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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...

  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

    ... Application To Export Electric Energy; IPR-GDF SUEZ Energy Marketing North America, Inc. AGENCY: Office of... Marketing North America, Inc. (GSEMNA) has applied for authority to transmit electric energy from the United..., Federal power marketing agencies, and other entities within the United States. The existing...

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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. PMID:24430093

  9. Crystal structure of human GDF11.

    PubMed

    Padyana, Anil K; Vaidialingam, Bhamini; Hayes, David B; Gupta, Priyanka; Franti, Michael; Farrow, Neil A

    2016-03-01

    Members of the TGF-β family of proteins are believed to play critical roles in cellular signaling processes such as those involved in muscle differentiation. The extent to which individual family members have been characterized and linked to biological function varies greatly. The role of myostatin, also known as growth differentiation factor 8 (GDF8), as an inhibitor of muscle differentiation is well understood through genetic linkages. In contrast, the role of growth differentiation factor 11 (GDF11) is much less well understood. In humans, the mature forms of GDF11 and myostatin are over 94% identical. In order to understand the role that the small differences in sequence may play in the differential signaling of these molecules, the crystal structure of GDF11 was determined to a resolution of 1.50 Å. A comparison of the GDF11 structure with those of other family members reveals that the canonical TGF-β domain fold is conserved. A detailed structural comparison of GDF11 and myostatin shows that several of the differences between these proteins are likely to be localized at interfaces that are critical for the interaction with downstream receptors and inhibitors. PMID:26919518

  10. Control of glioma cell migration and invasiveness by GDF-15

    PubMed Central

    Codó, Paula; Weller, Michael; Kaulich, Kerstin; Schraivogel, Daniel; Silginer, Manuela; Reifenberger, Guido; Meister, Gunter; Roth, Patrick

    2016-01-01

    Growth and differentiation factor (GDF)-15 is a member of the transforming growth factor (TGF)-β family of proteins. GDF-15 levels are increased in the blood and cerebrospinal fluid of glioblastoma patients. Using a TCGA database interrogation, we demonstrate that high GDF-15 expression levels are associated with poor survival of glioblastoma patients. To elucidate the role of GDF-15 in glioblastoma in detail, we confirmed that glioma cells express GDF-15 mRNA and protein in vitro. To allow for a detailed functional characterization, GDF-15 expression was silenced using RNA interference in LNT-229 and LN-308 glioma cells. Depletion of GDF-15 had no effect on cell viability. In contrast, GDF-15-deficient cells displayed reduced migration and invasion, in the absence of changes in Smad2 or Smad1/5/8 phosphorylation. Conversely, exogenous GDF-15 stimulated migration and invasiveness. Large-scale expression profiling revealed that GDF-15 gene silencing resulted in minor changes in the miRNA profile whereas several genes, including members of the plasminogen activator/inhibitor complex, were deregulated at the mRNA level. One of the newly identified genes induced by GDF-15 gene silencing was the serpin peptidase inhibitor, clade E nexin group 1 (serpine1) which is induced by TGF-β and known to inhibit migration and invasiveness. However, serpine1 down-regulation alone did not mediate GDF-15-induced promotion of migration and invasiveness. Our findings highlight the complex contributions of GDF-15 to the invasive phenotype of glioma cells and suggest anti-GDF-15 approaches as a promising therapeutic strategy. PMID:26741507

  11. GDF15 Is a Novel Biomarker for Impaired Fasting Glucose

    PubMed Central

    Hong, Jun Hwa; Chung, Hyo Kyun; Park, Hye Yoon; Joung, Kyong-Hye; Lee, Ju Hee; Jung, Jin Gyu; Kim, Koon Soon; Kim, Hyun Jin

    2014-01-01

    Background Growth differentiation factor-15 (GDF15) is a protein that belongs to the transforming growth factor β superfamily. An elevated serum level of GDF15 was found to be associated with type 2 diabetes mellitus (T2DM). T2DM is an inflammatory disease that progresses from normal glucose tolerance (NGT) to impaired fasting glucose (IFG). Hence, we aimed to validate the relationship between GDF15 and IFG. Methods The participants were divided into the following three groups: NGT (n=137), IFG (n=29), and T2DM (n=75). The controls and T2DM outpatients visited the hospital for routine health check-ups. We used fasting blood glucose to detect IFG in nondiabetic patients. We checked the body mass index (BMI), C-reactive protein level, metabolic parameters, and fasting serum GDF15 level. Results Age, BMI, triglyceride, insulin, glucose, homeostatic model assessment-insulin resistance (HOMA-IR), and GDF15 levels were elevated in the IFG and T2DM groups compared to the NGT group. In the correlation analysis between metabolic parameters and GDF15, age and HOMA-IR had a significant positive correlation with GDF15 levels. GDF15 significantly discriminated between IFG and NGT, independent of age, BMI, and HOMA-IR. The serum levels of GDF15 were more elevated in men than in women. As a biomarker for IFG based on the receiver operating characteristic curve analysis, the cutoff value of GDF15 was 510 pg/mL in males and 400 pg/mL in females. Conclusion GDF15 had a positive correlation with IR independent of age and BMI, and the serum level of GDF15 was increased in the IFG and T2DM groups. GDF15 may be a novel biomarker for detecting IFG in nondiabetic patients. PMID:25541611

  12. Oil potential of western Gulf of Suez

    SciTech Connect

    Hargras, M.; Hunter, G.; Nairn, A.E.M.

    1983-03-01

    Since 1886, Egyptian and foreign companies have explored the Gulf of Suez by classical mapping and geophysical techniques. During that time 13 oil and as fields have been discovered. Average daily production currently is of the order of 50,000 BOPD. Structurally, the western Gulf of Suez is divided into two major provinces: West Bakr and West Zeit. Within each province, fields are located over structural traps. As a result of drilling it is apparent that the structures resulted from major movement during the early Miocene. A major unconformity occurs at the top of the lower Miocene Nukhul Formation; and the beds of the overlying middle Miocene Belayim Formation transgress on to rocks as old as Precambrian. The Nubia Sandstone, one of the best reservoirs, is a blanket deposit over the whole gulf ranging in thickness from 130 m (425 ft) to in excess of 660 m (2150 ft). The Miocene sands are more sporadic in their distribution and thickness. Three depocenters are known in West Bakr, Shukheir, and Wacdi Dib areas. Further reservoirs of lesser importance are Cretaceous sands, 6.5 m (21 ft) to 32 m (105 ft) thick throughout the area, Eocene carbonates, and Miocene reefs. Production up to the present has been from structural traps; future expansion of production will depend upon our ability to locate stratigraphic traps. Sands sourced by the shales have seldom given high yields. The hope is that through the generation of depositional environment models it will be possible to define prospects where the optimum sand/shale ratio of 1/4 to 1/6 can be found.

  13. IDENTIFICATION OF A TENDON PHENOTYPE IN GDF6 DEFICIENT MICE

    PubMed Central

    Mikic, Borjana; Rossmeier, Kerri; Bierwert, LouAnn

    2009-01-01

    Increasing evidence suggests that the growth/differentiation factors, GDFs 5, 6, and 7 in particular, may play a role in tendon and ligament biology. Mice with genetic mutations in Gdf5 have altered tendon composition and mechanical behavior, while animals with functional null mutations in Gdf7 have a more subtle tendon phenotype. The present study demonstrates for the first time that a null mutation in Gdf6 is associated with substantially lower levels of tail tendon collagen content (−33%) in four-week-old male mice, which has direct functional consequences for the mechanical integrity of the tissue (45-50% reduction in material properties). These data support a role for GDF6 in tendon matrix modeling. PMID:19248159

  14. Foxg1 promotes olfactory neurogenesis by antagonizing Gdf11.

    PubMed

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

    2009-05-01

    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 TGFbeta 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 TGFbeta 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

  15. 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

  16. Can Serum Gdf-15 be Associated with Functional Iron Deficiency in Hemodialysis Patients?

    PubMed

    Yilmaz, Hakki; Cakmak, Muzaffer; Darcin, Tahir; Inan, Osman; Bilgic, Mukadder Ayse; Bavbek, Nuket; Akcay, Ali

    2016-06-01

    Functional iron deficiency (FID) incidence is gradually increasing in hemodialysis (HD) patients. Recently, high levels of GDF-15 supressed the iron regulatory protein hepcidin and GDF-15 expression increased in iron-deficient patients. The relationship between FID, GDF-15, and hepcidin is currently unknown. The present study aimed to evaluate the association between GDF-15, hepcidin, and FID in chronic HD patients. Serum GDF-15 and hepcidin concentrations were measured in 105 HD patients and 40 controls. FID is defined as serum ferritin >800 ng/mL, TSAT <25 %, Hb levels <11 g/dL, and reticulocyte haemoglobin content (CHr) <29 pg. Serum GDF-15 and hepcidin levels were increased significantly in HD patients with FID, compared to HD patients without anemia and controls. GDF-15 correlated with ferritin, hepcidin, and CRP in the entire cohort. GDF-15 was related to ferritin and CRP in HD patients with FID. GDF-15 is better diagnostic marker than hepcidin for detection of FID [AUC = 0.982 (0.013) versus AUC = 0.921 (0.027); P = 0.0324]. GDF-15 appears to be a promising tool for detection of FID. High levels of ferritin and CRP correlated with GDF-15. Our results support GDF-15 as a new mediator of FID via hepcidin, chronic inflammation, or unknown pathways. PMID:27065587

  17. 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.

  18. Gdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice.

    PubMed

    Machado, Venissa; Gilsbach, Ralf; Das, Richa; Schober, Andreas; Bogatyreva, Lioudmila; Hauschke, Dieter; Krieglstein, Kerstin; Unsicker, Klaus; Spittau, Björn

    2016-08-01

    Growth/differentiation factor-15 (Gdf-15) is a member of the transforming growth factor-β (Tgf-β) superfamily and has been shown to be a potent neurotrophic factor for midbrain dopaminergic (DAergic) neurons both in vitro and in vivo. Gdf-15 has also been shown to be involved in inflammatory processes. The aim of this study was to identify the role of endogenous Gdf-15 in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease (PD) by comparing Gdf-15 (+/+) and Gdf-15 (-/-) mice. At 4 days and 14 days post-MPTP administration, both Gdf-15 (+/+) and Gdf-15 (-/-) mice showed a similar decline in DAergic neuron numbers and in striatal dopamine (DA) levels. This was followed by a comparable restorative phase at 90 days and 120 days, indicating that the absence of Gdf-15 does not affect the susceptibility or the recovery capacity of the nigrostriatal system after MPTP administration. The MPTP-induced microglial and astrocytic response was not significantly altered between the two genotypes. However, pro-inflammatory and anti-inflammatory cytokine profiling revealed the differential expression of markers in Gdf-15 (+/+) and Gdf-15 (-/-) mice after MPTP administration. Thus, the MPTP mouse model fails to uncover a major role of endogenous Gdf-15 in the protection of MPTP-lesioned nigrostriatal DAergic neurons, in contrast to its capacity to protect the 6-hydroxydopamine-intoxicated nigrostriatal system. PMID:27115420

  19. Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease.

    PubMed

    Schafer, Marissa J; Atkinson, Elizabeth J; Vanderboom, Patrick M; Kotajarvi, Brian; White, Thomas A; Moore, Matthew M; Bruce, Charles J; Greason, Kevin L; Suri, Rakesh M; Khosla, Sundeep; Miller, Jordan D; Bergen, H Robert; LeBrasseur, Nathan K

    2016-06-14

    Growth and differentiation factor 11 (GDF11) is a transforming growth factor β superfamily member with a controversial role in aging processes. We have developed a highly specific LC-MS/MS assay to quantify GDF11, resolved from its homolog, myostatin (MSTN), based on unique amino acid sequence features. Here, we demonstrate that MSTN, but not GDF11, declines in healthy men throughout aging. Neither GDF11 nor MSTN levels differ as a function of age in healthy women. In an independent cohort of older adults with severe aortic stenosis, we show that individuals with higher GDF11 were more likely to be frail and have diabetes or prior cardiac conditions. Following valve replacement surgery, higher GDF11 at surgical baseline was associated with rehospitalization and multiple adverse events. Cumulatively, our results show that GDF11 levels do not decline throughout aging but are associated with comorbidity, frailty, and greater operative risk in older adults with cardiovascular disease. PMID:27304512

  20. 46 CFR 69.7 - Vessels transiting the Panama and Suez Canals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) All vessels intending to transit the Panama Canal, other than vessels of war, must be measured and certificated under the system prescribed in 35 CFR part 135. (b) All vessels intending to transit the Suez... Navigation, part IV. (c) Panama Canal and Suez Canal tonnage certificates are in addition to...

  1. 46 CFR 69.7 - Vessels transiting the Panama and Suez Canals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) All vessels intending to transit the Panama Canal, other than vessels of war, must be measured and certificated under the system prescribed in 35 CFR part 135. (b) All vessels intending to transit the Suez... Navigation, part IV. (c) Panama Canal and Suez Canal tonnage certificates are in addition to...

  2. 46 CFR 69.7 - Vessels transiting the Panama and Suez Canals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) All vessels intending to transit the Panama Canal, other than vessels of war, must be measured and certificated under the system prescribed in 35 CFR part 135. (b) All vessels intending to transit the Suez... Navigation, part IV. (c) Panama Canal and Suez Canal tonnage certificates are in addition to...

  3. 46 CFR 69.7 - Vessels transiting the Panama and Suez Canals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) All vessels intending to transit the Panama Canal, other than vessels of war, must be measured and certificated under the system prescribed in 35 CFR part 135. (b) All vessels intending to transit the Suez... Navigation, part IV. (c) Panama Canal and Suez Canal tonnage certificates are in addition to...

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

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) All vessels intending to transit the Panama Canal, other than vessels of war, must be measured and certificated under the system prescribed in 35 CFR part 135. (b) All vessels intending to transit the Suez... Navigation, part IV. (c) Panama Canal and Suez Canal tonnage certificates are in addition to...

  5. GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective.

    PubMed

    Adela, Ramu; Banerjee, Sanjay K

    2015-01-01

    Growth differentiation factor-15 (GDF-15) is a stress responsive cytokine. It is highly expressed in cardiomyocytes, adipocytes, macrophages, endothelial cells, and vascular smooth muscle cells in normal and pathological condition. GDF-15 increases during tissue injury and inflammatory states and is associated with cardiometabolic risk. Increased GDF-15 levels are associated with cardiovascular diseases such as hypertrophy, heart failure, atherosclerosis, endothelial dysfunction, obesity, insulin resistance, diabetes, and chronic kidney diseases in diabetes. Increased GDF-15 level is linked with the progression and prognosis of the disease condition. Age, smoking, and environmental factors are other risk factors that may increase GDF-15 level. Most of the scientific studies reported that GDF-15 plays a protective role in different tissues. However, few reports show that the deficiency of GDF-15 is beneficial against vascular injury and inflammation. GDF-15 protects heart, adipose tissue, and endothelial cells by inhibiting JNK (c-Jun N-terminal kinase), Bad (Bcl-2-associated death promoter), and EGFR (epidermal growth factor receptor) and activating Smad, eNOS, PI3K, and AKT signaling pathways. The present review describes the different animal and clinical studies and patent updates of GDF-15 in diabetes and cardiovascular diseases. It is a challenge for the scientific community to use GDF-15 information for patient monitoring, clinical decision-making, and replacement of current treatment strategies for diabetic and cardiovascular diseases. PMID:26273671

  6. Role of GDF15 (growth and differentiation factor 15) in pulmonary oxygen toxicity.

    PubMed

    Tiwari, Kirti Kumar; Moorthy, Bhagavatula; Lingappan, Krithika

    2015-10-01

    GDF15 (growth and differentiation factor 15) is a secreted cytokine, a direct target of p53 and plays a role in cell proliferation and apoptosis. It is induced by oxidative stress and has anti-apoptotic effects. The role of GDF15 in hyperoxic lung injury is unknown. We tested the hypothesis that GDF15 will be induced in vitro, in a model of pulmonary oxygen toxicity, and will play a critical role in decreasing cell death and oxidative stress. BEAS-2B (human bronchial epithelial cells) and human pulmonary vascular endothelial cells (HPMEC) were exposed to hyperoxia, and expression of GDF15 and effect of GDF15 disruption on cell viability and oxidative stress was determined. Furthermore, we studied the effect of p53 knockdown on GDF15 expression. In vitro, both BEAS-2B and HPMEC cells showed a significant increase in GDF15 expression upon exposure to hyperoxia. After GDF15 knockdown, there was a significant decrease in cell viability and increase in oxidative stress compared to control cells transfected with siRNA with a scrambled sequence. Knockdown of p53 significantly decreased the induction of GDF15 by hyperoxia. In conclusion, we show that GDF15 has a pro-survival and anti-oxidant role in hyperoxia and that p53 plays a key role in its induction. PMID:26004619

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

    PubMed Central

    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. PMID:26733738

  8. Lack of evidence for GDF11 as a rejuvenator of aged skeletal muscle satellite cells.

    PubMed

    Hinken, Aaron C; Powers, Janine M; Luo, Guizhen; Holt, Jason A; Billin, Andrew N; Russell, Alan J

    2016-06-01

    Recent high-profile studies report GDF11 to be a key circulating 'anti-aging' factor. However, a screen of extracellular proteins attempting to identify factors with 'anti-aging' phenotypes in aged murine skeletal muscle satellite cells did not identify GDF11 activity. We have been unable to confirm the reported activity of GDF11, similar to other laboratories offering conflicting data and describe our attempts to do so in this short take. PMID:27139744

  9. Brachydactyly type A2 associated with a defect in proGDF5 processing.

    PubMed

    Plöger, Frank; Seemann, Petra; Schmidt-von Kegler, Mareen; Lehmann, Katarina; Seidel, Jörg; Kjaer, Klaus W; Pohl, Jens; Mundlos, Stefan

    2008-05-01

    We investigated a family with a brachydactyly type A2 and identified a heterozygous arginine to glutamine (R380Q) substitution in the growth/differentiation factor 5 (GDF5) in all affected individuals. The observed mutation is located at the processing site of the protein, at which the GDF5 precursor is thought to be cleaved releasing the mature molecule from the prodomain. In order to test the effect of the mutation, we generated the GDF5-R380Q mutant and a cleavage-resistant proGDF5 mutant (R380A/R381A) in vitro. Both mutants were secreted from chicken micromass cultures, but showed diminished biological activity. Western blot analyses showed that wt GDF5 was processed by the chicken micromass cells, whereas the mutants were not, indicating that the mutations interfere with processing and that this leads to a strong reduction of biological activity. To test the requirements for GDF5 processing in vitro we produced recombinant human (rh) proGDF5 wild-type protein in Escherichia coli. The results show that unprocessed (rh) proGDF5 is virtually inactive but can be proteolytically activated by different enzymes such as trypsin, furin, and MMP3. (rh) proGDF5 could thus be used as a locally administered depot form with retarded release of activity. In contrast to mature rhGDF5, (rh) proGDF5 shows a high solubility at physiological pH, a characteristic that might be useful for therapeutic applications. PMID:18203755

  10. 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.

  11. Extensional hard linkages, eastern Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    McClay, Ken; Khalil, Samir

    1998-06-01

    The Araba Abu Durba area on the eastern margin of the Gulf of Suez exhibits two superb outcrop examples of extensional hard linkages in a rift basin. Here, three large, domino-style, basement-cored, northeast-dipping fault blocks are formed by a series of major northwest-trending normal faults. These are offset by two north-northeast trending sinistral oblique-slip transfer faults that terminate in horsetail normal fault splays. The transfer faults do not extend across the entire rift basin. Detailed mapping and structural analysis show that they developed by breakage of initial low-strain relay ramps along reactivated north-northeast trending basement fabrics between overlapping northwest-trending normal fault segments. Paleostrain analysis of fault-slip indicators shows that both the normal and the sinistral oblique-slip transfer faults were formed synchronously in response to northeast-southwest extension, perpendicular to the main northwest rift trend.

  12. 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.

  13. 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. PMID:26520384

  14. 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

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

    PubMed

    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

  16. 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

  17. 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

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

    PubMed

    Lee, Yun-Sil; Lee, Se-Jin

    2013-09-24

    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

  19. Epigenetic Regulation of GDF2 Suppresses Anoikis in Ovarian and Breast Epithelia1

    PubMed Central

    Varadaraj, Archana; Patel, Pratik; Serrao, Anne; Bandyopadhay, Tirthankar; Lee, Nam Y.; Jazaeri, Amir A.; Huang, Zhiqing; Murphy, Susan K.; Mythreye, Karthikeyan

    2015-01-01

    Anoikis, a cell death mechanism triggered upon cell-matrix detachment, is regarded as a physiological suppressor of metastasis that can be regulated by a diverse array of signals. The protein encoded by GDF2 is BMP9 and is a member of the bone morphogenetic protein family and the transforming growth factor (TGF) β superfamily with emerging yet controversial roles in carcinogenesis. In an attempt to identify the function of growth and differentiation factor 2 (GDF2) in epithelial systems, we examined the signaling machinery that is involved and cell fate decisions in response to GDF2 in ovarian and breast epithelia. We find that GDF2 can robustly activate the SMAD1/5 signaling axis by increasing complex formation between the type I receptor serine threonine kinases activin receptor-like kinase (ALK) 3 and ALK6 and the type II receptor serine threonine kinase BMPRII. This activation is independent of cross talk with the SMAD2-transforming growth factor β pathway. By activating SMAD1/5, epithelial cells regulate anchorage-independent growth by increasing anoikis sensitivity that is dependent on GDF2’s ability to sustain the activation of SMAD1/5 via ALK3 and ALK6. Consistent with a role for GDF2 in promoting anoikis susceptibility, the analysis of cell lines and patient data suggests epigenetic silencing of GDF2 in cancer cell lines and increased promoter methylation in patients. These findings collectively indicate an antimetastatic role for GDF2 in ovarian and breast cancer. The work also implicates loss of GDF2 via promoter methylation-mediated downregulation in promotion of carcinogenesis with significant relevance for the use of epigenetic drugs currently in clinical trials. PMID:26678910

  20. 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.

  1. 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.

  2. Carbonate diagenesis and rifting in the Gulf of Suez

    SciTech Connect

    Purser, B.H.; Orszag-Sperber, F.; Aissaoui, D.M. )

    1988-08-01

    Lower Miocene carbonates of the northwest Red Sea and Gulf of Suez have been deposited on a series of structural blocks where bathymetric relief, created by early rift tectonics, has strongly influenced both sedimentation and early diagenesis. Initial submarine cementation by fibrous calcite and aragonite strongly affects slope deposits, destroying most primary porosity. It was followed by several phases of regional dolomitization whose isotopic signatures suggest nonmarine influence. Undolomitized sediments are the exception. An intense dissolution is the principal agent determining petrophysical qualities of the series. Nonmarine sparitic cements are not important, indicating the dissolved carbonate has been flushed out of the system. Finally, large-scale sulfate replacement affects dolomites adjacent to the middle Miocene primary evaporites. These secondary sulfates are associated with a zone of calcitized dolomite (dedolomite). This diagenetic activity obviously reflects repeated changes in the composition of interstitial waters. Its exceptional intensity is explained by the contemporaneous basin relief; the presence of numerous subparallel blocks has resulted in the development of separate bodies of water relating to both meteoric influx and evaporation. Together with normal marine waters, these fluids of variable density have penetrated the intervening sedimentary platforms via the numerous slopes. It is clear that multiphased carbonate diagenesis is one of the many expressions of early rifting.

  3. 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

  4. Effect of growth differentiation factor-9 (GDF-9) on the progression of buffalo follicles in vitrified-warmed ovarian tissues.

    PubMed

    Abdel-Ghani, M A; El-Sherry, T M; Abdelhafeez, H H

    2016-10-01

    To improve the reproductive performance of water buffalo to level can satisfy our needs, the mechanisms controlling ovarian follicular growth and development should be thoroughly investigated. Therefore, in this study, the expressions of growth differentiation factor-9 (GDF-9) in buffalo ovaries were examined by immunohistochemistry, and the effects of GDF-9 treatment on follicle progression were investigated using a buffalo ovary organ culture system. Frozen-thawed buffalo ovarian follicles within slices of ovarian cortical tissue were cultured for 14 days in the presence or absence of GDF-9. After culture, ovarian slices were fixed, sectioned and stained. The follicles were morphologically analysed and counted. Expression pattern of GDF-9 was detected in oocytes from primordial follicles onwards, besides, also presented in granulosa cells. Moreover, GDF-9 was detected in mural granulosa cells and theca cells of pre-antral follicles. In antral follicles, cumulus cells and theca cells displayed positive expression of GDF-9. In corpora lutea, GDF-9 was expressed in both granulosa and theca lutein cells. After in vitro culture, there was no difference in the number of primordial follicles between cultured plus GDF-9 and cultured control that indicated the GDF-9 treatment has no effect on the primordial to primary follicle transition. GDF-9 treatment caused a significant decrease in the number of primary and secondary follicles compared with controls accompanied with a significant increase in pre-antral and antral follicles. These results suggest that a larger number of primary and secondary follicles were stimulated to progress to later developmental stages when treated with GDF-9. Vitrification/warming of buffalo ovarian tissue had a little remarkable effect, in contrast to culturing for 14 days, on the expression of GDF-9. In conclusion, treatment with GDF-9 was found to promote progression of primary follicle that could provide an alternative approach to

  5. Oil window in the Gulf of Suez basin, Egypt

    SciTech Connect

    Shahin, A.N. )

    1988-08-01

    Petroleum in the Gulf of Suez is multisourced mainly by restricted marine Cretaceous to Eocene beds. The Campanian carbonates of the Sudr Formation and the Turonian shales of the Abu Qada Formation are high-quality sources. Other proven sources are carbonate and shale intervals within other sub-Miocene formations. Geothermal modeling calibrated by maturation measurements suggests that the organic-rich lower Miocene marls may not be mature enough to expel hydrocarbons north of the Morgan-Amal fields area but are mature to the south. This could be related mainly to a gradual increase in thermal gradient from north to south (20-55{degree}C/km). A few anomalies do exist, however. Thermal gradients are generally higher in areas where oil accumulated. The depth of peak generation ranges between 5,200 m to the north and 3,300 m to the south. The geographic variations in heat flow, maturation depths, and age of source rocks are not reflected in the timing of hydrocarbon migration. During the middle Miocene, a short-lived salinity crisis resulted in the deposition of massive thick evaporites that form the ultimate seal in the Gulf. The accompanying rapid burial of the underlying sub-Miocene potential source intervals caused them all to sequentially enter the oil window, within a very short time, soon after the evaporites accumulated. This timing was perfect for hydrocarbon preservation: after seal deposition and major disturbing regional tectonic events. The almost simultaneous migration from all the source beds resulted in mixed multisourced hydrocarbon accumulations.

  6. Differential effects of GDF5 on the medial and lateral rat ventral mesencephalon.

    PubMed

    Clayton, Kevin B; Sullivan, Aideen M

    2007-11-12

    Growth/differentiation factor 5 (GDF5) is a member of the transforming growth factor-beta (TGF-beta) superfamily that has potent neurotrophic and protective effects on dopaminergic neurones and is expressed in the developing rat substantia nigra (the ventral mesencephalon; VM). GDF5 has the potential to be used in the treatment of Parkinson's disease (PD), a neurodegenerative disorder characterised by the selective degeneration of nigrostriatal dopaminergic neurones. One therapy being explored for PD involves transplantation of fetal VM tissue into the striatum in order to replace lost dopaminergic neurones. The majority of transplantation studies have used transplants incorporating the whole VM. The principal location of dopaminergic neurones in the E14 rat VM is in the medial VM. In the present study, the effects of GDF5 on cultures prepared from medial, lateral and whole E14 rat VM tissue were compared. GDF5 treatment increased the number of dopaminergic neurones in whole and lateral, but not in medial, VM cultures, whereas it increased total cell number in medial, but not in whole or lateral, VM cultures. RT-PCR studies showed that the receptors for GDF5 were differentially expressed in E14 VM; the expression of BMPR-IB and Ror2 was low in medial but high in lateral VM tissue. This study suggests that GDF5 increases the number of dopaminergic neurones in whole VM cultures by acting on BMPR-IB and Ror2-expressing cells in the lateral VM. PMID:17935884

  7. 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

  8. Serum GDF-8 levels change dynamically during controlled ovarian hyperstimulation in patients undergoing IVF/ICSI-ET.

    PubMed

    Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

    2016-01-01

    Growth differentiation factor-8 (GDF-8) is found in the human serum, follicular fluid and granulosa cells. Our previous studies have shown that the human cumulus expansion and steroidogenesis can be regulated by GDF-8. However, thus far, the expression profile of GDF-8 in serum and whether the level of serum GDF-8 influences pregnancy results for patients treated with in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) is totally unknown. In this study, we showed that GDF-8 had a dynamic trend during controlled ovarian hyperstimulation (COH) procedure. On human chorionic gonadotropin (hCG) administration day, patients with a GDF-8 level higher than 4.7 ng/ml had lower progesterone levels and a higher pregnancy rate. From hCG day to oocyte pick-up day, patients with a GDF-8 decrease greater than 1.3 ng/ml had a higher progesterone increase and a higher pregnancy rate. Importantly, the levels of GDF-8 were negatively correlated with progesterone levels. Our findings provide evidences that GDF-8 plays an important role in ensuring successful pregnancy by regulating progesterone levels. PMID:27329327

  9. Serum GDF-8 levels change dynamically during controlled ovarian hyperstimulation in patients undergoing IVF/ICSI-ET

    PubMed Central

    Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

    2016-01-01

    Growth differentiation factor-8 (GDF-8) is found in the human serum, follicular fluid and granulosa cells. Our previous studies have shown that the human cumulus expansion and steroidogenesis can be regulated by GDF-8. However, thus far, the expression profile of GDF-8 in serum and whether the level of serum GDF-8 influences pregnancy results for patients treated with in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) is totally unknown. In this study, we showed that GDF-8 had a dynamic trend during controlled ovarian hyperstimulation (COH) procedure. On human chorionic gonadotropin (hCG) administration day, patients with a GDF-8 level higher than 4.7 ng/ml had lower progesterone levels and a higher pregnancy rate. From hCG day to oocyte pick-up day, patients with a GDF-8 decrease greater than 1.3 ng/ml had a higher progesterone increase and a higher pregnancy rate. Importantly, the levels of GDF-8 were negatively correlated with progesterone levels. Our findings provide evidences that GDF-8 plays an important role in ensuring successful pregnancy by regulating progesterone levels. PMID:27329327

  10. 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.

  11. 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. PMID:26845859

  12. 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. PMID:26909594

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

    PubMed Central

    Park, Hyejin; Kim, Chun-Ho; Jeong, Jae-Hoon

    2016-01-01

    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. PMID:26909594

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

    PubMed Central

    2016-01-01

    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. PMID:27510384

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

    PubMed

    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. 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. PMID:27510384

  17. 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

  18. Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15) Gene Deletion Promotes Cancer Growth in TRAMP Prostate Cancer Prone Mice

    PubMed Central

    Husaini, Yasmin; Lockwood, Glen P.; Nguyen, Trung V.; Tsai, Vicky Wang-Wei; Mohammad, Mohammad G.; Russell, Pamela J.; Brown, David A.; Breit, Samuel N.

    2015-01-01

    The divergent TGF-β superfamily member, macrophage inhibitory cytokine-1 (MIC-1/GDF15), is overexpressed by most cancers, including prostate cancer (PCa). Whilst its circulating levels are linked to cancer outcome, the role MIC-1/GDF15 plays in cancer development and progression is incompletely understood. To investigate its effect on PCa development and spread, we have used TRAMP prostate cancer prone mice bearing a germline deletion of MIC-1/GDF15 (TRAMPMIC-/-). On average TRAMPMIC-/- mice died about 5 weeks earlier and had larger prostatic tumors compared with TRAMP mice that were wild type for MIC-1/GDF15 (TRAMPMIC+/+). Additionally, at the time of death or ethical end point, even when adjusted for lifespan, there were no significant differences in the number of mice with metastases between the TRAMPMIC+/+ and TRAMPMIC-/- groups. However, consistent with our previous data, more than twice as many TRAMP mice overexpressing MIC-1/GDF15 (TRAMPfmsmic-1) had metastases than TRAMPMIC+/+ mice (p<0.0001). We conclude that germ line gene deletion of MIC-1/GDF15 leads to increased local tumor growth resulting in decreased survival consistent with an overall protective role for MIC-1/GDF15 in early primary tumor development. However, in advancing disease, as we have previously noted, MIC-1/GDF15 overexpression may promote local invasion and metastatic spread. PMID:25695521

  19. Macrophage inhibitory cytokine-1 (MIC-1/GDF15) gene deletion promotes cancer growth in TRAMP prostate cancer prone mice.

    PubMed

    Husaini, Yasmin; Lockwood, Glen P; Nguyen, Trung V; Tsai, Vicky Wang-Wei; Mohammad, Mohammad G; Russell, Pamela J; Brown, David A; Breit, Samuel N

    2015-01-01

    The divergent TGF-β superfamily member, macrophage inhibitory cytokine-1 (MIC-1/GDF15), is overexpressed by most cancers, including prostate cancer (PCa). Whilst its circulating levels are linked to cancer outcome, the role MIC-1/GDF15 plays in cancer development and progression is incompletely understood. To investigate its effect on PCa development and spread, we have used TRAMP prostate cancer prone mice bearing a germline deletion of MIC-1/GDF15 (TRAMPMIC-/-). On average TRAMPMIC-/- mice died about 5 weeks earlier and had larger prostatic tumors compared with TRAMP mice that were wild type for MIC-1/GDF15 (TRAMPMIC+/+). Additionally, at the time of death or ethical end point, even when adjusted for lifespan, there were no significant differences in the number of mice with metastases between the TRAMPMIC+/+ and TRAMPMIC-/- groups. However, consistent with our previous data, more than twice as many TRAMP mice overexpressing MIC-1/GDF15 (TRAMPfmsmic-1) had metastases than TRAMPMIC+/+ mice (p<0.0001). We conclude that germ line gene deletion of MIC-1/GDF15 leads to increased local tumor growth resulting in decreased survival consistent with an overall protective role for MIC-1/GDF15 in early primary tumor development. However, in advancing disease, as we have previously noted, MIC-1/GDF15 overexpression may promote local invasion and metastatic spread. PMID:25695521

  20. 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

  1. Effects of GDF5 overexpression on embryonic rat dopaminergic neurones in vitro and in vivo.

    PubMed

    O'Sullivan, David B; Harrison, Patrick T; Sullivan, Aideen M

    2010-05-01

    Transplantation of embryonic dopaminergic neurones has shown promise for the treatment of Parkinson's disease (PD), but this approach is limited by the poor survival of the transplanted cells. Exogenous dopaminergic neurotrophic factors such as growth/differentiation factor 5 (GDF5) have been found to enhance the survival of transplanted dopaminergic neurones. However, this approach is limited by the rapid degradation of such factors in vivo; thus, methods for long-term delivery of these factors are under investigation. The present study shows, using optimised lipid-mediated transfection procedures, that overexpression of GDF5 significantly improves the survival of dopaminergic neurones in cultures of embryonic day (E) 13 rat ventral mesencephalon (VM) and protects them against 6-hydroxydopamine (6-OHDA)-induced toxicity. In another experiment, E13 VM cells were transfected with GDF5 after 1 day in vitro (DIV), then transplanted into 6-OHDA-lesioned adult rat striata after 2 DIV. The survival of these E13 VM dopaminergic neurones after transfection and transplantation was as least as high as that of freshly dissected E14 VM dopaminergic neurones, demonstrating that transfection was not detrimental to these cells. Furthermore, GDF5-overexpressing E13 VM transplants significantly reduced amphetamine-induced rotational asymmetry in the lesioned rats. This study shows that lipid-mediated transfection in vitro prior to transplantation is a valid approach for the introduction of neurotrophic proteins such as GDF5, as well as lending further support to the potential use of GDF5 in neuroprotective therapy for PD. PMID:20349094

  2. 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.

  3. 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. PMID:24092254

  4. Integral Role of GDF-9 and BMP-15 in Ovarian Function

    PubMed Central

    Otsuka, Fumio; McTavish, Kirsten; Shimasaki, Shunichi

    2011-01-01

    The oocyte plays an important role in regulating and promoting follicle growth, and thereby its own development, by the production of oocyte growth factors that predominantly act on supporting granulosa cells via paracrine signaling. Genetic studies in mice demonstrated critical roles of two key oocyte-derived growth factors belonging to the transforming growth factor-β (TGF-β) superfamily, growth and differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15) in ovarian function. The identification of Bmp15 and Gdf9 gene mutations as the causal mechanism underlying the highly prolific or infertile nature of several sheep strains in a dosage-sensitive manner also highlighted the crucial role these two genes play in ovarian function. Similarly, large numbers of mutations in the GDF9 and BMP15 genes have been identified in women with premature ovarian failure and in mothers of dizygotic twins. The purpose of this article is to review the genetic studies of GDF-9 and BMP-15 mutations identified in women and sheep as well as describing the various knockout and over-expressing mouse models, and to summarize the molecular and biological functions that underlie the crucial role of these two oocyte factors in female fertility. PMID:21226076

  5. Genetic effects of GDF8 and CAPN1 for carcass and meat traits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to improve genetic marker effect estimates of SNP previously associated with muscle traits in beef cattle (F94L marker in GDF8 and 316 marker of CAPN1). Multiyear selection in a composite population segregating both SNP increased minor allele frequency (MAF) to intermediate levels...

  6. Regeneration of periodontal tissues in non-human primates with rhGDF-5 and beta-tricalcium phosphate.

    PubMed

    Emerton, K B; Drapeau, S J; Prasad, H; Rohrer, M; Roffe, P; Hopper, K; Schoolfield, J; Jones, A; Cochran, D L

    2011-12-01

    The application of growth factors has been advocated in support of periodontal regeneration. Recombinant human growth and differentiation factor-5 (rhGDF-5), a member of the bone morphogenetic protein family, has been used to encourage periodontal tissue regeneration. This study evaluated the dose response of rhGDF-5 lyophilized onto beta-tricalcium phosphate (bTCP) granules for periodontal tissue regeneration in a baboon model. Periodontal defects were created bilaterally in 12 baboons by a split-mouth design. Plaque was allowed to accumulate around wire ligatures to create chronic disease. After 2 mos, the ligatures were removed, and a notch was placed at the base of the defect. Two teeth on each side of the mouth were randomly treated with bTCP only, 0.5, 1.0, or 2.0 mg rhGDF-5/g bTCP. Animals were sacrificed 5 mos post-treatment, with micro-CT and histomorphometric analysis performed. After 5 mos, analysis showed alveolar bone, cementum, and periodontal ligament formation in all treatment groups, with a dose-dependent increase in rhGDF-5-treated groups. Height of periodontal tissues also increased with the addition of rhGDF-5, and the amount of residual graft material decreased with rhGDF-5 treatment. Therefore, rhGDF-5 delivered on bTCP demonstrated effective regeneration of all 3 tissues critical for periodontal repair. PMID:21940517

  7. 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. PMID:23680368

  8. Epigenetic silencing of GDF1 disrupts SMAD signaling to reinforce gastric cancer development.

    PubMed

    Yang, W; Mok, M T S; Li, M S M; Kang, W; Wang, H; Chan, A W; Chou, J-L; Chen, J; Ng, E K W; To, K-F; Yu, J; Chan, M W Y; Chan, F K L; Sung, J J Y; Cheng, A S L

    2016-04-21

    Accumulating evidence reveals the effectiveness of epigenetic therapy in gastric cancer. However, the molecular mechanisms and targets underlying such therapeutic responses remain elusive. Herein, we report an aberrant yet therapeutically rectifiable epigenetic signaling in gastric carcinogenesis. Administration of DNA-demethylating drug 5-aza-2'-deoxycytidine (5-aza-dC) reduced gastric cancer incidence by ~74% (P<0.05) in N-nitroso-N-methylurea-treated mice. Through genome-wide methylation scanning, novel promoter hypermethylation-silenced and drug-targeted genes were identified in the resected murine stomach tumors and tissues. We uncovered that growth/differentiation factor 1 (Gdf1), a member of the transforming growth factor-β superfamily, was silenced by promoter hypermethylation in control tumor-bearing mice, but became reactivated in 5-aza-dC-treated mice (P<0.05). In parallel, the downregulated SMAD2/3 phosphorylation in gastric cancer was revived by 5-aza-dC in vivo. Such hypermethylation-dependent silencing and 5-aza-dC-mediated reactivation of GDF1-SMAD2/3 activity was conserved in human gastric cancer cells (P<0.05). Subsequent functional characterization further revealed the antiproliferative activity of GDF1, which was exerted through activation of SMAD2/3/4-mediated signaling, transcriptional controls on p15, p21 and c-Myc cell-cycle regulators and phosphorylation of retinoblastoma protein. Clinically, hypermethylation and loss of GDF1 was significantly associated with reduced phosphorylated-SMAD2/3 and poor survival in stomach cancer patients (P<0.05). Taken together, we demonstrated a causal relationship between DNA methylation and a tumor-suppressive pathway in gastric cancer. Epigenetic silencing of GDF1 abrogates the growth-inhibitory SMAD signaling and renders proliferation advantage to gastric epithelial cells during carcinogenesis. This study lends support to epigenetic therapy for gastric cancer chemoprevention and identifies a potential

  9. Temporal expression of GDF-9 and BMP-15 mRNAs in canine ovarian follicles.

    PubMed

    Palomino, Jaime; De Los Reyes, Monica

    2016-10-01

    This study aimed to investigate the expression profiles of growth differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP-15) mRNA in canine oocytes and follicular cells throughout development at the different phases of the estrus cycle. Ovarian structures (follicles and CL) and plasma progesterone concentration were used to confirm the physiological status of each donor. Denuded oocytes and their follicular cells were recovered from follicles (n = 675) distributed into 4 types (preantral, small antral ∼0.2-0.39 mm, medium antral ∼0.4-5.9 mm, and large antral ∼6-8 mm). Total RNA was extracted and reverse transcribed, and the levels of expression for these 2 genes were determined using a quantitative real-time polymerase chain reaction technique; the data were evaluated by ANOVA. Relative expressions levels of GDF-9 and BMP-15 transcripts were detected in the oocyte and follicular cells in all follicular stages evaluated, showing differential changes (P < 0.05) during development over the estrus cycle. The expression patterns of both transcripts were highly correlated between follicles cells and oocytes (r > 0.8; P < 0.05 for GDF-9 and BMP-15), although GDF-9 was expressed at higher levels (P < 0.05) in the oocyte compared with the follicle cells. All cell types showed more GDF-9 mRNA abundance at early developing stages, mainly in the anestrus phase, and declining levels in the later stages (P < 0.05), whereas BMP-15 mRNA levels increased (P < 0.05) in follicular cells and oocytes from the preantral to the later stages, and remained constant during the final preovulatory stage. In conclusion, these two genes were detected in follicular cells and oocytes and were differentially expressed during the follicular development across the estrus cycle. PMID:27341772

  10. 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.

  11. Pattern of Blood Stream Infections within Neonatal Intensive Care Unit, Suez Canal University Hospital, Ismailia, Egypt

    PubMed Central

    Kishk, Rania Mohammed; Mandour, Mohamed Fouad; Farghaly, Rasha Mohamed; Ibrahim, Ahmed; Nemr, Nader Attia

    2014-01-01

    Introduction. Blood stream infection (BSI) is a common problem of newborn in neonatal intensive care units (NICUs). Monitoring neonatal infections is increasingly regarded as an important contributor to safe and high-quality healthcare. It results in high mortality rate and serious complications. So, our aim was to determine the incidence and the pattern of BSIs in the NICU of Suez Canal University Hospital, Egypt, and to determine its impact on hospitalization, mortality, and morbidity. Methods. This study was a prospective one in which all neonates admitted to the NICUs in Suez Canal University hospital between January, 2013 and June 2013 were enrolled. Blood stream infections were monitored prospectively. The health care associated infection rate, mortality rate, causative organism, and risk factors were studied. Results. A total of 317 neonates were admitted to the NICU with a mortality rate of 36.0%. During this study period, 115/317 (36.3%) developed clinical signs of sepsis and were confirmed as BSIs by blood culture in only 90 neonates with 97 isolates. The total mean length of stay was significantly longer among infected than noninfected neonates (34.5 ± 18.3 and 10.8 ± 9.9 days, resp., P value < 0.001). The overall mortality rates among infected and noninfected neonates were 38.9% and 34.8%, respectively, with a significant difference. Klebsiella spp. were the most common pathogen (27.8%) followed by Pseudomonas (21.6%) and Staphylococcus aureus (15.4%). Conclusion. The rate of BSIs in NICU at Suez Canal University Hospital was relatively high with high mortality rate (36.0%). PMID:25389439

  12. Pattern of Blood Stream Infections within Neonatal Intensive Care Unit, Suez Canal University Hospital, Ismailia, Egypt.

    PubMed

    Kishk, Rania Mohammed; Mandour, Mohamed Fouad; Farghaly, Rasha Mohamed; Ibrahim, Ahmed; Nemr, Nader Attia

    2014-01-01

    Introduction. Blood stream infection (BSI) is a common problem of newborn in neonatal intensive care units (NICUs). Monitoring neonatal infections is increasingly regarded as an important contributor to safe and high-quality healthcare. It results in high mortality rate and serious complications. So, our aim was to determine the incidence and the pattern of BSIs in the NICU of Suez Canal University Hospital, Egypt, and to determine its impact on hospitalization, mortality, and morbidity. Methods. This study was a prospective one in which all neonates admitted to the NICUs in Suez Canal University hospital between January, 2013 and June 2013 were enrolled. Blood stream infections were monitored prospectively. The health care associated infection rate, mortality rate, causative organism, and risk factors were studied. Results. A total of 317 neonates were admitted to the NICU with a mortality rate of 36.0%. During this study period, 115/317 (36.3%) developed clinical signs of sepsis and were confirmed as BSIs by blood culture in only 90 neonates with 97 isolates. The total mean length of stay was significantly longer among infected than noninfected neonates (34.5 ± 18.3 and 10.8 ± 9.9 days, resp., P value < 0.001). The overall mortality rates among infected and noninfected neonates were 38.9% and 34.8%, respectively, with a significant difference. Klebsiella spp. were the most common pathogen (27.8%) followed by Pseudomonas (21.6%) and Staphylococcus aureus (15.4%). Conclusion. The rate of BSIs in NICU at Suez Canal University Hospital was relatively high with high mortality rate (36.0%). PMID:25389439

  13. Neogene tectono-stratigraphic events in Gulf of Suez rift area, Egypt

    SciTech Connect

    Evans, A.L.

    1987-05-01

    Micropaleontologic and sedimentologic studies of Miocene outcrop and borehole sections from the flanks and axial trough of the Suez rift have documented five major tectono-stratigraphic events, or hiatuses, during the Neogene. The first Neogene hiatus spans the late(.) Oligocene to earliest Miocene and separates Miocene from pre-Miocene strata throughout the Gulf of Suez. This erosional event resulted from both low global sea levels in the Oligocene and the initiation of Suez rifting. A second hiatus, from 21 to 19(.) Ma, separates the poorly dated shallow marine Nukhul formation from overlying middle Burdigalian and younger (NN3-NN5) upper bathyal shales of the Rudeis Formation. This hiatus resulted from both low early Burdigalian sea levels and increased rift-related tectonism. A third major event occurs within the Rudeis around 16 Ma (N7, NN4). This mid-Clysmic event of Garfunkel and Bartove is characterized by accelerated uplift of the rift margins and subsidence of the axial trough. Local unconformities are seen over paleohighs, while coarse clastics are deposited in more basinal areas in submarine fans and turbidites. A fourth hiatus at 14 to 13 Ma (N10-N11) separates the middle Miocene (N9) Kareem Formation from the overlying Belayim Formation evaporites. This hiatus may correlate with the initiation of rifting along the Dead Sea-Aqaba system. The fifth Neogene event is a tectonic pulse in the early (.) Pliocene that further rotated many tilted fault blocks. This event is roughly synchronous with the initiation of Red Sea sea-floor spreading and accelerated sinistral motion along the Dead Sea transform at approx. 5 Ma.

  14. 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. PMID:26407862

  15. 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

  16. Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2.

    PubMed

    Seemann, Petra; Schwappacher, Raphaela; Kjaer, Klaus W; Krakow, Deborah; Lehmann, Katarina; Dawson, Katherine; Stricker, Sigmar; Pohl, Jens; Plöger, Frank; Staub, Eike; Nickel, Joachim; Sebald, Walter; Knaus, Petra; Mundlos, Stefan

    2005-09-01

    Here we describe 2 mutations in growth and differentiation factor 5 (GDF5) that alter receptor-binding affinities. They cause brachydactyly type A2 (L441P) and symphalangism (R438L), conditions previously associated with mutations in the GDF5 receptor bone morphogenetic protein receptor type 1b (BMPR1B) and the BMP antagonist NOGGIN, respectively. We expressed the mutant proteins in limb bud micromass culture and treated ATDC5 and C2C12 cells with recombinant GDF5. Our results indicated that the L441P mutant is almost inactive. The R438L mutant, in contrast, showed increased biological activity when compared with WT GDF5. Biosensor interaction analyses revealed loss of binding to BMPR1A and BMPR1B ectodomains for the L441P mutant, whereas the R438L mutant showed normal binding to BMPR1B but increased binding to BMPR1A, the receptor normally activated by BMP2. The binding to NOGGIN was normal for both mutants. Thus, the brachydactyly type A2 phenotype (L441P) is caused by inhibition of the ligand-receptor interaction, whereas the symphalangism phenotype (R438L) is caused by a loss of receptor-binding specificity, resulting in a gain of function by the acquisition of BMP2-like properties. The presented experiments have identified some of the main determinants of GDF5 receptor-binding specificity in vivo and open new prospects for generating antagonists and superagonists of GDF5. PMID:16127465

  17. Age Related Changes in Craniofacial Morphology in GDF-8 (Myostatin) Deficient Mice

    PubMed Central

    Vecchione, Lisa; Miller, Jeffrey; Byron, Craig; Cooper, Gregory M.; Barbano, Timothy; Cray, James; Losee, Joseph E.; Hamrick, Mark W.; Sciote, James J.; Mooney, Mark P.

    2011-01-01

    It is well recognized that masticatory muscle function helps determine morphology, although the extent of function on final form is still debated. GDF-8 (myostatin), a transcription factor is a negative regulator of skeletal muscle growth. A recent study has shown that mice homozygous for the myostatin mutation had increased muscle mass and craniofacial dysmorphology in adulthood. However, it is unclear whether such dysmorphology is present at birth. This study examines the onset and relationship between hypermuscularity and craniofacial morphology in neonatal and adult mice with GDF-8 deficiency. Fifteen (8 wild-type and 7 GDF-8 −/−), 1 day old and 16 (9 wt and 7 GDF-8 −/−), 180 day old male CD-1 mice were used. Standardized radiographs were taken of each head, scanned, traced, and cephalometric landmarks identified. Significant mean differences were assessed using a group × age, two-way ANOVA. Myostatin-deficient mice had significantly (p<0.01) smaller body and masseter muscle weights and craniofacial skeletons at 1 day of age and significantly greater body and masseter muscle weights at 180 days of age compared to controls. Myostatin-deficient mice showed significantly (p<0.001) longer and “rocker-shaped” mandibles and shorter and wider crania compared to controls at 180 days. Significant correlations were noted between masseter muscle weight and all cephalometric measurements in 180 day old Myostatin-deficient mice. Results suggest in this mouse model, there may be both early systemic skeletal growth deficiencies and later compensatory changes from hypermuscularity. These findings reiterate the role that masticatory muscle function plays on the ontogeny of the cranial vault, base, and most notably the mandible. PMID:19899116

  18. Freeze-Dried Tendon Allografts as Tissue Engineering Scaffolds for Gdf5 Gene Delivery

    PubMed Central

    Basile, Patrick; Dadali, Tulin; Jacobson, Justin; Hasslund, Sys; Ulrich-Vinther, Michael; Søballe, Kjeld; Nishio, Yasuhiko; Drissi, M Hicham; Langstein, Howard N; Mitten, David J; O’Keefe, Regis J; Schwarz, Edward M; Awad, Hani A

    2009-01-01

    Tendon reconstruction using grafts often results in adhesions that limit joint flexion. These adhesions are precipitated by inflammation, fibrosis, and paucity of tendon differentiation signals during healing. To study this problem, we developed a mouse model in which the FDL tendon is reconstructed using a live autograft or a freeze-dried allograft and identified Gdf5 as a therapeutic target. Here we investigate the potential of rAAV-Gdf5 coated freeze-dried tendon allografts as “therapeutically-endowed” tissue engineering scaffolds to reduce adhesions. In reporter gene studies we demonstrate that rAAV-coated tendon allografts mediate efficient transduction of adjacent soft tissues, with expression peaking at 7-days. We also demonstrate that rAAV-Gdf5 vector significantly accelerates wound healing in an in vitro fibroblast scratch model, and when loaded onto freeze-dried FDL tendon allografts significantly improves the metatarsophalangeal joint flexion compared to rAAV-lacZ controls. Collectively, our data demonstrate the feasibility and efficacy of therapeutic tendon allograft processing as a novel paradigm in tissue engineering to address difficult clinical problems such as tendon adhesions. PMID:18180771

  19. GDF6, a Novel Locus for a Spectrum of Ocular Developmental Anomalies

    PubMed Central

    Asai-Coakwell, Mika ; French, Curtis R. ; Berry, Karyn M. ; Ye, Ming ; Koss, Ron ; Somerville, Martin ; Mueller, Rosemary ; van Heyningen, Veronica ; Waskiewicz, Andrew J. ; Lehmann, Ordan J. 

    2007-01-01

    Colobomata represent visually impairing ocular closure defects that are associated with a diverse range of developmental anomalies. Characterization of a chromosome 8q21.2-q22.1 segmental deletion in a patient with chorioretinal coloboma revealed elements of nonallelic homologous recombination and nonhomologous end joining. This genomic architecture extends the range of chromosomal rearrangements associated with human disease and indicates that a broader spectrum of human chromosomal rearrangements may use coupled homologous and nonhomologous mechanisms. We also demonstrate that the segmental deletion encompasses GDF6, encoding a member of the bone-morphogenetic protein family, and that inhibition of gdf6a in a model organism accurately recapitulates the proband’s phenotype. The spectrum of disorders generated by morpholino inhibition and the more severe defects (microphthalmia and anophthalmia) observed at higher doses illustrate the key role of GDF6 in ocular development. These results underscore the value of integrated clinical and molecular investigation of patients with chromosomal anomalies. PMID:17236135

  20. Structures and sequence stratigraphy of the Miocene successions, southwestern Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Abd El Naby, Ahmed; Abdel-Rahman, Ahmed; Abd El-Aal, Mohamed; Alhamshry, Asmaa

    2016-05-01

    The subsurface structural evolution, facies changes and sequence stratigraphic interpretations of the Miocene successions of the southwestern part of the Gulf of Suez, Egypt, were studied by seismic reflection data of Twenty seven 3D seismic sections supported by the composite, velocity and vertical seismic profiles (VSP) logs of eight wells. Among them five sections and two geoseismic cross sections were selected to reveal the structural framework and depositional history of the study area. The analysis of depth-structure contour maps revealed that the Miocene strata are dissected by two major faults trends: The NW-SE trending faults (Clysmic trend) and the NE-SW trending cross faults running nearly perpendicular to the Clysmic faults. The facies changes of the syn-depositional Miocene units are controlled by the structural framework of the southern part of the Gulf of Suez being evolving diapiric structure of South Gharib Formation. The Miocene units are subdivided into two major 3rd order depositional sequences: S1 and S2.

  1. 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.

  2. 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.

  3. [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. PMID:12555606

  4. Crustal and uppermost mantle structure beneath the continental rifting area of the Gulf of Suez from earthquake tomography

    NASA Astrophysics Data System (ADS)

    El Khrepy, Sami; Koulakov, Ivan; Al-Arifi, Nassir

    2016-02-01

    Suez rift is one of the active seismic zones in the northward continuation of the Red Sea, as indicated by recent earthquake records from the Egyptian National Seismological Network (ENSN). We present a new model of P and S wave velocities in the crust and uppermost mantle beneath the Gulf of Suez and surrounding areas, including the northern portion of the Red Sea. Using the records from 94 seismic stations, we analyzed ~ 66,000 P and ~ 17,000 S wave arrival times from 9700 events. The travel time tomography inversion was performed using the iterative LOTOS code. The spatial resolutions of the derived models were assessed using several synthetic tests. The most prominent anomaly is a sharp high-velocity anomaly beneath the Red Sea, which is observed in both the P and S models at all depth intervals. We interpret this anomaly to be oceanic crust that was formed through extension associated with a dispersed system of spreading centers. Beneath the Gulf of Suez, the upper and middle crusts appear to be strongly heterogeneous and are dominated by low-velocity anomalies, indicative of the continental nature of the crusts. In contrast, at a depth of 30 km, we observe a prominent high-velocity anomaly along Gulf of Suez, which is interpreted to be the result of crustal thinning associated with extension between the Sinai block and the African Plate. The thickness of the crust beneath the rift is estimated to be approximately 25 km, whereas that in the surrounding areas appears to be 30-35 km. In the northwestern part of the area, we observe a low-velocity zone in the middle and lower crusts that coincide with intense seismicity and a well-developed system of recent faults on the surface. This region may mark a possible area of northward propagation of the Suez Rift zone.

  5. GDF-15 inhibits integrin activation and mouse neutrophil recruitment through the ALK-5/TGF-βRII heterodimer.

    PubMed

    Artz, Annette; Butz, Stefan; Vestweber, Dietmar

    2016-07-28

    Growth differentiation factor 15 (GDF-15) is the first cytokine known to counteract chemokine-induced activation of leukocyte integrins. We showed recently that this activity dampens neutrophil recruitment into inflamed tissue and is required for survival of myocardial infarction in mice. The receptor responsible for this GDF-15-triggered anti-inflammatory mechanism on myeloid cells is not known. Here, we identify this receptor as transforming growth factor β receptor I (TGF-βRI) (activin receptor-like kinase 5 [ALK-5]) and TGF-β receptor II (TGF-βRII). We show that interference with these receptors by small-molecule inhibitors, antibodies, or small interfering RNA, blocked the GDF-15 effect on leukocyte integrin activation. Likewise, gene inactivation of each of the 2 receptors in neutrophils isolated from conditional gene-deficient mice abolished the inhibitory effect of GDF-15 on CXCL1-induced β2-integrin activation and neutrophil diapedesis. Rapid neutrophil arrest induced by CXCL1 in vivo was inhibited by GDF-15 in an ALK-5 and TGF-βRII dependent way. As for GDF-15 gene-deficient mice, we found that extravasation of neutrophils deficient for ALK-5 or TGF-βRII was strongly increased in the interleukin-1β inflamed cremaster. The inhibitory effects of GDF-15 on neutrophil integrin activation and in vivo neutrophil arrest were also found for TGF-β1. Mechanistically, GDF-15 and TGF-β1 interfered with integrin activation by inhibiting the activation of Ras-related protein 1 (Rap-1), an effect that depended on CalDAG- guanine nucleotide exchange factor 1 (GEF1) and cell division control protein 42 homolog. We conclude that both GDF-15 and TGF-β1 counteract chemokine-induced integrin activation on neutrophils via the ALK-5/TGF-βRII heterodimer. This represents a novel, rapid anti-inflammatory activity of the 2 TGF-β receptors and of TGF-β1. PMID:27235139

  6. 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

  7. 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

    2015-02-01

    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

  8. Oligocene lacustrine tuff facies, Abu Treifeya, Cairo-Suez Road, Egypt

    NASA Astrophysics Data System (ADS)

    Abdel-Motelib, Ali; Kabesh, Mona; El Manawi, Abdel Hamid; Said, Amir

    2015-02-01

    Field investigations in the Abu Treifeya area, Cairo-Suez District, revealed the presence of Oligocene lacustrine volcaniclastic deposits of lacustrine sequences associated with an Oligocene rift regime. The present study represents a new record of lacustrine zeolite deposits associated with saponite clay minerals contained within reworked clastic vitric tuffs. The different lithofacies associations of these clastic sequences are identified and described: volcaniclastic sedimentary facies represent episodic volcaniclastic reworking, redistribution and redeposition in a lacustrine environment and these deposits are subdivided into proximal and medial facies. Zeolite and smectite minerals are mainly found as authigenic crystals formed in vugs or crusts due to the reaction of volcanic glasses with saline-alkaline water or as alteration products of feldspars. The presence of abundant smectite (saponite) may be attributed to a warm climate, with alternating humid and dry conditions characterised by the existence of kaolinite. Reddish iron-rich paleosols record periods of non-deposition intercalated with the volcaniclastic tuff sequence.

  9. Geology and habitat of oil in Ras Budran field, Gulf of Suez, Egypt

    SciTech Connect

    Chowdhary, L.R.; Taha, S.

    1987-10-01

    The Ras Budran structure at the deepest mappable seismic reflector, the top of the Kareem Formation (middle Miocene), is a broad northeast-southwest-trending anticlinal feature with an anomalous strike nearly at right angles to the main Gulf of Suez trend. Oil is produced from three units of Nubian Formation sandstone from a depth of 11,000-12,000 ft (3352-3657 m). The lower unit of Paleozoic age averages 10% porosity and has up to 200 md in-situ permeability. Wells completed in this unit produce up to 2000 BOPD. In contrast, the sands to the upper two units of the Early Cretaceous have 15-20% porosity and up to 700 md permeability. Wells completed in this unit produce 6000-8000 BOPD. The Ras Budran structure was formed primarily during an intra-Rudeis tectonic phase (lower Miocene). Oil migration for accumulation in the structure started in the late Miocene or Pliocene when the Santonian Brown Limestone and the Eocene Thebes Formation, the main source beds in the Gulf of Suez, reached the threshold of oil generation at a burial depth of approximately 10,000 ft (3048 m). At this depth, the organic matter in the source beds had a high transformation ratio (0.10 to 0.15), high yields of C/sub 15+/ soluble organic matter and C/sub 15+/ saturated hydrocarbons, vitrinite reflectance (R/sub 0/) of 0.62%, and a time-temperature index (TTI) value of 15. Oil migration from mature source beds in adjoining lows into low-potential Nubian reservoirs is easily explained by fault planes that acted as conduits for oil migration. 16 figures, 3 tables.

  10. The role of growth/differentiation factor 5 (GDF5) in the induction and survival of midbrain dopaminergic neurones: relevance to Parkinson's disease treatment.

    PubMed

    Sullivan, Aideen M; O'Keeffe, Gerard W

    2005-09-01

    Growth/differentiation factor-5 (GDF5) is a member of the transforming growth factor-beta superfamily which has potent effects on dopaminergic neurones in vitro and in vivo. GDF5 is under investigation as a potential therapeutic agent for Parkinson's disease (PD), which is caused by the progressive degeneration of dopaminergic neurones projecting from the substantia nigra (SN) to the striatum. In the rat ventral mesencephalon (VM; the developing SN), GDF5 expression peaks at embryonic day 14, the time at which dopaminergic neurones undergo terminal differentiation. Addition of GDF5 protein to cultures of embryonic rat VM increases the survival and improves the morphology of dopaminergic neurones in these cultures. GDF5 treatment also increases the number of cells which adopt a dopaminergic phenotype in cultures of VM progenitor cells. Intracerebral administration of GDF5 has potent neuroprotective and restorative effects on the nigrostriatal pathway in animal models of PD. Furthermore, addition of GDF5 protein to embryonic rat dopaminergic neuronal transplants improves their survival and function in a rat model of PD. Thus, GDF5 has potential applications to PD therapy as a dopaminergic neuroprotective agent and as a factor that may induce a dopaminergic neuronal fate in unrestricted progenitor cells. PMID:16185246

  11. Stokes emission in GdF3:Nd3+ nanoparticles for bioimaging probes

    NASA Astrophysics Data System (ADS)

    Pokhrel, M.; Mimun, L. C.; Yust, B.; Kumar, G. A.; Dhanale, A.; Tang, L.; Sardar, D. K.

    2014-01-01

    There is increasing interest in rare earth (RE) doped nanoparticles (NPs) due to their sharp absorption and photoluminescence (PL) in the near infrared (NIR) spectral region. These NIR based nanoparticles (NPs) could allow biological imaging at substantial depths with enhanced contrast and high spatial resolution due to the absence of auto fluorescence in biological samples under infrared excitation. Here, we present the highly efficient infrared photoluminescence in GdF3:Nd3+ nanoparticles under 800 nm excitation within the hydrodynamic size limitations for bio-applications. The downconversion (Stokes emission) absolute quantum yields (QY) in powder, polymaleic anhydride-alt-1-octadicene (PMAO) coated powder and colloidal solutions have been investigated. QY measurements have revealed that downconversion (Stokes emission) QYs of approximately 5 +/- 2 nm sized GdF3:1% Nd3+ colloidal NPs are 2000 times higher than those of efficient upconversion (UC) particles NaYF4:20% Er/2% Yb of the same size. Furthermore, the utility of these NIR emitting nanoparticles for bioimaging probes has been demonstrated by confocal imaging and spectroscopic study.There is increasing interest in rare earth (RE) doped nanoparticles (NPs) due to their sharp absorption and photoluminescence (PL) in the near infrared (NIR) spectral region. These NIR based nanoparticles (NPs) could allow biological imaging at substantial depths with enhanced contrast and high spatial resolution due to the absence of auto fluorescence in biological samples under infrared excitation. Here, we present the highly efficient infrared photoluminescence in GdF3:Nd3+ nanoparticles under 800 nm excitation within the hydrodynamic size limitations for bio-applications. The downconversion (Stokes emission) absolute quantum yields (QY) in powder, polymaleic anhydride-alt-1-octadicene (PMAO) coated powder and colloidal solutions have been investigated. QY measurements have revealed that downconversion (Stokes emission) QYs

  12. Tendon tissue engineering: Adipose 1 derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems

    PubMed Central

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

    2011-01-01

    Tendon tissue engineering with a biomaterial scaffold that mimics the tendon extracellular matrix (ECM) and is biomechanically suitable 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 stromal cells (ADSCs) that were cultured on poly(DL-lactide-co-glycolide) PLAGA fiber scaffold and compared to 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 7 – 8 fold at 1 week with GDF-5 treatment when cultured on 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 4 fold starting at 1 week on treatment with 100ng/mL 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 PLAGA fiber scaffold to produce a soft, collagenous musculoskeletal tissue that fulfills the need for tendon regeneration. PMID:21436509

  13. Characterization of oocyte-expressed GDF9 gene in buffalo and mapping of its TSS and putative regulatory elements.

    PubMed

    Roy, B; Rajput, S; Raghav, S; Kumar, P; Verma, A; Jain, A; Jain, T; Singh, D; De, S; Goswami, S L; Datta, T K

    2013-05-01

    Summary In spite of emerging evidence about the vital role of GDF9 in determination of oocyte competence, there is insufficient information about its regulation of oocyte-specific expression, particularly in livestock animals. Because of the distinct prominence of buffalo as a dairy animal, the present study was undertaken to isolate and characterize GDF9 cDNA using orthologous primers based on the bovine GDF9 sequence. GDF9 transcripts were found to be expressed in oocytes irrespective of their follicular origin, and shared a single transcription start site (TSS) at -57 base pairs (bp) upstream of ATG. Assignment of the TSS is consistent with the presence of a TATA element at -23 of the TSS mapped in this study. Localization of a buffalo-specific minimal promoter within 320 bp upstream of ATG was consolidated by identification of an E-box element at -113bp. Presence of putative transcription factor binding sites and other cis regulatory elements were analyzed at ~5 kb upstream of TSS. Various germ cell-specific cis-acting regulatory elements (BNCF, BRNF, NR2F, SORY, Foxh1, OCT1, LHXF etc.) have been identified in the 5' flanking region of the buffalo GDF9 gene, including NOBOX DNA binding elements and consensuses E-boxes (CANNTG). Presence of two conserved E-boxes found on buffalo sequence at -520 and -718 positions deserves attention in view of its sequence deviation from other species. Two NOBOX binding elements (NBE) were detected at the -3471 and -203 positions. The fall of the NBE within the putative minimal promoter territory of buffalo GDF9 and its unique non-core binding sequence could have a possible role in the control of the core promoter activity. PMID:22230197

  14. 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. PMID:27388285

  15. Serum Levels of Human MIC-1/GDF15 Vary in a Diurnal Pattern, Do Not Display a Profile Suggestive of a Satiety Factor and Are Related to BMI.

    PubMed

    Tsai, Vicky Wang-Wei; Macia, Laurence; Feinle-Bisset, Christine; Manandhar, Rakesh; Astrup, Arne; Raben, Anne; Lorenzen, Janne Kunchel; Schmidt, Peter T; Wiklund, Fredrik; Pedersen, Nancy L; Campbell, Lesley; Kriketos, Adamandia; Xu, Aimin; Pengcheng, Zhou; Jia, Weiping; Curmi, Paul M G; Angstmann, Christopher N; Lee-Ng, Ka Ki Michelle; Zhang, Hong Ping; Marquis, Christopher P; Husaini, Yasmin; Beglinger, Christoph; Lin, Shu; Herzog, Herbert; Brown, David A; Sainsbury, Amanda; Breit, Samuel N

    2015-01-01

    The TGF-b superfamily cytokine MIC-1/GDF15 circulates in the blood of healthy humans. Its levels rise substantially in cancer and other diseases and this may sometimes lead to development of an anorexia/cachexia syndrome. This is mediated by a direct action of MIC-1/GDF15 on feeding centres in the hypothalamus and brainstem. More recent studies in germline gene deleted mice also suggest that this cytokine may play a role in physiological regulation of energy homeostasis. To further characterize the role of MIC-1/GDF15 in physiological regulation of energy homeostasis in man, we have examined diurnal and food associated variation in serum levels and whether variation in circulating levels relate to BMI in human monozygotic twin pairs. We found that the within twin pair differences in serum MIC-1/GDF15 levels were significantly correlated with within twin pair differences in BMI, suggesting a role for MIC-1/GDF15 in the regulation of energy balance in man. MIC-1/GDF15 serum levels altered slightly in response to a meal, but comparison with variation its serum levels over a 24 hour period suggested that these changes are likely to be due to bimodal diurnal variation which can alter serum MIC-1/GDF15 levels by about plus or minus 10% from the mesor. The lack of a rapid and substantial postprandial increase in MIC-1/GDF15 serum levels suggests that MIC1/GDF15 is unlikely to act as a satiety factor. Taken together, our findings suggest that MIC-1/GDF15 may be a physiological regulator of energy homeostasis in man, most probably due to actions on long-term regulation of energy homeostasis. PMID:26207898

  16. 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. PMID:26587008

  17. The Barrett-associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk.

    PubMed

    Becker, Jessica; May, Andrea; Gerges, Christian; Anders, Mario; Schmidt, Claudia; Veits, Lothar; Noder, Tania; Mayershofer, Rupert; Kreuser, Nicole; Manner, Hendrik; Venerito, Marino; Hofer, Jan-Hinnerk; Lyros, Orestis; Ahlbrand, Constantin J; Arras, Michael; Hofer, Sebastian; Heinrichs, Sophie K M; Weise, Katharina; Hess, Timo; Böhmer, Anne C; Kosiol, Nils; Kiesslich, Ralf; Izbicki, Jakob R; Hölscher, Arnulf H; Bollschweiler, Elfriede; Malfertheiner, Peter; Lang, Hauke; Moehler, Markus; Lorenz, Dietmar; Ott, Katja; Schmidt, Thomas; Nöthen, Markus M; Hackelsberger, Andreas; Schumacher, Brigitte; Pech, Oliver; Vashist, Yogesh; Vieth, Michael; Weismüller, Josef; Knapp, Michael; Neuhaus, Horst; Rösch, Thomas; Ell, Christian; Gockel, Ines; Schumacher, Johannes

    2016-05-01

    Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) represent two stages within the esophagitis-metaplasia-dysplasia-adenocarcinoma sequence. Previously genetic risk factors have been identified that confer risk to BE and EAC development. However, to which extent the genetic variants confer risk to different stages of the BE/EAC sequence remains mainly unknown. In this study we analyzed three most recently identified BE variants at the genes GDF7 (rs3072), TBX5 (rs2701108), and ALDH1A2 (rs3784262) separately in BE and EAC samples in order to determine their risk effects during BE/EAC sequence. Our data show that rs3072 at GDF7 and rs2701108 at TBX5 are also associated with EAC and conclude that both loci confer disease risk also at later stages of the BE/EAC sequence. In contrast, rs3784262 at ALDH1A2 was highly significantly associated with BE, but showed no association with EAC. Our data do not provide evidence that the ALDH1A2 locus confers equal risk in early and late stages of BE/EAC sequence. PMID:26783083

  18. 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.

  19. Geology and habitat of oil in Ras Budran field, Gulf of Suez, Egypt

    SciTech Connect

    Chowdhary, L.R.; Taha, S.

    1987-05-01

    Deminex discovered the Ras Budran oil field in 1978. Discovery well EE 85-1 was drilled in about 140 ft of water, 4 km off the Sinai coast of the Gulf of Suez. Appraisal drilling (EE 85-2, 3, and 4 wells) confirmed the presence of a major field with an estimated 700 million bbl oil in place. The field, developed from three wellhead platforms, went on production in April 1983. To date, 20 development wells have been drilled. The Ras Budran structure at the deepest mappable seismic reflector, top Kareem (middle Miocene), is a broad northeast-southwest-trending anticlinal feature striking nearly at right angles to the main Gulf of Suez trend. At pre-Miocene producing horizons, the structure is complex and consists of a northeast-dipping flank (14-15) broken into several blocks by faults and limited to the south and west by major bounding faults. Oil is produced from three units of Nubian sandstone at a depth of 11,000 to 12,000 ft. The lower unit of Paleozoic age averages 10% porosity and up to 200 md in -situ permeability. The wells completed in this unit produce up to 2000 BOPD. In contrast, the sands of the upper two units of Lower Cretaceous age have a 15-20% porosity and up to 700 md permeability. The wells completed in these units produce 6000-8000 BOPD. The Ras Budran structure was primarily formed during the intra-Rudeis tectonic phase (lower Miocene). Migration of oil for accumulation in Ras Budran started late in the upper Miocene or Pliocene when the Santonian Brown Limestone and the Eocene Thebes Formation, the main source beds in the Gulf, reached the threshold of oil generation at a burial depth of about 10,000 ft (3000 m). At these depths, the organic matter in the source beds have a transformation ratio (0.10 to 0.15), increased yields of C15 + soluble organic matter and C15 + saturated hydrocarbons, a vitrinite reflectance of 0.62%, and a TTI value of 15.

  20. 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. PMID:21887500

  1. GDF15 regulates Kv2.1-mediated outward K+ current through the Akt/mTOR signalling pathway in rat cerebellar granule cells

    PubMed Central

    Wang, Chang-Ying; Huang, An-Qi; Zhou, Meng-Hua; Mei, Yan-Ai

    2014-01-01

    GDF15 (growth/differentiation factor 15), a novel member of the TGFβ (transforming growth factor β) superfamily, plays critical roles in the central and peripheral nervous systems, but the signal transduction pathways and receptor subtypes involved are not well understood. In the present paper, we report that GDF15 specifically increases the IK (delayed-rectifier outward K+ current) in rat CGNs (cerebellar granule neurons) in time- and concentration-dependent manners. The GDF15-induced amplification of the IK is mediated by the increased expression and reduced lysosome-dependent degradation of the Kv2.1 protein, the main α-subunit of the IK channel. Exposure of CGNs to GDF15 markedly induced the phosphorylation of ERK (extracellular-signal-regulated kinase), Akt and mTOR (mammalian target of rapamycin), but the GDF15-induced IK densities and increased expression of Kv2.1 were attenuated only by Akt and mTOR, and not ERK, inhibitors. Pharmacological inhibition of the Src-mediated phosphorylation of TGFβR2 (TGFβ receptor 2), not TGFβR1, abrogated the effect of GDF15 on IK amplification and Kv2.1 induction. Immunoprecipitation assays showed that GDF15 increased the tyrosine phosphorylation of TGFβRII in the CGN lysate. The results of the present study reveal a novel regulation of Kv2.1 by GDF15 mediated through the TGFβRII-activated Akt/mTOR pathway, which is a previously uncharacterized Smad-independent mechanism of GDF15 signalling. PMID:24597762

  2. 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

  3. Timing of structural development of oil traps in Gulf of Suez, Egypt

    SciTech Connect

    Chowdhary, L.R.; Shaheen, S.

    1988-01-01

    To date, more than 40 oil fields with an estimated 25billion bbl of oil in place have been discovered in the Gulf of Suez, Egypt. These oil accumulations are present both in the pre-graben and graben-fill cycles which are separated by Oligocene tectonic phase, hitherto considered to be responsible for differentiation and formation of oil traps. In the present study, the structural development of many oil traps is related to intra-Rudeis tectonic phase of late early Miocene age. Presence of an a

  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. Facies and sequence stratigraphy of some Miocene sediments in the Cairo-Suez District, Egypt

    NASA Astrophysics Data System (ADS)

    Tawfik, Mohamed; El-Sorogy, Abdelbaset; Mowafi, Ahmed; Al-Malky, Mazen

    2015-01-01

    The shallow-water siliciclastics and carbonates of the Miocene sediments in the Cairo-Suez District, Egypt represent an epiric ramp. The facies are characterized by stacked high-frequency cycles with restricted ramp to shoal margin sequences. Based on an extensive micro- and biofacies documentation, six lithofacies associations were defined and their respective depositional environments were interpreted. A sequence-stratigraphic analysis was carried out by integrating lithostratigraphic marker beds, facies relationships, stratigraphic cycles, and biostratigraphy. The investigated sections were subdivided into three third-order sequences, named S1, S2 and S3. S1, is interpreted to correspond to the Late Burdigalian stage (18-16.38 My), S2 corresponds to the Late Burdigalian-Early Langhian stage (16.38-14.78 My), and S3 represents the Late Langhain-Early Serravallian stage (14.78-13.66 My). Each of the three sequences was further subdivided into fourth order cycle sets and fifth-order cycles.

  6. Mechanical stratigraphy of sedimentary section - implications for petroleum exploration, Gulf of Suez, Egypt

    SciTech Connect

    Gawarecki, S.L.; Coffield, D.Q.; Schamel, S.

    1987-05-01

    Mechanical response of sedimentary units to extension varies, depending on their rheology. In the Gulf of Suez, knowledge of the mechanical stratigraphy assures better control for seismic interpretation, structural analysis, and delineation of possible hydrocarbon traps. Recent field studies and seismic analysis allow delineation of the structural response of a range of prerift and synrift lithologies. The prerift section is divided into three major mechanical/stratigraphic units: Precambrian basement, Nubian sandstone, and Cenomanian through Eocene shallow marine platform rocks. Single fault planes in the basement are expressed in the overlying Nubian sandstone as closely spaced parallel faults and fractures. In contrast, the inhomogeneous Late Cretaceous-Paleogene section of alternating brittle and ductile beds drapes over the underlying normal faults. The synrift section may comprise three mechanical/stratigraphic units: (1) early Miocene carbonates and clastics; (2) middle-late Miocene evaporites; and (3) Pliocene-Recent clastics. The lower synrift rocks respond to faulting much like the Cenomanian-Eocene units. The evaporite section acts as a major detachment zone, with underlying faults dying out upward. Onshore, faults in the more brittle passive cover rocks sole into the underlying evaporites. Thus, faults at the surface may be entirely decoupled from master faults in the early synrift and prerift strata. Mechanical response in the synrift section is complicated by syntectonic processes such as growth faulting, compaction, and lateral facies changes.

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

    PubMed

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

    2014-03-01

    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 Gd(3+) and Tb(3+) ions in the nanocrystals enhances the scintillation efficiency. PMID:24610960

  8. 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

  9. Hydrocarbon potential, structural setting and depositional environments of Hammam Faraun Member of the Belayim Formation, Southern Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Nabawy, Bassem S.; El Sharawy, Mohamed S.

    2015-12-01

    The Middle Miocene Belayim Formation is one of the most prolific formations in the Southern Gulf of Suez. It consists of four members; two members are evaporitic (Baba and Feiran) and the other two members are prospective, mostly clastics (Hammam Faraun and Sidri). The hydrocarbon potential and depositional environment of Hammam Faraun Member, the target of the present study, have been studied in 11 wells distributed in the southern province of the Gulf of Suez. The traditional well log data, as well as the Spectral Gamma-Ray logs 'SGR' and dipmeter data were used to evaluate the petrophysical properties and distribution of the Hammam Faraun Member in the Southern Gulf of Suez. It varies greatly in thickness with the greatest thicknesses in GS 365 (372 ft) and GS 373 (430 ft) fields in the central parts and the thinnest at the basin margins of the studied area at GH376 (65 ft) and Ras El Bahar (67.5 ft) fields. It is composed of clastic rocks, mainly shales and sometimes reef carbonates. The very good petrophysical properties of the studied sequence indicate a good reservoir in some fields with good to very good porosity (13.5 ≤ ∅ ≤ 25.0%). The shale volume of this reservoir sequence is less than 33% and the water saturation is less than 42.3%, while the net-pay thickness is up to 58 ft. The SGR and Pe logs indicate that, the studied rocks were deposited mostly in lagoonal to shallow marine environments, with illite and montmorillonite as dominant clay minerals. The dipmeter data obtained in some wells indicate slightly tilted beds, mostly less than 20° with an overall dip direction towards the SW, which represents the regional dip in the Southern Gulf of Suez. Based on dipmeter data, two major angular unconformities can be detected; one at the top of the sequence, separating it from the overlying South Gharib evaporates, and another one at the base of the sequence, separating it from the underlying Feiran Member.

  10. S100A4 influences cancer stem cell-like properties of MGC803 gastric cancer cells by regulating GDF15 expression.

    PubMed

    Guo, Junfu; Bian, Yue; Wang, Yu; Chen, Lisha; Yu, Aiwen; Sun, Xiuju

    2016-08-01

    Many studies have revealed that S100A4 is involved in cancer progression by affecting a variety of biological functions. Our previous study showed that S100A4 influences many biological properties of gastric cancer cells; however, the underlying mechanisms are far from clear. In this study, we used cDNA microarray analysis to investigate the global alterations in gene expression in MGC803 gastric cancer cells after siRNA-mediated S100A4 inhibition. Among the total genes investigated, 179 differentially expressed genes (38 upregulated and 141 downregulated) were detected in S100A4-siRNA transfected MGC803 cells compared with NC-siRNA transfected cells. We focused on the GDF15 gene, which was significantly downregulated after S100A4 inhibition. ChIP studies showed that the S100A4 protein binds to the GDF15 promoter, implicating S100A4 in GDF15 regulation at the transcriptional level. GDF15 overexpression promoted CSC-like properties of MGC803 cells, such as spheroid and soft-agar colony forming abilities. S100A4 inhibition suppressed the CSC-like properties of the cells, whereas, GV141-GDF15 vector transfection reversed these effects. Our results suggest that S100A4 influences the CSC-like properties of MGC803 gastric cancer cells by regulating GDF15 expression. PMID:27278086

  11. Combined Secretomics and Transcriptomics Revealed Cancer-Derived GDF15 is Involved in Diffuse-Type Gastric Cancer Progression and Fibroblast Activation

    PubMed Central

    Ishige, Takayuki; Nishimura, Motoi; Satoh, Mamoru; Fujimoto, Mai; Fukuyo, Masaki; Semba, Toshihisa; Kado, Sayaka; Tsuchida, Sachio; Sawai, Setsu; Matsushita, Kazuyuki; Togawa, Akira; Matsubara, Hisahiro; Kaneda, Atsushi; Nomura, Fumio

    2016-01-01

    Gastric cancer is classified into two subtypes, diffuse and intestinal. The diffuse-type gastric cancer (DGC) has poorer prognosis, and the molecular pathology is not yet fully understood. The purpose of this study was to identify functional secreted molecules involved in DGC progression. We integrated the secretomics of six gastric cancer cell lines and gene expression analysis of gastric cancer tissues with publicly available microarray data. Hierarchical clustering revealed characteristic gene expression differences between diffuse- and intestinal-types. GDF15 was selected as a functional secreted molecule owing to high expression only in fetal tissues. Protein expression of GDF15 was higher in DGC cell lines and tissues. Serum levels of GDF15 were significant higher in DGC patients as compared with healthy individuals and chronic gastritis patients, and positively correlated with wall invasion and lymph node metastasis. In addition, the stimulation of GDF15 on NIH3T3 fibroblast enhanced proliferation and up-regulated expression of extracellular matrix genes, which were similar to TGF-β stimulation. These results indicate that GDF15 contributes to fibroblast activation. In conclusion, this study revealed that GDF15 may be a novel functional secreted molecule for DGC progression, possibly having important roles for cancer progression via the affecting fibroblast function, as well as TGF-β. PMID:26892343

  12. Novel indel Mutation in the GDF5 Gene Is Associated with Brachydactyly Type C in a Four-Generation Turkish Family

    PubMed Central

    Uyguner, Z.O.; Kocaoğlu, M.; Toksoy, G.; Basaran, S.; Kayserili, H.

    2014-01-01

    Heterozygous loss-of-function mutations of GDF5 are reported to cause hypoplasia/aplasia of certain skeletal elements (brachydactyly), and heterozygous gain-of-function mutations, occurring either on the gene itself or through the loss of its inhibitor noggin, result in joint fusion (symphalangism). We present here the clinical and molecular investigation of a family with disproportionate shortness of the second and third fingers which comprises 9 variably affected members spanning 4 generations. In this study, we performed clinical and radiographical examinations of 2 patients of this family, sequencing of GDF5 and 3D protein modeling of the wildtype and mutated polypeptide to predict the structural alteration. Diagnoses were compatible with familial brachydactyly type C. GDF5 analysis revealed a novel heterozygous in-frame indel mutation (c.803_ 827del25ins25), involving the propeptide domain of GDF5 that alters the number of random coil and beta-strand structures, creating a 1-turn-helix at the mutated site. The mutation described here is the second indel reported in GDF5. The previously published homozygous indel mutation affected the TGF-beta like domain and was associated with Du Pan syndrome. The novel mutation reported here presents further allelic heterogeneity and a probable intrafamilial variable clinical expressivity of GDF5. PMID:24715855

  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. 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.

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

    PubMed Central

    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. PMID:26114631

  16. 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

  17. Estrogen Promotes the Development of Mouse Cumulus Cells in Coordination with Oocyte-Derived GDF9 and BMP15

    PubMed Central

    Sugiura, Koji; Su, You-Qiang; Li, Qinglei; Wigglesworth, Karen; Matzuk, Martin M.; Eppig, John J.

    2010-01-01

    The differentiation and function of cumulus cells depend upon oocyte-derived paracrine factors, but studies on the estrogen receptor knockout mice suggested that estrogen also participates in these processes. This study investigates the possible coordination of estrogen and oocytes in the development and function of cumulus cells using cumulus expansion and the expression of transcripts required for expansion as functional endpoints. Preantral granulosa cell-oocyte complexes developed in vitro with 17β-estradiol (E2) exhibited increased levels of cumulus expansion and Has2 transcripts, encoding hyaluronan synthase 2, compared with those developed without E2. Moreover, cumulus cell-oocyte complexes (COCs) isolated from antral follicles and maintained in culture without E2 exhibited reduced cumulus expansion and Has2 mRNA levels compared with freshly isolated COCs. Exogenous E2, provided during the maintenance culture, alleviated these deficiencies. However, when oocytes were removed from COCs, E2 supplementation did not maintain competence to undergo expansion; the presence in culture of either fully grown oocytes or recombinant growth differentiation factor 9 (GDF9) was required. Recombinant bone morphogenetic protein 15, but not fibroblast growth factor 8, augmented the GDF9 effect. Oocytes or GDF9 suppressed cumulus cell levels of Nrip1 transcripts encoding nuclear receptor-interacting protein 1, a potential inhibitor of estrogen receptor signals. Therefore, E2 and oocyte-derived paracrine factors GDF9 and bone morphogenetic protein 15 coordinate to promote the development of cumulus cells and maintain their competence to undergo expansion. Furthermore, suppression of Nrip1 expression in cumulus cells by oocyte may be one mechanism mediating cross talk between oocyte and E2 signals that promotes follicular development. PMID:21047911

  18. Association of GDF5, SMAD3 and RUNX2 polymorphisms with temporomandibular joint osteoarthritis in female Han Chinese.

    PubMed

    Xiao, J-L; Meng, J-H; Gan, Y-H; Zhou, C-Y; Ma, X-C

    2015-07-01

    Temporomandibular joint osteoarthritis (TMJOA) is a complex disease and has a strong genetic component in its pathogenesis. Experimental evidence suggests the involvement of biological pathway in the disease. This case-control study was designed to investigate whether five common single nucleotide polymorphisms (SNPs) in GDF5, SMAD3, RUNX2, TGFβ1 and CHST11, respectively, are associated with TMJOA in female Han Chinese patients. A total of 240 participants were evaluated comprising 114 female patients diagnosed with TMJOA based on Research Diagnostic Criteria for Temporomandibular Disorders and 126 healthy female controls. The SNPs of the five genes in the genomic DNA were examined by sequencing, and their allelic, genotypic and carriage rate frequency distributions, as well as the triple combination of the risk genotypes, were analysed using the logistic regression model. The SNP in GDF5 or SMAD3 showed significant association with TMJOA, a relatively weak association was observed in RUNX2. In the triple combinational analysis, the risk of TMJOA grew 5·09 times in the patients with five or six risk alleles (P < 0·01). This is the first study to evaluate the association of GDF5, SMAD3, RUNX2, TGFβ1 and CHST11 with TMJOA in female Han Chinese. Our study suggests that the SNPs of genes related to TGFβ family might contribute to the risk of TMJOA. PMID:25757091

  19. 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. PMID:21148168

  20. 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

  1. 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.

  2. 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

  3. Synthesis, modified optical properties, and energy transfer of Tb3+ doped GdF3

    NASA Astrophysics Data System (ADS)

    Cao, Chunyan; Guo, Siling; Kee Moon, Byung; Chun Choi, Byung; Hyun Jeong, Jung

    2013-08-01

    By controlling the volume of HF and the alkaline earth ion introducing, a series of GdF3 samples have been synthesized by a hydrothermal method without any surfactant. The samples are characterized by X-ray diffraction (XRD) patterns, field emission scanning electron microscopy (FE-SEM) images, energy-dispersive spectroscopy (EDS) spectra, photoluminescence (PL) excitation and emission spectra as well as the luminescence dynamic decay curves. The optical properties of Tb3+ and the energy transfer from host Gd3+ to Tb3+ have been investigated and discussed in detail based on the volume of HF used in the synthesis procedure and the alkaline earth ion introducing. The experimental results suggest that the optical properties of Tb3+ can be controlled by the deliberately ion introducing as well as the volume of HF used in the synthesis procedure. Though the optical properties of Tb3+ can be adjusted by different ways, a green, easy, and cost saving way, such as deliberately ion introducing, is a good choice in modifying the optical properties of Tb3+.

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

    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

    2016-04-01

    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

  10. 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

  11. GDF9 is Transiently Expressed in Oocytes before Follicle Formation in the Human Fetal Ovary and is Regulated by a Novel NOBOX Transcript

    PubMed Central

    Bayne, Rosemary A. L.; Kinnell, Hazel L.; Coutts, Shiona M.; He, Jing; Childs, Andrew J.; Anderson, Richard A.

    2015-01-01

    During human fetal ovary development, the process of primordial follicle formation is immediately preceded by a highly dynamic period of germ cell and somatic cell reorganisation. This is regulated by germ-cell specific transcription regulators, by the conserved RNA binding proteins DAZL and BOLL and by secreted growth factors of the TGFβ family, including activin βA: these all show changing patterns of expression preceding follicle formation. In mice, the transcription factor Nobox is essential for follicle formation and oocyte survival, and NOBOX regulates the expression of GDF9 in humans. We have therefore characterised the expression of GDF9 in relation to these known key factors during follicle formation in the human fetal ovary. mRNA levels of GDF9, BMP15 and NOBOX were quantified by qRT-PCR and showed dramatic increases across gestation. GDF9 protein expression was localised by immunohistochemistry to the same population of germ cells as those expressing activin βA prior to follicle formation but did not co-localise with either BOLL or DAZL. A novel NOBOX isoform was identified in fetal ovary that was shown to be capable of up-regulating the GDF9 promoter in reporter assays. Thus, during oogenesis in humans, oocytes go through a dynamic and very sharply demarcated sequence of changes in expression of these various proteins, even within individual germ cell nests, likely to be of major functional significance in determining selective germ cell survival at this key stage in ovarian development. Transcriptional variation may contribute to the range of age of onset of POI in women with NOBOX mutations. PMID:25790371

  12. 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.

  13. 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

    2016-01-01

    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. PMID:27394584

  14. 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.

  15. Organic tracers in sediments from the coastal zone of Ras Abu el-Darag, Gulf of Suez

    NASA Astrophysics Data System (ADS)

    Rushdi, Ahmed I.; Kassim, Tarek A. T. A.; Simoneit, Bernd R. T.

    2009-10-01

    Sediment samples from the coastal zone of the Gulf of Suez contain a variety of organic compounds from anthropogenic and natural sources. A total of 12 surface samples of bottom sediments were collected with an Ekman grab sampler along an off-shore transect south of Ras Abu el-Darag. The samples were extracted with a mixture of dichloromethane and methanol (3:1 v/v) after drying and sieving through 250 μm mesh. The extracts were derivatized and analyzed by gas chromatography-mass spectrometry in order to characterize the chemical composition and sources of the organic components. Marine with minor terrestrial biota were the major natural sources of organic tracers and included n-alkanoic acids, sterols and saccharides (5.7-76.7%). Anthropogenic sources, from petroleum related activities, detergent usage for spill cleaning and littering, are indicated by the presence of n-alkanes with carbon preference index ≤1.0, hopanes, steranes, unresolved complex mixture of branched and cyclic hydrocarbons, alkyl nitriles, alkamides and plasticizers. Their total relative concentrations ranged from 23.3 to 97.3% of the total extracts. Petroleum residues from natural seepage may also be part of these hydrocarbons. The levels of anthropogenic inputs decrease from about 94% in coastal zone sediments to about 20% in sediments from the reef front.

  16. Differential expression of GDF9, TGFB1, TGFB2 and TGFB3 in porcine oocytes isolated from follicles of different size before and after culture in vitro.

    PubMed

    Jackowska, Marta; Kempisty, Bartosz; Woźna, Magdalena; Piotrowska, Hanna; Antosik, Paweł; Zawierucha, Piotr; Bukowska, Dorota; Nowicki, Michał; Jaśkowski, Jędrzej M; Brüssow, Klaus-Peter

    2013-03-01

    The TGFB superfamily genes are involved in several important cell functions, including proliferation and differentiation, and the role of the expression of these genes in growth and development of theca and granulosa cells is well recognised. However, the dependence between the stage of oocyte maturation or follicular size and the expression of these genes in pigs is still not entirely known. This study was aimed at investigating the expression pattern of GDF9, TGFB1, TGFB2 and TGFB3 in porcine oocytes before and after in vitro maturation (IVM) as well as in oocytes collected from follicles of different sizes. RQ-PCR was performed to analyse the expression of GDF9, TGFB1, TGFB2 and TGFB3 in oocytes before and after IVM (oocytes cultured for 44 h in TCM-199), isolated from large (> 5 mm), medium (3-5 mm) and small (< 3 mm) follicles collected from ovaries of 28 puberal crossbred Landrace gilts after slaughter. We found an increased expression of both TGFB1 and TGFB2 in oocytes before IVM collected from large as compared to medium and small follicles (P < 0.05, P < 0.001, P < 0.01, P < 0.05, respectively). In these groups of oocytes we did not observe differences in GDF9 and TGFB3 mRNA levels. However, after IVM, GDF9 protein distribution in oocytes was significantly higher in large and medium follicles as compared to small ones (P < 0.01, P < 0.001, respectively). Moreover, an increased TGFB1, TGFB2 and TGFB3 proteins pattern was observed in oocytes of large compared to small follicles. The highest GDF9 and TGFB1 mRNA levels were found in oocytes after IVM compared to those before IVM. Based on our study we can suppose that the distribution pattern of TGFB superfamily genes is associated with the stage of maturation of porcine oocytes and the follicle size. Furthermore, GDF9 and TGFB1 may serve as molecular markers of the develop-mental potential of porcine oocytes. The confocal microscopic observation revealed that TGFB1 and TGFB3 were translocated between the zona

  17. 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.

  18. 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.

  19. 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

  20. 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. PMID:26620888

  1. 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

  2. Genotyping of Novel SNPs in BMPR1B, BMP15, and GDF9 Genes for Association with Prolificacy in Seven Indian Goat Breeds.

    PubMed

    Ahlawat, Sonika; Sharma, Rekha; Roy, Manoranjan; Mandakmale, Sanjay; Prakash, Ved; Tantia, M S

    2016-07-01

    Goats form the backbone of rural livelihood and financial security systems in India but their population is showing decreasing trend. Improvement of reproductive traits such as prolificacy offers a solution to stabilize the decreasing goat population and to meet the nutritional needs of growing human population. In the present study, six novel SNPs in three candidate genes for prolificacy (BMPR1B, BMP15, and GDF9) were genotyped in seven breeds of Indian goats to evaluate their association with litter size. Tetra primer ARMS-PCR and PCR-RFLP based protocols were developed for genotyping six novel SNPs, namely, T(-242)C in BMPR1B; G735A and C808G in BMP15; and C818T, A959C, and G1189A in GDF9 gene. The effect of breed was highly significant (p ≤ 0.01) on litter size but the effect of genotype was nonsignificant. The effect of parity on litter size was also significant in the prolific Black Bengal breed. The litter size differences observed between breeds are attributed to breed differences. Novel mutations observed at different loci in GDF9, BMP15, and BMPR1B genes do not contribute to the reproductive capability of the investigated breeds. Further studies with more number of breeds and animals exploring association of these novel SNPs with reproductive traits may be fruitful. PMID:27135147

  3. 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

  4. Gdf5 progenitors give rise to fibrocartilage cells that mineralize via hedgehog signaling to form the zonal enthesis.

    PubMed

    Dyment, Nathaniel A; Breidenbach, Andrew P; Schwartz, Andrea G; Russell, Ryan P; Aschbacher-Smith, Lindsey; Liu, Han; Hagiwara, Yusuke; Jiang, Rulang; Thomopoulos, Stavros; Butler, David L; Rowe, David W

    2015-09-01

    The sequence of events that leads to the formation of a functionally graded enthesis is not clearly defined. The current study demonstrates that clonal expansion of Gdf5 progenitors contributes to linear growth of the enthesis. Prior to mineralization, Col1+ cells in the enthesis appose Col2+ cells of the underlying primary cartilage. At the onset of enthesis mineralization, cells at the base of the enthesis express alkaline phosphatase, Indian hedgehog, and ColX as they mineralize. The mineralization front then extends towards the tendon midsubstance as cells above the front become encapsulated in mineralized fibrocartilage over time. The hedgehog (Hh) pathway regulates this process, as Hh-responsive Gli1+ cells within the developing enthesis mature from unmineralized to mineralized fibrochondrocytes in response to activated signaling. Hh signaling is required for mineralization, as tissue-specific deletion of its obligate transducer Smoothened in the developing tendon and enthesis cells leads to significant reductions in the apposition of mineralized fibrocartilage. Together, these findings provide a spatiotemporal map of events - from expansion of the embryonic progenitor pool to synthesis of the collagen template and finally mineralization of this template - that leads to the formation of the mature zonal enthesis. These results can inform future tendon-to-bone repair strategies to create a mechanically functional enthesis in which tendon collagen fibers are anchored to bone through mineralized fibrocartilage. PMID:26141957

  5. Feed restriction as a biostimulant of the production of oocyte, their quality and GDF-9 gene expression in rabbit oocytes.

    PubMed

    Daoud, Niveen M; Mahrous, Karima F; Ezzo, Omaima H

    2012-12-01

    The use of short-term feed restriction (R) without or with subsequent refeeding (F) as biostimulant of rabbit fertility was examined in this study. A total of 40 mature, non-pregnant, non-lactating New Zealand white female rabbits were allocated to five treatments. The rabbits were individually caged and fed a complete pelleted diet (16.7% CP; 13.1 CF; 2490kcalDE/kg). Rabbits on the control (C) treatment received 150g/d of the diet. Two groups of 8 rabbits received 70% of the control daily feed intake (105g/d; moderate restriction; M) and the other two groups received 50% of the control feed intake (75g/d; severe restriction; S) for 21d. At the end of this period, one group each of M and S fed rabbits were slaughtered for oocyte recovery. Rabbits in the remaining three groups (C, MF and SF) were retained for a further 8d before slaughter and fed the control level of the diet during this period. The effects on body weight, oocyte number and quality, GDF-9 gene expression in oocytes, and changes in serum levels of leptin and IGF-1 were recorded. Initial mean body weights were not significantly different ranging from 2.50±0.33kg (S) to 2.58±0.24kg (C). After 3wk on treatment the C rabbits were significantly heavier (2.65±0.32kg; P<0.05) than rabbits on the M (2.26±0.33kg) or S (2.10±0.33kg) treatments. Following 8d of refeeding, the remaining group of S treated rabbits (SF) were still significantly lighter (2.40±0.21kg; P<0.05) than C (2.71±0.31kg) with MF rabbits having an intermediate weight (2.50±0.20kg). The number of mature grade A oocytes recovered per ovary was significantly lower for control (3.3±0.35) than the refed treatments (MF 4.0±0.30; SF 4.5±0.39; P<0.05). Semi-quantitative PCR analysis of GDF-9 expression showed that control mature grade A oocytes had significantly lower levels of expression (1.27±0.20; P<0.05) than those of refed rabbits (MF 1.60±0.10; SF 1.39±0.01). Leptin and IGF-1 values for refed rabbits were significantly higher (P

  6. Purification, crystallization and preliminary data analysis of the ligand–receptor complex of the growth and differentiation factor 5 variant R57A (GDF5R57A) and BMP receptor IA (BRIA)

    PubMed Central

    Nickel, Joachim; Kotzsch, Alexander; Sebald, Walter; Mueller, Thomas D.

    2011-01-01

    The binary ligand–receptor complex of human growth and differentiation factor 5 (GDF5) bound to its type I receptor BMP receptor IA (BRIA) was prepared and crystallized. By utilizing the GDF5 variant R57A, which exhibits a high affinity in the subnanomolar range for BRIA, the binary complex of GDF5R57A bound to the extracellular domain of BRIA could be produced and purified. Crystals of this complex belonged to a monoclinic space group: either I2, with unit-cell parameters a = 63.81, b = 62.85, c = 124.99 Å, β = 95.9°, or C2, with unit-cell parameters a = 132.17, b = 62.78, c = 63.53 Å, β = 112.8°. PMID:21543859

  7. 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.

  8. 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. PMID:24783778

  9. 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

  10. 77 FR 1690 - Granting of Request for Early Termination of the Waiting Period Under the Premerger Notification...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... Corporation 20120214 G Quantum (Choctaw) Utility Investments I, LLC; GDF SUEZ S.A.; Quantum (Choctaw) Utility... V LP 12/22/2011 20120307 G Raytheon Company; Henggeler Computer Consultants, Inc.; Raytheon...

  11. 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

  12. Oocytes lacking O-glycans alter follicle development and increase fertility by increasing follicle FSH sensitivity, decreasing apoptosis, and modifying GDF9:BMP15 expression.

    PubMed

    Grasa, Patricia; Ploutarchou, Panayiota; Williams, Suzannah A

    2015-02-01

    The number of eggs ovulated varies within and between species and is influenced by many variables. However, the regulatory mechanisms remain poorly understood. We previously demonstrated a key role for the oocyte because mice generating oocytes deficient in core 1-derived O-glycans ovulate ∼40-50% more eggs than Controls. Here we analyze the basis of this phenotype using Mutant [core 1 β1,3-galactosyltransferase 1 (C1galt1)(FF):zona pellucida glycoprotein 3 Cre (ZP3Cre)] and Control (C1galt1(FF)) female mice. In culture, Mutant follicles exhibited delayed antrum formation [indicative of follicle stimulant hormone (FSH) dependence] and increased sensitivity to FSH. Although the Mutant estrous cycle was extended, comprehensive endocrine changes were not observed; rather FSH, LH, inhibin B, and anti-Mullerian hormone were temporally altered, revealing estrous cycle stage-specific modifications to the hypothalamic-pituitary-gonadal axis. At proestrus, when FSH levels were decreased in Mutants, ovaries contained more, smaller, preantral follicles. Mutant follicles exhibited reduced levels of apoptosis, and both B-cell lymphoma 2 (Bcl-2) and BCL-2-associated X protein (Bax) were altered compared with Controls. Mutant ovaries also had an increase in the expression ratio of growth differentiation factor 9 (GDF9):bone morphogenetic protein 15 (BMP15) at diestrus. On the basis of these data, we propose that modified oocyte glycoproteins alter GDF9:BMP15 expression modifying follicle development resulting in the generation of more follicles. Thus, the oocyte is a key regulator of follicle development and has a crucial role in determining ovulation rate. PMID:25416550

  13. 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.

  14. 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

  15. Geophysical Constraints on the Hydrogeologic and Structural Settings of the Gulf of Suez Rift-Related Basins: Case Study from the El Qaa Plain, Sinai, Egypt

    NASA Astrophysics Data System (ADS)

    Ahmed, Mohamed; Sauck, William; Sultan, Mohamed; Yan, Eugene; Soliman, Farouk; Rashed, Mohamed

    2013-11-01

    Groundwater has been identified as one of the major freshwater sources that can potentially meet the growing demands of Egypt's population. Gravity data (from 381 ground gravity stations) were collected, processed, and analyzed together with the available aeromagnetic (800 line-km) data to investigate the hydrogeologic and structural settings, areal distribution, geometry, and water storage of the aquifers in El Qaa coastal plain in the southwest Sinai Peninsula, and to assess their longevity given projected extraction rates. Findings include (1) complete Bouguer anomaly and total magnetic intensity maps show two connected sub-basins separated by a narrow saddle with an average basin length of 43 km and an average width of 12 km; (2) two-dimensional modeling of both gravity and magnetic data indicates basin fill with a maximum thickness of 3.5 km; (3) using anomalous residual gravity, the volume of water in storage was estimated at 40-56 km3; and (4) progressive increases in extraction rates over time will deplete up to 40 % of the aquifers' volume in 200-230 years and will cause the water quality to deteriorate due to seawater intrusion in 45 years. Similar geophysical exploration campaigns, if conducted over the entire coastal plains of the Red Sea and the Gulfs of Suez and Aqaba, could assist in the development of sound and sustainable management schemes for the freshwater resources in these areas. The adopted techniques could pave the way toward the establishment of sustainable utilization schemes for a much larger suite of similar aquifers worldwide.

  16. Infrared study of lattice dynamics and spin-phonon and electron-phonon interactions in multiferroic TbF e3(BO3) 4 and GdF e3(BO3) 4

    NASA Astrophysics Data System (ADS)

    Klimin, S. A.; Kuzmenko, A. B.; Kashchenko, M. A.; Popova, M. N.

    2016-02-01

    We present a comparative far-infrared reflection spectroscopy study of phonons, phase transitions, spin-phonon, and electron-phonon interactions in isostructural multiferroic iron borates of gadolinium and terbium. The behavior of phonon modes registered in a wide temperature range is consistent with a weak first-order structural phase transition [Ts=143 for GdF e3(BO3) 4 and 200 K for TbF e3(BO3) 4 ] from a high-symmetry high-temperature R 32 structure into a low-symmetry low-temperature P 3121 one. The temperature dependences of frequencies, oscillator strengths, and damping constants of some low-frequency modes reveal an appreciable lattice anharmonicity. Peculiarities in the phonon mode behavior in both compounds at the temperature of an antiferromagnetic ordering [TN=32 K for GdF e3(BO3) 4 and 40 K for TbF e3(BO3) 4 ] evidence the spin-phonon interaction. In the energy range of phonons, GdF e3(BO3) 4 has no electronic levels, but TbF e3(BO3) 4 possesses several. We observe an onset of new bands in the excitation spectrum of TbF e3(BO3) 4 due to a resonance interaction between a lattice phonon and 4 f electronic crystal-field (CF) excitations of T b3 + . This interaction causes delocalization of the CF excitations, their Davydov splitting, and formation of coupled electron-phonon modes.

  17. 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. PMID:19347364

  18. 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

  19. 77 FR 56210 - Granting of Request for Early Termination of the Waiting Period Under the Premerger Notification...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-12

    ... Management LLC; KRG Capital Fund IV, L.P. 20121238 G ArcLight Energy Partners Fund V, L.P.; Manulife... 08/01/2012 20120945 G Technip S.A.; The Shaw Group Inc.; Technip S.A. 20121154 G DTE Energy Company; GDF Suez S.A.; DTE Energy Company. 20121155 G DTE Energy Company; Duke Energy Corporation; DTE...

  20. 78 FR 7424 - Combined Notice of Filings #1

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-01

    .... Comments Due: 5 p.m. ET 2/15/13. Docket Numbers: ER13-798-000. Applicants: GDF SUEZ Energy Marketing NA... accessible in the Commission's eLibrary system by clicking on the links or querying the docket number....

  1. 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.

  2. 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.

  3. 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…

  4. Modelisation des systemes geothermiques a boucles horizontales pour chauffer les batiments et prevenir la fonte du pergelisol

    NASA Astrophysics Data System (ADS)

    Fontaine, Pier-Olivier

    2011-12-01

    In northern regions, due to climate change, the increase in the annual mean air temperature increases the depth at which the permanently frozen ground (permafrost) is located. This melting causes soil instability and therefore, the instability of the buildings and transport structures above it. These regions are highly dependent on fossil fuels as a large quantity is used to heat buildings and generate electricity. A solution to these problems is presented in this memoir. It involves using a heat exchanger coupled to a horizontal geothermal heat pump for both heating a building and maintaining the integrity of the permafrost beneath it. A new analytical model for horizontal ground heat exchanger based on the finite line source is presented. This model extends to the transient case in the soil and to any desired pipe layout the steady state results for parallel horizontal pipes of Claesson et Dunand (1983). The heat transfer ratio can change along the pipe. The analytical model can not account for the groundwater phase change given the complexity of the phenomenon. When there is no phase change the analytical model is validated by a 3D finite element numerical model. When the phase change is accounted for in the numerical model, for weather data from northern regions, the analytical model still provides good approximations to the ground temperature during the intensive heating season, hence allowing to compute the heat extracted by the ground heat exchanger (GHE). However, summer ground temperature and thaw depth are overestimated by the analytical model, so that the analytical model gives conservative results. A case study using a geoexchange thermal system is presented. It consists in freezing the ground under a building and heat it at the same time. A typical building in Kuujjuaq (northern Canada) is analyzed. The GHE layout follows a spiral pattern characterized globally by 3 parameters : length L, depth D and spacing S. The influence of each parameter on the amount of heat extracted from the ground and on the maximum ground temperature at a control point is assessed. This study shows that the proposed solution is feasible. An impact analysis shows the most important external parameters for the system design. The thermal properties of the frozen ground prove to be decisive parameters. The model, the case study and the impact analysis provide useful GHE design guidelines in cold regions for the double purpose of ground freezing and heat extraction.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. A 12-year cavern abandonment test

    NASA Astrophysics Data System (ADS)

    Bérest, P.; Brouard, B.; Hévin, G.

    2010-06-01

    In 1997-1998, an abandonment test was performed in a 950-m deep, 8000-m3 salt cavern operated by GDF SUEZ at Etrez, France. In this relatively small brine-filled cavern, which had been kept idle for 15 years before the test, thermal equilibrium was reached. A special system was designed to monitor leaks, which proved to be exceedingly small. In these conditions, brine permeation and cavern creep closure are the only factors to play significant roles in pressure evolution. This test strongly suggested that obtaining an equilibrium pressure such that the effects of these two factors were exactly equal would be reached in the long term. Four years later, pressure monitoring in the closed cavern resumed. Pressure evolution during the 2002-2009 period confirmed that cavern brine pressure will remain constant and significantly smaller than geostatic pressure in the long term, precluding any risk of fracturing and brine seepage to the overburden layers.

  14. 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.

  15. 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

  16. 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.

  17. 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. PMID:16605103

  18. CAPN1 and GDF8 genetic marker effects on heifer performance, reproduction, and first calf performance traits in beef cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To increase the accuracy of effect estimation and assess potential unintended correlated effects for two marker systems used commercially for muscling and meat tenderness, a composite beef cattle population segregating the markers was selected for multiple years to increase minor allele frequency (M...

  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. 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. PMID:23688834

  1. Petrography, geochemistry and primary origin of spheroidal dolomite from the Upper Cretaceous/Lower Tertiary Maghra El-Bahari Formation at Gabal Ataqa, Northwest Gulf of Suez, Egypt

    NASA Astrophysics Data System (ADS)

    Wanas, H. A.

    2002-08-01

    Field, petrographical, and geochemical studies of the Maghra El-Bahari Formation at Gabal Ataqa in Egypt indicate an occurrence of spheroidal dolomite as a primary precipitate. Petrographically, this dolomite is microcrystalline (10-40 μm in diameter) and lacks any direct or indirect evidence of a precursor mineral. Each dolomite spherule is composed of a cluster of coalesced incomplete rhombohedral sub-units exhibiting a globular body with a hollow core. This dolomite is commonly associated with authigenic palygorskite and gypsum. Based on its associations, the spheroidal dolomite occurs in two modes: (i) siliciclastic-disseminated dolomite and (ii) evaporitic-associated dolomite. On the basis of its elemental and stable isotopic signature, the spheroidal dolomite is subdivided into two types: Type A and Type B. Type A is Ca-rich (with average CaCO 3 and MgCO 3 equal to 58.20 and 39.91 mol%, respectively) and with average Sr=108 ppm, average Na=656 ppm, average Mn=72 ppm, and δ18O ranges from -0.4 to +0.9‰ PDB. Type B, compared with Type A, is nearly stoichiometric (with average CaCO 3 and MgCO 3 equal to 49.32 and 43.75 mol%, respectively) with higher average Sr (508 ppm), average Na (3008 ppm), average Mn (171 ppm), and δ18O (+0.98 to +1.8‰ PDB). Slightly positive values of δ13C (+0.18 to +2.10‰ PDB) are recorded for the two types of dolomite. Type A belongs to the siliciclastic-disseminated dolomite, whereas Type B is of the evaporitic-associated dolomite. It is interpreted that the spheroidal dolomite directly precipitated from a solution that was supersaturated with respect to dolomite components and did not develop by dolomitization of precursor carbonates. Two main sources are suggested for dolomite precipitation: hypersaline water and mixed saline-fresh water.

  2. Influence of substrate temperatures on the properties of GdF(3) thin films with quarter-wave thickness in the ultraviolet region.

    PubMed

    Jin, Jingcheng; Jin, Chunshui; Li, Chun; Deng, Wenyuan; Yao, Shun

    2015-06-01

    High-quality coatings of fluoride materials are in extraordinary demand for use in deep ultraviolet (DUV) lithography. Gadolinium fluoride (GdF3) thin films were prepared by a thermal boat evaporation process at different substrate temperatures. GdF3 thin film was set at quarter-wave thickness (∼27  nm) with regard to their common use in DUV/vacuum ultraviolet optical stacks; these thin films may significantly differ in nanostructural properties at corresponding depositing temperatures, which would crucially influence the performance of the multilayers. The measurement and analysis of optical, structural, and mechanical properties of GdF3 thin films have been performed in a comprehensive characterization cycle. It was found that depositing GdF3 thin films at relative higher temperature would form a rather dense, smooth, homogeneous structure within this film thickness scale. PMID:26192673

  3. TGF-β1 and GDF5 Act Synergistically to Drive the Differentiation of Human Adipose Stromal Cells toward Nucleus Pulposus-like Cells.

    PubMed

    Colombier, Pauline; Clouet, Johann; Boyer, Cécile; Ruel, Maëva; Bonin, Gaëlle; Lesoeur, Julie; Moreau, Anne; Fellah, Borhane-Hakim; Weiss, Pierre; Lescaudron, Laurent; Camus, Anne; Guicheux, Jérôme

    2016-03-01

    Degenerative disc disease (DDD) primarily affects the central part of the intervertebral disc namely the nucleus pulposus (NP). DDD explains about 40% of low back pain and is characterized by massive cellular alterations that ultimately result in the disappearance of resident NP cells. Thus, repopulating the NP with regenerative cells is a promising therapeutic approach and remains a great challenge. The objectives of this study were to evaluate the potential of growth factor-driven protocols to commit human adipose stromal cells (hASCs) toward NP-like cell phenotype and the involvement of Smad proteins in this differentiation process. Here, we demonstrate that the transforming growth factor-β1 and the growth differentiation factor 5 synergistically drive the nucleopulpogenic differentiation process. The commitment of the hASCs was robust and highly specific as attested by the expression of NP-related genes characteristic of young healthy human NP cells. In addition, the engineered NP-like cells secreted an abundant aggrecan and type II collagen rich extracellular matrix comparable with that of native NP. Furthermore, we demonstrate that these in vitro engineered cells survived, maintained their specialized phenotype and secretory activity after in vivo transplantation in nude mice subcutis. Finally, we provide evidence suggesting that the Smad 2/3 pathway mainly governed the acquisition of the NP cell molecular identity while the Smad1/5/8 pathway controlled the NP cell morphology. This study offers valuable insights for the development of biologically-inspired treatments for DDD by generating adapted and exhaustively characterized autologous regenerative cells. Stem Cells 2016;34:653-667. PMID:26661057

  4. 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 ingdf6a, a gene encoding a BMP family member previously implicated in dorsoventral patterning of the eye. We show thatgdf6amutant 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 togdf6amutants. We provide evidence that RA regulates the timing of RPC differentiation by promoting cell cycle exit. Furthermore, reducing RA signalling ingdf6amutants 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 expressedgdf6alimits RA pathway activity to control the transition from proliferation to differentiation in the growing eye. PMID:26893342

  5. Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes.

    PubMed

    Ferland-McCollough, D; Fernandez-Twinn, D S; Cannell, I G; David, H; Warner, M; Vaag, A A; Bork-Jensen, J; Brøns, C; Gant, T W; Willis, A E; Siddle, K; Bushell, M; Ozanne, S E

    2012-06-01

    Nutrition during early mammalian development permanently influences health of the adult, including increasing the risk of type 2 diabetes and coronary heart disease. However, the molecular mechanisms underlying such programming are poorly defined. Here we demonstrate that programmed changes in miRNA expression link early-life nutrition to long-term health. Specifically, we show that miR-483-3p is upregulated in adipose tissue from low-birth-weight adult humans and prediabetic adult rats exposed to suboptimal nutrition in early life. We demonstrate that manipulation of miR-483-3p levels in vitro substantially modulates the capacity of adipocytes to differentiate and store lipids. We show that some of these effects are mediated by translational repression of growth/differentiation factor-3, a target of miR-483-3p. We propose that increased miR-483-3p expression in vivo, programmed by early-life nutrition, limits storage of lipids in adipose tissue, causing lipotoxicity and insulin resistance and thus increasing susceptibility to metabolic disease. PMID:22223106

  6. 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

  7. 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, building, and pavillon'") (Helene…

  8. Growth differentiation factor 15 stimulates rapamycin-sensitive ovarian cancer cell growth and invasion.

    PubMed

    Griner, Samantha E; Joshi, Jayashree P; Nahta, Rita

    2013-01-01

    Identification of novel molecular markers and therapeutic targets may improve survival rates for patients with ovarian cancer. In the current study, immunohistochemical (IHC) analysis of two human ovarian tumor tissue arrays showed high staining for GDF15 in a majority of tissues. Exogenous stimulation of ovarian cancer cell lines with recombinant human GDF15 (rhGDF15) or stable over-expression of a GDF15 expression plasmid promoted anchorage-independent growth, increased invasion, and up-regulation of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF). MMP inhibition suppressed GDF15-mediated invasion. In addition, IHC analysis of human ovarian tumor tissue arrays indicated that GDF15 expression correlated significantly with high MMP2 and MMP9 expression. Exogenous and endogenous GDF15 over-expression stimulated phosphorylation of p38, Erk1/2, and Akt. Pharmacologic inhibition of p38, MEK, or PI3K suppressed GDF15-stimulated growth. Further, proliferation, growth, and invasion of GDF15 stable clones were blocked by rapamycin. IHC analysis demonstrated significant correlation between GDF15 expression and phosphorylation of mTOR. Finally, knockdown of endogenous GDF15 or neutralization of secreted GDF15 suppressed invasion and growth of a GDF15-over-expressing ovarian cancer cell line. These data indicate that GDF15 over-expression, which occurred in a majority of human ovarian cancers, promoted rapamycin-sensitive invasion and growth of ovarian cancer cells. Inhibition of mTOR may be an effective therapeutic strategy for ovarian cancers that over-express GDF15. Future studies should examine GDF15 as a novel molecular target for blocking ovarian cancer progression. PMID:23085437

  9. 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.

  10. 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

  11. 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

  12. Circulating Growth Differentiation Factor 11/8 Levels Decline With Age

    PubMed Central

    Poggioli, Tommaso; Vujic, Ana; Yang, Peiguo; Macias-Trevino, Claudio; Uygur, Aysu; Loffredo, Francesco S.; Pancoast, James R.; Cho, Miook; Goldstein, Jill; Tandias, Rachel M.; Gonzalez, Emilia; Walker, Ryan G.; Thompson, Thomas B.; Wagers, Amy J.; Fong, Yick W.; Lee, Richard T.

    2016-01-01

    Rationale Growth differentiation factor 11 (GDF11) and GDF8 are members of the transforming growth factor-β superfamily sharing 89% protein sequence homology. We have previously shown that circulating GDF11 levels decrease with age in mice. However, a recent study by Egerman et al reported that GDF11/8 levels increase with age in mouse serum. Objective Here, we clarify the direction of change of circulating GDF11/8 levels with age and investigate the effects of GDF11 administration on the murine heart. Methods and Results We validated our previous finding that circulating levels of GDF11/8 decline with age in mice, rats, horses, and sheep. Furthermore, we showed by Western analysis that the apparent age-dependent increase in GDF11 levels, as reported by Egerman et al, is attributable to cross-reactivity of the anti-GDF11 antibody with immunoglobulin, which is known to increase with age. GDF11 administration in mice rapidly activated SMAD2 and SMAD3 signaling in myocardium in vivo and decreased cardiac mass in both young (2-month-old) and old (22-month-old) mice in a dose-dependent manner after only 9 days. Conclusions Our study confirms an age-dependent decline in serum GDF11/8 levels in multiple mammalian species and that exogenous GDF11 rapidly activates SMAD signaling and reduces cardiomyocyte size. Unraveling the molecular basis for the age-dependent decline in GDF11/8 could yield insight into age-dependent cardiac pathologies. PMID:26489925

  13. 78 FR 21364 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-10

    ... Working Agreement Asia to USEC and PNW-Suez/PNW & Panama Loops. Parties: A.P. Moller-Maersk A/S and CMA..., South Asia, Middle East (including the Persian Gulf region), Spain, Italy, Egypt, Panama, Jamaica, and Canada, on the one hand, and U.S. East Coast ports via the Panama and Suez canals, on the other hand,...

  14. Is Growth Differentiation Factor 11 a Realistic Therapeutic for Aging-Dependent Muscle Defects?

    PubMed

    Harper, Shavonn C; Brack, Andrew; MacDonnell, Scott; Franti, Michael; Olwin, Bradley B; Bailey, Beth A; Rudnicki, Michael A; Houser, Steven R

    2016-04-01

    This "Controversies in Cardiovascular Research" article evaluates the evidence for and against the hypothesis that the circulating blood level of growth differentiation factor 11 (GDF11) decreases in old age and that restoring normal GDF11 levels in old animals rejuvenates their skeletal muscle and reverses pathological cardiac hypertrophy and cardiac dysfunction. Studies supporting the original GDF11 hypothesis in skeletal and cardiac muscle have not been validated by several independent groups. These new studies have either found no effects of restoring normal GDF11 levels on cardiac structure and function or have shown that increasing GDF11 or its closely related family member growth differentiation factor 8 actually impairs skeletal muscle repair in old animals. One possible explanation for what seems to be mutually exclusive findings is that the original reagent used to measure GDF11 levels also detected many other molecules so that age-dependent changes in GDF11 are still not well known. The more important issue is whether increasing blood [GDF11] repairs old skeletal muscle and reverses age-related cardiac pathologies. There are substantial new and existing data showing that GDF8/11 can exacerbate rather than rejuvenate skeletal muscle injury in old animals. There is also new evidence disputing the idea that there is pathological hypertrophy in old C57bl6 mice and that GDF11 therapy can reverse cardiac pathologies. Finally, high [GDF11] causes reductions in body and heart weight in both young and old animals, suggestive of a cachexia effect. Our conclusion is that elevating blood levels of GDF11 in the aged might cause more harm than good. PMID:27034276

  15. Serum Levels of Growth Differentiation Factor 11 Are Independently Associated with Low Hemoglobin Values in Hemodialysis Patients.

    PubMed

    Yamagishi, Sho-Ichi; Matsui, Takanori; Kurokawa, Yuka; Fukami, Kei

    2016-01-01

    Circulating levels of growth differentiation factor 11 (GDF11) have been shown to decrease with age in several mammalian species, and supplementation of GDF11 by heterochronic parabiosis or systemic administration reverses age-related organ damage. However, there is some controversy about the pathophysiological role of GDF11 in aging-associated organ damage. Since aging process is accelerated in uremia, we compared serum levels of GDF11 in hemodialysis (HD) patients with those in age-matched healthy controls, and then determined the independent clinical correlates of GDF11 in HD subjects. Sixty-two maintenance HD patients (34 male and 28 female; mean age, 52.6 years; mean duration of HD, 7.7 months) were enrolled in the present study. Twenty-nine age-matched subjects were used as a control. GDF11 was measured by a commercially available enzyme-linked immunosorbent assay kit. Serum GDF11 levels in HD patients were significantly higher than those in controls (9.4 ± 5.1 pg/mL vs. 7.3 ± 5.9 pg/mL). A statistical significance was demonstrated between GDF11 and hemoglobin (inversely). Multiple stepwise regression analysis revealed that hemoglobin (p < 0.001) was a sole independent correlate of GDF11 levels in HD patients (R (2) = 0.168). Our present study suggests that kinetics and regulation of circulating GDF11 may differ between normal physiological aging process and accelerated pathological aging conditions, such as uremia. Given that GDF11 has been shown to inhibit erythroid maturation in mice, elevation of GDF11 levels may be involved in erythropoietin-resistant anemia in HD patients. PMID:27298756

  16. 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

  17. Serum Levels of Growth Differentiation Factor 11 Are Independently Associated with Low Hemoglobin Values in Hemodialysis Patients

    PubMed Central

    Yamagishi, Sho-ichi; Matsui, Takanori; Kurokawa, Yuka; Fukami, Kei

    2016-01-01

    Abstract Circulating levels of growth differentiation factor 11 (GDF11) have been shown to decrease with age in several mammalian species, and supplementation of GDF11 by heterochronic parabiosis or systemic administration reverses age-related organ damage. However, there is some controversy about the pathophysiological role of GDF11 in aging-associated organ damage. Since aging process is accelerated in uremia, we compared serum levels of GDF11 in hemodialysis (HD) patients with those in age-matched healthy controls, and then determined the independent clinical correlates of GDF11 in HD subjects. Sixty-two maintenance HD patients (34 male and 28 female; mean age, 52.6 years; mean duration of HD, 7.7 months) were enrolled in the present study. Twenty-nine age-matched subjects were used as a control. GDF11 was measured by a commercially available enzyme-linked immunosorbent assay kit. Serum GDF11 levels in HD patients were significantly higher than those in controls (9.4 ± 5.1 pg/mL vs. 7.3 ± 5.9 pg/mL). A statistical significance was demonstrated between GDF11 and hemoglobin (inversely). Multiple stepwise regression analysis revealed that hemoglobin (p < 0.001) was a sole independent correlate of GDF11 levels in HD patients (R2 = 0.168). Our present study suggests that kinetics and regulation of circulating GDF11 may differ between normal physiological aging process and accelerated pathological aging conditions, such as uremia. Given that GDF11 has been shown to inhibit erythroid maturation in mice, elevation of GDF11 levels may be involved in erythropoietin-resistant anemia in HD patients. PMID:27298756

  18. 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.

  19. 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.

  20. Adenovirus-mediated expression of growth and differentiation factor-5 promotes chondrogenesis of adipose stem cells

    PubMed Central

    FENG, GANG; WAN, YUQING; BALIAN, GARY; LAURENCIN, CATO T.; LI, XUDONG

    2010-01-01

    The repair of articular cartilage injuries is impeded by the avascular and non-innervated nature of cartilage. Transplantation of autologous chondrocytes has a limited ability to augment the repair process due to the highly differentiated state of chondrocytes and the risks of donor-site morbidity. Mesenchymal stem cells can undergo chondrogenesis in the presence of growth factors for cartilage defect repair. Growth and differentiation factor-5 (GDF5) plays an important role in chondrogenesis. In this study, we examined the effects of GDF5 on chondrogenesis of adipose-derived stem cells (ADSCs) and evaluate the chondrogenic potentials of GDF5 genetically engineered ADSCs using an in vitro pellet culture model. Rat ADSCs were grown as pellet cultures and treated with chondrogenic media (CM). Induction of GDF5 by an adenovirus (Ad-GDF5) was compared with exogenous supplementation of GDF5 (100 ng/ml) and transforming growth factor-β (TGF-β1; 10 ng/ml). The ADSCs underwent chondrogenic differentiation in response to GDF5 exposure as demonstrated by production of proteoglycan, and up-regulation of collagen II and aggrecan at the protein and mRNA level. The chondrogenic potential of a one-time infection with Ad-GDF5 was weaker than exogenous GDF5, but equal to that of TGF-β1. Stimulation with growth factors or CM alone induced transient expression of the mRNA for collagen X, indicating a need for optimization of the CM. Our findings indicate that GDF5 is a potent inducer of chondrogenesis in ADSCs, and that ADSCs genetically engineered to express prochondrogenic growth factors, such as GDF5, may be a promising therapeutic cell source for cartilage tissue engineering. PMID:18569021

  1. 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

  2. Application of marker selection to enhance estimation of genetic effects and gene interaction in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Selection on important genetic markers can improve estimates of additive and dominance association effects. A composite population of beef cattle was selected for intermediate frequencies of myostatin (GDF8) F94L and µ-calpain (CAPN1) polymorphisms. Important additive associations of the GDF8 locu...

  3. In Vitro Osteogenic Differentiation Enhanced by Zirconia Coated with Nano-Layered Growth and Differentiation Factor-5.

    PubMed

    Yoon, Sun Jung; Yang, Dae Hyeok; Kim, Eun-Cheol; Noh, Kwantae; Lee, Deok-Won

    2016-01-01

    Zirconia (Zr) is also known as a biocompatible material with favorable mechanical properties as well as low plaque adhesion. In this study, we examined the efficacy of Zr coated with growth and differentiation factor-5 (GDF-5) bonded via click reaction as a substrate to support osteogenic differentiation of MC3T3-E1 cells. Pristine and surface-modified Zr surfaces were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), resulting that GDF-5 was successfully coated to the pristine Zr surface. GDF-5 coated to Zr surfaces was released for 28 days in a sustained manner. New bone formation onto GDF-5 coated Zr (Zr/GDF-5) surface was confirmed by in vitro test including cell proliferation, alkaline phosphatase activity and calcium deposition assays, and in vivo test including real-time polymerase chain reaction (qPCR) assay including osterix (OSX), runt-related transcription factor 2 (Runx 2), COL 1 (type I collagen) and osteocalcin (OC). Cell proliferation, alkaline phosphatase activity, and calcium deposition of MC3T3- E1 cells were significantly enhanced when the cells were cultured on Zr/GDF-5. Additionally, the results of qPCR revealed that genes related with osteogenic differentiation were up regulated when the cells were cultured on Zr/GDF-5. Our findings demonstrate that Zr/GDF-5 could be used as a material for enhancing the efficacy of osteogenic differentiation. PMID:27398455

  4. 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.

  5. Instability patterns in a miscible core annular flow

    NASA Astrophysics Data System (ADS)

    D'Olce, Marguerite; Martin, Jerome; Rakotomalala, Nicole; Salin, Dominique; Talon, Laurent

    2006-11-01

    Laboratoire FAST, batiment 502, campus universitaire, 91405 Orsay Cedex (France). Experiments are performed with two miscible fluids of equal density but different viscosities. The fluids are injected co-currently and concentrically into a cylindrical pipe. The so-obtained base state is an axisymmetric parallel flow, for which the ratio of the flow rates of the two fluids monitors the relative amount (and so the radius) of the fluids. Depending on this relative amount and on the total flow rate of the fluids, unstable axisymmetric patterns such as mushrooms and pearls are observed. We delineate the diagram of occurrence of the two patterns and characterize the instabilities.

  6. 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. PMID:26393302

  7. Growth differentiation factor-15 promotes glutamate release in medial prefrontal cortex of mice through upregulation of T-type calcium channels

    PubMed Central

    Liu, Dong-Dong; Lu, Jun-Mei; Zhao, Qian-Ru; Hu, Changlong; Mei, Yan-Ai

    2016-01-01

    Growth differentiation factor-15 (GDF-15) has been implicated in ischemic brain injury and synapse development, but its involvement in modulating neuronal excitability and synaptic transmission remain poorly understood. In this study, we investigated the effects of GDF-15 on non-evoked miniature excitatory post-synaptic currents (mEPSCs) and neurotransmitter release in the medial prefrontal cortex (mPFC) in mice. Incubation of mPFC slices with GDF-15 for 60 min significantly increased the frequency of mEPSCs without effect on their amplitude. GDF-15 also significantly elevated presynaptic glutamate release, as shown by HPLC. These effects were blocked by dual TGF-β type I receptor (TβRI) and TGF-β type II receptor (TβRII) antagonists, but not by a TβRI antagonist alone. Meanwhile, GDF-15 enhanced pERK level, and inhibition of MAPK/ERK activity attenuated the GDF-15-induced increases in mEPSC and glutamate release. Blocking T-type calcium channels reduced the GDF-15 induced up-regulation of synaptic transmission. Membrane-protein extraction and use of an intracellular protein-transport inhibitor showed that GDF-15 promoted CaV3.1 and CaV3.3 α-subunit expression by trafficking to the membrane. These results confirm previous findings in cerebellar granule neurons, in which GDF-15 induces its neurobiological effects via TβRII and activation of the ERK pathway, providing novel insights into the mechanism of GDF-15 function in cortical neurons. PMID:27353765

  8. Grandidierella bonnieroides Stephensen, 1948 (Amphipoda, Aoridae)-first record of an established population in the Mediterranean Sea.

    PubMed

    Brutto, Sabrina Lo; Iaciofano, Davide; Lubinevsky, Hadas; Galil, Bella S

    2016-01-01

    The first record in the Mediterranean Sea of the invasive aorid amphipod crustacean Grandidierella bonnieroides is presented. A widespread circumtropical species, recorded off the Saudi coast of the Arabian Gulf, the Red Sea and the Suez Canal, it may have been introduced into the Mediterranean through the Suez Canal. This tube-builder species of soft bottoms recently established a population in the polluted Haifa Bay, Israel. Further, this is the first Mediterranean record of the genus. PMID:27394471

  9. 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

  10. Modifications of human growth differentiation factor 9 to improve the generation of embryos from low competence oocytes.

    PubMed

    Li, Jing-Jie; Sugimura, Satoshi; Mueller, Thomas D; White, Melissa A; Martin, Georgia A; Ritter, Lesley J; Liang, Xiao-Yan; Gilchrist, Robert B; Mottershead, David G

    2015-01-01

    Growth differentiation factor 9 (GDF9) is an oocyte-derived growth factor that plays a critical role in ovarian folliculogenesis and oocyte developmental competence and belongs to the TGF-β family of proteins. Recombinant human GDF9 (hGDF9) is secreted in a latent form, which in the case of the fully processed protein, has the proregion noncovalently associated with the mature region. In this study, we investigated a number of amino acid residues in the mature region of hGDF9 that are different from the corresponding residues in the mouse protein, which is not latent. We designed, expressed, and purified 4 forms of chimeric hGDF9 (M1-M4) that we found to be active in a granulosa cell bioassay. Using a porcine in vitro maturation model with inherent low developmental competence (yielding 10%-20% blastocysts), we tested the ability of the chimeric hGDF9 proteins to improve oocyte maturation and developmental competence. Interestingly, one of the chimeric proteins, M3, was able to significantly increase the level of embryo production using such low competence oocytes. Our molecular modeling studies suggest that in the case of hGDF9 the Gly(391)Arg mutation probably increases receptor binding affinity, thereby creating an active protein for granulosa cells in vitro. However, for an improvement in oocyte developmental competence, a second mutation (Ser(412)Pro), which potentially decreases the affinity of the mature region for the proregion, is also required. PMID:25394262

  11. Plasma levels of growth differentiation factor-15 are associated with myocardial injury in patients undergoing off-pump coronary artery bypass grafting

    PubMed Central

    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

    2016-01-01

    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. PMID:27311391

  12. 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

  13. 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

    2016-01-01

    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. PMID:27311391

  14. 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. PMID:24860871

  15. 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. PMID:26482961

  16. Sampling and analytical methods of stable isotopes and dissolved inorganic carbon from CO2 injection sites

    NASA Astrophysics Data System (ADS)

    van Geldern, Robert; Myrttinen, Anssi; Becker, Veith; Barth, Johannes A. C.

    2010-05-01

    enough to cover the sample concentrations. In order to assure methodological reproducibility, this 'calibration set' should be included in every sequence analysed with the Gasbench CF-IRMS system. The standards, therefore, should also be treated in the same way as the samples. For accurate determination, it is essential to know the exact amount of water in the vial and the density of the sample. This requires weighing of each vial before and after injection of the water sample. For stable isotope analysis, the required signal height can be adjusted by the sample amount. Therefore this method is suitable for analysing samples with highly differing DIC concentrations. Reproducibility and accuracy of the quantitative analysis of the dissolved inorganic carbon need to be verified by independent control standards, treated as samples. This study was conducted as a part of the R&D programme CLEAN, which is funded by the German Federal Ministry of Education in the framework of the programme GEOTECHNOLOGIEN. We would like to thank GDF SUEZ for permitting us to conduct sampling campaigns at their site.

  17. CLEAN - Large-Scale CO2 Storage for Enhanced Gas Recovery in a depleted German Gasfield

    NASA Astrophysics Data System (ADS)

    Kühn, Michael; Baltrusch, Steffi; Dahmke, Andreas; Förster, Andrea; Großmann, Jochen; Meyer, Robert; Reinicke, Kurt

    2010-05-01

    The joint research project CLEAN is a German research and development (R&D) alliance of 16 partners from science and industry. The main theme of this pilot project is to enhance gas recovery (EGR) by injection of CO2 into an almost depleted natural gas field. The research focus is on the assessment of all processes associated with the injection. At the same time, the CO2 long-term storage safety of Europe's second largest onshore gas field is analysed and evaluated. The CLEAN study site is located in Saxony-Anhalt (Germany) and is part of the natural gas field Altmark owned by GDF SUEZ E&P Deutschland GmbH. Here, the test field Altensalzwedel, which covers an area of 14 km2, represents a structurally and hydraulically enclosed substructure. The structure is characterized in detail by 12 existing deep wells. Fluviatile silt- and sandstones from Upper Rotliegend built the reservoir in around 3,500 metres depth. The caprock above the reservoir consists of massive Zechstein formations with significant deposits of evaporites. These salt layers with average thickness of several hundred metres 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 and 50 bar, due to the gas production. For the substructure of Altensalzwedel it is assessed that the natural gas reservoir is depleted by 90 %. In the course of the pilot project CLEAN, less than 100,000 tonnes of CO2 will be injected for the EGR measures. An enhanced R&D program is performed to control existing wells, to advance the monitoring, and to improve the process modelling as a solid basis for a decent risk assessment, which is prerequisite for a future large-scale EGR project associated with the injection and storage of CO2. Within this field, some fundamental scientific, ecological and economical questions will be addressed and answered: Which technology is the most efficient and safe one to

  18. 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

  19. 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.

  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. 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.

  2. Growth differentiation factor 15 is a promising diagnostic and prognostic biomarker in colorectal cancer.

    PubMed

    Li, Chen; Wang, Xiaobing; Casal, Ignacio; Wang, Jingyu; Li, Peiwei; Zhang, Wei; Xu, Enping; Lai, Maode; Zhang, Honghe

    2016-08-01

    Although various studies have demonstrated that growth differentiation factor 15 (GDF15) might be a potential diagnostic and prognostic marker in colorectal cancer (CRC) patients, the results are inconsistent and the statistical power of individual studies is also insufficient. An original study was conducted to explore the diagnostic and prognostic value of serum GDF15 in CRC patients. We also conducted a meta-analysis study which aimed to summarize the diagnostic and prognostic performance of serum GDF15 in CRC. We searched PubMed and ISI Web of Knowledge up to 1 November 2014 for eligible studies. In order to explore the diagnostic performance of GDF15, standardized mean difference (SMD) and their 95% confidence intervals (CI) were estimated and receiver-operating characteristic (ROC) curves were constructed. For prognostic meta-analysis, study-specific hazard ratios (HRs) of serum GDF15 for survival were summarized. A total of eight studies were included in the meta-analyses. Our results revealed that serum GDF15 levels in CRC patients were higher than those in healthy controls (SMD = 1.08, 95% CI: 0.56-1.59, P < 0.001). For discriminating CRC from healthy controls, the AUC of GDF15 was 0.816 (95% CI: 0.792-0.838). The sensitivity and specificity were 58.9% (95% CI: 55.0-62.8) and 92.08% (95% CI: 89.2-94.4), respectively, when a cut-off value of 1099 pg/ml was established. Besides, higher GDF15 expression level was associated with worse overall survival for CRC patients (pooled HR = 2.09, 95% CI: 1.47-2.96). In conclusion, the present meta-analysis suggests that serum GDF15 may be a useful diagnostic and prognostic biomarker for CRC. PMID:26990020

  3. Growth differentiation factor 8 down-regulates pentraxin 3 in human granulosa cells.

    PubMed

    Chang, Hsun-Ming; Fang, Lanlan; Cheng, Jung-Chien; Klausen, Christian; Sun, Ying-Pu; Leung, Peter C K

    2015-03-15

    Growth differentiation factor 8 (GDF8), also known as myostatin, is highly expressed in the mammalian musculoskeletal system and plays critical roles in the regulation of skeletal muscle growth. Though not exclusively expressed in the musculoskeletal system, the expression and biological function of GDF8 has never been examined in the human ovary. Pentraxin 3 (PTX3) plays a key role in the assembly of extracellular matrix, which is essential for cumulus expansion, ovulation and in vivo fertilization. The aim of this study was to investigate GDF8 expression and function in human granulosa cells and to examine its underlying molecular determinants. An established immortalized human granulosa cell line (SVOG), granulosa cell tumor cell line (KGN) and primary granulosa-lutein cells were used as study models. We now demonstrate for the first time that GDF8 is expressed in human granulosa cells and follicular fluid. All 16 follicular fluid samples tested contained GDF8 protein at an average concentration of 3 ng/ml. In addition, GDF8 treatment significantly decreased PTX3 mRNA and protein levels. These suppressive effects, along with the induction of SMAD2/3 phosphorylation, were abolished by co-treatment with the ALK4/5/7 inhibitor SB431542. Knockdown of ALK5, ACVR2A/ACVR2B or SMAD4 reversed the effects of GDF8-induced PTX3 suppression. These results indicate that GDF8 down-regulates PTX3 expression via ACVR2A/ACVR2B-ALK5-mediated SMAD-dependent signaling in human granulosa cells. These novel findings support a potential role for GDF8 in the regulation of follicular function, likely via autocrine effects on human granulosa cells. PMID:25641196

  4. 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

  5. Association of Serum Level of Growth Differentiation Factor 15 with Liver Cirrhosis and Hepatocellular Carcinoma

    PubMed Central

    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. PMID:25996938

  6. Evolving New Skeletal Traits by cis-Regulatory Changes in Bone Morphogenetic Proteins.

    PubMed

    Indjeian, Vahan B; Kingman, Garrett A; Jones, Felicity C; Guenther, Catherine A; Grimwood, Jane; Schmutz, Jeremy; Myers, Richard M; Kingsley, David M

    2016-01-14

    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 map 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. 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. PMID:23726162

  8. Effect of Serum Growth Differentiation Factor-15 and the Syntax Score on 2-Year Outcomes in Patients With Acute Coronary Syndrome.

    PubMed

    Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; Avanzas, Pablo; Consuegra-Sanchez, Luciano

    2016-05-15

    Growth differentiation factor-15 (GDF-15) is produced by cardiomyocytes and atherosclerotic lesions under stress conditions, but little is known about its relation with severity and complexity of coronary lesions. The aim of this study was to investigate the association between GDF-15 and the syntax score for risk prediction of major adverse cardiovascular events (MACE) at 2-year follow-up in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). This is a prospective cohort study of 502 patients with NSTEACS. The syntax score was calculated from baseline coronary angiography. Blood samples were obtained at study entry for the assessment of GDF-15 and high-sensitivity C reactive protein. One hundred and three patients (20.5%) showed MACE at 2-year follow-up. Patients who developed MACE had greater GDF-15 concentrations and syntax score (p <0.001) compared to patients who did not. There was a positive, but moderate, correlation between GDF-15 and syntax score (ρ = 0.45, p <0.0001). On Cox regression analysis, only GDF-15 levels (p <0.001), body mass index (p = 0.04), and syntax score (p <0.001) remained independent predictors of the MACE. The area under the curve of GDF-15 (0.912, 95% confidence interval 0.894 to 0.944) was significantly greater compared to high-sensitivity C reactive protein and syntax score. In conclusion, in patients with NSTEACS, levels of GDF-15 at admission were correlated with the syntax score and independently associated with an increased risk of MACE during 2-year follow-up. PMID:27013387

  9. 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.

  10. [Regulation of osteoclastogenesis by osteocytes through growth differentiation factor-15].

    PubMed

    Hinoi, Eiichi

    2014-01-01

    Osteocytes are the most abundant cells in bone. However, little attention has been paid to their role in bone remodeling. In this study, osteoclast differentiation was significantly enhanced by conditioned media derived from cultures of osteocytic MLO-Y4 cells that were cultured under hypoxic conditions. Using microarray analysis, we identified growth differentiation factor-15 (GDF15) as a pivotal factor secreted from osteocytes under hypoxia. Indeed, treatment with recombinant GDF15 markedly increased osteoclast differentiation in vitro. Further to investigate the importance of GDF15 in vivo, we used a hypoxic murine model that involved ligation of the right femoral artery. The volume of cancellous bone in the proximal tibia of the ligated limb was significantly reduced, together with a significant increase in osteoclast-related parameters. Addition of anti-GDF15 antibody prevented bone loss and osteoclastic activation in the tibiae of mice that had undergone femoral artery ligation. These results suggest that GDF15, which is secreted from osteocytes under hypoxia during bone remodeling, may be a positive regulator of osteoclastic differentiation. The in vivo usefulness of the anti-GDF15 antibody might provide insights for the development of novel therapeutics for bone disorders related to hypoxia or ischemic insults. PMID:25452236

  11. 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

  12. Growth differentiation factor 11 signals through the transforming growth factor-beta receptor ALK5 to regionalize the anterior-posterior axis.

    PubMed

    Andersson, Olov; Reissmann, Eva; Ibáñez, Carlos F

    2006-08-01

    Growth differentiation factor 11 (GDF11) contributes to regionalize the mouse embryo along its anterior-posterior axis by regulating the expression of Hox genes. The identity of the receptors that mediate GDF11 signalling during embryogenesis remains unclear. Here, we show that GDF11 can interact with type I receptors ALK4, ALK5 and ALK7, but predominantly uses ALK4 and ALK5 to activate a Smad3-dependent reporter gene. Alk5 mutant embryos showed malformations in anterior-posterior patterning, including the lack of expression of the posterior determinant Hoxc10, that resemble defects found in Gdf11-null mutants. A heterozygous mutation in Alk5, but not in Alk4 or Alk7, potentiated Gdf11(-/-)-like phenotypes in vertebral, kidney and palate development in an Acvr2b(-/-) background, indicating a genetic interaction between the two receptor genes. Thus, the transforming growth factor-beta (TGF-beta) receptor ALK5, which until now has only been associated with the biological functions of TGF-beta1 to TGF-beta3 proteins, mediates GDF11 signalling during embryogenesis. PMID:16845371

  13. MiR-132-3p Regulates the Osteogenic Differentiation of Thoracic Ligamentum Flavum Cells by Inhibiting Multiple Osteogenesis-Related Genes

    PubMed Central

    Qu, Xiaochen; Chen, Zhongqiang; Fan, Dongwei; Sun, Chuiguo; Zeng, Yan

    2016-01-01

    Ossification of the ligamentum flavum (OLF) is a disorder of heterotopic ossification of spinal ligaments and is the main cause of thoracic spinal canal stenosis. Previous studies suggested that miR-132-3p negatively regulates osteoblast differentiation. However, whether miR-132-3p is involved in the process of OLF has not been investigated. In this study, we investigated the effect of miR-132-3p and its target genes forkhead box O1 (FOXO1), growth differentiation factor 5 (GDF5) and SRY-box 6 (SOX6) on the osteogenic differentiation of ligamentum flavum (LF) cells. We demonstrated that miR-132-3p was down-regulated during the osteogenic differentiation of LF cells and negatively regulated the osteoblast differentiation. Further, miR-132-3p targeted FOXO1, GDF5 and SOX6 and down-regulated the protein expression of these genes. Meanwhile, FOXO1, GDF5 and SOX6 were up-regulated after osteogenic differentiation and the down-regulation of endogenous FOXO1, GDF5 or SOX6 suppressed the osteogenic differentiation of LF cells. In addition, we also found FOXO1, GDF5 and SOX6 expression in the ossification front of OLF samples. Overall, these results suggest that miR-132-3p inhibits the osteogenic differentiation of LF cells by targeting FOXO1, GDF5 and SOX6. PMID:27556448

  14. Growth differentiating factor 15 enhances the tumor-initiating and self-renewal potential of multiple myeloma cells

    PubMed Central

    Tanno, Toshihiko; Lim, Yiting; Wang, Qiuju; Chesi, Marta; Bergsagel, P. Leif; Matthews, Geoff; Johnstone, Ricky W.; Ghosh, Nilanjan; Borrello, Ivan; Huff, Carol Ann

    2014-01-01

    Disease relapse remains a major factor limiting the survival of cancer patients. In the plasma cell malignancy multiple myeloma (MM), nearly all patients ultimately succumb to disease relapse and progression despite new therapies that have improved remission rates. Tumor regrowth indicates that clonogenic growth potential is continually maintained, but the determinants of self-renewal in MM are not well understood. Normal stem cells are regulated by extrinsic niche factors, and the tumor microenvironment (TME) may similarly influence tumor cell clonogenic growth and self-renewal. Growth differentiation factor 15 (GDF15) is aberrantly secreted by bone marrow stromal cells (BMSCs) in MM. We found that GDF15 is produced by BMSCs after direct contact with plasma cells and enhances the tumor-initiating potential and self-renewal of MM cells in a protein kinase B- and SRY (sex-determining region Y)-box–dependent manner. Moreover, GDF15 induces the expansion of MM tumor-initiating cells (TICs), and changes in the serum levels of GDF15 were associated with changes in the frequency of clonogenic MM cells and the progression-free survival of MM patients. These findings demonstrate that GDF15 plays a critical role in mediating the interaction among mature tumor cells, the TME, and TICs, and strategies targeting GDF15 may affect long-term clinical outcomes in MM. PMID:24345755

  15. 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

  16. 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. PMID:26928288

  17. 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. PMID:20736313

  18. 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. PMID:26254468

  19. 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

  20. Comparison of Inflammatory Biomarkers in Outpatients With Prior Myocardial Infarction.

    PubMed

    Minamisawa, Masatoshi; Motoki, Hirohiko; Izawa, Atsushi; Kashima, Yuichiro; Hioki, Hirofumi; Abe, Naoyuki; Miura, Takashi; Ebisawa, Soichiro; Miyashita, Yusuke; Koyama, Jun; Ikeda, Uichi

    2016-01-01

    Inflammatory biomarkers have been proposed for use in the risk stratification of patients with acute myocardial infarction (AMI). We examined the value of inflammatory biomarkers over clinical features for predicting cardiovascular (CV) events in stable outpatients with MI. We enrolled 430 post-MI patients and measured their levels of high-sensitivity C reactive protein (hs-CRP), growth differentiation factor-15 (GDF-15), and the interleukin-1 receptor family member called ST2 (ST2), one month after AMI. Patients were prospectively followed for 3 years. In our study cohort (mean age, 66 ± 12 years; left ventricular ejection fraction, 55 ± 13%), CV events were observed in 39 patients (9.1%). Kaplan- Meier analysis revealed that patients with high levels of GDF-15 (≥ 1221.0 ng/L) showed poorer prognoses than those with low levels of GDF-15 (< 1221.0 ng/L) (20.4% versus 3.6%, P < 0.001); hs-CRP and ST2 did not show a similar correlation with prognoses. GDF-15 remained associated with CV events after adjusting for age, chronic kidney disease, and B-type natriuretic peptide (hazard ratio, 1.001; 95% confidence interval, 1.000 - 1.001; P = 0.046). GDF-15 provided an incremental predictive value for CV events over clinical features (incremental value in global χ(2) = 43.81, P < 0.001). In outpatients with prior MI, GDF-15 was an independent indicator of CV events, unlike hs-CRP and ST2. GDF15 provided an incremental prognostic value over clinical features. PMID:26742699

  1. Growth differentiation factor-15 and white matter hyperintensities in cognitive impairment and dementia.

    PubMed

    Chai, Yuek Ling; Hilal, Saima; Chong, Jenny P C; Ng, Yan Xia; Liew, Oi Wah; Xu, Xin; Ikram, Mohammad Kamran; Venketasubramanian, Narayanaswamy; Richards, A Mark; Lai, Mitchell K P; Chen, Christopher P

    2016-08-01

    Vascular pathology plays an important role in the development of cognitive decline and dementia. In this context, growth differentiation factor-15 (GDF-15) has been suggested to be a biomarker due to its regulatory roles in inflammatory and trophic responses during tissue injury. However, limited data exist on the associations of GDF-15 with either cerebrovascular disease (CeVD) burden or the spectrum of cognitive impairment. Therefore, we aimed to study peripheral levels of GDF-15 incognitive impairment no dementia (CIND) or Alzheimer disease (AD) subjects assessed for CeVD using a case-control cohort design, with cases recruited from memory clinics and controls from memory clinics and the community. All subjects underwent detailed neuropsychological assessment, 3-Tesla magnetic resonance imaging, and venous blood draw. Subjects were classified as CIND or AD based on clinical criteria, while significant CeVD was defined as the presence of cortical infarcts and/or 2 lacunes or more, and/or confluent white matter hyperintensities (WMHs) in 2 or more brain regions. A total of 324 subjects were included in the study, of whom 80 had no cognitive impairment, 144 CIND and 100with AD. Higher GDF-15 levels were significantly associated with disease groups, especially in the presence of CeVD, namely, CIND with CeVD (odds ratios [OR]: 7.21; 95% confidence interval [CI]: 2.14-24.27) and AD with CeVD (OR: 21.87; 95% CI: 2.01-237.43). Among the different CeVD markers, only WMH was associated with higher GDF-15 levels (OR: 3.97; 95% CI: 1.79-8.83). The associations between GDF-15 and cognitive impairment as well as with WMH remained significant after excluding subjects with cardiovascular diseases. In conclusion, we showed that increased GDF-15 may be a biomarker for CIND and AD in subjects with WMH. PMID:27537582

  2. Lower growth factor expression in follicular fluid undergone in-vitro fertilization

    PubMed Central

    Park, Seung Bin; Park, Bang Ja

    2011-01-01

    Objective This study was performed to identify whether growth and differentiation factor-9 (GDF-9) and transforming growth factor-β1 (TGF-β1) expressions would be lower in the follicular fluid (FF) of those over age 35 who underwent IVF than under age 35. Methods A total of 24 IVF cycles (20 patients) were included in this study. All of patients were stimulated for IVF by the GnRH short protocol and divided into two groups for analysis, according to their age: <35 group (14 cycles, 11 patients) vs. ≥35 group (10 cycles, 9 patients). The expression levels of GDF-9 and TGF-β1 were determined by western blotting and quantitative enzyme-linked immunosorbent assay. Results The numbers of retrieved oocytes and metaphase II oocytes were significantly lower in the ≥35 group. Lower expression of GDF-9 and TGF-β1 by western blotting in the ≥35 group were observed as well. The mean GDF-9 and TGF-β1 levels by enzyme-linked immunosorbent assay were lower in the ≥35 group. The values were 6,850.5±928.4 ng/L vs. 3,333.3±1,089.2 ng/L of GDF-9 (p<0.05) and 3,844.1±571.1 ng/L vs. 2,187.7±754.0 ng/L of TGF-β1 (p<0.05). A negative correlation between GDF-9 and age was observed (r=-0.546, p=0.006). Conclusion GDF-9 and TGF-β1 production from stimulated ovaries during IVF appears to decrease with age. PMID:22384444

  3. 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

  4. Knockdown of platinum-induced growth differentiation factor 15 abrogates p27-mediated tumor growth delay in the chemoresistant ovarian cancer model A2780cis

    PubMed Central

    Meier, Julia C; Haendler, Bernard; Seidel, Henrik; Groth, Philip; Adams, Robert; Ziegelbauer, Karl; Kreft, Bertolt; Beckmann, Georg; Sommer, Anette; Kopitz, Charlotte

    2015-01-01

    Molecular mechanisms underlying the development of resistance to platinum-based treatment in patients with ovarian cancer remain poorly understood. This is mainly due to the lack of appropriate in vivo models allowing the identification of resistance-related factors. In this study, we used human whole-genome microarrays and linear model analysis to identify potential resistance-related genes by comparing the expression profiles of the parental human ovarian cancer model A2780 and its platinum-resistant variant A2780cis before and after carboplatin treatment in vivo. Growth differentiation factor 15 (GDF15) was identified as one of five potential resistance-related genes in the A2780cis tumor model. Although A2780-bearing mice showed a strong carboplatin-induced increase of GDF15 plasma levels, the basal higher GDF15 plasma levels of A2780cis-bearing mice showed no further increase after short-term or long-term carboplatin treatment. This correlated with a decreased DNA damage response, enhanced AKT survival signaling and abrogated cell cycle arrest in the carboplatin-treated A2780cis tumors. Furthermore, knockdown of GDF15 in A2780cis cells did not alter cell proliferation but enhanced cell migration and colony size in vitro. Interestingly, in vivo knockdown of GDF15 in the A2780cis model led to a basal-enhanced tumor growth, but increased sensitivity to carboplatin treatment as compared to the control-transduced A2780cis tumors. This was associated with larger necrotic areas, a lobular tumor structure and increased p53 and p16 expression of the carboplatin-treated shGDF15-A2780cis tumors. Furthermore, shRNA-mediated GDF15 knockdown abrogated p27 expression as compared to control-transduced A2780cis tumors. In conclusion, these data show that GDF15 may contribute to carboplatin resistance by suppressing tumor growth through p27. These data show that GDF15 might serve as a novel treatment target in women with platinum-resistant ovarian cancer. PMID:25490861

  5. Connective tissue growth factor mediates growth differentiation factor 8-induced increase of lysyl oxidase activity in human granulosa-lutein cells.

    PubMed

    Chang, Hsun-Ming; Fang, Ying; Liu, Pang-Pin; Cheng, Jung-Chien; Yang, Xiaokui; Leung, Peter C K

    2016-10-15

    Lysyl oxidase (LOX) is an essential enzyme for the stabilization of the extracellular matrix (ECM) and the subsequent follicle and oocyte maturation. Currently, there is limited information pertaining to the regulation of LOX activity in human ovarian tissue. Growth differentiation factor 8 (GDF8) is a unique member of the transforming growth factor-β superfamily that is expressed in human granulosa cells and has important roles in regulating a variety of ovarian functions. The aim of the present study was to investigate the effects of GDF8 on the regulation of LOX expression and activity in human granulosa cells and to examine the underlying molecular determinants. An established immortalized human granulosa cell line (SVOG) and primary granulosa-lutein cells were used as study models. Using dual inhibition approaches (TGF-β type I inhibitor SB505124 and small interfering RNAs) and ChIP analyses, we have demonstrated that GDF8 up-regulated the expression of connective tissue growth factor (CTGF) through the activin receptor-like kinase 5-mediated SMAD2/3-SMAD4 signaling pathways. In addition, the increase in CTGF expression contributed to the GDF8-induced increase in LOX expression and activity. Our findings suggest that GDF8 and CTGF may play critical roles in the regulation of ECM formation in human granulosa cells. PMID:27392496

  6. 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

  7. 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

  8. 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. PMID:26577677

  9. 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

  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 activities,…