence distribution, whereas changes in the clastic input controlled the variations in facies associations within each depositional sequence.

  1. Use of remote sensing techniques and aeromagnetic data to study episodic oil seep discharges along the Gulf of Suez in Egypt.

    PubMed

    Kaiser, M F; Aziz, A M; Ghieth, B M

    2013-07-15

    Four successive oil discharges were observed during the last 2 years following the recording of the earthquake events. Oil slicks were clearly observed in the thermal band of the Enhanced Thematic Mapper images acquired during the discharge events. Lineaments were extracted from the ETM+ image data and SRTM (DEM). The seismic activity is conformable in time and spatially related to active major faults and structural lineaments. The concerned site was subjected to a numerous earthquakes with magnitudes ranging from 3 to 5.4 Mb. Aeromagnetic field data analyses indicated the existence of deep major faults crossing the Gebel El-Zeit and the Mellaha basins (oil reservoirs). The magnetic field survey showed major distinctive fault striking NE-SW at 7000 m depth. Occurrence of these faults at great depth enables the crude oil to migrate upward and appear at the surfaces as oil seeps onshore and as offshore slicks in the Gemsa-Hurghada coastal zone.

  2. Evaluation of groundwater potentiality survey in south Ataqa-northwestern part of Gulf of Suez by using resistivity data and site-selection modeling

    NASA Astrophysics Data System (ADS)

    Sultan, Sultan Awad; Essa, Khalid Sayed Ahmed Tawfik; Khalil, Mohamed Hassan; El-Nahry, Alaa Eldin Hassan; Galal, Alaa Nayef Hasan

    2017-06-01

    The integration between advanced techniques for groundwater exploration is necessary to manage and protect the vital resources. Direct current (DC) resistivity geoelectrical technique, Enhanced Thematic Mapper Landsat (ETM+) images and a geographic information system (GIS) are integrated to identify the groundwater potentiality in the study area. The interpretation of the one-dimensional (1-D) inversion of the acquired resistivity data are implemented for mapping the fresh to slightly brackish water aquifer. This number of vertical electric sounding is quite enough for different geologic mapping. The depth to the top of the ground water table (obtained from the existing Water well) and subsurface lithological information are used to calibrate the results of the resistivity data inversion. This research discussed how the integration between the geoelectrical parameters and hydrological data, could be used to determine the appropriate locations of dams construction and recommend the appropriate methods for management and rehabilitation of the aquifer.

  3. Anorexia‐cachexia syndrome in hepatoma tumour‐bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC‐1/GDF15

    PubMed Central

    Borner, Tito; Arnold, Myrtha; Ruud, Johan; Breit, Samuel N.; Langhans, Wolfgang; Lutz, Thomas A.; Blomqvist, Anders

    2016-01-01

    Abstract Background The cancer‐anorexia‐cachexia syndrome (CACS) negatively affects survival and therapy success in cancer patients. Inflammatory mediators and tumour‐derived factors are thought to play an important role in the aetiology of CACS. However, the central and peripheral mechanisms contributing to CACS are insufficiently understood. The area postrema (AP) and the nucleus tractus solitarii are two important brainstem centres for the control of eating during acute sickness conditions. Recently, the tumour‐derived macrophage inhibitory cytokine‐1 (MIC‐1) emerged as a possible mediator of cancer anorexia because lesions of these brainstem areas attenuated the anorectic effect of exogenous MIC‐1 in mice. Methods Using a rat hepatoma tumour model, we examined the roles of the AP and of vagal afferents in the mediation of CACS. Specifically, we investigated whether a lesion of the AP (APX) or subdiaphragmatic vagal deafferentation (SDA) attenuate anorexia, body weight, muscle, and fat loss. Moreover, we analysed MIC‐1 levels in this tumour model and their correlation with tumour size and the severity of the anorectic response. Results In tumour‐bearing sham‐operated animals mean daily food intake significantly decreased. The anorectic response was paralleled by a significant loss of body weight and muscle mass. APX rats were protected against anorexia, body weight loss, and muscle atrophy after tumour induction. In contrast, subdiaphragmatic vagal deafferentation did not attenuate cancer‐induced anorexia or body weight loss. Tumour‐bearing rats had substantially increased MIC‐1 levels, which positively correlated with tumour size and cancer progression and negatively correlated with food intake. Conclusions These findings demonstrate the importance of the AP in the mediation of cancer‐dependent anorexia and body weight loss and support a pathological role of MIC‐1 as a tumour‐derived factor mediating CACS, possibly via an AP‐dependent action. PMID:28025863

  4. Four new species of Ceratomyxa Thelohan 1892 (Myxozoa: Myxosporea: Ceratomyxidae) infecting the gallbladder of some Red Sea fishes.

    PubMed

    Abdel-Ghaffar, F; Ali, M A; Al Quraishy, S; Al Rasheid, K; Al Farraj, S; Abdel-Baki, A S; Bashtar, A-R

    2008-08-01

    Four new Ceratomyxa species were described from the gallbladder of four Red Sea fishes at Suez and Hurghada, Egypt. These species are Ceratomyxa bassoni sp. n. from Plectorhinchus gaterinus (Forsskal 1775) at Suez and Hurghada, Ceratomyxa entzerothi sp. n. from Valamugil seheli (Forsskal 1775) at Suez and Hurghada, Ceratomyxa swaisi sp. n. from Saurida undosquamis (Richardson 1848) at Suez only and Ceratomyxa hurghadensis sp. n. from Fistularia commersonii Ruppell 1838 at Hurghada only. Their taxonomic affinities to other species are discussed.

  5. CLEAN - Large-Scale CO2 Storage for Enhanced Gas Recovery in a depleted German Gasfield

    NASA Astrophysics Data System (ADS)

    Kuehn, M.; Förster, A.; Grossmann, J.; Meyer, R.; Pilz, P.; Reinicke, K.; Schaefer, D.; Tesmer, M.; Wendel, H.

    2011-12-01

    The project CLEAN was a German research and development (R&D) alliance of 16 partners from science and industry that conducted research from July 2008 until June 2011 on Enhanced Gas Recovery (EGR) with regard to Europe's second largest onshore gas field. The gas field is located in the Altmark (Germany) and is owned by GDF SUEZ E&P Deutschland GmbH. Activities focused on the Altensalzwedel sub-field, having the size of 14 sq.km. The Altensalzwedel sub-field is a structurally and hydraulically closed block, bound by faults. Subsurface data are available from 12 existing wells drilled into the Rotliegend reservoir, which is at >3000 m depth. About 30 wells from an area of 30 sq.km, surrounding the Altensalzwedel block, provided additional data for the generation of an integrated earth model. Fluviatile silt- and sandstones from Upper Rotliegend built the reservoir at depth. The caprock above the reservoir consists of massive Zechstein formations with significant deposits of evaporites. These salt layers with an average thickness of several hundred meters represent a natural seal of the reservoir. At present the reservoir temperature is about 125 °C and reservoir pressures decreased from initially 425 bar to pressures between 30 bar and 50 bar, due to the former gas production from the field. For the substructure of Altensalzwedel it is assessed that the natural gas reservoir is depleted by 90 %. Within the 3 years project following results, developments, methods and concepts were achieved and will be presented: (1) well bore conditions, (2) risk base monitoring schemes to detect possible technical leakage at well bores, (3) strategies to avoid and mitigate technical leakage, (4) permanent geological sealing of well bores, (5) quality of the reservoir facies and mineral-pore-interface and related fluid-rock reactions, (6) chemical alteration of fluid and rock from laboratory experiments, (7) models and simulations of coupled processes, (8) data management system, (9

  6. Impact of Thermal Stresses on Wellbore Integrity during CO2 Injection

    NASA Astrophysics Data System (ADS)

    Roy, P.; Walsh, S.; Morris, J.; Carroll, S.; Hao, Y.; Iyer, J.; Torsater, M.; Gawel, K.; Todorovic, J.

    2015-12-01

    Thermal stresses caused by injection of cold CO2 into warmer storage reservoirs could create leakage pathways out of the storage reservoir. Although few studies have been conducted to investigate the well bore integrity subjected to thermal cycling during CO2injection, a systematic investigation on thermally induced expansion and contraction affecting the debonding and cracking of the well barrier materials has not yet been performed. In this work, we have analyzed the thermo-mechanical characteristics of the well barrier materials undergoing repeated thermal cycling using a multiscale, multiphysics platform named GEOS. More specifically, we model the modes of failure during thermal cycling to assess the temperature range for minimal impact on well integrity. A finite element solver was used for the geomechanics and a finite volume solver was used for the thermal diffusion. Results of the initiation and propagation of fractures due to temperature variations in the cement sheath are presented. Preliminary results suggest that radial fracture develops as the cement is heated while debonding occurs in the casing-cement and cement-rock interfaces during the cooling period. The effects of different confinement conditions based on in-situ stresses were also analyzed. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under the Contract DE-AC52-07NA27344. This work has been produced with support from the BIGCCS Centre, performed under the Norwegian research program Centres for Environment-friendly Energy Research (FME) and the KPN project "Ensuring well integrity during CO2 injection". The authors acknowledge the following partners for their contributions: Gassco, Shell, Statoil, TOTAL, GDF SUEZ and the Research Council of Norway (193816/S60 and 23389).

  7. Growth differentiation factor-15: a p53- and demethylation-upregulating gene represses cell proliferation, invasion, and tumorigenesis in bladder carcinoma cells

    PubMed Central

    Tsui, Ke-Hung; Hsu, Shu-Yuan; Chung, Li-Chuan; Lin, Yu-Hsiang; Feng, Tsui-Hsia; Lee, Tzu-Yi; Chang, Phei-Lang; Juang, Horng-Heng

    2015-01-01

    Growth differentiation factor-15 (GDF15), a member of the TGF-β superfamily, affects tumor biology of certain cancers, but remains poorly understood in bladder cancer cells. This study determined the expression, regulation, function, and potential downstream target genes of GDF15 in bladder carcinoma cells. The transitional papilloma carcionoma cells (RT4) expressed higher levels of GDF15 as compared with the bladder carcinoma cells (HT1376 and T24). Treatments of recombinant human GDF15 (rhGDF15) reduced the proliferations of HT1376 and T24 cells. Expression of GDF15 was upregulated via DNA demethylation and p53. The cell proliferation, invasion, and tumorigenesis were reduced in ectopic overexpression of GDF15, while enhanced in GDF15 knockdown. The expressions of mammary serine protease inhibitor (MASPIN) and N-myc downstream-regulated family genes (NDRG1, NDRG2, and NDRG3) were upregulated by GDF15 overexpressions and rhGDF15 treatments in bladder carcinoma cells. GDF15 knockdown induced epithelial-mesenchymal transition (EMT) and F-actin polarization in HT1376 cells. Our results suggest that enhanced expressions of MASPIN and N-myc downstream-regulated family genes and the modulation of EMT may account for the inhibitory functions of GDF15 in the cell proliferation, invasion, and tumorigenesis of bladder carcinoma cells. The GDF15 should be considered as a tumor suppressor in human bladder carcinoma cells. PMID:26249737

  8. Uncovering the Role of BMP Signaling in Melanocyte Development and Melanoma Tumorigenesis

    DTIC Science & Technology

    2015-06-01

    loss of function studies in zebrafish embryos and mammalian cultured cells to determine if GDF6 antagonizes melanocyte development. In this task...studies in zebrafish and mammalian cultured cells were proposed to determine the effects of gdf6b overexpression and gdf6b loss on melanocyte...which gdf6b acts. We have also performed knockdown and overexpression experiments in human cultured melanoma cells. As described below, alteration

  9. Bone Morphogenetic Proteins, Antagonists and Receptors in Prostate Cancer

    DTIC Science & Technology

    2005-01-01

    Absent 220053_at GDF-3 Absent ɚ 207145at MSTN myostatin = GDF-8 Absent Absent Up 221314_at GDF-9 Present no change ɚ 221576_at PLAB = prostate...Res 1991;51:4716-20. 1998;102:2106-14. 40. Ling MT, Wang X, Ouyang XS, et al. Id-I expression promotes cell survival through 26. Miyazono K, Suzuki H

  10. Growth differentiation factor 15 as a radiation-induced marker in oral carcinoma increasing radiation resistance.

    PubMed

    Schiegnitz, Eik; Kämmerer, Peer W; Rode, Katharina; Schorn, Thomas; Brieger, Jürgen; Al-Nawas, Bilal

    2016-01-01

    Growth differentiation factor 15 (GDF15) is involved in tumor pathogenesis of oral squamous cell carcinoma (OSCC). The aim of this study was an investigation of the potential influence of GDF15 on radioresistance of OSCC cells in vitro. Oral squamous cell carcinoma cell lines were irradiated with 0, 2, or 6 Gy, and GDF15 expression in the supernatant per survived cell colony was examined with ELISA. Non-irradiated and OSCC cell lines irradiated with 6 Gy were evaluated for GDF15 expression using immunofluorescent staining. For further investigation of GDF15 effects on radioresistance, a GDF15 knockdown model in a human OSCC cell line was established, and apoptotic activity after radiation was measured using the Caspase-Glo 3/7 system. ELISA and immunofluorescent staining indicated an increased GDF15 expression in 5 OSCC cell lines compared with human gingival epithelial cells. Irradiation with two and six gray resulted in a significant elevation of GDF15 expression per survived cell colony in the irradiated OSCC cell lines (P < 0.001). Furthermore, a dose-dependent expression of GDF15 was seen. Immunofluorescent staining confirmed an elevated GDF15 expression in irradiated OSCC cell lines (n = 10; P ≤ 0.001). Apoptotic activity was significantly increased after irradiation in the GDF15 knockdown group compared with control cells (n = 24; P < 0.001). This study describes for the first time the vital role of GDF15 both in tumorigenesis and in radioresistance of OSCC cells. With its anti-apoptotic effects, GDF15 possibly promotes tumor progression and might protect carcinoma cells against irradiation effects. Consequently, GDF15 may be a promising therapeutic target in oral cancer. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Deep microbial life in the Altmark natural gas reservoir: baseline characterization prior CO2 injection

    NASA Astrophysics Data System (ADS)

    Morozova, Daria; Shaheed, Mina; Vieth, Andrea; Krüger, Martin; Kock, Dagmar; Würdemann, Hilke

    2010-05-01

    the quantification of those microorganisms as well as the determination of microbial activity was not yet possible. Microbial monitoring methods have to be further developed to study microbial activities under these extreme conditions to access their influence on the EGR technique and on enhancing the long term safety of the process by fixation of carbon dioxide by precipitation of carbonates. We would like to thank GDF SUEZ for providing the data for the Rotliegend reservoir, sample material and enabling sampling campaigns. The CLEAN project is funded by the German Federal Ministry of Education and Research (BMBF) in the frame of the Geotechnologien Program.

  12. X-ray CT analyses, models and numerical simulations: a comparison with petrophysical analyses in an experimental CO2 study

    NASA Astrophysics Data System (ADS)

    Henkel, Steven; Pudlo, Dieter; Enzmann, Frieder; Reitenbach, Viktor; Albrecht, Daniel; Ganzer, Leonhard; Gaupp, Reinhard

    2016-06-01

    An essential part of the collaborative research project H2STORE (hydrogen to store), which is funded by the German government, was a comparison of various analytical methods for characterizing reservoir sandstones from different stratigraphic units. In this context Permian, Triassic and Tertiary reservoir sandstones were analysed. Rock core materials, provided by RWE Gasspeicher GmbH (Dortmund, Germany), GDF Suez E&P Deutschland GmbH (Lingen, Germany), E.ON Gas Storage GmbH (Essen, Germany) and RAG Rohöl-Aufsuchungs Aktiengesellschaft (Vienna, Austria), were processed by different laboratory techniques; thin sections were prepared, rock fragments were crushed and cubes of 1 cm edge length and plugs 3 to 5 cm in length with a diameter of about 2.5 cm were sawn from macroscopic homogeneous cores. With this prepared sample material, polarized light microscopy and scanning electron microscopy, coupled with image analyses, specific surface area measurements (after Brunauer, Emmet and Teller, 1938; BET), He-porosity and N2-permeability measurements and high-resolution microcomputer tomography (μ-CT), which were used for numerical simulations, were applied. All these methods were practised on most of the same sample material, before and on selected Permian sandstones also after static CO2 experiments under reservoir conditions. A major concern in comparing the results of these methods is an appraisal of the reliability of the given porosity, permeability and mineral-specific reactive (inner) surface area data. The CO2 experiments modified the petrophysical as well as the mineralogical/geochemical rock properties. These changes are detectable by all applied analytical methods. Nevertheless, a major outcome of the high-resolution μ-CT analyses and following numerical data simulations was that quite similar data sets and data interpretations were maintained by the different petrophysical standard methods. Moreover, the μ-CT analyses are not only time saving, but also

  13. Observing the Arctic Ocean under melting ice - the UNDER-ICE project

    NASA Astrophysics Data System (ADS)

    Sagen, Hanne; Ullgren, Jenny; Geyer, Florian; Bergh, Jon; Hamre, Torill; Sandven, Stein; Beszczynska-Möller, Agnieszka; Falck, Eva; Gammelsrød, Tor; Worcester, Peter

    2014-05-01

    The sea ice cover of the Arctic Ocean is gradually diminishing in area and thickness. The variability of the ice cover is determined by heat exchange with both the atmosphere and the ocean. A cold water layer with a strong salinity gradient insulates the sea ice from below, preventing direct contact with the underlying warm Atlantic water. Changes in water column stratification might therefore lead to faster erosion of the ice. As the ice recedes, larger areas of surface water are open to wind mixing; the effect this might have on the water column structure is not yet clear. The heat content in the Arctic strongly depends on heat transport from other oceans. The Fram Strait is a crucial pathway for the exchange between the Arctic and the Atlantic Ocean. Two processes of importance for the Arctic heat and freshwater budget and the Atlantic meridional overturning circulation take place here: poleward heat transport by the West Spitzbergen Current and freshwater export by the East Greenland Current. A new project, Arctic Ocean under Melting Ice (UNDER-ICE), aims to improve our understanding of the ocean circulation, water mass distribution, fluxes, and mixing processes, sea ice processes, and net community primary production in ice-covered areas and the marginal ice zone in the Fram Strait and northward towards the Gakkel Ridge. The interdisciplinary project brings together ocean acoustics, physical oceanography, marine biology, and sea ice research. A new programme of observations, integrated with satellite data and state-of-the-art numerical models, will be started in order to improve the estimates of heat, mass, and freshwater transport between the North Atlantic and the Arctic Ocean. On this poster we present the UNDER-ICE project, funded by the Research Council of Norway and GDF Suez E&P Norge AS for the years 2014-2017, and place it in context of the legacy of earlier projects in the area, such as ACOBAR. A mooring array for acoustic tomography combined with

  14. Crisis Stability and Long-Range Strike: A Comparative Analysis of Fighters, Bombers, and Missiles

    DTIC Science & Technology

    2013-01-01

    nationalize the Suez Canal IL-28 bombers, Meteor and Vampire attack aircraft no Israel, Britain, France: Regain control of the Suez Canal and neuter...Deny pakistan control of Kashmir B-57s, hawker hunters, Vampires no war Arab-Israeli 1967 Crisis egypt, Iraq, Jordan, Syria: Destroy Israel or

  15. The relationship between insulin resistance and the cardiovascular biomarker growth differentiation factor-15 in obese patients.

    PubMed

    Vila, Greisa; Riedl, Michaela; Anderwald, Christian; Resl, Michael; Handisurya, Ammon; Clodi, Martin; Prager, Gerhard; Ludvik, Bernhard; Krebs, Michael; Luger, Anton

    2011-02-01

    Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine linked to obesity comorbidities such as cardiovascular disease, inflammation, and cancer. GDF-15 also has adipokine properties and recently emerged as a prognostic biomarker for cardiovascular events. We evaluated the relationship of plasma GDF-15 concentrations with parameters of obesity, inflammation, and glucose and lipid metabolism in a cohort of 118 morbidly obese patients [mean (SD) age 37.2 (12) years, 89 females, 29 males] and 30 age- and sex-matched healthy lean individuals. All study participants underwent a 75-g oral glucose tolerance test; 28 patients were studied before and 1 year after Roux-en-Y gastric bypass surgery. Obese individuals displayed increased plasma GDF-15 concentrations (P < 0.001), with highest concentrations observed in patients with type 2 diabetes. GDF-15 was positively correlated with age, waist-to-height ratio, mean arterial blood pressure, triglycerides, creatinine, glucose, insulin, C-peptide, hemoglobin A(1c), and homeostatic model assessment insulin resistance index and negatively correlated with oral glucose insulin sensitivity. Age, homeostatic model assessment index, oral glucose insulin sensitivity, and creatinine were independent predictors of GDF-15 concentrations. Roux-en-Y gastric bypass led to a significant reduction in weight, leptin, insulin, and insulin resistance, but further increased GDF-15 concentrations (P < 0.001). The associations between circulating GDF-15 concentrations and age, insulin resistance, and creatinine might account for the additional cardiovascular predictive information of GDF-15 compared to traditional risk factors. Nevertheless, GDF-15 changes following bariatric surgery suggest an indirect relationship between GDF-15 and insulin resistance. The clinical utility of GDF-15 as a biomarker might be limited until the pathways directly controlling GDF-15 concentrations are better understood.

  16. Growth differentiation factor 15 increases following oral glucose ingestion: effect of meal composition and obesity.

    PubMed

    Schernthaner-Reiter, Marie Helene; Kasses, Dominik; Tugendsam, Christina; Riedl, Michaela; Peric, Slobodan; Prager, Gerhard; Krebs, Michael; Promintzer-Schifferl, Miriam; Clodi, Martin; Luger, Anton; Vila, Greisa

    2016-12-01

    Growth differentiation factor 15 (GDF15) is a cardiovascular biomarker belonging to the transforming growth factor-β superfamily. Increased GDF15 concentrations are associated with insulin resistance, diabetes and obesity. We investigated the physiological effects of meal composition and obesity on the regulation of systemic GDF15 levels. Lean (n = 8) and obese (n = 8) individuals received a carbohydrate- or fat-rich meal, a 75 g oral glucose load (OGTT) or short-term fasting. OGTTs were performed in severely obese patients (n = 6) pre- and post-bariatric surgery. Circulating serum GDF15 concentrations were studied in lean and obese individuals in response to different meals, OGTT or short-term fasting, and in severely obese patients pre- and post-bariatric surgery. Regulation of GDF15 mRNA levels and protein release were evaluated in the human hepatic cell line HepG2. GDF15 concentrations steadily decrease during short-term fasting in lean and obese individuals. Carbohydrate- and fat-rich meals do not influence GDF15, whereas an OGTT leads to a late increase in GDF15 levels. The positive effect of OGTT on GDF15 levels is also preserved in severely obese patients, pre- and post-bariatric surgery. We further studied the regulation of GDF15 mRNA levels and protein release in HepG2, finding that glucose and insulin independently stimulate both GDF15 transcription and secretion. In summary, high glucose and insulin peaks upregulate GDF15 transcription and release. The nutrient-induced increase in GDF15 levels depends on rapid glucose and insulin excursions following fast-digesting carbohydrates, but not on the amount of calories taken in. © 2016 European Society of Endocrinology.

  17. Deficiency of Growth Differentiation Factor 3 Protects against Diet-Induced Obesity by Selectively Acting on White Adipose

    PubMed Central

    Shen, Joseph J.; Huang, Lihua; Li, Liunan; Jorgez, Carolina; Matzuk, Martin M.; Brown, Chester W.

    2009-01-01

    Growth differentiation factor 3 (GDF3) is a member of the TGFβ superfamily. White adipose is one of the tissues in which Gdf3 is expressed, and it is the only tissue in which expression increases in response to high-fat diet. We generated Gdf3−/− mice, which were indistinguishable from wild-type mice and had normal weight curves on regular diet. However, on high-fat diet Gdf3−/− mice were resistant to the obesity that normally develops in wild-type mice. Herein we investigate the physiological and molecular mechanisms that underlie this protection from diet-induced obesity and demonstrate that GDF3 deficiency selectively affects white adipose through its influence on basal metabolic rates. Our results are consistent with a role for GDF3 in adipose tissue, with consequential effects on energy expenditure that ultimately impact adiposity. PMID:19008465

  18. The role of growth differentiation factor 15 in the pathogenesis of primary myelofibrosis

    PubMed Central

    Uchiyama, Tatsuki; Kawabata, Hiroshi; Miura, Yasuo; Yoshioka, Satoshi; Iwasa, Masaki; Yao, Hisayuki; Sakamoto, Soichiro; Fujimoto, Masakazu; Haga, Hironori; Kadowaki, Norimitsu; Maekawa, Taira; Takaori-Kondo, Akifumi

    2015-01-01

    Growth differentiation factor 15 (GDF15) is a pleiotropic cytokine that belongs to the transforming growth factor-β superfamily. Elevated serum concentrations of this cytokine have been reported in patients with various malignancies. To assess the potential roles of GDF15 in hematologic malignancies, we measured its serum levels in patients with these diseases. We found that serum GDF15 levels were elevated in almost all these patients, particularly in patients with primary myelofibrosis (PMF). Immunohistochemical staining of bone marrow (BM) specimens revealed that GDF15 was strongly expressed by megakaryocytes, which may be sources of increased serum GDF15 in PMF patients. Therefore, we further assessed the contribution of GDF15 to the pathogenesis of PMF. Recombinant human (rh) GDF15 enhanced the growth of human BM mesenchymal stromal cells (BM-MSCs), and it enhanced the potential of these cells to support human hematopoietic progenitor cell growth in a co-culture system. rhGDF15 enhanced the growth of human primary fibroblasts, but it did not affect their expression of profibrotic genes. rhGDF15 induced osteoblastic differentiation of BM-MSCs in vitro, and pretreatment of BM-MSCs with rGDF15 enhanced the induction of bone formation in a xenograft mouse model. These results suggest that serum levels of GDF15 in PMF are elevated, that megakaryocytes are sources of this cytokine in BM, and that GDF15 may modulate the pathogenesis of PMF by enhancing proliferation and promoting osteogenic differentiation of BM-MSCs. PMID:26276681

  19. Circulating and Placental Growth-Differentiation Factor 15 in Preeclampsia and in Pregnancy Complicated by Diabetes Mellitus

    PubMed Central

    Sugulle, Meryam; Dechend, Ralf; Herse, Florian; Weedon-Fekjaer, M. Susanne; Johnsen, Guro M.; Brosnihan, K. Bridget; Anton, Lauren; Luft, Friedrich C.; Wollert, Kai C.; Kempf, Tibor; Staff, Anne Cathrine

    2014-01-01

    Abstract Growth-differentiation factor 15 (GDF-15), a stress-responsive transforming growth factor-β–related cytokine, is emerging as a new risk marker in patients with cardiovascular disease. We explored GDF-15 in preeclampsia and in diabetic pregnancies, because these conditions are associated with augmented risk for cardiovascular disease, both in mother and in offspring. Plasma from pregnant women (n=267; controls: n=59, preeclampsia: n=85, diabetes mellitus: n=112, and superimposed preeclampsia in diabetes mellitus: n=11), fetal plasma (n=72), and amniotic fluid (n=99) were analyzed by immunoassay for GDF-15. Placental GDF-15 mRNA and protein expression levels were analyzed by quantitative real-time PCR and immunoblots in 78 and 18 pregnancies, respectively. Conditioned media from preeclamptic (n=6) and control (n=6) villous placenta explants were analyzed by immunoassay for GDF-15. Median maternal GDF-15 concentration was elevated in those with diabetes mellitus, as compared with controls (91 549 versus 79 875 ng/L; P=0.02). Median GDF-15 concentration was higher in patients with preeclampsia than in controls in term maternal blood samples (127 061 versus 80 319 ng/L; P<0.001). In the fetal circulation and amniotic fluid, GDF-15 was elevated in preeclampsia and superimposed preeclampsia in diabetes mellitus, as compared with controls. GDF-15 placental mRNA expression was elevated in preeclampsia, as compared with controls (P=0.002). Placenta immunoblots confirmed a single GDF-15 protein band, and a time-dependent increase in GDF-15 protein was detected in the conditioned media. Our study is the first to show that GDF-15 is dysregulated, both in preeclampsia and in diabetic pregnancies. The mechanisms and diagnostic implications of these findings remain to be explored. PMID:19470878

  20. Differentially Expressed Genes Associated with Low-Dose Gamma Radiation

    NASA Astrophysics Data System (ADS)

    Hegyesi, Hargita; Sándor, Nikolett; Schilling, Boglárka; Kis, Enikő; Lumniczky, Katalin; Sáfrány, Géza

    We have studied low dose radiation induced gene expression alterations in a primary human fibroblast cell line using Agilent's whole human genome microarray. Cells were irradiated with 60Co γ-rays (0; 0.1; 0.5 Gy) and 2 hours later total cellular RNA was isolated. We observed differential regulation of approximately 300-500 genes represented on the microarray. Of these, 126 were differentially expressed at both doses, among them significant elevation of GDF-15 and KITLG was confirmed by qRT-PCR. Based on the transcriptional studies we selected GDF-15 to assess its role in radiation response, since GDF-15 is one of the p53 gene targets and is believed to participate in mediating p53 activities. First we confirmed gamma-radiation induced dose-dependent changes in GDF-15 expression by qRT-PCR. Next we determined the effect of GDF-15 silencing on radiosensitivity. Four GDF-15 targeting shRNA expressing lentiviral vectors were transfected into immortalized human fibroblast cells. We obtained efficient GDF-15 silencing in one of the four constructs. RNA interference inhibited GDF-15 gene expression and enhanced the radiosensitivity of the cells. Our studies proved that GDF-15 plays an essential role in radiation response and may serve as a promising target in radiation therapy.

  1. Growth differentiation factor 15 in anaemia of chronic disease, iron deficiency anaemia and mixed type anaemia.

    PubMed

    Theurl, Igor; Finkenstedt, Armin; Schroll, Andrea; Nairz, Manfred; Sonnweber, Thomas; Bellmann-Weiler, Rosa; Theurl, Milan; Seifert, Markus; Wroblewski, Victor J; Murphy, Anthony T; Witcher, Derrick; Zoller, Heinz; Weiss, Günter

    2010-02-01

    Recently, the iron and erythropoiesis-controlled growth differentiation factor 15 (GDF15) has been shown to inhibit the expression of hepcidin in beta-thalassaemia patients, thereby increasing iron absorption despite iron overload. To access the diagnostic and pathogenic impact of GDF15 in inflammatory anaemia the association of GDF15 expression with serum iron parameters and hepcidin was studied in patients suffering from iron deficiency anaemia (IDA), anaemia of chronic disease (ACD) and ACD subjects with true iron deficiency (ACD/IDA). GDF15 was significantly increased in both ACD and ACD/IDA, but not in IDA subjects as compared to controls. In contrast, hepcidin levels were significantly lower in IDA and ACD/IDA subjects than in ACD patients. IDA and ACD/IDA, but not ACD, showed an association between GDF15 and soluble transferrin receptor, an indicator of iron requirement for erythropoiesis. However, GDF15 did not correlate to hepcidin in either patient group. While GDF15 levels were linked to the needs for erythropoiesis and iron homeostasis in IDA, the immunity-driven increase of GDF15 may not primarily affect iron homeostasis and hepcidin expression. This indicates that other ACD-related factors may overcome the regulatory effects of GDF15 on hepcidin expression during inflammation.

  2. Molecular characterization of growth differentiation factor 9 and its spatio-temporal expression pattern in gibel carp (Carassius auratus gibelio).

    PubMed

    Liu, Zhiwei; Chen, Aqin; Yang, Zhigang; Wei, Hua; Leng, Xiangjun

    2012-04-01

    Growth differentiation factor 9 (GDF9) is a member of the transforming growth factor β (TGF-β) superfamily with a key role in regulating follicle development. In this study, the GDF9 full-length genomic DNA and cDNA were isolated and characterized from the gibel carp ovary using rapid-amplification of cDNA ends (RACE) and LD-PCR. The full-length genomic DNA and cDNA sequences of GDF9 are 3979 and 2044 bp which code 428 amino acid residues with a specific RKKR protease cleavage site of TGF-β superfamily. Sequence analysis showed that gibel carp was similar to zebrafish and other fish species. Spatio-temporal expression analysis using real-time quantitative PCR revealed that GDF9 mRNA was largely expressed in ovary and testis. GDF9 is mainly present at stage I follicles indicating its important role in early follicles development. The same result was obtained in immunohistochemistry localization of GDF9 protein. Within the follicle, the follicle layer cells were barely expressed whereas GDF9 mRNA was mostly expressed in the oocytes. Supplemented with human chorionic gonadotropin (hCG) in isolated follicles, the expression of GDF9 mRNA was increased firstly and then decreased. The results of this study indicated that GDF9 gene played a role in fish during development of follicles, especially in the early stage follicles.

  3. iss016e019375

    NASA Image and Video Library

    2008-05-02

    ISS016-E-019375 (30 Dec. 2007) --- Port of Suez, Egypt is featured in this image photographed by an Expedition 16 crewmember on the International Space Station. The Port of Suez is located in Egypt along the northern coastline of the Gulf of Suez. The port and city are the southern terminus of the Suez Canal that transits through Egypt and debouches into the Mediterranean Sea near Port Said. The port serves vessels transporting general cargo, oil tankers, and both commercial and private passenger vessels. The port is also an important waypoint for Muslim pilgrims traveling to and from Mecca in Saudi Arabia. Several large vessels are visible in the Gulf of Suez and berthed at various docks around the port. An extensive petroleum refinery complex forms the southern coastal boundary of the Port of Suez. At the time this image was acquired, gaseous byproducts of petroleum processing were being burned off -- as indicated by a smoke plume extending southwards into the Gulf of Suez (lower right). This view also captures several regions of greenish blue coloration in the Gulf. These are most probably sediments stirred up by passage of ships traveling to and from the Port. Similarly-colored regions along the coastline are bottom sediments visible through the shallow water column.

  4. Cardioprotective role of growth/differentiation factor 1 in post-infarction left ventricular remodelling and dysfunction.

    PubMed

    Bao, Ming-Wei; Zhang, Xiao-Jing; Li, Liangpeng; Cai, Zhongxiang; Liu, Xiaoxiong; Wan, Nian; Hu, Gangying; Wan, Fengwei; Zhang, Rui; Zhu, Xueyong; Xia, Hao; Li, Hongliang

    2015-07-01

    Growth/differentiation factor 1 (GDF1) is a secreted glycoprotein of the transforming growth factor-β (TGF-β) superfamily that mediates cell differentiation events during embryonic development. GDF1 is expressed in several tissues, including the heart. However, the functional role of GDF1 in myocardial infarction (MI)-induced cardiac remodelling and dysfunction is not known. Here, we performed gain-of-function and loss-of-function studies using cardiac-specific GDF1 transgenic (TG) and knockout (KO) mice to determine the role of GDF1 in the pathogenesis of functional and architectural cardiac remodelling after MI, which was induced by surgical left anterior descending coronary artery ligation. Our results demonstrate that overexpression of GDF1 in the heart causes a significant decrease in MI-derived mortality post-MI and leads to attenuated infarct size expansion, left ventricular (LV) dilatation, and cardiac dysfunction at 1 week and 4 weeks after MI injury. Compared with control animals, cardiomyocyte apoptosis, inflammation, hypertrophy, and interstitial fibrosis were all remarkably reduced in the GDF1-TG mice following MI. In contrast, GDF1 deficiency greatly exacerbated the pathological cardiac remodelling response after infarction. Further analysis of the in vitro and in vivo signalling events indicated that the beneficial role of GDF1 in MI-induced cardiac dysfunction and LV remodelling was associated with the inhibition of non-canonical (MEK-ERK1/2) and canonical (Smad) signalling cascades. Overall, our data reveal that GDF1 in the heart is a novel mediator that protects against the development of post-infarction cardiac remodelling via negative regulation of the MEK-ERK1/2 and Smad signalling pathways. Thus, GDF1 may serve as a valuable therapeutic target for the treatment of MI. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  5. PI3K/Akt is involved in brown adipogenesis mediated by growth differentiation factor-5 in association with activation of the Smad pathway

    SciTech Connect

    Hinoi, Eiichi; Iezaki, Takashi; Fujita, Hiroyuki; Watanabe, Takumi; Odaka, Yoshiaki; Ozaki, Kakeru; Yoneda, Yukio

    2014-07-18

    Highlights: • Akt is preferentially phosphorylated in BAT and sWAT of aP2-GDF5 mice. • PI3K/Akt signaling is involved in GDF5-induced brown adipogenesis. • PI3K/Akt signaling regulates GDF5-induced Smad5 phosphorylation. - Abstract: We have previously demonstrated promotion by growth differentiation factor-5 (GDF5) of brown adipogenesis for systemic energy expenditure through a mechanism relevant to activating the bone morphological protein (BMP) receptor/mothers against decapentaplegic homolog (Smad)/peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) pathway. Here, we show the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in brown adipogenesis mediated by GDF5. Overexpression of GDF5 in cells expressing adipocyte protein-2 markedly accelerated the phosphorylation of Smad1/5/8 and Akt in white and brown adipose tissues. In brown adipose tissue from heterozygous GDF5{sup Rgsc451} mutant mice expressing a dominant-negative (DN) GDF5 under obesogenic conditions, the basal phosphorylation of Smad1/5/8 and Akt was significantly attenuated. Exposure to GDF5 not only promoted the phosphorylation of both Smad1/5/8 and Akt in cultured brown pre-adipocytes, but also up-regulated Pgc1a and uncoupling protein-1 expression in a manner sensitive to the PI3K/Akt inhibitor Ly294002 as well as retroviral infection with DN-Akt. GDF5 drastically promoted BMP-responsive luciferase reporter activity in a Ly294002-sensitive fashion. Both Ly294002 and DN-Akt markedly inhibited phosphorylation of Smad5 in the nuclei of brown pre-adipocytes. These results suggest that PI3K/Akt signals play a role in the GDF5-mediated brown adipogenesis through a mechanism related to activation of the Smad pathway.

  6. A comparison of current serum biomarkers as diagnostic indicators of mitochondrial diseases

    PubMed Central

    Davis, Ryan L.; Liang, Christina

    2016-01-01

    Objective: To directly compare the diagnostic utility of growth differentiation factor–15 (GDF-15) with our previous fibroblast growth factor–21 (FGF-21) findings in the same adult mitochondrial disease cohort. Methods: Serum GDF-15 levels were measured using a quantitative ELISA. Statistical analyses of GDF-15 data were compared with our published FGF-21 findings. Results: Median serum GDF-15 concentrations were elevated in patients with mitochondrial disease and differed between all experimental groups, mirroring group results for FGF-21. There was a difference between patients diagnosed by muscle biopsy and genetic diagnosis, suggesting that serum GDF-15 measurement may be more broadly specific for mitochondrial disease than for muscle manifesting mitochondrial disease, in contrast to FGF-21. GDF-15 showed a markedly higher diagnostic odds ratio when compared with FGF-21 (75.3 vs 45.7), was a better predictor of disease based on diagnostic sensitivity (77.8% vs 68.5%), and outperformed FGF-21 on receiver operating characteristic curve analysis (area under the curve 94.1% vs 91.1%). Combining both biomarkers did not improve the area under the curve remarkably over GDF-15 alone. GDF-15 was the best predictor of mitochondrial disease (p < 0.002) following multivariate logistic regression analysis. Conclusions: GDF-15 outperforms FGF-21 as an indicator of mitochondrial diseases. Our data suggest that GDF-15 is generally indicative of inherited mitochondrial disease regardless of clinical phenotype, whereas FGF-21 seems to be more indicative of mitochondrial disease when muscle manifestations are present. Classification of evidence: This study provides Class III evidence that serum GDF-15 accurately distinguishes patients with mitochondrial diseases from those without them. PMID:27164684

  7. Growth/differentiation factor-5: a candidate therapeutic agent for periodontal regeneration? A review of pre-clinical data.

    PubMed

    Moore, Yolanda R; Dickinson, Douglas P; Wikesjö, Ulf M E

    2010-03-01

    Therapeutic concepts involving the application of matrix, growth and differentiation factors have been advocated in support of periodontal wound healing/regeneration. Growth/differentiation factor-5 (GDF-5), a member of the bone morphogenetic protein family, represents one such factor. The purpose of this review is to provide a background of the therapeutic effects of GDF-5 expressed in various musculoskeletal settings using small and large animal platforms. A comprehensive literature search was conducted to identify all reports in the English language evaluating GDF-5 using the PubMed and Google search engines, and a manual search of the reference lists from the electronically retrieved reports. Two reviewers independently screened the titles and abstracts from a total of 69 reports, 22 of which were identified as pre-clinical (in vivo) evaluations of GDF-5. The full-length article of the 22 pre-clinical reports was then reviewed. Various applications including cranial and craniofacial bone formation, spine fusion, long bone fracture healing, cartilage, and tendon/ligament repair using a variety of small and large animal platforms evaluating GDF-5 as a therapeutic agent were identified. A majority of studies, using biomechanical, radiographic, and histological analysis, demonstrated significant dose-dependent effects of GDF-5. These include increased/enhanced local bone formation, fracture healing/repair, and cartilage and tendon/ligament formation. GDF-5 frequently was shown to accelerate wound maturation. Several studies demonstrated GDF-5 to be a realistic alternative to autograft bone. Studies using pre-clinical models and human histology suggest GDF-5 may also increase/enhance periodontal wound healing/regeneration. GDF-5 appears a promising therapeutic agent for periodontal wound healing/regeneration as GDF-5 supports/accelerates bone and tendon/ligament formation in several musculoskeletal settings including periodontal tissues.

  8. 78 FR 34966 - Approval and Promulgation of Air Quality Implementation Plans; Wisconsin; Removal of Gasoline...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-11

    ... types of emission control systems that capture fuel vapors from vehicle gas tanks during refueling. Stage II systems are specifically installed at gasoline dispensing facilities (GDF) and capture the... storage tank at the GDF to prevent the vapors from escaping to the atmosphere. ORVR systems are...

  9. The trajectory prediction of spacecraft by grey method

    NASA Astrophysics Data System (ADS)

    Wang, Qiyue; Zhang, Zili; Wang, Zhongyu; Wang, Yanqing; Zhou, Weihu

    2016-08-01

    The real-time and high-precision trajectory prediction of a moving object is a core technology in the field of aerospace engineering. The real-time monitoring and tracking technology are also significant guarantees of aerospace equipment. A dynamic trajectory prediction method called grey dynamic filter (GDF) which combines the dynamic measurement theory and grey system theory is proposed. GDF can use coordinates of the current period to extrapolate coordinates of the following period. At meantime, GDF can also keep the instantaneity of measured coordinates by the metabolism model. In this paper the optimal model length of GDF is firstly selected to improve the prediction accuracy. Then the simulation for uniformly accelerated motion and variably accelerated motion is conducted. The simulation results indicate that the mean composite position error of GDF prediction is one-fifth to that of Kalman filter (KF). By using a spacecraft landing experiment, the prediction accuracy of GDF is compared with the KF method and the primitive grey method (GM). The results show that the motion trajectory of spacecraft predicted by GDF is much closer to actual trajectory than the other two methods. The mean composite position error calculated by GDF is one-eighth to KF and one-fifth to GM respectively.

  10. A Building-Resolved Wind Field Library for Vancouver: Facilitating CBRN Emergency Response for the 2010 Winter Olympic Games

    DTIC Science & Technology

    2010-06-01

    dans d’autres environnements urbains composes de differents reseaux de rues et configurations de ba,timents). vi DRDC Suffield TM 2010-088 Table of...and 123° 14’ 53" W). The internal coordinate system used in urbanSTREAM is shown in Figure 1(a) , where the southwest corner of the modelling region...chosen in this case to be A ref = 36 1.124 m. Hence, in this internal coordinate system, the 4 DRDC Suffield TM 2010-088 N t (:t) Modf’l dom :tin N

  11. Earth Observations taken by Expedition 30 crewmember

    NASA Image and Video Library

    2012-02-25

    ISS030-E-112823 (25 Feb. 2012) --- This nighttime image photographed by one of the Expedition 30 crew members aboard the International Space Station provides a look toward the Mediterranean Sea. Along the left side, the night lights clearly depict the high population associated with the Nile River and its delta and the Alexandria, Egypt area (top left center). The Gulf of Suez and the Suez Canal are seen to the right.

  12. Earth Observations taken by Expedition 30 crewmember

    NASA Image and Video Library

    2012-02-25

    ISS030-E-112822 (25 Feb. 2012) --- This nighttime image photographed by one of the Expedition 30 crew members aboard the International Space Station provides a look toward the Mediterranean Sea. Along the left side, the night lights clearly depict the high population associated with the Nile River and its delta and the Alexandria, Egypt area (top left center). The Gulf of Suez and the Suez Canal are seen to the right.

  13. Identification of Follistatin-Like 1 by Expression Cloning as an Activator of the Growth Differentiation Factor 15 Gene and a Prognostic Biomarker in Acute Coronary Syndrome

    PubMed Central

    Widera, Christian; Giannitsis, Evangelos; Kempf, Tibor; Korf-Klingebiel, Mortimer; Fiedler, Beate; Sharma, Sarita; Katus, Hugo A.; Asaumi, Yasuhide; Shimano, Masayuki; Walsh, Kenneth; Wollert, Kai C.

    2012-01-01

    BACKGROUND Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine and biomarker that is produced after myocardial infarction and that is related to prognosis in acute coronary syndrome (ACS). We hypothesized that secreted proteins that activate GDF15 production may represent new ACS biomarkers. METHODS We expressed clones from an infarcted mouse heart cDNA library in COS1 cells and assayed for activation of a luciferase reporter gene controlled by a 642-bp fragment of the mouse growth differentiation factor 15 (GDF15) gene promoter. We measured the circulating concentrations of follistatin-like 1 (FSTL1) and GDF15 in 1369 patients with ACS. RESULTS One cDNA clone that activated the GDF15 promoter–luciferase reporter encoded the secreted protein FSTL1. Treatment with FSTL1 activated GDF15 production in cultured cardiomyocytes. Transgenic production of FSTL1 stimulated GDF15 production in the murine heart, whereas cardiomyocyte-selective deletion of FSTL1 decreased production of GDF15 in cardiomyocytes, indicating that FSTL1 is sufficient and required for GDF15 production. In ACS, FSTL1 emerged as the strongest independent correlate of GDF15 (partial R2 = 0.26). A total of 106 patients died of a cardiovascular cause during a median follow-up of 252 days. Patients with an FSTL1 concentration in the top quartile had a 3.7-fold higher risk of cardiovascular death compared with patients in the first 3 quartiles (P < 0.001). FSTL1 remained associated with cardiovascular death after adjustment for clinical, angiographic, and biochemical variables. CONCLUSIONS Our study is the first to use expression cloning for biomarker discovery upstream of a gene of interest and to identify FSTL1 as an independent prognostic biomarker in ACS. PMID:22675198

  14. Growth Differentiation Factor-8 Decreases StAR Expression Through ALK5-Mediated Smad3 and ERK1/2 Signaling Pathways in Luteinized Human Granulosa Cells.

    PubMed

    Fang, Lanlan; Chang, Hsun-Ming; Cheng, Jung-Chien; Yu, Yiping; Leung, Peter C K; Sun, Ying-Pu

    2015-12-01

    Growth differentiation factor-8 (GDF-8) has been recently shown to be expressed in human granulosa cells, and the mature form of GDF-8 protein can be detected in the follicular fluid. However, the biological function and significance of this growth factor in the human ovary remains to be determined. Here, we investigated the effects of GDF-8 on steroidogenic enzyme expression and the potential mechanisms of action in luteinized human granulosa cells. We demonstrated that treatment with GDF-8 did not affect the mRNA levels of P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase, whereas it significantly down-regulated steroidogenic acute regulatory protein (StAR) expression and decreased progesterone production. The suppressive effect of GDF-8 on StAR expression was abolished by the inhibition of the TGF-β type I receptor. In addition, treatment with GDF-8 activated both Smad2/3 and ERK1/2 signaling pathways. Furthermore, knockdown of activin receptor-like kinase 5 reversed the effects of GDF-8 on Smad2/3 phosphorylation and StAR expression. The inhibition of Smad3 or ERK1/2 signaling pathways attenuated the GDF-8-induced down-regulation of StAR and production of progesterone. Interestingly, the concentrations of GDF-8 were negatively correlated with those of progesterone in human follicular fluid. These results indicate a novel autocrine function of GDF-8 to down-regulate StAR expression and decrease progesterone production in luteinized human granulosa cells, most likely through activin receptor-like kinase 5-mediated Smad3 and ERK1/2 signaling pathways. Our findings suggest that granulosa cells might play a critical role in the regulation of progesterone production to prevent premature luteinization during the final stage of folliculogenesis.

  15. Twist promotes invasion and cisplatin resistance in pancreatic cancer cells through growth differentiation factor 15.

    PubMed

    Ji, Hong; Lu, Hong-Wei; Li, Yi-Ming; Lu, Le; Wang, Jin-Long; Zhang, Ya-Fei; Shang, Hao

    2015-09-01

    Pancreatic cancer (PC) is an aggressive and devastating disease with a poor prognosis. Cisplatin, a commonly used chemotherapeutic agent for solid tumors, is effective as a single agent or in combination with other drugs for the treatment of PC. Previous studies have suggested that Twist and growth differentiation factor 15 (GDF15) are involved in the progression of PC. However, the role of Twist and GDF15 in PC remains to be elucidated. In the present study, the individual effect of and interaction between Twist and GDF15 in PC cell invasion and chemoresistance to cisplatin was examined. Twist and/or GDF15 were stably overexpressed or knocked down in ASPC‑1 and BXPC‑3 human PC cells. Overexpression of Twist in the two cell lines markedly increased GDF15 expression, cell invasion, matrix metalloproteinase‑2 expression/activity and the half maximal inhibitory concentration (IC50) values of cisplatin, which was eradicated by GDF15 knockdown or the selective p38 mitogen‑activated protein kinase (MAPK) inhibitor SB203580 (10 µM). By contrast, Twist knockdown significantly decreased GDF15 expression, cell invasion, matrix metalloproteinase‑2 expression/activity and the IC50 values of cisplatin, which was completely reversed by overexpression of GDF15. In addition, while overexpression and knockdown of Twist increased and decreased p38 MAPK activity, respectively, GDF15 demonstrated no significant effect on p38 MAPK activity in PC cells. In conclusion, the present study, for the first time, to the best of our knowledge, demonstrated that Twist promotes PC cell invasion and cisplatin chemoresistance through inducing GDF15 expression via a p38 MAPK‑dependent mechanism. The present study provides new insights into the molecular mechanisms underlying PC progression and chemoresistance.

  16. Growth differentiation factor-9 stimulates progesterone synthesis in granulosa cells via a prostaglandin E2/EP2 receptor pathway.

    PubMed

    Elvin, J A; Yan, C; Matzuk, M M

    2000-08-29

    Growth differentiation factor-9 (GDF-9), an oocyte-secreted member of the transforming growth factor beta superfamily, progesterone receptor, cyclooxygenase 2 (Cox2; Ptgs2), and the EP2 prostaglandin E(2) (PGE(2)) receptor (EP2; Ptgerep2) are required for fertility in female but not male mice. To define the interrelationship of these factors, we used a preovulatory granulosa cell culture system in which we added recombinant GDF-9, prostaglandins, prostaglandin receptor agonists, or cyclooxygenase inhibitors. GDF-9 stimulated Cox2 mRNA within 2 h, and PGE(2) within 6 h; however, progesterone was not increased until 12 h after addition of GDF-9. This suggested that Cox2 is a direct downstream target of GDF-9 but that progesterone synthesis required an intermediate. To determine whether prostaglandin synthesis was required for progesterone production, we analyzed the effects of PGE(2) and cyclooxygenase inhibitors on this process. PGE(2) can stimulate progesterone synthesis by itself, although less effectively than GDF-9 (3-fold vs. 6-fold increase over 24 h, respectively). Furthermore, indomethacin or NS-398, inhibitors of Cox2, block basal and GDF-9-stimulated progesterone synthesis. However, addition of PGE(2) to cultures containing both GDF-9 and NS-398 overrides the NS-398 block in progesterone synthesis. To further define the PGE(2)-dependent pathway, we show that butaprost, a specific EP2 agonist, stimulates progesterone synthesis and overrides the NS-398 block. In addition, GDF-9 stimulates EP2 mRNA synthesis by a prostaglandin- and progesterone-independent pathway. Thus, GDF-9 induces an EP2 signal transduction pathway which appears to be required for progesterone synthesis in cumulus granulosa cells. These studies further demonstrate the importance of oocyte-somatic cell interactions in female reproduction.

  17. A Prodomain Fragment from the Proteolytic Activation of Growth Differentiation Factor 11 Remains Associated with the Mature Growth Factor and Keeps It Soluble.

    PubMed

    Pepinsky, Blake; Gong, Bang-Jian; Gao, Yan; Lehmann, Andreas; Ferrant, Janine; Amatucci, Joseph; Sun, Yaping; Bush, Martin; Walz, Thomas; Pederson, Nels; Cameron, Thomas; Wen, Dingyi

    2017-08-22

    Growth differentiation factor 11 (GDF11), a member of the transforming growth factor β (TGF-β) family, plays diverse roles in mammalian development. It is synthesized as a large, inactive precursor protein containing a prodomain, pro-GDF11, and exists as a homodimer. Activation requires two proteolytic processing steps that release the prodomains and transform latent pro-GDF11 into active mature GDF11. In studying proteolytic activation in vitro, we discovered that a 6-kDa prodomain peptide containing residues 60-114, PDP60-114, remained associated with the mature growth factor. Whereas the full-length prodomain of GDF11 is a functional antagonist, PDP60-114 had no impact on activity. The specific activity of the GDF11/PDP60-114 complex (EC50 = 1 nM) in a SMAD2/3 reporter assay was identical to that of mature GDF11 alone. PDP60-114 improved the solubility of mature GDF11 at neutral pH. As the growth factor normally aggregates/precipitates at neutral pH, PDP60-114 can be used as a solubility-enhancing formulation. Expression of two engineered constructs with PDP60-114 genetically fused to the mature domain of GDF11 through a 2x or 3x G4S linker produced soluble monomeric products that could be dimerized through redox reactions. The construct with a 3x G4S linker retained 10% activity (EC50 = 10 nM), whereas the construct connected with a 2x G4S linker could only be activated (EC50 = 2 nM) by protease treatment. Complex formation with PDP60-114 represents a new strategy for stabilizing GDF11 in an active state that may translate to other members of the TGF-β family that form latent pro/mature domain complexes.

  18. Nuclear factor-κB is a common upstream signal for growth differentiation factor-5 expression in brown adipocytes exposed to pro-inflammatory cytokines and palmitate

    SciTech Connect

    Hinoi, Eiichi; Iezaki, Takashi; Ozaki, Kakeru; Yoneda, Yukio

    2014-10-03

    Highlights: • GDF5 expression is up-regulated by IL-1β, TNF-α and palmitate in brown pre-adipocytes. • NF-κB stimulates promoter activity and expression of GDF5 in brown pre-adipocytes. • Recruitment of NF-κB to the GDF5 promoter is facilitated in BAT from ob/ob mice. • An NF-κB inhibitor prevents upregulation of GDF5 expression in brown pre-adipocytes. - Abstract: We have previously demonstrated that genetic and acquired obesity similarly led to drastic upregulation in brown adipose tissue (BAT), rather than white adipose tissue, of expression of both mRNA and corresponding protein for the bone morphogenic protein/growth differentiation factor (GDF) member GDF5 capable of promoting brown adipogenesis. In this study, we evaluated expression profiles of GDF5 in cultured murine brown pre-adipocytes exposed to pro-inflammatory cytokines and free fatty acids (FFAs), which are all shown to play a role in the pathogenesis of obesity. Both interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were effective in up-regulating GDF5 expression in a concentration-dependent manner, while similar upregulation was seen in cells exposed to the saturated FFA palmitate, but not to the unsaturated FFA oleate. In silico analysis revealed existence of the putative nuclear factor-κB (NF-κB) binding site in the 5′-flanking region of mouse GDF5, whereas introduction of NF-κB subunits drastically facilitated both promoter activity and expression of GDF5 in brown pre-adipocytes. Chromatin immunoprecipitation analysis confirmed significant facilitation of the recruitment of NF-κB to the GDF5 promoter in lysed extracts of BAT from leptin-deficient ob/ob obese mice. Upregulation o GDF5 expression was invariably inhibited by an NF-κB inhibitor in cultured brown pre-adipocytes exposed to IL-1β, TNF-α and palmitate. These results suggest that obesity leads to upregulation of GDF5 expression responsible for the promotion of brown adipogenesis through a mechanism

  19. Characterization of the deep microbial life in the Altmark natural gas reservoir

    NASA Astrophysics Data System (ADS)

    Morozova, D.; Alawi, M.; Vieth-Hillebrand, A.; Kock, D.; Krüger, M.; Wuerdemann, H.; Shaheed, M.

    2010-12-01

    ., Adicdovorax sp., Ralstonia sp., Pseudomonas sp.), thiosulfate-oxidising bacteria (Diaphorobacter sp.) and biocorrosive thermophilic microorganisms, which have not previously been cultivated. Furthermore, several uncultivated microorganisms were found, that were similar to representatives from other saline, hot, anoxic, deep environments. However, due to the hypersaline and hyperthermophilic reservoir conditions, cell numbers are low, so that the quantification of those microorganisms as well as the determination of microbial activity was not yet possible. Microbial monitoring methods have to be further developed to study microbial activities under these extreme conditions to access their influence on the EGR technique and on enhancing the long term safety of the process by fixation of carbon dioxide by precipitation of carbonates. We thank GDF SUEZ for providing the data for the Rotliegend reservoir, sample material and supporting sampling campaigns. The CLEAN project is funded by the German Federal Ministry of Education and Research (BMBF) in the framework of the GEOTECHNOLOGIEN Program.

  20. Analysis of active microorganisms and their potential role in carbon dioxide turnover in the natural gas reservoirs Altmark and Schneeren (Germany)

    NASA Astrophysics Data System (ADS)

    Gniese, Claudia; Muschalle, Thomas; Mühling, Martin; Frerichs, Janin; Krüger, Martin; Kassahun, Andrea; Seifert, Jana; Hoth, Nils

    2010-05-01

    RECOBIO-2, part of the BMBF-funded Geotechnologien consortium, investigates the presence of active microorganisms and their potential role in CO2 turnover in the formation waters of the Schneeren and Altmark gas fields, which are both operated by GDF SUEZ E&P Germany GmbH. Located to the north west of Hannover the natural gas reservoir Schneeren is composed of compacted Westfal-C sandstones that have been naturally fractured into a subsalinar horst structure. This gas field is characterized by a depth of 2700 to 3500m, a bottom-hole temperature between 80 and 110° C as well as a moderate salinity (30-60g/l) and high sulfate contents (~1000mg/l). During RECOBIO-1 produced formation water collected at wells in Schneeren was already used to conduct long term laboratory experiments. These served to examine possible microbial processes of the autochthonous biocenosis induced by the injection of CO2 (Ehinger et al. 2009 submitted). Microorganisms in particular sulfate-reducing bacteria and methanogens were able to grow in the presence of powdered rock material, CO2 and H2 without any other added nutrients. The observed development of DOC was now proven in another long term experiment using labelled 13CO2. In contrast to Schneeren, the almost depleted natural gas reservoir Altmark exhibits an average depth of 3300m, a higher bottom-hole temperature (111° C to 120° C), a higher salinity (275-350g/l) but sulfate is absent. This Rotliegend formation is located in the southern edge of the Northeast German Basin and is of special interest for CO2 injection because of favourable geological properties. Using molecular biological techniques two types of samples are analyzed: formation water collected at the well head (November 2008) and formation water sampled in situ from a depth of around 3000m (May 2009). Some of the wells are treated frequently with a foaming agent while others are chemically untreated. Despite the extreme environmental conditions in the Altmark gas field

  1. One year continuous soil gas monitoring above an EGR test site

    NASA Astrophysics Data System (ADS)

    Furche, Markus; Schlömer, Stefan; Faber, Eckhard; Dumke, Ingolf

    2010-05-01

    information about hardware configurations at the stations, maintenance carried out and special events which might have influenced the results. An interactive database application has been developed to allow versatile graphical output and statistical processing of the collected time series. On a large scale CO2 concentrations show natural seasonal variations with higher values during summer (July to September) and lower values during winter. This behaviour is expected and mainly caused by temperature dependent activities of bacterial CO2 production. Absolute concentrations however vary extremely between different locations. While several stations show more than 10% CO2 during summer, others stay below 0.1% at the same time. The conclusion is that individual baselines at all sites for a sufficient time without CO2 sequestration are necessary. The CLEAN project is financed by the German Federal Ministry of Education and Research (BMBF) within the special program Geotechnologien. We would like to thank GDF SUEZ E&P Deutschland GmbH for supporting our field work at the well sites.

  2. Characterization of CO2-induced (?) bleaching phenomena in German red bed sediments by combined geochemical and evolved gas analysis

    NASA Astrophysics Data System (ADS)

    Hilse, Ulrike; Goepel, Andreas; Pudlo, Dieter; Heide, Klaus; Gaupp, Reinhard

    2010-05-01

    We investigated varied coloured Buntsandstein and Rotliegend sandstones in Central Germany (Thuringian Vorderrhön, Altmark) by thermogravimetric/pyrolytic (DEGAS- directly coupled evolved gas analysis) and geochemical (ICP-MS/OES) means to evaluate geochemical/mineralogical characteristics of red bed rocks and their presumably altered, bleached modifications. Commonly bleaching of primary red bed sediments is regarded as a result of fluid-rock reactions by the participation of CO2. This study is performed in the framework of the special research program 'GEOTECHNOLOGIEN' (funded by the German Ministry of Education and Research - BMBF) and is part of two BMBF sponsored projects - 'COMICOR', an analogue study on potential effects of CO2-bearing fluids on Buntsandstein and Rotliegend deposits in Hesse and Thuringia and 'CLEAN', an enhanced gas recovery (EGR) pilot project in cooperation with GDF SUEZ E&P Deutschland GmbH. The intention of CLEAN is to evaluate the feasibility of EGR techniques and the suitability of depleted natural gas reservoirs for potential industrial CO2 sequestration projects. According to rock colour variations two slices of handspecimens (M49, A1) were split into 12 and 15 equally sized samples for analytical work. The medium grained Lower Buntsandstein sample M49 from Thuringia is of fluvial origin and partially bleached with transitions from red (unbleached) to light colours (bleached). Bulk rock geochemistry of red bed and bleached subsamples of M49 are almost similar, including rare earth element (REE) content. Only the content of iron and related metals is depleted in bleached samples compared to the red bed types. All PAAS normalized pattern of M49 show positive Eu and slightly negative Ce anomalies, most likely caused by the presence of apatite and illite in the rocks. The degassing behavior observed by DEGAS of M49 subsamples is mainly controlled by the breakdown of sheet silicates, hydroxides and hydrates, as well as of carbonates and

  3. Erythropoiesis-driven regulation of hepcidin in human red cell disorders is better reflected through concentrations of soluble transferrin receptor rather than growth differentiation factor 15.

    PubMed

    Fertrin, Kleber Yotsumoto; Lanaro, Carolina; Franco-Penteado, Carla Fernanda; de Albuquerque, Dulcinéia Martins; de Mello, Mariana Rezende Bandeira; Pallis, Flávia Rubia; Bezerra, Marcos André Cavalcanti; Hatzlhofer, Betania Lucena Domingues; Olbina, Gordana; Saad, Sara Terezinha Olalla; da Silva Araújo, Aderson; Westerman, Mark; Costa, Fernando Ferreira

    2014-04-01

    Growth differentiation factor 15 (GDF-15) is a bone marrow-derived cytokine whose ability to suppress iron regulator hepcidin in vitro and increased concentrations found in patients with ineffective erythropoiesis (IE)suggest that hepcidin deficiency mediated by GDF-15 may be the pathophysiological explanation for nontransfusional iron overload. We aimed to compare GDF-15 production in anemic states with different types of erythropoietic dysfunction. Complete blood counts, biochemical markers of iron status, plasma hepcidin, GDF-15, and known hepcidin regulators [interleukin-6 and erythropoietin (EPO)] were measured in 87 patients with red cell disorders comprising IE and hemolytic states: thalassemia, sickle cell anemia, and cobalamin deficiency. Healthy volunteers were also evaluated for comparison. Neither overall increased EPO,nor variable GDF-15 concentrations correlated with circulating hepcidin concentrations (P = 0.265 and P = 0.872). Relative hepcidin deficiency was found in disorders presenting with concurrent elevation of GDF-15 and soluble transferrin receptor (sTfR), a biomarker of erythropoiesis, and sTfR had the strongest correlation with hepcidin (r(s) = 0.584, P < 0.0001). Our data show that high concentrations of GDF-15 in vivo are not necessarily associated with pathological hepcidin reduction, and hepcidin deficiency was only found when associated with sTfR overproduction. sTfR elevation may be a necessary common denominator of erythropoiesis-driven mechanisms to favor iron absorption in anemic states and appears a suitable target for investigative approaches to iron disorders.

  4. Growth differentiation factor 9 of Megalobrama amblycephala: molecular characterization and expression analysis during the development of early embryos and growing ovaries.

    PubMed

    Huang, Chun Xiao; Wei, Xin Lan; Chen, Nan; Zhang, Jie; Chen, Li Ping; Wang, Wei Min; Li, Jun Yan; Wang, Huan Ling

    2014-02-01

    Growth differentiation factor 9 (GDF9) is a member of the transforming growth factorβ superfamily and plays an essential role during follicle maturation in mammals. In the present study, the full-length complementary DNA (cDNA) of gdf9 was obtained from Megalobrama amblycephala. The cDNA sequence is 2,061 bp in length with an open reading frame of 1,287 bp encoding 428 amino acid residues. The deduced amino acid sequence shared identities of about 42-86 % with the homologues of other vertebrates. During the early development of embryos, the gdf9 mRNA was detected in zygote with significantly high level and declined sharply by 47 and 87 % at 4 hours post-fertilization (hpf) and 6 hpf and even to an undetectable level through advancing stages. Expression analysis based on quantitative real-time PCR revealed that gdf9 mRNA was mainly expressed in ovary, but much lower levels were also found in some nonovarian tissues. Within the follicle, gdf9 mRNA was localized both in the oocytes and the follicle layer cells by in situ hybridization. During the ovarian cycle, gdf9 mRNA significantly decreased after the previtellogenic stage and became to increase again after the fully grown stage. The results imply that Gdf9 may play critical physiological functions in M. amblycephala early embryonic development and reproduction.

  5. The Relationship of Serum Macrophage Inhibitory Cytokine – 1 Levels with Gray Matter Volumes in Community-Dwelling Older Individuals

    PubMed Central

    Jiang, Jiyang; Wen, Wei; Brown, David A.; Crawford, John; Thalamuthu, Anbupalam; Smith, Evelyn; Breit, Samuel N.; Liu, Tao; Zhu, Wanlin; Brodaty, Henry; Baune, Bernhard T.; Trollor, Julian N.; Sachdev, Perminder S.

    2015-01-01

    Using circulating inflammatory markers and magnetic resonance imaging (MRI), recent studies have associated inflammation with brain volumetric measures. Macrophage Inhibitory Cytokine–1 (MIC-1/GDF15) is a divergent transforming growth factor – beta (TGF-β) superfamily cytokine. To uncover the underlying mechanisms of the previous finding of a negative association between MIC-1/GDF15 serum levels and cognition, the present study aimed to examine the relationship of circulating MIC-1/GDF15 levels with human brain gray matter (GM) volumes, in a community-dwelling sample aged 70–90 years over two years (Wave 1: n = 506, Wave 2: n = 327), of which the age-related brain atrophy had been previously well defined. T1-weighted MRI scans were obtained at both waves and analyzed using the FMRIB Software Library and FreeSurfer. The results showed significantly negative associations between MIC-1/GDF15 serum levels and both subcortical and cortical GM volumes. GM volumes of the whole brain, cortex, temporal lobe, thalamus and accumbens showed significant mediating effects on the associations between MIC-1/GDF15 serum levels and global cognition scores. Increases in MIC-1/GDF15 serum levels were associated with decreases in cortical and subcortical GM volume over two years. In conclusion, MIC-1/GDF15 serum levels were inversely associated with GM volumes both cross-sectionally and longitudinally. PMID:25867953

  6. Expression of growth differentiation factor 15 is not elevated in individuals with iron deficiency secondary to volunteer blood donation.

    PubMed

    Tanno, Toshihiko; Rabel, Antoinette; Lee, Y Terry; Yau, Yu Ying; Leitman, Susan F; Miller, Jeffery L

    2010-07-01

    Low serum hepcidin levels provide a physiologic response to iron demand in patients with iron deficiency (ID). Based on a discovery of suppressed hepcidin expression by a cytokine named growth differentiation factor 15 (GDF15), it was hypothesized that GDF15 may suppress hepcidin expression in humans with ID due to blood loss. To test this hypothesis, GDF15 and hepcidin levels were measured in peripheral blood from subjects with iron-deficient erythropoiesis before and after iron supplementation. Iron variables and hepcidin levels were significantly suppressed in iron-deficient blood donors compared to healthy volunteers. However, ID was not associated with elevated serum levels of GDF15. Instead, iron-deficient subjects' GDF15 levels were slightly lower than those measured in the control group of subjects (307 +/- 90 and 386 +/- 104 pg/mL, respectively). Additionally, GDF15 levels were not significantly altered by iron repletion. ID due to blood loss is not associated with a significant change in serum levels of GDF15.

  7. Diabetes mellitus related biomarker: The predictive role of growth-differentiation factor-15.

    PubMed

    Berezin, Alexander E

    2016-01-01

    Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine, which belongs to super family of the transforming growth factor beta. GDF-15 is widely presented in the various cells (macrophages, vascular smooth muscle cells, adipocytes, cardiomyocytes, endothelial cells, fibroblasts), tissues (adipose tissue, vessels, tissues of central and peripheral nervous system) and organs (heart, brain, liver, placenta) and it plays an important role in the regulation of the inflammatory response, growth and cell differentiation. Elevated GDF-15 was found in patients with established CV diseases including hypertension, stable coronary artery disease, acute coronary syndrome, myocardial infarction, ischemic and none ischemic-induced cardiomyopathies, heart failure, atrial fibrillation, as well as stroke, type two diabetes mellitus (T2DM), chronic kidney disease, infection, liver cirrhosis, malignancy. Therefore, aging, smoking, and various environmental factors, i.e. chemical pollutants are other risk factors that might increase serum GDF-15 level. Although GDF-15 has been reported to be involved in energy homoeostasis and weight loss, to have anti-inflammatory properties, and to predict CV diseases and CV events in general or established CV disease population, there is no large of body of evidence regarding predictive role of elevated GDF-15 in T2DM subjects. The mini review is clarified the role of GDF-15 in T2DM subjects.

  8. Growth-differentiation factor 15 as a predictor of mortality in patients with heart failure: a meta-analysis.

    PubMed

    Zeng, Xiaocong; Li, Lang; Wen, Hong; Bi, Qi

    2017-02-01

    Measurement of the biomarker growth-differentiation factor 15 (GDF-15) in patients with heart failure may help in risk stratification. We assessed the relationship between GDF-15 and mortality in patients with heart failure by conducting a meta-analysis. PubMed, Embase, ISI Web of Science, SCOPUS, and Cochrane Library databases were searched for studies that reported data on the baseline GDF-15 levels and all-cause or cardiovascular mortality. Pooled hazard ratios for mortality were calculated and presented with 95% confidence intervals (CIs). Potential sources of heterogeneity were assessed by meta-regression, subgroup, and sensitivity analyses. Eight studies with a total of 4126 heart failure patients were included. Pooled results showed that overexpression of GDF-15 was associated with poor survival in heart failure patients (log unit GDF-15: hazard ratio = 1.86, 95% CI = 1.37-2.52). Subgroup analyses revealed similar results. However, there was evidence of heterogeneity and publication bias. The association disappeared after correction using the trim-and-fill method (log unit GDF-15: hazard ratio 1.07, 95% CI 0.80-1.42). The results of this meta-analysis indicate an association of elevated GDF-15 levels with increased risk of mortality in patients with heart failure. However, the results should be interpreted with caution due to substantial heterogeneity and publication bias among the studies included in the meta-analysis.

  9. Identification and characterization of canine growth differentiation factor-9 and its splicing variant

    PubMed Central

    Hashimoto, Osamu; Takagi, Ryohei; Yanuma, Fuminari; Doi, Satoru; Shindo, Junji; Endo, Hideki; Hasegawa, Yoshihisa; Shimasaki, Shunichi

    2012-01-01

    Growth differentiation factor-9 (GDF-9), a member of the transforming growth factor-β (TGF-β) superfamily, is expressed exclusively in the oocyte within the ovary and plays essential roles in the ovarian function in mammals. However, a possible involvement of GDF-9 in canine ovarian physiology that has a unique ovulation process among mammals has not been studied. Interestingly, we have isolated two types of cDNA clones generated by an alternative splicing from a canine ovarian total RNA. The predominant long form cDNA shares a common precursor structure with GDF-9s in other species whereas the minor short form cDNA has a 172 amino acid truncation in the proregion. Using a transient expression system, we found that the long form cDNA has a defect in mature protein production whereas the short form cDNA readily produces mature protein. However, mutations at one or two N-glycosylation sites in the mature domain of the short form GDF-9 caused a loss in mature protein production. These results suggest that the prodomain and N-linked glycosylation of the mature domain regulate proper processing and secretion of canine GDF-9. Based on the biological functions of GDF-9, these characteristics of canine GDF-9 could be causatively linked to the unique ovulation process in the Canidae. PMID:22446043

  10. Plasma levels of growth differentiation factor-15 are associated with myocardial injury in patients undergoing off-pump coronary artery bypass grafting.

    PubMed

    Yuan, Zhize; Li, Haiqing; Qi, Quan; Gong, Wenhui; Qian, Cheng; Dong, Rong; Zang, Yi; Li, Jia; Zhou, Mi; Cai, Junfeng; Wang, Zhe; Chen, Anqing; Ye, Xiaofeng; Zhao, Qiang

    2016-06-17

    Growth differentiation factor-15 (GDF-15) has recently emerged as a risk predictor in patients with cardiovascular diseases. We therefore aimed to investigate the role of GDF-15 in the occurrence of cardiac injury during off-pump coronary artery bypass grafting (OPCAB). 55 consecutive patients with coronary artery diseases were recruited in this prospective, observational study. All patients were operated for OPCAB surgery. Serial blood samples were collected preoperatively, 12 hours and 36 hours after surgery. GDF-15, together with C-reactive protein, cardiac troponin I, creatine kinase MB and N-terminal pro B-type natriuretic peptide levels in plasma were measured at each time-point. GDF-15 levels increased significantly at 12 hours after surgery, attaining nearly 2.5 times the baseline levels (p < 0.001). Postoperative GDF-15 levels correlated positively with cTnI (p = 0.003) and EuroSCORE II (p = 0.013). According to the ROC curves, postoperative plasma GDF-15 was found to be the best biomarker to predict perioperative cardiac injury, compared with cTnI, CK-MB and EuroSCORE II. Circulating GDF-15 is a promising novel biomarker for identifying perioperative myocardial injury in patients undergoing OPCAB.

  11. Growth differentiation factor 15: a prognostic marker for recurrence in colorectal cancer

    PubMed Central

    Wallin, U; Glimelius, B; Jirström, K; Darmanis, S; Nong, R Y; Pontén, F; Johansson, C; Påhlman, L; Birgisson, H

    2011-01-01

    Background: Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta superfamily and has been associated with activation of the p53 pathway in human cancer. The aim of this study was to assess the prognostic value of GDF15 in patients with colorectal cancer (CRC). Methods: Immunohistochemistry and tissue microarrays were used to analyse GDF15 protein expression in 320 patients with CRC. In a subgroup of 60 patients, the level of GDF15 protein in plasma was also measured using a solid-phase proximity ligation assay. Results: Patients with CRC with moderate to high intensity of GDF15 immunostaining had a higher recurrence rate compared with patients with no or low intensity in all stages (stages I–III) (HR, 3.9; 95% CI, 1.16–13.15) and in stage III (HR, 10.32; 95% CI, 1.15–92.51). Patients with high plasma levels of GDF15 had statistically shorter time to recurrence (P=0.041) and reduced overall survival (P=0.002). Conclusion: Growth differentiation factor 15 serves as a negative prognostic marker in CRC. High expression of GDF15 in tumour tissue and high plasma levels correlate with an increased risk of recurrence and reduced overall survival. PMID:21468045

  12. Scintillation characteristics of nonstoichiometric phases formed in MF 2-GdF 3-CeF 3 systems Part III. Dense Gd 1- x- yM xCe yF 3- x tysonite-related crystals (M=Ca, Sr)

    NASA Astrophysics Data System (ADS)

    Kobayashi, M.; Ishii, M.; Sobolev, B. P.; Zhmurova, Z. I.; Krivandina, E. A.; Nikl, M.

    1999-01-01

    We evaluated the scintillation characteristics and the radiation hardness of Gd 1- xCa xF 3- x and Gd 1- xSr xF 3- x tysonite-type solid solutions (close to 6.6 g/cm 3 in density) doped with Ce which were grown from the congruent melt. As the Ce concentration increased, the Ce 3+ emission at 345 nm increased to a level comparable with the Gd 3+ emission at 310 nm. Both emissions, however, were slow with the decay constant in the order of ms. The radiation hardness, which was roughly 10 4 rad, tends to degrade as the wavelength decreases and/or the Ce concentration increases. Both spontaneous recovery and UV annealing of the radiation damages were significant. The intensity of the γ-ray excited luminescence, integrated over time, was as large as 50% of that in BaF 2 (12% of that in CdWO 4). When the Ce concentration is nil or only small, the yellow-green luminescence for UV excitation was as intense as in CdWO 4. Although the present crystals are not good for the applications in high-energy physics experiments, they may find applications in display devices, thermal neutron monitors, etc.

  13. Growth differentiation factor 15 predicts advanced fibrosis in biopsy-proven non-alcoholic fatty liver disease.

    PubMed

    Koo, Bo Kyung; Um, Sung Hee; Seo, Dong Soo; Joo, Sae Kyung; Bae, Jeong Mo; Park, Jeong Hwan; Chang, Mee Soo; Kim, Jung Ho; Lee, Jieun; Jeong, Won-Il; Kim, Won

    2017-09-12

    We explored whether growth differentiation factor 15 (GDF15) affects the histological severity of non-alcoholic fatty liver disease (NAFLD) independent of insulin resistance. In a biopsy-proven NAFLD cohort, we measured serum GDF15 levels using enzyme-linked immunosorbent assays. Among 190 subjects (mean age, 53±14 years; men, 52.1%), 72 (men, 65.3%) and 78 (men, 44.9%) were diagnosed with biopsy-proven non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), respectively. GDF15 levels were significantly higher in NASH patients than in controls (P = 0.010) or NAFL patients (P = 0.001). Subjects with advanced fibrosis (≥F3) also showed higher GDF15 levels compared to the others (F0-2; P <0.001). Among NAFLD patients, the highest quartile of GDF15 levels was significantly associated with a risk of advanced fibrosis even after adjustment for age, gender, body mass index, smoking status, hypertension, diabetes, aspartate aminotransferase, platelet, albumin, insulin resistance, and low skeletal muscle mass (odds ratio, 4.27; 95% confidence interval, 1.04-17.63), but not with NASH risk. GDF15 levels showed a significant positive correlation with liver stiffness (Spearman's ρ, 0.525; P < 0.001). Palmitate treatment increased the GDF15 mRNA expression level significantly in Kupffer cells, but not in hepatocytes. In LX-2 cells, GDF15 treatment resulted in enhanced expression of α-smooth muscle actin and collagen I, as well as phosphorylation of SMAD2 and SMAD3. Our findings suggest that GDF15 may serve as a novel biomarker of advanced fibrosis in NAFLD, thereby indicating the need for urgent anti-fibrotic pharmacotherapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  14. Dynamic medium containing growth differentiation factor-9 and FSH maintains survival and promotes in vitro growth of caprine preantral follicles after long-term in vitro culture.

    PubMed

    Alves, A M C V; Chaves, R N; Rocha, R M P; Lima, L F; Andrade, P M; Lopes, C A P; Souza, C E A; Moura, A A A; Campello, C C; Báo, S N; Smitz, J; Figueiredo, J R

    2013-01-01

    The aim of the present study was to evaluate the effects of growth differentiation factor 9 (GDF-9) and FSH on the in vitro development of caprine preantral follicles cultured for 16 days. Ovarian fragments were cultured in αMEM⁺ (α-minimum essential medium, pH 7.2-7.4, 10 μg mL⁻¹ insulin, 5.5 μg mL⁻¹ transferrin, 5.0 ng mL⁻¹ selenium, 2 mM glutamine, 2 mM hypoxanthine and 1.25 mg mL⁻¹ bovine serum albumin) in the absence or presence of 200 ng mL⁻¹ GDF-9 and/or 50 ng mL⁻¹ FSH added during the first (Days 0-8) and/or second (Days 8-16) half of the culture period. Non-cultured and cultured fragments were processed for histological and ultrastructural analyses. After 16 days, all treatments using GDF-9 or FSH showed higher rates of follicular survival compared with αMEM⁺ alone. Compared with non-cultured control, sequential culture media containing GDF-9 and/or FSH significantly increased the percentage of developing follicles and follicle diameter. Moreover, a progressive increase in oocyte diameter was observed only with sequential culture medium containing GDF-9 until Day 8 followed by FSH (GDF-9/FSH) in the second half of the culture period. After 16 days of culture, ultrastructural analysis confirmed the integrity of follicles cultured in the presence of GDF-9/FSH. In conclusion, a dynamic medium containing GDF-9 and FSH (GDF-9/FSH) maintained follicular integrity and promoted activation of primordial follicles and growth during long-term in vitro culture of goat preantral follicles.

  15. Macrophage inhibitory cytokine-1 is associated with cognitive impairment and predicts cognitive decline - the Sydney Memory and Aging Study.

    PubMed

    Fuchs, Talia; Trollor, Julian N; Crawford, John; Brown, David A; Baune, Bernhard T; Samaras, Katherine; Campbell, Lesley; Breit, Samuel N; Brodaty, Henry; Sachdev, Perminder; Smith, Evelyn

    2013-10-01

    Higher levels of macrophage inhibitory cytokine-1, also known as growth differentiation factor 15 (MIC-1/GDF15), are associated with adverse health outcomes and all-cause mortality. The aim of this study was to examine the relationships between MIC-1/GDF15 serum levels and global cognition, five cognitive domains, and mild cognitive impairment (MCI), at baseline (Wave 1) and prospectively at 2 years (Wave 2), in nondemented participants aged 70-90 years. Analyses were controlled for age, sex, education, Framingham risk score, history of cerebrovascular accident, acute myocardial infarction, angina, cancer, depression, C-reactive protein, tumor necrosis factor-α, interleukins 6 and 12, and apolipoprotein ε4 genotype. Higher MIC-1/GDF15 levels were significantly associated with lower global cognition at both waves. Cross-sectional associations were found between MIC-1/GDF15 and all cognitive domains in Wave 1 (all P < 0.001) and between processing speed, memory, and executive function in Wave 2 (all P < 0.001). Only a trend was found for the prospective analyses, individuals with high MIC-1/GDF15 at baseline declined in global cognition, executive function, memory, and processing speed. However, when categorizing MIC-1/GDF15 by tertiles, prospective analyses revealed statistically significant lower memory and executive function in Wave 2 in those in the upper tertile compared with the lower tertile. Receiver operating characteristics (ROC) analysis was used to determine MIC-1/GDF15 cutoff values associated with cognitive decline and showed that a MIC-1/GDF15 level exceeding 2764 pg/ml was associated with a 20% chance of decline from normal to MCI or dementia. In summary, MIC-1/GDF15 levels are associated with cognitive performance and cognitive decline. Further research is required to determine the pathophysiology of this relationship. © 2013 The Anatomical Society and John Wiley & Sons Ltd.

  16. Growth-differentiation factor 15 for long-term prognostication in patients with non-ST-elevation acute coronary syndrome: an Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy.

    PubMed

    Damman, Peter; Kempf, Tibor; Windhausen, Fons; van Straalen, Jan P; Guba-Quint, Anja; Fischer, Johan; Tijssen, Jan G P; Wollert, Kai C; de Winter, Robbert J; Hirsch, Alexander

    2014-03-15

    No five-year long-term follow-up data is available regarding the prognostic value of GDF-15. Our aim is to evaluate the long-term prognostic value of admission growth-differentiation factor 15 (GDF-15) regarding death or myocardial infarction (MI) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). This is a subanalysis from the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) trial, including troponin positive NSTE-ACS patients. The main outcome for the current analysis was 5-year death or spontaneous MI. GDF-15 samples were available in 1151 patients. The prognostic value of GDF-15, categorized into <1200 ng/L, 1200-1800 ng/L and >1800 ng/L, was assessed in unadjusted and adjusted Cox regression models. Adjustments were made for identified univariable risk factors. The additional discriminative and reclassification value of GDF-15 beyond the independent risk factors was assessed by the category-free net reclassification improvement (1/2 NRI(>0)) and the integrated discrimination improvement (IDI) RESULTS: Compared to GDF-15<1200 ng/L, a GDF-15>1800 ng/L was associated with an increased hazard ratio for death or spontaneous MI, mainly driven by mortality. GDF-15 levels were predictive after adjustments for other identified predictors. Additional discriminative value was shown with the IDI, not with the NRI. In patients presenting with NSTE-ACS and elevated troponin T, GDF-15 provides prognostic information in addition to identified predictors for mortality and spontaneous MI and can be used to identify patients at high risk during long-term follow-up. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Association study between growth differentiation factor 5 polymorphism and non-contact anterior cruciate ligament rupture in Chinese Han population

    PubMed Central

    Chen, Biao; Li, Bin; Qi, Yong-Jian; Tie, Kai; Chen, Liao-Bin

    2015-01-01

    Background: Anterior cruciate ligament (ACL) rupture is the most common ligamentous injury for active adolescents and young adults each year. However, the precise etiologies of ACL injury are not fully understood. The present study was to investigate +104T/C polymorphism of growth differentiation factor 5 (GDF5) gene in patients with ACL rupture, and evaluate the effects of polymorphism on GDF5 mRNA levels in ligament of patients with ACL rupture in central China. Methods: A total of 286 Chinese patients with ACL rupture and 500healthy controls were enrolled in this study. The +104T/C polymorphism in GDF5 gene were genotyped by DNA sequencing. GDF5 mRNA expressions levels in ligament were determined by quantitative PCR. Results: The frequency of the TT genotype tended to be higher in ACL rupture group than in control group (62.6% vs. 48.0%, P< 0.001, OR = 1.81, 95% CI: 1.35-2.44). T allele of the GDF5 +104T/C polymorphism was more common in ACL rupture group than in control group (P< 0.001). Patients carrying TT genotype expressed lower levels of GDF5 mRNA than C carriers (P = 0.005) among ACL rupture. Conclusion: Our study indicated that GDF5 +104T/C polymorphism was associated with ACL rupture patients in central China. This is likely from decreased expressions of GDF5 mRNA. Further studies are necessary to explore the functional implication of the GDF5 +104T/C polymorphism in Chinese ACL rupture patients. PMID:26885231

  18. Association study between growth differentiation factor 5 polymorphism and non-contact anterior cruciate ligament rupture in Chinese Han population.

    PubMed

    Chen, Biao; Li, Bin; Qi, Yong-Jian; Tie, Kai; Chen, Liao-Bin

    2015-01-01

    Anterior cruciate ligament (ACL) rupture is the most common ligamentous injury for active adolescents and young adults each year. However, the precise etiologies of ACL injury are not fully understood. The present study was to investigate +104T/C polymorphism of growth differentiation factor 5 (GDF5) gene in patients with ACL rupture, and evaluate the effects of polymorphism on GDF5 mRNA levels in ligament of patients with ACL rupture in central China. A total of 286 Chinese patients with ACL rupture and 500healthy controls were enrolled in this study. The +104T/C polymorphism in GDF5 gene were genotyped by DNA sequencing. GDF5 mRNA expressions levels in ligament were determined by quantitative PCR. The frequency of the TT genotype tended to be higher in ACL rupture group than in control group (62.6% vs. 48.0%, P< 0.001, OR = 1.81, 95% CI: 1.35-2.44). T allele of the GDF5 +104T/C polymorphism was more common in ACL rupture group than in control group (P< 0.001). Patients carrying TT genotype expressed lower levels of GDF5 mRNA than C carriers (P = 0.005) among ACL rupture. Our study indicated that GDF5 +104T/C polymorphism was associated with ACL rupture patients in central China. This is likely from decreased expressions of GDF5 mRNA. Further studies are necessary to explore the functional implication of the GDF5 +104T/C polymorphism in Chinese ACL rupture patients.

  19. Association of serum level of growth differentiation factor 15 with liver cirrhosis and hepatocellular carcinoma.

    PubMed

    Liu, Xiuying; Chi, Xiumei; Gong, Qiaoling; Gao, Lei; Niu, Yuqiang; Chi, Xiaojing; Cheng, Min; Si, Youhui; Wang, Maorong; Zhong, Jin; Niu, Junqi; Yang, Wei

    2015-01-01

    Hepatocellular carcinoma (HCC) and liver cirrhosis are associated with high mortality worldwide. Currently, alpha-fetoprotein (AFP) is used as a standard serum marker for the detection of HCC, but its sensitivity and specificity are unsatisfactory, and optimal diagnostic markers for cirrhosis are lacking. We previously reported that growth differentiation factor 15 (GDF15) was significantly induced in HCV-infected hepatocytes. This study aimed to investigate GDF15 expression and its correlation with hepatitis virus-related liver diseases. A total of 412 patients with various liver diseases were studied. Healthy and Mycobacterium tuberculosis-infected subjects were included as controls. Serum and tissue GDF15 levels were measured. Serum GDF15 levels were significantly increased in patients with HCC (6.66±0.67 ng/mL, p<0.0001) and cirrhosis (6.51±1.47 ng/mL, p<0.0001) compared with healthy controls (0.31±0.01 ng/mL), though the GDF15 levels in HBV and HCV carriers were moderately elevated (1.34±0.19 ng/mL and 2.13±0.53 ng/mL, respectively). Compared with HBV or HCV carriers, GDF15 had a sensitivity of 63.1% and a specificity of 86.6% at the optimal cut-off point of 2.463 ng/mL in patients with liver cirrhosis or HCC. In HCC patients, the area under the receiver operating curve was 0.84 for GDF15 and 0.76 for AFP, but 0.91 for the combined GDF15 and AFP. Serum GDF15 levels did not significantly differ between the high-AFP and low-AFP groups. GDF15 protein expression in HCC was significantly higher than that in the corresponding adjacent paracarcinomatous tissue and normal liver. Using a combination of GDF15 and AFP will improve the sensitivity and specificity of HCC diagnosis. Further research and the clinical implementation of serum GDF15 measurement as a biomarker for HCC and cirrhosis are recommended.

  20. Utility of Growth Differentiation Factor-15, A Marker of Oxidative Stress and Inflammation, in Chronic Heart Failure: Insights From the HF-ACTION Study.

    PubMed

    Sharma, Abhinav; Stevens, Susanna R; Lucas, Joseph; Fiuzat, Mona; Adams, Kirkwood F; Whellan, David J; Donahue, Mark P; Kitzman, Dalane W; Piña, Ileana L; Zannad, Faiez; Kraus, William E; O'Connor, Christopher M; Felker, G Michael

    2017-10-01

    This study sought to determine the relationship between growth differentiation factor (GDF)-15 and clinical outcomes in ambulatory patients with heart failure and reduced ejection fraction (HFrEF). The prognostic utility of GDF-15, a member of the transforming growth factor-β cytokine family, among patients with HF is unclear. We assessed GDF-15 levels in 910 patients enrolled in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial, a randomized clinical trial of exercise training in patients with HFrEF. Median follow-up was 30 months. Cox proportional hazard models assessed the relationships between GDF-15 and clinical outcomes. The median GDF-15 concentration was 1,596 pg/ml. Patients in the highest tertile of GDF-15 were older and had measurements of more severe HF (higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] concentrations and lower peak oxygen uptake on cardiopulmonary exercise testing [CPX]). GDF-15 therapy was a significant predictor of all-cause death (unadjusted hazard ratio [HR]: 2.03 when GDF-15 was doubled; p < 0.0001). This association persisted after adjustment for demographic and clinical and biomarkers including high sensitivity troponin T (hs-TnT) and NT-proBNP (HR: 1.30 per doubling of GDF-15; p = 0.029). GDF-15 did not improve discrimination (as measured by changes in c-statistics and the integrated discrimination improvement) in addition to baseline variables, including hs-TnT and NT-proBNP or variables found in CPX testing. In demographically diverse, well-managed patients with HFrEF, GDF-15 therapy provided independent prognostic information in addition to established predictors of outcomes. These data support a possible role for GDF-15 in the risk stratification of patients with chronic HFrEF. (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION]; NCT00047437). Copyright © 2017 American College of Cardiology Foundation

  1. Far East LPG sales will grow faster than in West

    SciTech Connect

    1996-12-30

    LPG sales through 2010 in regions east of the Suez Canal (East of Suez) will grow at more than twice those in regions west of the canal. East-of-Suez sales will grow at more than 4.0%/year, compared to slightly less than 2.0%/year growth in sales West of Suez. East-of-Suez sales will reach 92 million tons/year (tpy) by 2010, accounting for 39% of the worldwide total. This share was 31% in1995 and only 27% in 1990. LPG sales worldwide will reach 192 million tons in 2000 and 243 million tpy by 2010. In 1995, they were 163 million tons. These are some of the major conclusions of a recent study by Frank R. Spadine, Christine Kozar, and Rudy Clark of New York City-based consultant Poten and Partners Inc. Details of the study are in the fall report ``World Trade in LPG 1990--2010``. This paper discusses demand segments, seaborne balance, Western sources, largest trading region, North American supplies, and other supplies.

  2. Exploration concepts for syntectonic sediments of Triassic and Jurassic Age along northern and eastern rim of Gulf of Mexico basin

    SciTech Connect

    Rodgers, D.A.; Wilkerson, R.P.; Putnam, M.W.

    1985-02-01

    Current tectonic models for the formation of the Gulf of Mexico generally include continental rifting starting in the Triassic and continuing through the Jurassic. A comparison between the sedimentology and structural geology of known continental rifts (such as the Gulf of Suez, Egypt) and the Triassic and Jurassic of the Gulf of Mexico suggests the following. (1) The interior salt basins of Texas, Louisiana, Mississippi, and Alabama probably were deposited within a failed continental rift. (2) Positive features such as the Angelina-Caldwell flexure, Wiggins arch, and Middle ground arch probably represent the southern edge of the failed rift. (3) Positive features such as the Sabine uplift and Monroe arch are probably isolated horst blocks within the failed rift. Pre-evaporite sediments account for much of the production in the Gulf of Suez, and these rock sequences are well exposed there on shore. Depositional and structural histories for these rocks are similar in both the Gulf of Mexico and Gulf of Suez, and a careful comparison suggests new play concepts for the Gulf of Mexico. The post-evaporite sequences of the Gulf of Suez are also similar to the Norphlet and Smackover Formations of the Gulf of Mexico, although Smackover equivalents are currently being deposited in the Gulf of Suez. Comparisons between the two rift systems indicate that a clearer understanding of the structural setting of the Gulf of Mexico at the time of deposition of the Norphlet and Smackover should lead to better exploration plays for these syntectonic formations.

  3. The Global Drug Facility and its role in the market for tuberculosis drugs.

    PubMed

    Arinaminpathy, Nimalan; Cordier-Lassalle, Thierry; Vijay, Anant; Dye, Christopher

    2013-10-19

    Universal access to high-quality treatment is central to the Global Plan to Stop TB. The Global Drug Facility (GDF) was launched in 2001 to help to achieve this goal, through services including the supply of affordable, quality-assured drugs to countries in need. We assess the scale of GDF drug supplies worldwide and find that the GDF commands a substantial proportion of the market for drugs for first-line and second-line treatment regimens, having supplied, for example, first-line drugs for roughly 35% of cases reported worldwide in 2011. Significant potential remains for GDF expansion, especially in the provision of second-line drugs, which would be aided by future increases in case detection. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Switching axial progenitors from producing trunk to tail tissues in vertebrate embryos.

    PubMed

    Jurberg, Arnon Dias; Aires, Rita; Varela-Lasheras, Irma; Nóvoa, Ana; Mallo, Moisés

    2013-06-10

    The vertebrate body is made by progressive addition of new tissue from progenitors at the posterior embryonic end. Axial extension involves different mechanisms that produce internal organs in the trunk but not in the tail. We show that Gdf11 signaling is a major coordinator of the trunk-to-tail transition. Without Gdf11 signaling, the switch from trunk to tail is significantly delayed, and its premature activation brings the hindlimbs and cloaca next to the forelimbs, leaving extremely short trunks. Gdf11 activity includes activation of Isl1 to promote formation of the hindlimbs and cloaca-associated mesoderm as the most posterior derivatives of lateral mesoderm progenitors. Gdf11 also coordinates reallocation of bipotent neuromesodermal progenitors from the anterior primitive streak to the tail bud, in part by reducing the retinoic acid available to the progenitors. Our findings provide a perspective to understand the evolution of the vertebrate body plan. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Evaluation of generalized degrees of freedom for sparse estimation by replica method

    NASA Astrophysics Data System (ADS)

    Sakata, A.

    2016-12-01

    We develop a method to evaluate the generalized degrees of freedom (GDF) for linear regression with sparse regularization. The GDF is a key factor in model selection, and thus its evaluation is useful in many modelling applications. An analytical expression for the GDF is derived using the replica method in the large-system-size limit with random Gaussian predictors. The resulting formula has a universal form that is independent of the type of regularization, providing us with a simple interpretation. Within the framework of replica symmetric (RS) analysis, GDF has a physical meaning as the effective fraction of non-zero components. The validity of our method in the RS phase is supported by the consistency of our results with previous mathematical results. The analytical results in the RS phase are calculated numerically using the belief propagation algorithm.

  6. Evolving New Skeletal Traits by cis-Regulatory Changes in Bone Morphogenetic Proteins

    PubMed Central

    Indjeian, Vahan B.; Kingman, Garrett A.; Jones, Felicity C.; Guenther, Catherine A.; Grimwood, Jane; Schmutz, Jeremy; Myers, Richard M.; Kingsley, David M.

    2016-01-01

    SUMMARY Changes in bone size and shape are defining features of many vertebrates. Here we use genetic crosses and comparative genomics to identify specific regulatory DNA alterations controlling skeletal evolution. Armor bone size differences in sticklebacks maps to a major effect locus overlapping BMP family member GDF6. Freshwater fish express more GDF6 due in part to a transposon insertion, and transgenic overexpression of GDF6 phenocopies evolutionary changes in armor plate size. The human GDF6 locus also has undergone distinctive regulatory evolution, including complete loss of an enhancer that is otherwise highly conserved between chimps and other mammals. Functional tests show that the ancestral enhancer drives expression in hindlimbs but not forelimbs, in locations that have been specifically modified during the human transition to bipedalism. Both gain and loss of regulatory elements can localize BMP changes to specific anatomical locations, providing a flexible regulatory basis for evolving species-specific changes in skeletal form. PMID:26774823

  7. Association of growth differentiation factor 11/8, putative anti-ageing factor, with cardiovascular outcomes and overall mortality in humans: analysis of the Heart and Soul and HUNT3 cohorts.

    PubMed

    Olson, Kristoff A; Beatty, Alexis L; Heidecker, Bettina; Regan, Mathilda C; Brody, Edward N; Foreman, Trudi; Kato, Shintaro; Mehler, Robert E; Singer, Britta S; Hveem, Kristian; Dalen, Havard; Sterling, David G; Lawn, Richard M; Schiller, Nelson B; Williams, Stephen A; Whooley, Mary A; Ganz, Peter

    2015-12-21

    Growth differentiation factor 11 and/or its homologue growth differentiation factor 8 (GDF11/8) reverses age-related cardiac hypertrophy and vascular ageing in mice. We investigated whether GDF11/8 associates with cardiovascular outcomes, left ventricular hypertrophy (LVH), or age in humans. We measured plasma GDF11/8 levels in 928 participants with stable ischaemic heart disease in the Heart and Soul study. We adjudicated heart failure hospitalization, stroke, myocardial infarction, death, and their composite endpoint. Left ventricular hypertrophy was evaluated by echocardiography. We used multivariable Cox proportional hazards models to compare rates of cardiovascular events and death across GDF11/8 quartiles and logistic regression models to evaluate the association between GDF11/8 and LVH. Four hundred and fifty participants (48.5%) experienced a cardiovascular event or death during 8.9 years of follow-up. The adjusted risk of the composite endpoint was lower in the highest compared with the lowest GDF11/8 quartile [hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.33-0.60; P < 0.001]. We replicated this relationship of GDF11/8 to adverse events in 971 participants in the HUNT3 cohort (adjusted HR, 0.34; 95% CI, 0.23-0.51; P < 0.001). Left ventricular hypertrophy was present in 368 participants (39.7%) at baseline. Participants in the highest quartile of GDF11/8 were less likely to have LVH than those in the lowest quartile (adjusted OR, 0.55; 95% CI, 0.35-0.86; P = 0.009). GDF11/8 levels were lower in older individuals (P < 0.001). In patients with stable ischaemic heart disease, higher GDF11/8 levels are associated with lower risk of cardiovascular events and death. Our findings suggest that GDF11/8 has similar cardioprotective properties in humans to those demonstrated in mice. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  8. Growth-differentiation factor 15 and risk of major bleeding in atrial fibrillation: Insights from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial.

    PubMed

    Hijazi, Ziad; Oldgren, Jonas; Andersson, Ulrika; Connolly, Stuart J; Eikelboom, John W; Ezekowitz, Michael D; Reilly, Paul A; Yusuf, Salim; Siegbahn, Agneta; Wallentin, Lars

    2017-08-01

    To evaluate and validate the prognostic value of growth-differentiation factor 15 (GDF-15) beyond clinical characteristics and other biomarkers concerning bleeding and stroke outcomes in patients with atrial fibrillation in the RE-LY trial. GDF-15 was measured in samples collected at randomization in 8,474 patients with a median follow-up time of 1.9 years. Patients were stratified based on predefined GDF-15 cutoffs: group 1, <1,200 ng/L (the 90th percentile in healthy individuals); group 2, 1,200-1,800; and group 3, >1,800 ng/L (high-risk individuals). Efficacy and safety outcomes were compared across groups of GDF-15 in Cox models adjusted for baseline characteristics, cardiac (N-terminal pro-b-type natriuretic peptide, high-sensitive troponin T), inflammatory (interleukin 6, C-reactive protein) and coagulation (D-dimer) biomarkers, and randomized treatment. GDF-15 concentrations were <1,200 ng/L in 2,647 (31.2%), between 1,200 and 1,800 ng/L in 2,704 (31.9%), and >1,800 ng/L in 3,123 (36.9%) participants, respectively. Annual rates of stroke, major bleeding, and mortality increased with higher GDF-15 levels. The prognostic value of GDF-15 was independent of clinical characteristics for these outcomes. In models also adjusted for biomarkers, GDF-15 remained significantly associated with major bleeding (hazard ratio [95% CI] group 3 vs group 1 1.76 [1.28-2.42], P < .0005) and all-cause mortality (hazard ratio 1.72 [1.30-2.29], P < .0005). GDF-15 improved the c index of both the HAS-BLED (0.62-0.69) and ORBIT (0.68-0.71) bleeding risk scores. In patients with atrial fibrillation, GDF-15 is an independent risk indicator for major bleeding and all-cause mortality, but not for stroke. Therefore, GDF-15 seems useful as a specific marker of bleeding in patients with AF on oral anticoagulant treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Nebraska Prostate Cancer Research Program

    DTIC Science & Technology

    2011-05-01

    1. Brittany T. Jones, Poomy Pandey, Srustidhar Das and Surinder K. Batra. (2010) Therapeutic Potential of Curcumin : Inhibition of MIC-1/GDF-15...else has every thought. She’s currently working in Dr. Surinder K. Batra’s lab, where her research project is to monitor "What effect do Curcumin ...project is supported in part by DOD PC094594 and NCI CA88184.) Brittany Jones – Abstract Therapeutic Potential of Curcumin : Inhibition of MIC-1/GDF-15

  10. Uncovering the Role of BMP Signaling in Melanocyte Development and Melanoma Tumorigenesis

    DTIC Science & Technology

    2016-09-01

    validated zebrafish-specific array CGH platform. Genes Chromosomes Cancer, 48, 155-70. 10. North, T.E., Goessling, W., Peeters, M., Li, P., Ceol, C.J...number variation (CNV) in the melanoma genome. A major challenge in the field of cancer genomics has been to distinguish, from a chromosomal segment...tagged gdf6b, GST-gdf6b, into two guinea pigs. Antibodies were validated by comparing reactivity of 8 pre- and post-immune sera to bacterially

  11. Growth Differentiation Factor 15 Predicts Chronic Liver Disease Severity

    PubMed Central

    Lee, Eaum Seok; Kim, Seok Hyun; Kim, Hyun Jin; Kim, Kyung Hee; Lee, Byung Seok; Ku, Bon Jeong

    2017-01-01

    Background/Aims Growth differentiation factor 15 (GDF-15) belongs to the transforming growth factor-β superfamily. GDF-15 is emerging as a biomarker for several diseases. The aim of this study was to determine the clinical performances of GDF-15 for the prediction of liver fibrosis and severity in chronic liver disease. Methods The serum GDF-15 levels were examined via enzyme immunoassay in 145 patients with chronic liver disease and 101 healthy individuals. The patients with chronic liver disease consisted of 54 patients with chronic hepatitis, 44 patients with compensated liver cirrhosis, and 47 patients with decompensated liver cirrhosis. Results Of the patients with chronic liver diseases, the decompensated liver cirrhosis patients had an increased serum GDF-15 (3,483 ng/L) level compared with the patients with compensated liver cirrhosis (1,861 ng/L) and chronic hepatitis (1,232 ng/L). The overall diagnostic accuracies of GDF-15, as determined by the area under the receiver operating characteristic curves, were as follows: chronic hepatitis=0.656 (>574 ng/L, sensitivity, 53.7%; specificity, 79.2%), compensated liver cirrhosis=0.886 (>760 ng/L, sensitivity, 75.6%; specificity, 92.1%), and decompensated liver cirrhosis=0.984 (>869 ng/L, sensitivity, 97.9%; specificity, 94.1%). Conclusions This investigation represents the first study to demonstrate the availability of GDF-15 in chronic liver disease. GDF-15 comprised a useful biomarker for the prediction of liver fibrosis and severity in chronic liver disease. PMID:27728964

  12. Grout disposal facility vault exhauster: Technical background document on demonstration of best available control technology for toxics

    SciTech Connect

    Glissmeyer, J.A.; Glantz, C.S.; Rittman, P.D.

    1994-09-01

    The Grout Disposal Facility (GDF) is currently operated on the US Department of Energy`s Hanford Site. The GDF is located near the east end of the Hanford Site`s 200 East operations area, and is used for the treatment and disposal of low-level radioactive liquid wastes. In the grout treatment process, selected radioactive wastes from double-shell tanks are mixed with grout-forming solids; the resulting grout slurry is pumped to near-surface concrete vaults for solidification and permanent disposal. As part of this treatment process, small amounts of toxic particles and volatile organic compounds (VOCs) may be released to the atmosphere through the GDF`s exhaust system. This analysis constitutes a Best Available Control Technology for Toxics (T-BACT) study, as required in the Washington Administrative Code (WAC 173-460) to support a Notice of Construction for the operation of the GDF exhaust system at a modified flow rate that exceeds the previously permitted value. This report accomplishes the following: assesses the potential emissions from the GDF; estimates air quality impacts to the public from toxic air pollutants; identifies control technologies that could reduce GDF emissions; evaluates impacts of the control technologies; and recommends appropriate emissions controls.

  13. Recombinant human growth differentiation factor-9 improves oocyte reprogramming competence and subsequent development of bovine cloned embryos.

    PubMed

    Su, Jianmin; Hu, Guangdong; Wang, Yongsheng; Liang, Dong; Gao, Mingqing; Sun, Hongzheng; Zhang, Yong

    2014-08-01

    Previously, we found that oocyte-secreted factors (OSFs) secreted by denuded oocytes during in vitro maturation (IVM) enhance subsequent development of bovine somatic cell nuclear transfer (SCNT) embryos. This treatment requires many oocytes during IVM. Hence, the aim of this study was to investigate whether supplementing with recombinant growth differentiation factor-9 (GDF9), one of crucial OFSs, in oocyte maturation medium could improve developmental competence of bovine oocytes and subsequent development of cloned embryos. Cumulus-oocyte complexes (COCs) from antral follicles of bovine ovaries collected from an abattoir were cultured with (SCNT+GDF9 group) or without (SCNT group) 200 ng/mL recombinant human GDF9 in oocyte maturation medium. After 22 h, metaphase II (MII) oocytes were used for SCNT. The presence of 200 ng/mL GDF9 significantly increased oocyte maturation rates, the cleavage rate, and blastocyst formation rates of bovine cloned embryos. The blastocyst total, inner cell mass (ICM) cell numbers, and ratio of ICM:TE were higher, whereas the rate of apoptosis in bovine cloned blastocysts was lower in the SCNT+GDF9 group than in the SCNT group. The histone modifications at various sites were also different between each group. These results suggest that COCs cultured with recombinant GDF9 in oocyte maturation medium improve oocyte developmental competence and subsequent developmental competence of cloned embryo in cattle.

  14. Inhibition of follicular development induced by chronic unpredictable stress is associated with growth and differentiation factor 9 and gonadotropin in mice.

    PubMed

    Wu, Li-Min; Liu, Yu-Sheng; Tong, Xian-Hong; Shen, Ni; Jin, Ren-Tao; Han, Hui; Hu, Mei-Hong; Wang, Wei; Zhou, Gui-Xiang

    2012-04-01

    Chronic psychosocial stress negatively affects ovarian function. Ovarian follicular development is regulated by both pituitary-derived gonadotropins and intraovarian regulatory factors. To date, the suppressive effects of chronic stress on the ovary have been observed to be manifested mainly as an inhibition of gonadotropin release. It is not clear whether there are any other intraovarian regulatory mechanisms involved in this process. Growth and differentiation factor 9 (GDF9) is an important, oocyte-specific paracrine regulator required for follicular development. In this study, the chronic unpredictable mild stress model was used to produce psychosocial stress in mice. The number of different developmental stages of follicles was counted on ovarian sections stained with hematoxylin and eosin. Real-time PCR and Western blotting were used to detect the mRNA and protein levels, respectively, of GDF9. The results show that chronic unpredictable stress inhibits follicular development, increases follicular atresia, and suppresses GDF9 expression. Exogenous gonadotropin treatment partly restores the repressed antral follicular development, but has no effect on the repressed secondary follicular development associated with chronic stress. Treatment with recombinant GDF9 restores secondary follicular development. Cotreatments with GDF9 and gonadotropins restore both secondary and antral follicular development in stressed mice. These findings demonstrate that inhibition of follicular development induced by chronic unpredictable stress is associated with GDF9 and gonadotropin.

  15. Polymorphisms of the bovine growth differentiation factor 9 gene associated with superovulation performance in Chinese Holstein cows.

    PubMed

    Tang, K Q; Yang, W C; Li, S J; Yang, L-G

    2013-02-08

    Growth differentiation factor 9 (GDF9) belongs to the transforming growth factor β superfamily and plays a critical role in ovarian follicular development and ovulation rate. We examined the bovine GDF9 gene polymorphism and analyzed its association with superovulation performance. Based on the sequence of the bovine GDF9 gene, six pairs of primers were designed to detect single nucleotide polymorphisms of two exons and intron 1 of GDF9 using polymerase chain reaction-single-strand conformation polymorphism. Only the products amplified by primer 3-1 displayed polymorphisms. Sequencing revealed two mutations of A485T and A625T in intron 1 of the GDF9 gene in 171 Chinese Holstein cows treated for superovulation. Association analysis showed that these two single nucleotide polymorphisms of A485T and A625T had significant effects on the number of transferable embryos (P < 0.05), and the A625T polymorphism was significantly associated with the total number of ova (P < 0.05). In addition, a significant additive effect on the number of transferable embryos was detected in polymorphisms of A485T (P < 0.05). This study is the first to identify two polymorphisms in bovine GDF9 and describe their correlation with superovulation traits in Chinese Holstein cows.

  16. Folic acid protects against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1

    PubMed Central

    Ma, Yan; Zhang, Chen; Gao, Xiao-Bo; Luo, Hai-Yan; Chen, Yang; Li, Hui-hua; Ma, Xu; Lu, Cai-Ling

    2015-01-01

    As a nutritional factor, folic acid can prevent cardiac and neural defects during embryo development. Our previous study showed that arsenic impairs embryo development by down-regulating Dvr1/GDF1 expression in zebrafish. Here, we investigated whether folic acid could protect against arsenic-mediated embryo toxicity. We found that folic acid supplementation increases hatching and survival rates, decreases malformation rate and ameliorates abnormal cardiac and neural development of zebrafish embryos exposed to arsenite. Both real-time PCR analysis and whole in-mount hybridization showed that folic acid significantly rescued the decrease in Dvr1 expression caused by arsenite. Subsequently, our data demonstrated that arsenite significantly decreased cell viability and GDF1 mRNA and protein levels in HEK293ET cells, while folic acid reversed these effects. Folic acid attenuated the increase in subcellular reactive oxygen species (ROS) levels and oxidative adaptor p66Shc protein expression in parallel with the changes in GDF1 expression and cell viability. P66Shc knockdown significantly inhibited the production of ROS and the down-regulation of GDF1 induced by arsenite. Our data demonstrated that folic acid supplementation protected against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1/GDF1, and folic acid enhanced the expression of GDF1 by decreasing p66Shc expression and subcellular ROS levels. PMID:26537450

  17. Growth differentiation factor-9 has divergent effects on proliferation and steroidogenesis of bovine granulosa cells.

    PubMed

    Spicer, L J; Aad, P Y; Allen, D; Mazerbourg, S; Hsueh, A J

    2006-05-01

    In addition to gonadotropins, steroidogenesis and proliferation of granulosa cells during follicular development are controlled by a number of intraovarian factors including growth differentiation factor-9 (GDF-9), bone morphogenetic protein-4 (BMP-4), and IGF-I. The objective of this study was to determine the effect of GDF-9 and BMP-4 and their interaction with IGF-I and FSH on ovarian granulosa cell function in cattle. Granulosa cells from small (1-5 mm) and large (8-22 mm) follicles were collected from bovine ovaries and cultured for 48 h in medium containing 10% fetal calf serum and then treated with various hormones in serum-free medium for an additional 48 h. We evaluated the effects of GDF-9 (150-600 ng/ml) and BMP-4 (30 ng/ml) during a 2-day exposure on hormone-induced steroidogenesis and cell proliferation. In FSH plus IGF-I-treated granulosa cells obtained from small follicles, 300 ng/ml GDF-9 reduced (P < 0.05) progesterone production by 15% and 600 ng/ml GDF-9 completely blocked (P < 0.01) the IGF-I-induced increase in progesterone production. In comparison, 300 and 600 ng/ml GDF-9 decreased (P < 0.05) estradiol production by 27% and 71% respectively, whereas 150 ng/ml GDF-9 was without effect (P > 0.10). Treatment with 600 ng/ml GDF-9 increased (P < 0.05) numbers (by 28%) of granulosa cells from small follicles. In the same cells treated with FSH but not IGF-I, co-treatment with 600 ng/ml GDF-9 decreased (P < 0.05) progesterone production (by 28%), increased (P < 0.05) cell numbers (by 60%), and had no effect (P > 0.10) on estradiol production. In FSH plus IGF-I-treated granulosa cells obtained from large follicles, GDF-9 caused a dose-dependent decrease (P<0.05) in IGF-I-induced progesterone (by 13-48%) and estradiol (by 20-51%) production. In contrast, GDF-9 increased basal and IGF-I-induced granulosa cell numbers by over 2-fold. Furthermore, treatment with BMP-4 also inhibited (P < 0.05) steroidogenesis by 27-42% but had no effect on cell numbers

  18. Analyse des transferts de chaleur et de masse transitoires dans un arena a l'aide de la methode zonale

    NASA Astrophysics Data System (ADS)

    Daoud, Ahmed

    Cette these presente les resultats d'une etude sur le mouvement de l'air et les transferts thermiques et massiques dans les arenas en regime transitoire et en 3D. Pour la partie aeraulique, il a ete question de developper un modele base sur la methode zonale qui permet de calculer les debits de l'air (dus a la ventilation et aux gradients de temperature) et de l'humidite entre les differentes zones du batiment et de determiner l'age de l'air dans chacune des zones. Pour la partie thermique, un modele de calcul du rayonnement entre les surfaces interieures du batiment qui a ete couple a TRNSYS afin de calculer sur une base annuelle les charges de chauffage et de refrigeration; ces dernieres tiennent compte des transferts radiatif et convectif, de la chaleur latente due a la condensation de l'humidite sur la glace et du surfacage. Le document presente est constitue de 7 chapitres qui peuvent etre resumes comme suit: Les chapitres 1, 2 et 3 sont consacres respectivement: a l'introduction generale, a la revue bibliographique et a la description du batiment modelise. Le chapitre 4 decrit l'approche developpee et la contribution importante qui y est apportee. Il presente l'utilisation de la methode zonale comme une alternative pratique aux methodes CFD car elle permet de realiser des simulations dynamiques sur une annee avec des temps de simulation tres courts et une precision acceptable. Il s'agit d'une approche intermediaire entre les modeles CFD et les modeles a un noeud d'air (considerant la temperature homogene dans un local). Le chapitre 5 est consacre a la methode de resolution numerique. L'outil de simulation a ete developpe en utilisant l'interface du logiciel TRNSYS: Le type 56 de ce logiciel a ete adopte comme modele energetique tandis que les autres modeles ont ete developpes et programmes en utilisant le logiciel MATLAB. Le chapitre 6 presente les resultats de simulation pour un arena sans faux plafond et avec un faux plafond et les resultats de mesures

  19. Panoramic Sinai Peninsula, Red Sea

    NASA Image and Video Library

    1984-10-13

    An excellent panoramic view of the entire Sinai Peninsula (29.0N, 34.0E) and the nearby Nile River Delta and eastern Mediterranean coastal region. The Suez Canal, at the top of the scene just to the right of the Delta, connects the Mediterranean Sea with the Gulf of Suez on the west side of the Sinai Peninsula and the Gulf of Aqaba is on the west where they both flow into the Red Sea. At upper right, is the Dead Sea, Jordan River and Lake Tiberius.

  20. A prospective, randomized pilot study on the safety and efficacy of recombinant human growth and differentiation factor-5 coated onto β-tricalcium phosphate for sinus lift augmentation.

    PubMed

    Koch, Felix P; Becker, Jürgen; Terheyden, Hendrik; Capsius, Björn; Wagner, Wilfried

    2010-11-01

    The aim of this prospective, randomized clinical trial was to investigate the potential of recombinant human growth and differentiation factor-5 (rhGDF-5) coated onto β-tricalcium phosphate (β-TCP) (rhGDF-5/β-TCP) to support bone formation after sinus lift augmentation. In total, 31 patients participated in this multicenter clinical trial. They required a two-stage unilateral maxillary sinus floor augmentation (residual bone height <5 mm). According to a parallel-group design, the patients were randomized to three treatment groups: (a) augmentation with rhGDF-5/β-TCP and a 3-month healing period, (b) augmentation with rhGDF-5/β-TCP and a 4-month healing period and (c) medical device β-TCP mixed with autologous bone and a 4-month healing period. The primary study objective was the area of newly formed bone within the augmented area as assessed by histomorphometric evaluation of trephine bur biopsies. The osseous regeneration was similar in each treatment group; the amount of newly formed bone ranged between 28% (± 15.5%) and 31.8% (± 17.9%). Detailed analysis of histological data will be published elsewhere. As secondary efficacy variables, the augmentation height at the surgery site was measured by radiography. The largest augmentation was radiologically achieved in the rhGDF-5/β-TCP - 3-month and the rhGDF-5/β-TCP - 4-month treatment groups. As safety parameters, adverse events were recorded and anti-drug antibody levels were evaluated. Most of the adverse events were judged as unrelated to the study medication. Four out of 47 (8.5%) implants failed in patients treated with rhGDF-5/β-TCP, a result that is in agreement with the general implant failure rate of 5-15%. Transiently very low amounts of anti-rhGDF-5 antibodies were detected in some patients who received rhGDF-5, which was not related to the bone formation outcome. rhGDF-5/β-TCP was found to be effective and safe as the control treatment with autologous bone mixed β-TCP in sinus floor

  1. Growth Differentiation Factor-15–Induced Contractile Activity and Extracellular Matrix Production in Human Trabecular Meshwork Cells

    PubMed Central

    Muralidharan, Arumugam Ramachandran; Maddala, Rupalatha; Skiba, Nikolai P.; Rao, Ponugoti Vasantha

    2016-01-01

    Purpose To determine the role and regulation of growth differentiation factor-15 (GDF-15), a TGF-β–related cytokine in human trabecular meshwork (TM) cells in the context of aqueous humor (AH) outflow and IOP. Methods Regulation of expression by external cues, and the distribution and secretion of GDF-15 by human TM primary cell cultures, and the effects of recombinant (r) GDF-15 on TM cell contractile characteristics, actin cytoskeleton, cell adhesion, extracellular matrix (ECM), α-smooth muscle actin (αSMA), SMAD signaling, and gene expression were determined by immunoblot, immunofluorescence, mass spectrometry, cDNA microarray, and real-time quantitative PCR (RT-qPCR) analyses. Results Growth differentiation factor-15, a common constituent of ECM derived from the human TM cells, was confirmed to be distributed throughout the conventional aqueous humor outflow pathway of the human eye. Growth differentiation factor-15 protein levels were significantly increased in human TM cells in response to TGF-β2, dexamethasone, endothelin-1, lysophosphatidic acid, TNF-α, IL-1β treatment, and by cyclic mechanical stretch. Stimulation of human TM cells with rGDF-15 caused a significant increase in the formation of actin stress fibers and focal adhesions, myosin light chain phosphorylation, SMAD signaling, gene expression, and the levels of αSMA and ECM proteins. Conclusions The results of this study, including a robust induction of GDF-15 expression by several external factors known to elevate IOP, and rGDF-15–induced increase in contractility, cell adhesion, and the levels of ECM proteins and αSMA in TM cells, collectively suggest a potential role for GDF-15 in homeostasis and dysregulation of AH outflow and IOP in normal and glaucomatous eyes, respectively. PMID:27918822

  2. Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-β Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality.

    PubMed

    Mottershead, David G; Sugimura, Satoshi; Al-Musawi, Sara L; Li, Jing-Jie; Richani, Dulama; White, Melissa A; Martin, Georgia A; Trotta, Andrew P; Ritter, Lesley J; Shi, Junyan; Mueller, Thomas D; Harrison, Craig A; Gilchrist, Robert B

    2015-09-25

    Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-specific growth factors with central roles in mammalian reproduction, regulating species-specific fecundity, ovarian follicular somatic cell differentiation, and oocyte quality. In the human, GDF9 is produced in a latent form, the mechanism of activation being an open question. Here, we produced a range of recombinant GDF9 and BMP15 variants, examined their in silico and physical interactions and their effects on ovarian granulosa cells (GC) and oocytes. We found that the potent synergistic actions of GDF9 and BMP15 on GC can be attributed to the formation of a heterodimer, which we have termed cumulin. Structural modeling of cumulin revealed a dimerization interface identical to homodimeric GDF9 and BMP15, indicating likely formation of a stable complex. This was confirmed by generation of recombinant heterodimeric complexes of pro/mature domains (pro-cumulin) and covalent mature domains (cumulin). Both pro-cumulin and cumulin exhibited highly potent bioactivity on GC, activating both SMAD2/3 and SMAD1/5/8 signaling pathways and promoting proliferation and expression of a set of genes associated with oocyte-regulated GC differentiation. Cumulin was more potent than pro-cumulin, pro-GDF9, pro-BMP15, or the two combined on GC. However, on cumulus-oocyte complexes, pro-cumulin was more effective than all other growth factors at notably improving oocyte quality as assessed by subsequent day 7 embryo development. Our results support a model of activation for human GDF9 dependent on cumulin formation through heterodimerization with BMP15. Oocyte-secreted cumulin is likely to be a central regulator of fertility in mono-ovular mammals. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-β Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality*

    PubMed Central

    Mottershead, David G.; Sugimura, Satoshi; Al-Musawi, Sara L.; Li, Jing-Jie; Richani, Dulama; White, Melissa A.; Martin, Georgia A.; Trotta, Andrew P.; Ritter, Lesley J.; Shi, Junyan; Mueller, Thomas D.; Harrison, Craig A.; Gilchrist, Robert B.

    2015-01-01

    Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-specific growth factors with central roles in mammalian reproduction, regulating species-specific fecundity, ovarian follicular somatic cell differentiation, and oocyte quality. In the human, GDF9 is produced in a latent form, the mechanism of activation being an open question. Here, we produced a range of recombinant GDF9 and BMP15 variants, examined their in silico and physical interactions and their effects on ovarian granulosa cells (GC) and oocytes. We found that the potent synergistic actions of GDF9 and BMP15 on GC can be attributed to the formation of a heterodimer, which we have termed cumulin. Structural modeling of cumulin revealed a dimerization interface identical to homodimeric GDF9 and BMP15, indicating likely formation of a stable complex. This was confirmed by generation of recombinant heterodimeric complexes of pro/mature domains (pro-cumulin) and covalent mature domains (cumulin). Both pro-cumulin and cumulin exhibited highly potent bioactivity on GC, activating both SMAD2/3 and SMAD1/5/8 signaling pathways and promoting proliferation and expression of a set of genes associated with oocyte-regulated GC differentiation. Cumulin was more potent than pro-cumulin, pro-GDF9, pro-BMP15, or the two combined on GC. However, on cumulus-oocyte complexes, pro-cumulin was more effective than all other growth factors at notably improving oocyte quality as assessed by subsequent day 7 embryo development. Our results support a model of activation for human GDF9 dependent on cumulin formation through heterodimerization with BMP15. Oocyte-secreted cumulin is likely to be a central regulator of fertility in mono-ovular mammals. PMID:26254468

  4. Growth differentiation factor 9 signaling requires ERK1/2 activity in mouse granulosa and cumulus cells.

    PubMed

    Sasseville, Maxime; Ritter, Lesley J; Nguyen, Thao M; Liu, Fang; Mottershead, David G; Russell, Darryl L; Gilchrist, Robert B

    2010-09-15

    Ovarian folliculogenesis is driven by the combined action of endocrine cues and paracrine factors. The oocyte secretes powerful mitogens, such as growth differentiation factor 9 (GDF9), that regulate granulosa cell proliferation, metabolism, steroidogenesis and differentiation. This study investigated the role of the epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase 1 and 2 (ERK1/2; also known as MAPK3/1) signaling pathway on GDF9 action on granulosa cells. Results show that mitogenic action of the oocyte is prevented by pharmacological inhibition of the EGFR-ERK1/2 pathway. Importantly, EGFR-ERK1/2 activity as well as rous sarcoma oncogene family kinases (SFK) are required for signaling through SMADs, mediating GDF9, activin A and TGFbeta1 mitogenic action in granulosa cells. GDF9 could not activate ERK1/2 or affect EGF-stimulated ERK1/2 in granulosa cells. However, induction of the SMAD3-specific CAGA reporter by GDF9 in granulosa cells required active EGFR, SFKs and ERK1/2 as did GDF9-responsive gene expression. Finally, the EGFR-SFKs-ERK1/2 pathway was shown to be required for the maintenance of phosphorylation of the SMAD3 linker region. Together our results suggest that receptivity of granulosa cells to oocyte-secreted factors, including GDF9, is regulated by the level of activation of the EGFR and resulting ERK1/2 activity, through the requisite permissive phosphorylation of SMAD3 in the linker region. Our results indicate that oocyte-secreted TGFbeta-like ligands and EGFR-ERK1/2 signaling are cooperatively required for the unique granulosa cell response to the signal from oocytes mediating granulosa cell survival and proliferation and hence the promotion of follicle growth and ovulation.

  5. Tribulus terrestris Alters the Expression of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Rabbit Ovaries of Mothers and F1 Female Offspring.

    PubMed

    Abadjieva, Desislava; Kistanova, Elena

    2016-01-01

    Although previous research has demonstrated the key role of the oocyte-derived factors, bone morphogenetic protein (BMP) 15 and growth differentiation factor (GDF) 9, in follicular development and ovulation, there is a lack of knowledge on the impact of external factors, which females are exposed to during folliculogenesis, on their expression. The present study investigated the effect of the aphrodisiac Tribulus terrestris on the GDF9 and BMP15 expression in the oocytes and cumulus cells at mRNA and protein levels during folliculogenesis in two generations of female rabbits. The experiment was conducted with 28 New Zealand rabbits. Only the diet of the experimental mothers group was supplemented with a dry extract of T. terrestris for the 45 days prior to insemination. The expression of BMP15 and GDF9 genes in the oocytes and cumulus cells of mothers and F1 female offspring was analyzed using real-time polymerase chain reaction (RT-PCR). The localization of the GDF9 and BMP15 proteins in the ovary tissues was determined by immunohistochemical analysis. The BMP15 and GDF9 transcripts were detected in the oocytes and cumulus cells of rabbits from all groups. T. terrestris caused a decrease in the BMP15 mRNA level in the oocytes and an increase in the cumulus cells. The GDF9 mRNA level increased significantly in both oocytes and cumulus cells. The downregulated expression of BMP15 in the treated mothers' oocytes was inherited in the F1 female offspring born to treated mothers. BMP15 and GDF9 show a clearly expressed sensitivity to the bioactive compounds of T. terrestris.

  6. Characterization of the Ligand Binding Functionality of the Extracellular Domain of Activin Receptor Type IIB

    PubMed Central

    Sako, Dianne; Grinberg, Asya V.; Liu, June; Davies, Monique V.; Castonguay, Roselyne; Maniatis, Silas; Andreucci, Amy J.; Pobre, Eileen G.; Tomkinson, Kathleen N.; Monnell, Travis E.; Ucran, Jeffrey A.; Martinez-Hackert, Erik; Pearsall, R. Scott; Underwood, Kathryn W.; Seehra, Jasbir; Kumar, Ravindra

    2010-01-01

    The single transmembrane domain serine/threonine kinase activin receptor type IIB (ActRIIB) has been proposed to bind key regulators of skeletal muscle mass development, including the ligands GDF-8 (myostatin) and GDF-11 (BMP-11). Here we provide a detailed kinetic characterization of ActRIIB binding to several low and high affinity ligands using a soluble activin receptor type IIB-Fc chimera (ActRIIB.Fc). We show that both GDF-8 and GDF-11 bind the extracellular domain of ActRIIB with affinities comparable with those of activin A, a known high affinity ActRIIB ligand, whereas BMP-2 and BMP-7 affinities for ActRIIB are at least 100-fold lower. Using site-directed mutagenesis, we demonstrate that ActRIIB binds GDF-11 and activin A in different ways such as, for example, substitutions in ActRIIB Leu79 effectively abolish ActRIIB binding to activin A yet not to GDF-11. Native ActRIIB has four isoforms that differ in the length of the C-terminal portion of their extracellular domains. We demonstrate that the C terminus of the ActRIIB extracellular domain is crucial for maintaining biological activity of the ActRIIB.Fc receptor chimera. In addition, we show that glycosylation of ActRIIB is not required for binding to activin A or GDF-11. Together, our findings reveal binding specificity and activity determinants of the ActRIIB receptor that combine to effect specificity in the activation of distinct signaling pathways. PMID:20385559

  7. Tribulus terrestris Alters the Expression of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Rabbit Ovaries of Mothers and F1 Female Offspring

    PubMed Central

    2016-01-01

    Although previous research has demonstrated the key role of the oocyte-derived factors, bone morphogenetic protein (BMP) 15 and growth differentiation factor (GDF) 9, in follicular development and ovulation, there is a lack of knowledge on the impact of external factors, which females are exposed to during folliculogenesis, on their expression. The present study investigated the effect of the aphrodisiac Tribulus terrestris on the GDF9 and BMP15 expression in the oocytes and cumulus cells at mRNA and protein levels during folliculogenesis in two generations of female rabbits. The experiment was conducted with 28 New Zealand rabbits. Only the diet of the experimental mothers group was supplemented with a dry extract of T. terrestris for the 45 days prior to insemination. The expression of BMP15 and GDF9 genes in the oocytes and cumulus cells of mothers and F1 female offspring was analyzed using real-time polymerase chain reaction (RT-PCR). The localization of the GDF9 and BMP15 proteins in the ovary tissues was determined by immunohistochemical analysis. The BMP15 and GDF9 transcripts were detected in the oocytes and cumulus cells of rabbits from all groups. T. terrestris caused a decrease in the BMP15 mRNA level in the oocytes and an increase in the cumulus cells. The GDF9 mRNA level increased significantly in both oocytes and cumulus cells. The downregulated expression of BMP15 in the treated mothers’ oocytes was inherited in the F1 female offspring born to treated mothers. BMP15 and GDF9 show a clearly expressed sensitivity to the bioactive compounds of T. terrestris. PMID:26928288

  8. Growth/differentiation factor-5: pre-clinical and clinical evaluations of periodontal regeneration and alveolar augmentation--review.

    PubMed

    Lee, Jaebum; Wikesjö, Ulf M E

    2014-08-01

    Growth/differentiation factor-5 (GDF-5) plays critical roles in mesenchymal cell differentiation and stimulates human periodontal ligament cell proliferation. Potentially, GDF-5 may also play roles in wound healing including periodontal regeneration and alveolar augmentation. The objective of this review was to provide up-to-date information from pre-clinical/clinical studies evaluating GDF-5 for these indications. A comprehensive search using PubMed and Google search engines was conducted to identify reports on GDF-5 applied to periodontal and alveolar indications. Two reviewers independently screened the titles and abstracts from a total of 479 reports. Full-length articles of 17 pre-clinical and four clinical studies were selected and reviewed. Canine-, porcine- and non-human primate-based models as well as human clinical trials were used in the evaluation of GDF-5 in support of periodontal regeneration and alveolar augmentation. An absorbable collagen sponge (ACS), β-tricalcium phosphate (β-TCP) and a poly(lactic-co-glycolic) acid (PLGA) were evaluated as candidate carriers for GDF-5 using various dose and healing intervals demonstrating significantly enhanced periodontal regeneration/alveolar augmentation including cementum, periodontal ligament and alveolar bone with limited, if any, adverse effects. Growth/differentiation factor-5 supports periodontal regeneration/alveolar augmentation without aberrant healing events documented in qualified pre-clinical models and clinical pilot studies. In perspective, GDF-5 appears a promising technology for periodontal regeneration/alveolar augmentation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients

    PubMed Central

    Lerner, Lorena; Hayes, Teresa G; Tao, Nianjun; Krieger, Brian; Feng, Bin; Wu, Zhenhua; Nicoletti, Richard; Chiu, M Isabel; Gyuris, Jeno; Garcia, Jose M

    2015-01-01

    Background Cancer-related weight loss is associated with increased inflammation and decreased survival. The novel inflammatory mediator growth differentiation factor (GDF)15 is associated with poor prognosis in cancer but its role in cancer-related weight loss (C-WL) remains unclear. Our objective was to measure GDF15 in plasma samples of cancer subjects and controls and establish its association with other inflammatory markers and clinical outcomes. Methods We measured body weight, appetite, plasma GDF15, and other inflammatory markers in men with cancer-related weight loss (C-WL, n = 58), weight stable patients with cancer (C-WS, n = 72), and non-cancer controls (Co, n = 59) matched by age and pre-illness body mass index. In a subset of patients we also measured handgrip strength, appendicular lean body mass (aLBM), Eastern Cooperative Oncology Group (ECOG), and Karnofsky performance scores. Results GDF15, interleukin (IL)-6 and IL-8 were increased in C-WL versus other groups. IL-1 receptor antagonist, IL-4, interferon–gamma, tumour necrosis factor alpha, and vascular endothelial growth factor A were increased in C-WL versus C-WS, and Activin A was significantly downregulated in Co versus other groups. C-WL patients had lower handgrip strength, aLBM, and fat mass, and Eastern Cooperative Oncology Group and Karnofsky performance scores were lower in both cancer groups. GDF15, IL-6, and IL-8 significantly correlated with weight loss; GDF15 negatively correlated with aLBM, handgrip strength, and fat mass. IL-8 and Activin A negatively correlated with aLBM and fat mass. GDF15 and IL-8 predicted survival adjusting for stage and weight change (Cox regression P < 0.001 for both). Conclusion GDF15 and other inflammatory markers are associated with weight loss, decreased aLBM and strength, and poor survival in patients with cancer. GDF15 may serve as a prognostic indicator in cancer patients and is being evaluated as a potential therapeutic target for

  10. Association of Growth Differentiation Factor-15 with Coronary Atherosclerosis and Mortality in a Young, Multiethnic Population: Observations from the Dallas Heart Study

    PubMed Central

    Rohatgi, Anand; Patel, Parag; Das, Sandeep R.; Ayers, Colby R.; Khera, Amit; Martinez-Rumayor, Abelardo; Berry, Jarett D.; McGuire, Darren K.; de Lemos, James A.

    2013-01-01

    Background Growth differentiation factor 15 (GDF-15) is produced by cardiomyocytes and atherosclerotic lesions under stress conditions. Although higher circulating GDF-15 concentrations are associated with mortality across a spectrum of cardiovascular conditions, the relationship of GDF-15 with atherosclerosis and mortality in the general population remains undefined. Methods We measured plasma GDF-15 in 3219 participants of the Dallas Heart Study, a population sample of adults ages 30–65 years (55% women, 49% black). GDF-15 was analyzed in prespecified categories (<1200; 1200–1799; and ≥1800 ng/L) and continuously. End points included prevalent coronary artery calcium (CAC >10 Agatston units), increased CAC (CAC ≥100 Agatston units) by electron beam computed tomography, and mortality through a median 7.3 years of follow-up (120 deaths, 48 cardiovascular deaths). Results Increasing GDF-15 associated with older age, black race, hypertension, diabetes, smoking, left ventricular (LV) mass/body surface area, and worse renal function (P < 0.0001 for each). In multivariable models adjusted for traditional risk factors, renal function, and LV mass/body surface area, GDF-15 ≥1800 ng/L was associated with CAC >10 (odds ratio 2.1; 95% CI 1.2–3.7; P = 0.01), CAC ≥100 (odds ratio 2.6; 95% CI 1.4–4.9; P = 0.002), all-cause mortality (hazard ratio 3.5; 95% CI 2.1–5.9, P < 0.0001), and cardiovascular mortality (hazard ratio 2.5; 95% CI 1.1–5.8, P = 0.03). Adding log GDF-15 to fully adjusted models modestly improved the c statistic (P = 0.025), the integrated discrimination index (0.028; P < 0.0001) and the category-less net reclassification index (0.42; P = 0.002). These findings remained significant with further adjustment for high-sensitivity C-reactive protein, N-terminal pro–B-type natriuretic peptide, and cardiac troponin T. Conclusions GDF-15 is independently associated with subclinical coronary atherosclerosis and mortality, and its potential role for

  11. Association of growth differentiation factor-15 with coronary atherosclerosis and mortality in a young, multiethnic population: observations from the Dallas Heart Study.

    PubMed

    Rohatgi, Anand; Patel, Parag; Das, Sandeep R; Ayers, Colby R; Khera, Amit; Martinez-Rumayor, Abelardo; Berry, Jarett D; McGuire, Darren K; de Lemos, James A

    2012-01-01

    Growth differentiation factor 15 (GDF-15) is produced by cardiomyocytes and atherosclerotic lesions under stress conditions. Although higher circulating GDF-15 concentrations are associated with mortality across a spectrum of cardiovascular conditions, the relationship of GDF-15 with atherosclerosis and mortality in the general population remains undefined. We measured plasma GDF-15 in 3219 participants of the Dallas Heart Study, a population sample of adults ages 30-65 years (55% women, 49% black). GDF-15 was analyzed in prespecified categories (<1200; 1200-1799; and ≥1800 ng/L) and continuously. End points included prevalent coronary artery calcium (CAC>10 Agatston units), increased CAC (CAC≥100 Agatston units) by electron beam computed tomography, and mortality through a median 7.3 years of follow-up (120 deaths, 48 cardiovascular deaths). Increasing GDF-15 associated with older age, black race, hypertension, diabetes, smoking, left ventricular (LV) mass/body surface area, and worse renal function (P<0.0001 for each). In multivariable models adjusted for traditional risk factors, renal function, and LV mass/body surface area, GDF-15≥1800 ng/L was associated with CAC>10 (odds ratio 2.1; 95% CI 1.2-3.7; P=0.01), CAC≥100 (odds ratio 2.6; 95% CI 1.4-4.9; P=0.002), all-cause mortality (hazard ratio 3.5; 95% CI 2.1-5.9, P<0.0001), and cardiovascular mortality (hazard ratio 2.5; 95% CI 1.1-5.8, P=0.03). Adding log GDF-15 to fully adjusted models modestly improved the c statistic (P=0.025), the integrated discrimination index (0.028; P<0.0001) and the category-less net reclassification index (0.42; P=0.002). These findings remained significant with further adjustment for high-sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide, and cardiac troponin T. GDF-15 is independently associated with subclinical coronary atherosclerosis and mortality, and its potential role for risk stratification in the general population merits further evaluation.

  12. Teaching with Documents: A Cartoonist's View of the Eisenhower Years.

    ERIC Educational Resources Information Center

    Mueller, Jean West; Schamel, Wynell Burroughs

    1990-01-01

    Illustrates how to teach U.S. history through the use of original documents such as Charles Nickerson's cartoon, "Images of the Fifties from Disneyland to Suez." States that the original artwork for this cartoon, which portrays the Eisenhower years, is in the Dwight D. Eisenhower Library in Abilene, Kansas. Provides a pretest, teaching…

  13. Earth view over Egypt and the Nile River taken during STS-121

    NASA Image and Video Library

    2006-07-04

    STS121-334-026 (4-17 July 2006) --- This photo, featuring an easterly view of the Nile River, the Nile River Delta, Sinai Peninsula, the Suez Canal, Red Sea and part of the Mediterranean Sea, was taken by one of the STS-121 crewmembers aboard the Space Shuttle Discovery. Cairo, Egypt, can be seen at far right.

  14. AFT PLB

    NASA Image and Video Library

    2010-04-08

    S131-E-007836 (8 April 2010) --- The aft section of the docked space shuttle Discovery is featured in this image photographed by an STS-131 crew member on the International Space Station. The Gulf of Suez and Gulf of Aqaba are seen 215 miles below.

  15. The Arabian scad Trachurus indicus, a new Indo-Pacific species in the Mediterranean Sea.

    PubMed

    Dalyan, C; Eryilmaz, L

    2009-05-01

    The Arabian scad Trachurus indicus is recorded for the first time from the Mediterranean Sea (Iskenderun Bay, Turkey). The presence of this Indo-Pacific fish in the Mediterranean Sea is probably because of migration from the Red Sea via the Suez Canal.

  16. 75 FR 70736 - Combined Notice of Filings #1

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-18

    ... Suez S.A., International Power PLC. Description: Supplemental Affidavit of Julie R. Solomon submitted... plc and its Indicated United States Subsidiaries. Filed Date: 10/29/2010. Accession Number: 20101029... Holdings, LLC. Description: TPF Generation Holdings, LLC submits an application for authorization to...

  17. Mussolini's Marriage and a Game in the Playground: Using Analogy to Help Pupils Understand the Past

    ERIC Educational Resources Information Center

    Laffin, Diana; Wilson, Maggie

    2005-01-01

    Diana Laffin and Maggie Wilson want their pupils to connect with people in the past and to experience some of their emotions. The emotional factor is a difficult one in history, both for pupils and professional historians. When studying Eden's actions at Suez, for example, what we lack is a proper insight into the immediate pressures he faced and…

  18. United States’ Grand Strategy through the Lens of Lebanon in 1983 and Iraq in 2003

    DTIC Science & Technology

    2012-06-08

    grand strategy for the region. Some examples that immediately spring to mind are the closure of the Suez Canal, the oil embargo, the failed peace......first goal was tied to balance of power and the global policy of containment. The second goal of continuing the supply of oil to the free world was

  19. Saudi-Egyptian Relations: the Political and Military Dimensions of Saudi Financial Flows to Egypt,

    DTIC Science & Technology

    1980-01-01

    million 3 in 1978 were estimated to reach $1 billion bv 1980. The Suez- Mediter - ranean pipeline revenues and incremental productivitv increases have...for Egypt was meanwhile app roved. 2 There are several reasons why the Saudis have been intent on bolstering Egypt’s military capabilities in the

  20. JPRS Report, Near East & South Asia

    DTIC Science & Technology

    2007-11-02

    Corps of Engineers and that there are two new cities that theSe- cond Army is building by its own efforts, one of them east of the [Suez] Canal...civil aircraft!! Shim’on Perez , who is said to be a dove, described the American decision to hold a dialogue with the PLO as a "black day in

  1. Earth Observation taken by the Expedition 20 crew

    NASA Image and Video Library

    2009-10-02

    ISS020-E-045018 (2 Oct. 2009) --- Great Bitter Lake, Egypt is featured in this image photographed by an Expedition 20 crew member on the International Space Station. The Great Bitter Lake is one of several lakes located along the Suez Canal that connects the eastern Mediterranean and Red Seas. As the Canal is built only to allow ships to travel in a single lane, the Great Bitter Lake is a location where ships can change their position in line - much like a motor highway passing lane - before proceeding to either Port Said to the north, or the port of Suez to the south. The lake also provides an intermediate harborage for ships traversing the Canal ? a journey that typically takes 14 hours end-to-end. Several ships - some under power and some anchored ? are visible at right. Prior to the opening of the Suez Canal in 1869, Great Bitter Lake was a large salt flat, the typical geomorphic expression of basins in the arid Egyptian climate. Large expanses of white to tan sandy sediments at left and top attest to the desert conditions surrounding the Lake. Located at the approximate midpoint of the Suez Canal, Great Bitter Lake is now filled with water derived from both the Red and Mediterranean Seas and this steady influx of water balances the water lost to evaporation. The town of Fayid (also spelled as Fayed), visible along the western shore of the Lake (bottom) is a tourist destination frequented, particularly in the summer months, by residents of Cairo.

  2. The Role of United States Air Power in Peacekeeping

    DTIC Science & Technology

    1994-06-01

    humanitarian assistance (Bosnia, 1992) 6. Guarantee right of passage (Suez, 1956) 7. Interposition of a buffer force either internally (Cyprus, 1964) or at an...which include armistice observation, preservation of law and order, guaranteeing right of passage , interposition of buffer forces, show of force

  3. Earth Observations taken by the Expedition 13 crew

    NASA Image and Video Library

    2006-06-30

    ISS013-E-44847 (30 June 2006) --- Ship traffic on the Suez Canal, Egypt is featured in this image photographed by an Expedition 13 crewmember on the International Space Station. This oblique photograph captures a northbound convoy of cargo ships entering the Mediterranean Sea from the Suez Canal in Egypt (leftmost canal branch at image center). Oblique images are taken at an angle other than vertical, or nadir -- looking down a line connecting the station to the point on the Earth's surface directly below it -- and this provides a sense of perspective. In this case, the station was located above the eastern coast of Cyprus and the crewmember was looking at Egypt to the southwest. Regions of reduced clarity in the image are caused by thin variable cloud cover. The Suez Canal connects Port Said on the Mediterranean Sea with the port of Suez on the Red Sea, and provides an essentially direct route for transport of goods between Europe and Asia. The Canal is 163 kilometers long and 300 meters wide at its narrowest point -- sufficiently wide for ships as large as aircraft carriers to traverse it. Transit time from end to end is 14 hours on average.

  4. GEMINI-TITAN (GT)-4 - EARTH-SKY - OUTER SPACE

    NASA Image and Video Library

    1965-06-03

    S65-34776 (3-7 June 1965) --- This photograph shows the Nile Delta, Egypt, the Suez Canal, Israel, Jordan, Syria, Saudi Arabia, and Iraq as seen from the Gemini-Titan 4 (GT-4) spacecraft during its 12th revolution of Earth.

  5. The Flipped Classroom Model to Develop Egyptian EFL Students' Listening Comprehension

    ERIC Educational Resources Information Center

    Ahmad, Samah Zakareya

    2016-01-01

    The present study aimed at investigating the effect of the flipped classroom model on Egyptian EFL students' listening comprehension. A one-group pre-posttest design was adopted. Thirty-four 3rd-year EFL students at the Faculty of Education, Suez University, were pretested on listening comprehension before the experiment and then posttested after…

  6. To Defend the Temple: Innovation in the Israeli Defense Force

    DTIC Science & Technology

    1999-01-01

    believed that superior techmque and pllotmg skulls , that is, “physxs”, could defeat the Suez mrsslle array However, the Israeli &r force Commander, MaJor...profound change m Israeli rmhtary culture whxh has mstoncally emphasized the offense The Israeli development of the 1,501 kilometer-range Jericho II IRBM

  7. A bitter aftertaste: unintended effects of artificial sweeteners on the gut microbiome.

    PubMed

    Bokulich, Nicholas A; Blaser, Martin J

    2014-11-04

    Intestinal microbial communities regulate a range of host physiological functions, from energy harvest and glucose homeostasis to immune development and regulation. Suez et al. (2014) recently demonstrated that artificial sweeteners alter gut microbial communities, leading to glucose intolerance in both mice and humans.

  8. A bitter aftertaste: unintended effects of artificial sweeteners on the gut microbiome

    PubMed Central

    Bokulich, Nicholas A.; Blaser, Martin J.

    2015-01-01

    Intestinal microbial communities regulate a range of host physiological functions, from energy harvest and glucose homeostasis to immune development and regulation. Suez and colleagues (2014) recently demonstrated that artificial sweeteners alter gut microbial communities, leading to glucose intolerance in both mice and humans. PMID:25440050

  9. Gulf of Aqaba, Sinai Peninsula

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The Gulf of Aqaba separates the Sinai peninsula from Saudi Arabia in this scene of the Middle East (29.0N, 34.5E) showing the geomorphology and geology of this region including portions of Egypt, Israel, Jordon and Saudi Arabia. A small portion of the Gulf of Suez can be seen on the opposite side of the Sinai peninsula.

  10. Teaching with Documents: A Cartoonist's View of the Eisenhower Years.

    ERIC Educational Resources Information Center

    Mueller, Jean West; Schamel, Wynell Burroughs

    1990-01-01

    Illustrates how to teach U.S. history through the use of original documents such as Charles Nickerson's cartoon, "Images of the Fifties from Disneyland to Suez." States that the original artwork for this cartoon, which portrays the Eisenhower years, is in the Dwight D. Eisenhower Library in Abilene, Kansas. Provides a pretest, teaching…

  11. Mussolini's Marriage and a Game in the Playground: Using Analogy to Help Pupils Understand the Past

    ERIC Educational Resources Information Center

    Laffin, Diana; Wilson, Maggie

    2005-01-01

    Diana Laffin and Maggie Wilson want their pupils to connect with people in the past and to experience some of their emotions. The emotional factor is a difficult one in history, both for pupils and professional historians. When studying Eden's actions at Suez, for example, what we lack is a proper insight into the immediate pressures he faced and…

  12. Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA

    PubMed Central

    Suh, Hye-Young; Lee, Dong-Won; Lee, Kwang-Hoon; Ku, Bonsu; Choi, Sung-Jin; Woo, Jae-Sung; Kim, Yeon-Gil; Oh, Byung-Ha

    2010-01-01

    GDP-bound prenylated Rabs, sequestered by GDI (GDP dissociation inhibitor) in the cytosol, are delivered to destined sub-cellular compartment and subsequently activated by GEFs (guanine nucleotide exchange factors) catalysing GDP-to-GTP exchange. The dissociation of GDI from Rabs is believed to require a GDF (GDI displacement factor). Only two RabGDFs, human PRA-1 and Legionella pneumophila SidM/DrrA, have been identified so far and the molecular mechanism of GDF is elusive. Here, we present the structure of a SidM/DrrA fragment possessing dual GEF and GDF activity in complex with Rab1. SidM/DrrA reconfigures the Switch regions of the GTPase domain of Rab1, as eukaryotic GEFs do toward cognate Rabs. Structure-based mutational analyses show that the surface of SidM/DrrA, catalysing nucleotide exchange, is involved in GDI1 displacement from prenylated Rab1:GDP. In comparison with an eukaryotic GEF TRAPP I, this bacterial GEF/GDF exhibits high binding affinity for Rab1 with GDP retained at the active site, which appears as the key feature for the GDF activity of the protein. PMID:19942850

  13. Growth differentiation factor 5 is a key physiological regulator of dendrite growth during development.

    PubMed

    Osório, Catarina; Chacón, Pedro J; Kisiswa, Lilian; White, Matthew; Wyatt, Sean; Rodríguez-Tébar, Alfredo; Davies, Alun M

    2013-12-01

    Dendrite size and morphology are key determinants of the functional properties of neurons. Here, we show that growth differentiation factor 5 (GDF5), a member of the bone morphogenetic protein (BMP) subclass of the transforming growth factor β superfamily with a well-characterised role in limb morphogenesis, is a key regulator of the growth and elaboration of pyramidal cell dendrites in the developing hippocampus. Pyramidal cells co-express GDF5 and its preferred receptors, BMP receptor 1B and BMP receptor 2, during development. In culture, GDF5 substantially increased dendrite, but not axon, elongation from these neurons by a mechanism that depends on activation of SMADs 1/5/8 and upregulation of the transcription factor HES5. In vivo, the apical and basal dendritic arbours of pyramidal cells throughout the hippocampus were markedly stunted in both homozygous and heterozygous Gdf5 null mutants, indicating that dendrite size and complexity are exquisitely sensitive to the level of endogenous GDF5 synthesis.

  14. Growth differentiation factor 8 suppresses cell proliferation by up-regulating CTGF expression in human granulosa cells.

    PubMed

    Chang, Hsun-Ming; Pan, Hui-Hui; Cheng, Jung-Chien; Zhu, Yi-Min; Leung, Peter C K

    2016-02-15

    Connective tissue growth factor (CTGF) is a matricellular protein that plays a critical role in the development of ovarian follicles. Growth differentiation factor 8 (GDF8) is mainly, but not exclusively, expressed in the mammalian musculoskeletal system and is a potent negative regulator of skeletal muscle growth. The aim of this study was to investigate the effects of GDF8 and CTGF on the regulation of cell proliferation in human granulosa cells and to examine its underlying molecular determinants. Using dual inhibition approaches (inhibitors and small interfering RNAs), we have demonstrated that GDF8 induces the up-regulation of CTGF expression through the activin receptor-like kinase (ALK)4/5-mediated SMAD2/3-dependent signaling pathways. In addition, the increase in CTGF expression contributes to the GDF8-induced suppressive effect on granulosa cell proliferation. Our findings suggest that GDF8 and CTGF may play critical roles in the regulation of proliferative events in human granulosa cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA.

    PubMed

    Suh, Hye-Young; Lee, Dong-Won; Lee, Kwang-Hoon; Ku, Bonsu; Choi, Sung-Jin; Woo, Jae-Sung; Kim, Yeon-Gil; Oh, Byung-Ha

    2010-01-20

    GDP-bound prenylated Rabs, sequestered by GDI (GDP dissociation inhibitor) in the cytosol, are delivered to destined sub-cellular compartment and subsequently activated by GEFs (guanine nucleotide exchange factors) catalysing GDP-to-GTP exchange. The dissociation of GDI from Rabs is believed to require a GDF (GDI displacement factor). Only two RabGDFs, human PRA-1 and Legionella pneumophila SidM/DrrA, have been identified so far and the molecular mechanism of GDF is elusive. Here, we present the structure of a SidM/DrrA fragment possessing dual GEF and GDF activity in complex with Rab1. SidM/DrrA reconfigures the Switch regions of the GTPase domain of Rab1, as eukaryotic GEFs do toward cognate Rabs. Structure-based mutational analyses show that the surface of SidM/DrrA, catalysing nucleotide exchange, is involved in GDI1 displacement from prenylated Rab1:GDP. In comparison with an eukaryotic GEF TRAPP I, this bacterial GEF/GDF exhibits high binding affinity for Rab1 with GDP retained at the active site, which appears as the key feature for the GDF activity of the protein.

  16. Mutations in bone morphogenetic protein 15 and growth differentiation factor 9 genes are associated with increased litter size in fat-tailed sheep breeds.

    PubMed

    Javanmard, Arash; Azadzadeh, N; Esmailizadeh, Ali K

    2011-03-01

    The objective of this study was to investigate association between GDF9 and BMP15 gene polymorphism and litter size in fat-tailed sheep, a total of 97 mature ewes from four breeds (Afshari=19; Baluchi=18; Makui=30 and Mehraban=30) were genotyped for the BMP15 HinfI and GDF9 HhaI polymorphisms by PCR-RFLP technique. The highest and lowest mutant allele frequencies were found in Makui (0.27) and Afshari (0.10) sheep for the BMP15 gene and in Afshari (0.24) and Mehraban (0.18) sheep for the GDF9 gene, respectively. Litter size was significantly influenced by genotype of the ewe for two genes (P < 0.01). Heterozygous genotypes for both loci showed higher litter size than homozygous genotypes (P < 0.01). None of the individuals carried homozygous genotype for both of the GDF9 and BMP15 variants in these breeds. The individuals carrying the mutant allele for one of the investigated candidate gene still showed fertile phenotype. Thus, existence of homozygosity at one of the BMP15 and GDF9 variant is not probably able to block normal hormonal pathway of reproduction in fat-tailed sheep.

  17. Change in Growth Differentiation Factor 15, but Not C-Reactive Protein, Independently Predicts Major Cardiac Events in Patients with Non-ST Elevation Acute Coronary Syndrome

    PubMed Central

    Hernandez-Baldomero, Idaira F.; Bosa-Ojeda, Francisco

    2014-01-01

    Among the numerous emerging biomarkers, high-sensitivity C-reactive protein (hsCRP) and growth-differentiation factor-15 (GDF-15) have received widespread interest, with their potential role as predictors of cardiovascular risk. The concentrations of inflammatory biomarkers, however, are influenced, among others, by physiological variations, which are the natural, within-individual variation occurring over time. The aims of our study are: (a) to describe the changes in hsCRP and GDF-15 levels over a period of time and after an episode of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and (b) to examine whether the rate of change in hsCRP and GDF-15 after the acute event is associated with long-term major cardiovascular adverse events (MACE). Two hundred and Fifty five NSTE-ACS patients were included in the study. We measured hsCRP and GDF-15 concentrations, at admission and again 36 months after admission (end of the follow-up period). The present study shows that the change of hsCRP levels, measured after 36 months, does not predict MACE in NSTEACS-patients. However, the level of GDF-15 measured, after 36 months, was a stronger predictor of MACE, in comparison to the acute unstable phase. PMID:24839357

  18. Fluoride antireflection coatings for deep ultraviolet optics deposited by ion-beam sputtering.

    PubMed

    Yoshida, Toshiya; Nishimoto, Keiji; Sekine, Keiichi; Etoh, Kazuyuki

    2006-03-01

    Optically high quality coatings of fluoride materials are required in deep ultraviolet (DUV) lithography. We have applied ion-beam sputtering (IBS) to obtain fluoride films with smooth surfaces. The extinction coefficients were of the order of 10(-4) at the wavelength of 193 nm due to the reduction of their absorption loss. The transmittance of the MgF2/GdF3 antireflection coating was as high as 99.7% at the wavelength of 193 nm. The surfaces of the IBS deposited films were so smooth that the surface roughness of the A1F3/GdF3 film was comparable with that of the CaF2 substrate. The MgF2/GdF3 coating fulfilled the temperature and humidity requirements of military specification. Thus, the IBS deposited fluoride films are promising candidate for use in the DUV lithography optics.

  19. Association between Serum Selenium Concentrations and Levels of Proinflammatory and Profibrotic Cytokines-Interleukin-6 and Growth Differentiation Factor-15, in Patients with Alcoholic Liver Cirrhosis.

    PubMed

    Prystupa, Andrzej; Kiciński, Paweł; Luchowska-Kocot, Dorota; Błażewicz, Anna; Niedziałek, Jarosław; Mizerski, Grzegorz; Jojczuk, Mariusz; Ochal, Andrzej; Sak, Jarosław J; Załuska, Wojciech

    2017-04-21

    According to some authors, serum selenium levels are strongly associated with the severity of liver diseases, including liver cirrhosis. The aim of this study was to determine the relationship between the concentration of selenium and pro-inflammatory and profibrotic cytokines-interleukin-6 (IL-6) and growth differentiation factor 15 (GDF-15) in patients with alcoholic liver cirrhosis. The parameters studied were determined in the serum of 99 patients with alcoholic liver cirrhosis divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. In patients with liver cirrhosis, the serum selenium concentration was statistically lower, whereas serum IL-6 and GDF-15 concentrations were higher than those in the control group. Moreover, the concentration of selenium negatively correlated with the levels of GDF-15 and IL-6. The above results may indicate a role of selenium deficiency in the pathogenesis and progression of alcoholic liver disease.

  20. A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease.

    PubMed

    Fujiwara, Tohru; Ikeda, Takashi; Nagasaka, Yuki; Okitsu, Yoko; Katsuoka, Yuna; Fukuhara, Noriko; Onishi, Yasushi; Ishizawa, Kenichi; Ichinohasama, Ryo; Tomosugi, Naohisa; Harigae, Hideo

    2013-01-01

    Hepcidin is the principal iron regulatory hormone, controlling the systemic absorption and remobilization of iron from intracellular stores. The expression of the hepcidin gene, HAMP, is increased in patients with anemia of chronic disease. Previously, the synthetic compound K7174 was identified through chemical screening as a novel inhibitor of the adhesion of monocytes to cytokine-stimulated endothelial cells. K7174 also ameliorated anemia induced by inflammatory cytokines in mice, which suggests a possible involvement of hepcidin regulation. The present study was performed to assess the impact of K7174 on hepcidin expression in a human hematoma cell line and in mice in vivo. We first demonstrated that K7174 treatment in HepG2 cells significantly decreased HAMP expression. Then, we conducted microarray analysis to determine the molecular mechanism by which K7174 inhibits HAMP expression. Transcriptional profiling confirmed the downregulation of HAMP. Surprisingly, we found that K7174 strongly induced GDF15, known as a negative regulator of HAMP expression. Western blotting analysis as well as ELISA confirmed the induction of GDF15 by K7174 treatment. Furthermore, K7174-mediated HAMP suppression was rescued by the silencing of GDF15 expression. Interestingly, we found that K7174 also upregulates CEBPB. Promoter analysis and chromatin immunoprecipitation analysis revealed that CEBPB could contribute to K7174-mediated transcriptional activation of GDF15. Subsequently, we also examined whether K7174 inhibits hepcidin expression in mice. Quantitative RT-PCR analysis with liver samples from K7174-treated mice demonstrated significant upregulation of Gdf15 and downregulation of Hamp expression, as compared to control mice. Furthermore, serum hepcidin concentration was also significantly decreased in K7174-treated mice. In conclusion, K7174 inhibits hepcidin expression partly by inducing GDF15. K-7174 may be a potential therapeutic option to treat anemia of chronic

  1. Application of Gas Dynamical Friction for Planetesimals. II. Evolution of Binary Planetesimals

    NASA Astrophysics Data System (ADS)

    Grishin, Evgeni; Perets, Hagai B.

    2016-04-01

    One of the first stages of planet formation is the growth of small planetesimals and their accumulation into large planetesimals and planetary embryos. This early stage occurs long before the dispersal of most of the gas from the protoplanetary disk. At this stage gas-planetesimal interactions play a key role in the dynamical evolution of single intermediate-mass planetesimals (mp ˜ 1021-1025 g) through gas dynamical friction (GDF). A significant fraction of all solar system planetesimals (asteroids and Kuiper-belt objects) are known to be binary planetesimals (BPs). Here, we explore the effects of GDF on the evolution of BPs embedded in a gaseous disk using an N-body code with a fiducial external force accounting for GDF. We find that GDF can induce binary mergers on timescales shorter than the disk lifetime for masses above mp ≳ 1022 g at 1 au, independent of the binary initial separation and eccentricity. Such mergers can affect the structure of merger-formed planetesimals, and the GDF-induced binary inspiral can play a role in the evolution of the planetesimal disk. In addition, binaries on eccentric orbits around the star may evolve in the supersonic regime, where the torque reverses and the binary expands, which would enhance the cross section for planetesimal encounters with the binary. Highly inclined binaries with small mass ratios, evolve due to the combined effects of Kozai-Lidov (KL) cycles with GDF which lead to chaotic evolution. Prograde binaries go through semi-regular KL evolution, while retrograde binaries frequently flip their inclination and ˜50% of them are destroyed.

  2. Positive regulation of osteoclastic differentiation by growth differentiation factor 15 upregulated in osteocytic cells under hypoxia.

    PubMed

    Hinoi, Eiichi; Ochi, Hiroki; Takarada, Takeshi; Nakatani, Eri; Iezaki, Takashi; Nakajima, Hiroko; Fujita, Hiroyuki; Takahata, Yoshifumi; Hidano, Shinya; Kobayashi, Takashi; Takeda, Shu; Yoneda, Yukio

    2012-04-01

    Osteocytes are thought to play a role as a mechanical sensor through their communication network in bone. Although osteocytes are the most abundant cells in bone, little attention has been paid to their physiological and pathological functions in skeletogenesis. Here, we have attempted to delineate the pivotal functional role of osteocytes in regulation of bone remodeling under pathological conditions. We first found markedly increased osteoclastic differentiation by conditioned media (CM) from osteocytic MLO-Y4 cells previously exposed to hypoxia in vitro. Using microarray and real-time PCR analyses, we identified growth differentiation factor 15 (GDF15) as a key candidate factor secreted from osteocytes under hypoxia. Recombinant GDF15 significantly promoted osteoclastic differentiation in a concentration-dependent manner, with concomitant facilitation of phosphorylation of both p65 and inhibitory-κB in the presence of receptor activator of nuclear factor-κB ligand. To examine the possible functional significance of GDF15 in vivo, mice were subjected to ligation of the right femoral artery as a hypoxic model. A significant increase in GDF15 expression was specifically observed in tibias of the ligated limb but not in tibias of the normally perfused limb. Under these experimental conditions, in cancellous bone of proximal tibias in the ligated limb, a significant reduction was observed in bone volume, whereas a significant increase was seen in the extent of osteoclast surface/bone surface when determined by bone histomorphometric analysis. Finally, the anti-GDF15 antibody prevented bone loss through inhibiting osteoclastic activation in tibias from mice with femoral artery ligation in vivo, in addition to suppressing osteoclastic activity enhanced by CM from osteocytes exposed to hypoxia in vitro. These findings suggest that GDF15 could play a pivotal role in the pathogenesis of bone loss relevant to hypoxia through promotion of osteoclastogenesis after

  3. APPLICATION OF GAS DYNAMICAL FRICTION FOR PLANETESIMALS. II. EVOLUTION OF BINARY PLANETESIMALS

    SciTech Connect

    Grishin, Evgeni; Perets, Hagai B.

    2016-04-01

    One of the first stages of planet formation is the growth of small planetesimals and their accumulation into large planetesimals and planetary embryos. This early stage occurs long before the dispersal of most of the gas from the protoplanetary disk. At this stage gas–planetesimal interactions play a key role in the dynamical evolution of single intermediate-mass planetesimals (m{sub p} ∼ 10{sup 21}–10{sup 25} g) through gas dynamical friction (GDF). A significant fraction of all solar system planetesimals (asteroids and Kuiper-belt objects) are known to be binary planetesimals (BPs). Here, we explore the effects of GDF on the evolution of BPs embedded in a gaseous disk using an N-body code with a fiducial external force accounting for GDF. We find that GDF can induce binary mergers on timescales shorter than the disk lifetime for masses above m{sub p} ≳ 10{sup 22} g at 1 au, independent of the binary initial separation and eccentricity. Such mergers can affect the structure of merger-formed planetesimals, and the GDF-induced binary inspiral can play a role in the evolution of the planetesimal disk. In addition, binaries on eccentric orbits around the star may evolve in the supersonic regime, where the torque reverses and the binary expands, which would enhance the cross section for planetesimal encounters with the binary. Highly inclined binaries with small mass ratios, evolve due to the combined effects of Kozai–Lidov (KL) cycles with GDF which lead to chaotic evolution. Prograde binaries go through semi-regular KL evolution, while retrograde binaries frequently flip their inclination and ∼50% of them are destroyed.

  4. Association of a single nucleotide polymorphism in growth differentiate factor 5 with congenital dysplasia of the hip: a case-control study

    PubMed Central

    Dai, Jin; Shi, Dongquan; Zhu, Pengsheng; Qin, Jianghui; Ni, Haijian; Xu, Yong; Yao, Chen; Zhu, Lunqing; Zhu, Hongtao; Zhao, Baocheng; Wei, Jia; Liu, Baorui; Ikegawa, Shiro; Jiang, Qing; Ding, Yitao

    2008-01-01

    Introduction Congenital dysplasia of the hip is an abnormal seating of the femoral head in the acetabulum, mainly caused by shallow acetabulum and lax joint capsule. Genetic factors play a considerable role in the pathogenesis of congenital dysplasia of the hip. The gene growth differentiate factor 5 (GDF5) has been implicated in skeletal development and joint morphogenesis in humans and mice. A functional single nucleotide polymorphism (SNP) in the 5'-untranslated region of GDF5 (rs143383) was reported to be associated with osteoarthritis susceptibility. As a key regulator in morphogenesis of skeletal components and soft tissues in and around the joints, GDF5 may be involved in the aetiology and pathogenesis of congenital dysplasia of the hip. Our objective is to evaluate if the GDF5 SNP is associated with congenital dysplasia of the hip in people of Han Chinese origin. Methods The GDF5 SNP was genotyped in 338 children with congenital dysplasia of the hip and 622 control subjects. Results The SNP was significantly associated with congenital dysplasia of the hip (p = 0.0037; odds ration (OR) = 1.40; 95% confidence interval (CI) = 1.11 to 1.75). A significant difference was detected in female samples when stratified by gender (p = 0.0053; OR = 1.46; 95% CI = 1.21 to 1.91), and in hip dislocation when stratified by severity (p = 0.0078; OR = 1.43; 95% CI = 1.11 to 1.85). Conclusions Our results indicate that GDF5 is important in the aetiology of congenital dysplasia of the hip. To the authors' knowledge this is the first time that a definite association with the congenital dysplasia of the hip susceptibility has been detected. PMID:18947434

  5. Association of a single nucleotide polymorphism in growth differentiate factor 5 with congenital dysplasia of the hip: a case-control study.

    PubMed

    Dai, Jin; Shi, Dongquan; Zhu, Pengsheng; Qin, Jianghui; Ni, Haijian; Xu, Yong; Yao, Chen; Zhu, Lunqing; Zhu, Hongtao; Zhao, Baocheng; Wei, Jia; Liu, Baorui; Ikegawa, Shiro; Jiang, Qing; Ding, Yitao

    2008-01-01

    Congenital dysplasia of the hip is an abnormal seating of the femoral head in the acetabulum, mainly caused by shallow acetabulum and lax joint capsule. Genetic factors play a considerable role in the pathogenesis of congenital dysplasia of the hip. The gene growth differentiate factor 5 (GDF5) has been implicated in skeletal development and joint morphogenesis in humans and mice. A functional single nucleotide polymorphism (SNP) in the 5'-untranslated region of GDF5 (rs143383) was reported to be associated with osteoarthritis susceptibility. As a key regulator in morphogenesis of skeletal components and soft tissues in and around the joints, GDF5 may be involved in the aetiology and pathogenesis of congenital dysplasia of the hip. Our objective is to evaluate if the GDF5 SNP is associated with congenital dysplasia of the hip in people of Han Chinese origin. The GDF5 SNP was genotyped in 338 children with congenital dysplasia of the hip and 622 control subjects. The SNP was significantly associated with congenital dysplasia of the hip (p = 0.0037; odds ration (OR) = 1.40; 95% confidence interval (CI) = 1.11 to 1.75). A significant difference was detected in female samples when stratified by gender (p = 0.0053; OR = 1.46; 95% CI = 1.21 to 1.91), and in hip dislocation when stratified by severity (p = 0.0078; OR = 1.43; 95% CI = 1.11 to 1.85). Our results indicate that GDF5 is important in the aetiology of congenital dysplasia of the hip. To the authors' knowledge this is the first time that a definite association with the congenital dysplasia of the hip susceptibility has been detected.

  6. Growth differentiation factor 15, a marker of oxidative stress and inflammation, for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

    PubMed

    Wallentin, Lars; Hijazi, Ziad; Andersson, Ulrika; Alexander, John H; De Caterina, Raffaele; Hanna, Michael; Horowitz, John D; Hylek, Elaine M; Lopes, Renato D; Asberg, Signild; Granger, Christopher B; Siegbahn, Agneta

    2014-11-18

    Growth differentiation factor 15 (GDF-15), high-sensitivity troponin, and N-terminal pro-brain natriuretic peptide levels are predictive of death and cardiovascular events in healthy elderly subjects, patients with acute coronary syndrome, and patients with heart failure. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide are also prognostic in patients with atrial fibrillation. We evaluated the prognostic value of GDF-15 alone and in addition to clinical characteristics and other biomarkers in patients with atrial fibrillation. The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients. Efficacy and safety outcomes during 1.9 years of follow-up were compared across quartiles of GDF-15 by use of Cox analyses adjusted for clinical characteristics, randomized treatment, and other biomarkers. The GDF-15 level showed a median of 1383 ng/L (interquartile range, 977-2052 ng/L). Annual rates of stroke or systemic embolism ranged from 0.9% to 2.03% (P<0.001); of major bleeding, from 1.22% to 4.53% (P<0.001); and of mortality, from 1.34% to 7.19% (P<0.001) in the lowest compared with the highest GDF-15 quartile. The prognostic information provided by GDF-15 was independent of clinical characteristics and clinical risk scores. Adjustment for the other cardiac biomarkers attenuated the prognostic value for stroke, whereas the prognostic value for mortality and major bleeding remained. Apixaban consistently reduced stroke, mortality, and bleeding, regardless of GDF-15 levels. GDF-15 is a risk factor for major bleeding, mortality, and stroke in atrial fibrillation. The prognostic value for major bleeding and death remained even in the presence of N-terminal pro-brain natriuretic peptide and high-sensitivity troponin I. http://www.clinicaltrials.gov. Unique identifier

  7. Basement structural control on Cretaceous pull-apart basins of the central Eastern Egypt Desert

    NASA Astrophysics Data System (ADS)

    McCaffrey, K.; El Kazzaz, Y.; Holdsworth, B.

    2006-12-01

    The present-day Red Sea / Gulf of Suez rift system is attributed to extensional block faulting with along-axis segmentation into sub-basins with different dip polarities. The northwestern margin of the Red Sea - Gulf of Suez rift system is exposed for about 400 km along the northwestern Red Sea coast near Quseir to the tip of the Gulf of Suez at Suez City. This area contains elements of the pre-Red Sea structural pattern which has been viewed in similar terms as one of fault-related basin formation. Four distinct depocenters (sub-basins) separated by complex accommodation zones are present containing 500-700m thick section ranging in age from the Late Cretaceous to the Middle Eocene. Each sub-basin is asymmetric, bounded on one side by a major NW-trending border fault system with large throws (3-6 km in general) with a dominant strata dip direction toward the border fault system. These basins are arranged in en echelon patterns and now form separate elongated ridges surrounded by basement rocks. Our study of the tectonic evolution of the central eastern section of the Gulf of Suez rift and the Northwestern Red Sea has focused on the interaction of pre-existing basement fabrics with the pre-Red Sea structural development. The study involved analysis of LandsatTM images and aerial photographs integrated with results from reconnaissance geological mapping. Our provisional results indicate that the Gebel Um Hammad/Duwi and Hammadat sub-basins were sited in pull-apart structures created by dextral reactivation of E-W to ENE-WSW trending basement fault zones. We show how the basin-bounding fault systems, lower order normal faults and folds in both hangingwall sequences and in basement are compatible with a Late Cretaceous to Early Eocene strike-slip regime. In contrast, the main Red Sea Gulf of Suez rift shows no evidence for strike-slip influence with the main boundary faults cutting across basement fabrics, however, as pointed out by previous authors, rift segmentation

  8. Tectonic and climatic considerations for deep geological disposal of radioactive waste: A UK perspective.

    PubMed

    McEvoy, F M; Schofield, D I; Shaw, R P; Norris, S

    2016-11-15

    Identifying and evaluating the factors that might impact on the long-term integrity of a deep Geological Disposal Facility (GDF) and its surrounding geological and surface environment is central to developing a safety case for underground disposal of radioactive waste. The geological environment should be relatively stable and its behaviour adequately predictable so that scientifically sound evaluations of the long-term radiological safety of a GDF can be made. In considering this, it is necessary to take into account natural processes that could affect a GDF or modify its geological environment up to 1millionyears into the future. Key processes considered in this paper include those which result from plate tectonics, such as seismicity and volcanism, as well as climate-related processes, such as erosion, uplift and the effects of glaciation. Understanding the inherent variability of process rates, critical thresholds and likely potential influence of unpredictable perturbations represent significant challenges to predicting the natural environment. From a plate-tectonic perspective, a one million year time frame represents a very short segment of geological time and is largely below the current resolution of observation of past processes. Similarly, predicting climate system evolution on such time-scales, particularly beyond 200ka AP is highly uncertain, relying on estimating the extremes within which climate and related processes may vary with reasonable confidence. The paper highlights some of the challenges facing a deep geological disposal program in the UK to review understanding of the natural changes that may affect siting and design of a GDF.

  9. Biophysical and structural characterization of a folded core domain within the proregion of growth and differentiation factor-5.

    PubMed

    Thieme, Tino; Patzschke, Rica; Job, Florian; Liebold, Jens; Seemann, Petra; Lilie, Hauke; Balbach, Jochen; Schwarz, Elisabeth

    2014-11-01

    The structure and function(s) of the very large proregions of the transforming growth factor-β structure family are known in only a few cases. The proregion of growth and differentiation factor (GDF)5 comprises 354 residues. GDF5 therefore belongs to the group of those growth factors with the largest proregions. Here, we report a biophysical analysis of the proform (proGDF5) and the separate proregion. In the absence of the mature part, the proregion folds reversibly to form a monomeric polypeptide that is stabilized by an intramolecular disulfide bond. In the context of the mature part, i.e. in proGDF5, the proregion shows increased thermodynamic stability and contains a higher proportion of secondary structural elements than in its isolated form. A subdomain within the proregion represents a well-folded structure as monitored via biophysical analysis and NMR spectroscopy. Furthermore, two point mutations that are associated with skeletal malformations lead to reduced thermodynamic stability, which is interpreted on the basis of a homology model with the structure of the related latency-associated peptide, representing the proregion of transforming growth factor-β1. © 2014 FEBS.

  10. The procurement landscape of pediatric tuberculosis treatment: a Global Drug Facility perspective.

    PubMed

    Scott, C; Gardiner, E; de Lucia, A

    2015-12-01

    Simple, quality-assured, child-friendly formulations of existing first-line anti-tuberculosis (TB) drugs in the correct dosages are now becoming available. Efforts are currently underway by the TB Alliance, the World Health Organization (WHO), and its partners to make appropriate medicines available to treat children diagnosed with TB. The functioning of the current market and the distribution pathways in pediatric TB drugs now require characterization and understanding in order to develop appropriate strategies for delivery of these and other future pediatric TB medicines. The Stop TB Partnership's Global Drug Facility (GDF) plays a major role in supplying pediatric TB medications worldwide. GDF is considered to be the largest procurer of pediatric TB treatment and the largest supplier to national TB programs of quality pediatric drugs. Between 2007 and 2013, the GDF delivered more than 580, 000 treatments to children in over 50 countries, 14 of which are among the 22 high TB burden countries. We analyzed this data set in the context of WHO estimates of pediatric TB as well as other available information to assess the functioning of the current market, lessons learnt from the GDF experience in the market, and opportunities for future products.

  11. Regulation of androgen receptor signaling by ubiquitination during folliculogenesis and its possible dysregulation in polycystic ovarian syndrome.

    PubMed

    Lim, Jung Jin; Lima, Patricia D A; Salehi, Reza; Lee, Dong Ryul; Tsang, Benjamin K

    2017-08-31

    Although chronic hyperandrogenism suppresses antral follicular development, a phenomenon often observed in polycystic ovarian syndrome (PCOS), whether and how deregulation of androgen receptor (AR) signaling is involved, is not well understood. In the present study, we examined the role of ring finger protein 6 (RNF6) in AR ubiquitination and the possible dysregulation in the expression and actions of growth differentiation factor 9 (GDF9) and kit-ligand (Kitlg) in a chronic androgenized PCOS rat model. 5α-dihydrotestosterone (DHT) treatment in vivo inhibited antral follicle growth, a response mediated through increased RNF6 content, suppressed K63- but increased K48-linked AR ubiquitination as well as the mRNA expression and content of soluble KIT-L (sKitlg) and content of GDF9. These androgenic responses were attenuated by gonadotropin treatment in vivo. Growth of antral follicles from DHT-treated rats in vitro was significantly slower when compared to those of control but was significantly enhanced by exogenous GDF9, suggesting the DHT-induced antral follicular growth arrest is in part the results of GDF9 suppression. Our findings indicate how hyperandrogenism modulates RNF6 content and subsequently AR ubiquitination, resulting in antral follicle growth arrest in a chronically androgenized PCOS rat model.

  12. 40 CFR 63.11113 - When do I have to comply with this subpart?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 14 2011-07-01 2011-07-01 false When do I have to comply with this subpart? 63.11113 Section 63.11113 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... comply by January 24, 2014. (2) If your GDF is a new or reconstructed facility, you must comply by the...

  13. Transgenic overexpression of bone morphogenetic protein 11 propeptide in skeleton enhances bone formation

    USDA-ARS?s Scientific Manuscript database

    Bone morphogenetic protein 11 (BMP11) is a key regulatory protein in skeletal development. BMP11 propeptide has been shown to antagonize GDF11 activity in vitro. To explore the role of BMP11 propeptide in skeletal formation in vivo, we generated transgenic mice with skeleton-specific overexpression...

  14. Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility — A Review

    PubMed Central

    de Castro, Fernanda Cavallari; Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde

    2016-01-01

    Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-β) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review. PMID:26954112

  15. Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility - A Review.

    PubMed

    de Castro, Fernanda Cavallari; Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde

    2016-08-01

    Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-β) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review.

  16. Growth differentiation factor-9 and anti-Müllerian hormone expression in cultured human follicles from frozen-thawed ovarian tissue.

    PubMed

    Sadeu, J C; Smitz, J

    2008-10-01

    In-vitro growth of frozen-thawed human follicles is perceived as a potential option for restoring women's fertility. The aims of this study were: (i) to test the usefulness of a defined serum-free medium for growth of frozen-thawed human follicles; and (ii) to evaluate the expression of growth differentiation factor-9 (GDF-9) and anti-Müllerian hormone (AMH) in cultured follicles. Frozen-thawed ovarian cortical pieces from 7-, 12-, 25- and 27-year-old women were cultured for 0, 7, 14, 21 and 28 days. Follicle developmental quality was evaluated and expression of proliferating cell nuclear antigen (PCNA) (day 21), GDF-9 (days 14 and 28) and AMH (day 21) was assessed by immunohistochemistry. Primary follicles and enclosed oocytes underwent significant growth at the end of culture (P < 0.05). Cultured follicles from all patients studied reached the early secondary stage and a few follicles from two patients developed up to the secondary stage. The rate of atresia was variable throughout the culture periods. PCNA was expressed in the granulosa cells at all the different follicular stages. AMH and GDF-9 immunostaining were found respectively in the granulosa cells and oocytes after several weeks of culture. The transition from resting to growing follicles leading to the development of secondary follicles showed the normal expression patterns of GDF-9 and AMH.

  17. Uncovering the Role of BMP Signaling in Melanocyte Development and Melanoma Tumorigenesis

    DTIC Science & Technology

    2014-07-01

    gain and loss of function studies in zebrafish embryos and mammalian cultured cells to determine if GDF6 antagonizes melanocyte development. In...C.E. and Zon. L.I. (2008). Transparent adult zebrafish as a tool for in vivo transplantation analysis. Cell Stem Cell, 2, 183-9. 7. Langenau, D.M

  18. Genome walk of an unknown upstream region of myostatin gene in Spanish goats

    USDA-ARS?s Scientific Manuscript database

    Myostatin (MSTN) gene product also known as growth differentiation factor (GDF8) is a member of the TGF-ß family of secreted proteins. It is shown to be a negative regulator of muscle mass development. Mutations in the MSTN gene have been reported in mice, cattle and humans that lead to muscular hyp...

  19. Aerosol Studies at UMIST.

    DTIC Science & Technology

    1980-07-01

    treated by the advection- diffusion equation dn D2n - v n dr n is number of particles per unit volume v is velocity of fluid D is diffusion constant (See...September 1977 (GDF data) A weak trailing cold front, associated with a deep depresion over Western Russia, lying from Essex to Northern Ireland at OOh

  20. Effects of Trichostatin A on Cumulus Expansion during Mouse Oocyte Maturation.

    PubMed

    Du, Ming; Fu, Xiangwei; Zhou, Yanhua; Zhu, Shien

    2013-11-01

    This study was conducted to investigate the effects of Trichostatin A (TSA) on cumulus expansion during mouse oocyte maturation. TSA treatment inhibited cumulus expansion and significantly reduced the cumulus expansion index (CEI) (p<0.05). To determine the underlying mechanism, the expression levels of several key factors that play crucial roles in cumulus expansion including components of extracellular matrix (ECM) (Has2, Ptgs2, Ptx3, and Tnfaip6) and Growth differentiation factor 9 (GDF9) were measured in control and TSA treated samples by real-time PCR. The effect of TSA on ERK phosphorylation (p-ERK1/2) in cumulus cells and GDF9 protein level in fully grown oocytes (FGOs) were detected by Western blotting. The expression levels of the ECM genes were significantly decreased (p<0.05) by TSA treatment while GDF9 expression did not response to TSA (p>0.05). TSA treatment blocked the activation of ERK1/2 (p<0.05) and had no significant effect on GDF9 protein expression (p>0.05). Collectively, these results suggested that TSA treatment altered ECM gene expression and blocked ERK1/2 activation to inhibit cumulus expansion in the mouse.

  1. VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5

    PubMed Central

    Szumska, Dorota; Pieles, Guido; Essalmani, Rachid; Bilski, Michal; Mesnard, Daniel; Kaur, Kulvinder; Franklyn, Angela; El Omari, Kamel; Jefferis, Joanna; Bentham, Jamie; Taylor, Jennifer M.; Schneider, Jurgen E.; Arnold, Sebastian J.; Johnson, Paul; Tymowska-Lalanne, Zuzanna; Stammers, Dave; Clarke, Kieran; Neubauer, Stefan; Morris, Andrew; Brown, Steve D.; Shaw-Smith, Charles; Cama, Armando; Capra, Valeria; Ragoussis, Jiannis; Constam, Daniel; Seidah, Nabil G.; Prat, Annik; Bhattacharya, Shoumo

    2008-01-01

    We have identified an ethylnitrosourea (ENU)-induced recessive mouse mutation (Vcc) with a pleiotropic phenotype that includes cardiac, tracheoesophageal, anorectal, anteroposterior patterning defects, exomphalos, hindlimb hypoplasia, a presacral mass, renal and palatal agenesis, and pulmonary hypoplasia. It results from a C470R mutation in the proprotein convertase PCSK5 (PC5/6). Compound mutants (Pcsk5Vcc/null) completely recapitulate the Pcsk5Vcc/Vcc phenotype, as does an epiblast-specific conditional deletion of Pcsk5. The C470R mutation ablates a disulfide bond in the P domain, and blocks export from the endoplasmic reticulum and proprotein convertase activity. We show that GDF11 is cleaved and activated by PCSK5A, but not by PCSK5A-C470R, and that Gdf11-deficient embryos, in addition to having anteroposterior patterning defects and renal and palatal agenesis, also have a presacral mass, anorectal malformation, and exomphalos. Pcsk5 mutation results in abnormal expression of several paralogous Hox genes (Hoxa, Hoxc, and Hoxd), and of Mnx1 (Hlxb9). These include known Gdf11 targets, and are necessary for caudal embryo development. We identified nonsynonymous mutations in PCSK5 in patients with VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb malformation OMIM 192350) and caudal regression syndrome, the phenotypic features of which resemble the mouse mutation. We propose that Pcsk5, at least in part via GDF11, coordinately regulates caudal Hox paralogs, to control anteroposterior patterning, nephrogenesis, skeletal, and anorectal development. PMID:18519639

  2. Microbial degradation of isosaccharinic acid at high pH

    PubMed Central

    Bassil, Naji M; Bryan, Nicholas; Lloyd, Jonathan R

    2015-01-01

    Intermediate-level radioactive waste (ILW), which dominates the radioactive waste inventory in the United Kingdom on a volumetric basis, is proposed to be disposed of via a multibarrier deep geological disposal facility (GDF). ILW is a heterogeneous wasteform that contains substantial amounts of cellulosic material encased in concrete. Upon resaturation of the facility with groundwater, alkali conditions will dominate and will lead to the chemical degradation of cellulose, producing a substantial amount of organic co-contaminants, particularly isosaccharinic acid (ISA). ISA can form soluble complexes with radionuclides, thereby mobilising them and posing a potential threat to the surrounding environment or ‘far field'. Alkaliphilic microorganisms sampled from a legacy lime working site, which is an analogue for an ILW-GDF, were able to degrade ISA and couple this degradation to the reduction of electron acceptors that will dominate as the GDF progresses from an aerobic ‘open phase' through nitrate- and Fe(III)-reducing conditions post closure. Furthermore, pyrosequencing analyses showed that bacterial diversity declined as the reduction potential of the electron acceptor decreased and that more specialised organisms dominated under anaerobic conditions. These results imply that the microbial attenuation of ISA and comparable organic complexants, initially present or formed in situ, may play a role in reducing the mobility of radionuclides from an ILW-GDF, facilitating the reduction of undue pessimism in the long-term performance assessment of such facilities. PMID:25062127

  3. Single nucleotide polymorphisms in the bovine genome are associated with the number of oocytes collected during ovum pick up.

    PubMed

    Santos-Biase, W K F; Biase, F H; Buratini, J; Balieiro, J; Watanabe, Y F; Accorsi, M F; Ferreira, C R; Stranieri, P; Caetano, A R; Meirelles, F V

    2012-10-01

    The number of follicles recruited in each estrous cycle has gained practical importance in artificial reproductive technology, as it determines the oocyte yield from ultrasound-guided ovum pickup for in vitro embryo production. We aimed to identify single nucleotide polymorphisms (SNPs) in bovine genes related to reproductive physiology and evaluate the association between the candidate SNPs and the number of oocytes collected from ultrasound-guided ovum pickup. We sequenced genomic segments of GDF9, FGF8, FGF10 and BMPR2 and identified seventeen SNPs in the Bos taurus and Bos indicus breeds. Two SNPs cause amino acid changes in the proteins GDF9 and FGF8. Three SNPs in GDF9, FGF8 and BMPR2 were genotyped in 217 Nelore cows (B. indicus), while two previously identified mutations in LHCGR and mitochondrial DNA (mtDNA) were genotyped in the same group. The polymorphisms in GDF9, FGF8, BMRP2 and LHCGR were significantly associated (P<0.01) with the number of oocytes collected by ovum pickup, whereas the SNP in the mtDNA was not. In addition, we estimated an allelic substitution effect of 1.13±0.01 (P<0.01) oocytes for the SNP in the FGF8 gene. The results we report herein provide further evidence to support the hypothesis that genetic variability is an important component of the number of antral follicles in the bovine ovary. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. 77 FR 31859 - Government-Owned Inventions; Availability for Licensing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-30

    ... to detect expression of the NAG-1/GDF15 cleavage fragment in cells and media from cultured cells... complex can be extracted from the 3D image of a protein solution, or suspension of viruses or cells. These...; 301-435-5019; mish@codon.nih.gov . Collaborative Research Opportunity: The NCI Laboratory of Cell...

  5. Genetic Contributions to the Association between Adult Height and Testicular Germ Cell Tumors

    DTIC Science & Technology

    2011-01-01

    SL 3...rs143383—a 50 UTR poly- morphism which influences GDF5 transcriptional ac - tivity in chondrogenic and non-chondrogenic cell lines.30,31 In our study...ute 20% of variability to adult height in most modern, developed countries, are mainly active within a short time-window during early

  6. Growth differentiation factor 15 may protect the myocardium from no-reflow by inhibiting the inflammatory-like response that predominantly involves neutrophil infiltration

    PubMed Central

    ZHANG, MEI; PAN, KUNYING; LIU, QIANPING; ZHOU, XIN; JIANG, TIEMIN; LI, YUMING

    2016-01-01

    The aim of the current study was to investigate the time course of the expression of growth differentiation factor-15 (GDF-15) in rat ischemic myocardium with increasing durations of reperfusion, and to elucidate its physiopathological role in the no-reflow phenomenon. Wistar rats were randomly divided into ischemia reperfusion (I/R) and sham groups, and myocardial I/R was established by ligation of the left anterior descending coronary artery for 1 h followed by reperfusion for 2, 4, 6, 12, 24 h and 7 days whilst rats in the sham group were subjected to a sham operation. The expression levels of GDF-15 and ICAM-1 were measured, in addition to myeloperoxidase (MPO) activity. The myocardial anatomical no-reflow and infarction areas were assessed. The area at risk was not significantly different following various periods of reperfusion, while the infarct area and no-reflow area were significantly greater following 6 h of reperfusion (P<0.05). The mRNA and protein expression levels of GDF-15 were increased during the onset and development of no-reflow, and peaked following 24 h of reperfusion. MPO activity was reduced with increasing reperfusion duration, while ICAM-1 levels were increased. Hematoxylin and eosin staining demonstrated that myocardial neutrophil infiltration was significantly increased by I/R injury, in particular following 2, 4 and 6 h of reperfusion. GDF-15 expression levels were negatively correlated with MPO activity (r=−0.55, P<0.001), and the MPO activity was negatively correlated with the area of no-reflow (r=−0.46, P<0.01). By contrast, GDF-15 was significantly positively correlated with ICAM-1 levels (r=0.52, P<0.01), which additionally were demonstrated to be significantly positively associated with the size of the no-reflow area (r= 0.39, P<0.05). The current study demonstrated the time course effect of reperfusion on the expression of GDF-15 in the myocardial I/R rat model, with the shorter reperfusion times (6 h) resulting in

  7. The Nile River

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This image of the northern portion of the Nile River was captured by MISR's nadir camera on January 30, 2001 (Terra orbit 5956). The Nile is the longest river in the world, extending for about 6700 kilometers from its headwaters in the highlands of eastern Africa. At the apex of the fertile Nile River Delta is the Egyptian capital city of Cairo. To the west are the Great Pyramids of Giza. North of here the Nile branches into two distributaries, the Rosetta to the west and the Damietta to the east. Also visible in this image is the Suez Canal, a shipping waterway connecting Port Said on the Mediterranean Sea with the Gulf of Suez. The Gulf is an arm of the Red Sea, and is located on the righthand side of the picture. Image credit: NASA/GSFC/LaRC/JPL, MISR Team.

  8. Sinai Peninsula, Middle East as seen from STS-66 orbiter Atlantis

    NASA Image and Video Library

    1994-11-14

    A high oblique view of the Middle East centered at approximately 28.0 degrees north and 34.0 degrees east. Portions of the countries of Egypt, Israel, Jordan and Saudi Arabia are visible. The Dead Sea Rift Valley continuing into the Gulf of Aqaba marks the boundary between Israel and Jordan. The vegetation change in the Sinai Peninsula is the border between the Gaza Strip and Egypt. In Egypt, the Suez Canal connects the Gulf of Suez with the Mediterranean Sea and forms the western boundary of the Sinai Peninsula. The green ribbon of the Nile River is in marked contrast to this arid region. Even the Jordan River does not support large scale agriculture.

  9. GEMINI-7 - EARTH-SKY VIEW - MIDDLE-EAST AREA - OUTER SPACE

    NASA Image and Video Library

    1965-12-08

    S65-63849 (8 Dec. 1965) --- The eastern Mediterranean area as seen from the National Aeronautics and Space Administration's Gemini-7 spacecraft. The Nile Delta in Egypt is at bottom. The Suez Canal, Gulf of Suez and Red Sea are in the center of the photograph. The Sinai Peninsula is in the upper right corner of the picture. The body of water at the top edge of the photograph is the Gulf of Aqaba. The Dead Sea can be seen at top center. Israel, Palestine, Jordan and Syria are also at top center. The Island of Cyprus is at extreme left. Astronauts Frank Borman and James A. Lovell Jr. took this picture using a modified 70mm Hasselblad camera, with Eastman Kodak, Ektachrome MS (S.O. 217) color film. Photo credit: NASA

  10. The Nile River

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This image of the northern portion of the Nile River was captured by MISR's nadir camera on January 30, 2001 (Terra orbit 5956). The Nile is the longest river in the world, extending for about 6700 kilometers from its headwaters in the highlands of eastern Africa. At the apex of the fertile Nile River Delta is the Egyptian capital city of Cairo. To the west are the Great Pyramids of Giza. North of here the Nile branches into two distributaries, the Rosetta to the west and the Damietta to the east. Also visible in this image is the Suez Canal, a shipping waterway connecting Port Said on the Mediterranean Sea with the Gulf of Suez. The Gulf is an arm of the Red Sea, and is located on the righthand side of the picture. Image credit: NASA/GSFC/LaRC/JPL, MISR Team.

  11. Gamma ray spectrometry logs as a hydrocarbon indicator for clastic reservoir rocks in Egypt.

    PubMed

    Al-Alfy, I M; Nabih, M A; Eysa, E A

    2013-03-01

    Petroleum oil is an important source for the energy in the world. The Gulf of Suez, Nile Delta and South Valley are important regions for studying hydrocarbon potential in Egypt. A thorium normalization technique was applied on the sandstone reservoirs in the three regions to determine the hydrocarbon potentialities zones using the three spectrometric radioactive gamma ray-logs (eU, eTh and K% logs). The conventional well logs (gamma-ray, deep resistivity, shallow resistivity, neutron, density and sonic logs) are analyzed to determine the net pay zones in these wells. Indices derived from thorium normalized spectral logs indicate the hydrocarbon zones in petroleum reservoirs. The results of this technique in the three regions (Gulf of Suez, Nile Delta and South Valley) are in agreement with the results of the conventional well log analyses by ratios of 82%, 78% and 71% respectively.

  12. JPRS Report Near East & South Asia

    DTIC Science & Technology

    2007-11-02

    economic liberalization will include unifying the Central Bank pool exchange rate with the declared rates of the free bank foreign currency market ...The new system will establish two markets for foreign currency, the first including the present market where the Central Bank and authorized banks...conduct their transactions. Reve- nues from Suez Canal tolls, cotton exports, petroleum, and rice go into this market . Transactions in the second

  13. Selections from European Scientific Notes 1946 - 1976.

    DTIC Science & Technology

    1976-01-01

    certain Saltwater lines throughout the special facilities exclusively available aquarium are plastic. Sea water in- to the Institute. It is expected...completed through the heavy-duty of a large specimen, gear root, etc. crocodile clip on the gear (anode). The replica method is particularly The water...sipunculid, four struction of the Suez Canal (completed copepods, two amphipods, one cumacean, in 1809), hotever, was a saltwater pas- 33 decapods, one

  14. Assessing the Strategic Utility of the High North: The Colder War

    DTIC Science & Technology

    2016-12-01

    thirds of total world trade passing through the Suez Canal will be rerouted to the Northern Sea Route.2 This new ease of use in the High North oceanic ...October 14, 2016; The United Nations Convention on the Law of the Sea (A Historical Perspective), United Nations Division for Ocean Affairs and the...Arctic Oceans is now at its lowest level in 10 years.29 Figure 3 shows the annual warming temperatures over the past 70 years. In addition, Figure 4

  15. The Muslim Brotherhood in Egypt: Pursuing Moderation Within an Authoritarian Environment

    DTIC Science & Technology

    2011-06-01

    the military engagements, tourism decreased drastically, making the financial injury worse. Furthermore, the Arab world, especially Egypt, had to...differentiate between different Islamist movements’ political goals, and also too much impressed by dark visions of the future drawn by authoritarian...Quarterly (Fall 2003): 57– 65. Referring to Eldar, especially “the drop in tourism , lower oil prices, reduced incomes from the Suez Canal and from

  16. Egypt and Red Sea

    NASA Technical Reports Server (NTRS)

    1982-01-01

    A panaramic view of eastern Egypt, The Red Sea and Saudi Arabia beyond (24.0N, 33.0E). In this desert country, where water is life, the high Aswan Dam and the impounded waters of the Nile River in the foreground assure water availability into the next century. The Red Sea beyond, part of the Suez Canal seaway, serves as a commercial link to the world and separates Egypt from Saudi Arabia.

  17. Earth Observations taken by STS-115 crewmember

    NASA Image and Video Library

    2006-09-19

    S115-E-07595 (19 Sept. 2006) --- A crewmember aboard the Space Shuttle Atlantis recorded this digital still image of part of the eastern Mediterranean area. The Gulf of Suez, Gulf of Aqaba, Dead Sea, Tel Aviv and Jerusalem all are visible in the upper left quadrant. Jordan is in the lower left quadrant. The Golan Heights and Haifa appear in the lower right quarter.

  18. Earth Observations taken by STS-119 Crewmember.

    NASA Image and Video Library

    2009-03-27

    S119-E-010839 (27 March 2009) --- On its final full day in space before its scheduled return home on March 28, the crew of Space Shuttle Discovery took some pictures of the home planet, including this one of the Sinai Peninsula. The frame shows part of the Red Sea (top), Gulf of Suez (right of center), Nile River (far right edge), Gulf of Aqaba (center frame) and parts of the nations of Egypt, Jordan and Saudi Arabia.

  19. iss047e057822

    NASA Image and Video Library

    2016-04-14

    ISS047e057822 (04/14/2016) --- The Middle East is seen from 250 miles above in this photo from the International Space Station. Countries seen left to right along the Mediterranean coast include Egypt, Gaza, Saudi Arabia, Israel, Lebanon, Syria, and Turkey. The major waterways shown from left to right are the Nile River, Gulf of Suez, Gulf of Aqaba, and the Red Sea.

  20. JPRS Report, Near East and South Asia.

    DTIC Science & Technology

    1991-06-17

    jute, fibers, meat, and vegetable achieve integration between the African countries oils ). through a common African market? Nonetheless, the integrated...lift the burden borne by revenues from oil , tourism, and the Suez Canal had people living on fixed incomes. This would have been dropped, and revenues...Labor Party’s of extinguishing Kuwait’s burning oil wells which isSupreme Board, said, "The IMF’s prescription did not estimated to cost $20 billion. He

  1. Deployment of United Nations Peace Keeping Forces: The Nature of Transportation and Review of Current Methodologies.

    DTIC Science & Technology

    1980-06-06

    the support by the western countries. For example, the Suez Canal is a vital sea lane for trade between the industrialized developed nations of the west...lines Authority: Security Council Size: Maximum 89 Contributing Countries: Australia, Belgium, Canada, Chile, Denmark, Finland, Italy, Mexico , New...other specific public tasks. 3. Royal Netherlands Air Force (a) Organizacion For peace-keeping operations of the United Nations are earmarked: (1

  2. Egypt and Red Sea

    NASA Technical Reports Server (NTRS)

    1982-01-01

    A panaramic view of eastern Egypt, The Red Sea and Saudi Arabia beyond (24.0N, 33.0E). In this desert country, where water is life, the high Aswan Dam and the impounded waters of the Nile River in the foreground assure water availability into the next century. The Red Sea beyond, part of the Suez Canal seaway, serves as a commercial link to the world and separates Egypt from Saudi Arabia.

  3. United States Security Assistance 1977-1980: Human Rights Issues Affecting Arms Transfers.

    DTIC Science & Technology

    1995-09-01

    and faithful support. Their constant devotion and understanding made it all possible . Gary E. Gordon Table of Contents Page Acknowledgments u...Union to gain power in Greece and further the possibility of dominating the vital sea lane from the Mediterranean through the Suez Canal (Curti:771...By passing the act, the U.S. sent a clear message that U.S. efforts to promote peace and stability were based on the principle of "continuous and

  4. Aviation at the Operational Level of War: What Air Force Functions Properly Fall Under Army Aviation?

    DTIC Science & Technology

    1987-04-28

    missiles launched its weapons...over 3,000 tons of concentrated destruction...turned the Suez Canal into an inferno for 53 minutes. " (21) The combined...ce ’ The War MemToirs o-f Marshal of The 69yal air Foceg Lord Te992r G_-..., Boston: Little, Brown , and Company, 1966. White, William D., "’son. E 2FoC

  5. GT-12 - EARTH SKY - UNITED ARAB REPUBLIC (EGYPT)

    NASA Image and Video Library

    1966-11-14

    S66-63533 (14 Nov. 1966) --- United Arab Republic (Egypt) area as seen from the Gemini-12 spacecraft during its 39th revolution of Earth, looking southeast. Nile River is in center of picture. At bottom center is the Sinai Peninsula. Arabian Peninsula is at lower left. Large body of water is Red Sea. Gulf of Aqaba is on east side of Sinai Peninsula. Gulf of Suez separates Sinai from Egyptian mainland. Photo credit: NASA

  6. Implementation of MASW and waveform inversion techniques for new seismic hazard estimation technique

    NASA Astrophysics Data System (ADS)

    el-aziz abd el-aal, abd; Kamal, heba

    2016-04-01

    In this contribution, an integrated multi-channel analysis of Surface Waves (MASW) technique is applied to explore the geotechnical parameters of subsurface layers at the Zafarana Wind Farm site. The study area includes many active fault systems along the Gulf of Suez that cause many moderate and large earthquakes. Overall, the seismic activity of the area has recently become better understood following the use of waveform inversion method and software to develop accurate focal mechanism solutions for recent recorded earthquakes around the studied area. These earthquakes resulted in major stress-drops in the Eastern Desert and the Gulf of Suez area. These findings have helped to reshape the understanding of the seismotectonic environment of the Gulf of Suez area, which is a perplexing tectonic domain. Based on the collected new information and data, this study uses new an extended stochastic technique to re-examine the seismic hazard for the Gulf of Suez region, particularly the wind turbine towers sites at Zafarana Wind Farm and its vicinity. The essential characteristics of the extended stochastic technique are to obtain and simulate ground motion in order to minimize future earthquake consequences. The first step of this technique is defining the seismic sources which mostly affect the study area. Then, the maximum expected magnitude is defined for each of these seismic sources. It is followed by estimating the ground motion using an empirical attenuation relationship. Finally, the site amplification is implemented in calculating the peak ground acceleration (PGA) at each site of interest. Key words: MASW, waveform inversion, extended stochastic technique, Zafarana Wind Farm

  7. Egypt: The Key To Peace And Prosperity In The Middle East

    DTIC Science & Technology

    2017-02-03

    Approved for public release: distribution unlimited. 5 young and large growth in population as Egypt has over the last decade because the lack of a...provide jobs and economic growth . A young Egyptian population that sees the benefits of working and raising a family will have less interest in... population control over the Suez Canal, influential centers of Islamic education, active media enterprises and sizable well-equipped military. The spread

  8. Growth differentiation factor-9 mediates follicle-stimulating hormone-thyroid hormone interaction in the regulation of rat preantral follicular development.

    PubMed

    Kobayashi, Noriko; Orisaka, Makoto; Cao, Mingju; Kotsuji, Fumikazu; Leader, Arthur; Sakuragi, Noriaki; Tsang, Benjamin K

    2009-12-01

    FSH regulates follicular growth in a stage-development fashion. Although preantral follicle stage is gonadotropin responsive, FSH is not required for preantral follicular growth. With the antrum, the follicles continue growing under the influence of FSH and become gonadotropin dependent. Although thyroid hormone is important for normal female reproductive function, its role and interaction with FSH in the regulation of preantral ovarian follicular growth is yet to be defined. In the present study, we have examined the action and interaction of FSH and T(3) in the regulation of the growth of preantral follicles, especially in their transition from preantral to early antral stage, using an established follicle culture system and evaluated the involvement of growth differentiation factor-9 (GDF-9) in this process in vitro. We have demonstrated that although T(3) alone had no effect on follicular development, it markedly enhanced FSH-induced preantral follicular growth. Although FSH alone significantly down-regulated FSH receptor (FSHR) mRNA abundance in the preantral follicles and T(3) alone was ineffective, expression of the message was significantly increased in the presence of both hormones. In addition, intra-oocyte injection of GDF-9 antisense oligonucleotides (GDF-9 morpholino) induced follicular cell apoptosis and suppressed follicular growth induced by FSH and T(3). These responses were attenuated by exogenous GDF-9. Our findings support the concept that thyroid hormone regulates ovarian follicular development through its direct action on the ovary and that promotes FSH-induced preantral follicular growth through up-regulation of FSHR, a mechanism dependent on the expression and action of oocyte-derived GDF-9.

  9. Stratified whole genome linkage analysis of Chiari type I malformation implicates known Klippel-Feil syndrome genes as putative disease candidates.

    PubMed

    Markunas, Christina A; Soldano, Karen; Dunlap, Kaitlyn; Cope, Heidi; Asiimwe, Edgar; Stajich, Jeffrey; Enterline, David; Grant, Gerald; Fuchs, Herbert; Gregory, Simon G; Ashley-Koch, Allison E

    2013-01-01

    Chiari Type I Malformation (CMI) is characterized by displacement of the cerebellar tonsils below the base of the skull, resulting in significant neurologic morbidity. Although multiple lines of evidence support a genetic contribution to disease, no genes have been identified. We therefore conducted the largest whole genome linkage screen to date using 367 individuals from 66 families with at least two individuals presenting with nonsyndromic CMI with or without syringomyelia. Initial findings across all 66 families showed minimal evidence for linkage due to suspected genetic heterogeneity. In order to improve power to localize susceptibility genes, stratified linkage analyses were performed using clinical criteria to differentiate families based on etiologic factors. Families were stratified on the presence or absence of clinical features associated with connective tissue disorders (CTDs) since CMI and CTDs frequently co-occur and it has been proposed that CMI patients with CTDs represent a distinct class of patients with a different underlying disease mechanism. Stratified linkage analyses resulted in a marked increase in evidence of linkage to multiple genomic regions consistent with reduced genetic heterogeneity. Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of "CTD-negative" families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS). Interestingly, roughly 3-5% of CMI patients are diagnosed with KFS. In order to investigate the possibility that CMI and KFS are allelic, GDF3 and GDF6 were sequenced leading to the identification of a previously known KFS missense mutation and potential regulatory variants in GDF6. This study has demonstrated the value of reducing genetic heterogeneity by clinical stratification implicating several convincing biological candidates and further supporting the hypothesis that