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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. 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

  6. 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

  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. 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.

  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. 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

  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 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

  16. 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

  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. 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.

  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. 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.

  2. 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

  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. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  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. 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...

  5. 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

  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. 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

  9. 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

  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. 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.

  1. 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.

  2. 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.

  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

    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

  7. 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

  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. 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

  13. 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

  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. 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.

  4. 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.

  5. 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.

  6. 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

  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. 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

  11. 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

  12. 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

  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. 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

  17. 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

  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. 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.

  1. 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

  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. 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

  13. 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.

  14. 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.

  15. 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.

  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. 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.

  18. 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.

  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. 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....

  20. 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...

  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. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  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. 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

  3. 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

  4. 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

  5. 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

  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. 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

  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. Deep microbial life in the Altmark natural gas reservoir: baseline characterization prior CO2 injection

    NASA Astrophysics Data System (ADS)

    Morozova, Daria; Shaheed, Mina; Vieth, Andrea; Krüger, Martin; Kock, Dagmar; Würdemann, Hilke

    2010-05-01

    the quantification of those microorganisms as well as the determination of microbial activity was not yet possible. Microbial monitoring methods have to be further developed to study microbial activities under these extreme conditions to access their influence on the EGR technique and on enhancing the long term safety of the process by fixation of carbon dioxide by precipitation of carbonates. We would like to thank GDF SUEZ for providing the data for the Rotliegend reservoir, sample material and enabling sampling campaigns. The CLEAN project is funded by the German Federal Ministry of Education and Research (BMBF) in the frame of the Geotechnologien Program.

  12. 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. 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

  15. 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

  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. 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

  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. 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

  3. 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.

  4. 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...

  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. 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

  14. 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

  15. 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

  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 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

  3. 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

  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. [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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  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 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  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,…

  11. Gulf of Aqaba, Sinai Peninsula

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The Gulf of Aqaba separates the Sinai peninsula from Saudi Arabia in this scene of the Middle East (29.0N, 34.5E) showing the geomorphology and geology of this region including portions of Egypt, Israel, Jordon and Saudi Arabia. A small portion of the Gulf of Suez can be seen on the opposite side of the Sinai peninsula.

  12. Biogeochemistry of aragonite mud and oolites.

    NASA Technical Reports Server (NTRS)

    Mitterer, R. M.

    1972-01-01

    Amino acids were determined on an analyzer similar to that described by Hare (1969) in carbonate mud samples from locations in the Bahamas, Bermuda, Persian Gulf, and Florida Bay, and in oolites from the Gulf of Suez, the Abu Dhabi coast, the Bahamas, and Baffin Bay, Texas. A histogram, tables, and chromatograms of the results are given.

  13. Effect of Instruction in Story Grammar on the Narrative Writing of EFL Students.

    ERIC Educational Resources Information Center

    El-Koumy, Abdel Salam A.

    A study investigated the effects of explicit versus implicit instruction in story grammar on the narrative writing skills of English-as-a-Foreign-Language (EFL) students at the university level. Subjects were 83 freshmen enrolled in English at the Faculty of Education at Suez Canal University (Egypt). The subjects were randomly assigned to…

  14. [Clinical and preclinical application of PTH and BMP to dental treatment].

    PubMed

    Hata, Kenji

    2016-03-01

    Bone formation is the important factor which contributes to the successful periodontal tissue regeneration in periodontitis and osseointegration of implant placement. To achieve the sufficient bone volume in the process of dental treatment, several growth factors and hormones which enhance bone formation have been evaluated in clinical and preclinical studies. BMP2 and BMP7 have recently been approved for sinus augmentation by FDA. A phase2a randomized controlled clinical studies were conducted to evaluate the potential of GDF5 to stimulate periodontal tissue regeneration and GDF5 significantly stimulated alveolar bone regeneration compared to control. Moreover, increased alveolar bone formation was observed by the use of PTH (1-34) Teriparatide in patients of severe periodontitis. PTH and GDF5 are promising agents for future periodontitis treatment. PMID:26923987

  15. Role of growth differentiation factor-5 and bone morphogenetic protein type II receptor in the development of lumbar intervertebral disc degeneration

    PubMed Central

    Li, Yi-Fan; Tang, Xian-Zhong; Liang, Chao-Ge; Hui, Yao-Ming; Ji, Yun-Han; Xu, Wei; Qiu, WenJun; Cheng, Li-Ming

    2015-01-01

    The present study was designed to evaluate the role of growth differentiation factor-5 (GDF-5) and bone morphogenetic protein type II receptor (BMPR-II) in the development of lumbar intervertebral disc degeneration (IDD). A total of 24 patients with lumbar IDD (experiment group) and 6 patients with lumbar vertebral fracture (control group) were enrolled in the study. Tissue samples of IVD from the experiment group and control group were obtained during lumbar fusion operation, respectively. Fixation and decalcification of IVD tissue were performed, and then HE staining was carried out to observe the morphological changes of the lumbar IVD tissues. The expression of GDF-5 and BMPRII in human lumbar IVD was detected by immunohistochemical staining. HE staining results showed that non- and minimal degeneration was found in 11 cases (score range, 0-3), moderate degeneration in 12 cases (score range, 4-8), and severe degeneration in 7 cases (score range, 9-12). According to the immunohistochemical results, the positive expression rates of GDF-5 and BMPRII in NP were higher than those in AF of the non- and minimal degeneration group, moderate degeneration group and severe degeneration group (all P < 0.05). However, no significant difference in GDF-5 or BMPRII positive expression was observed among the normal, non- and minimal, moderate and severe degeneration groups in neither NP area nor AF area (all P > 0.05). In conclusion, our results showed that GDF-5 and BMPRII expressed both in normal and degenerated IVD tissues, and GDF-5 might have an inhibition effect on degenerated lumbar IVD, suggesting that gene therapy may be a useful approach in producing physiological effects during early- and late-phase of lumbar IDD. PMID:25755766

  16. Positive regulation of osteoclastic differentiation by growth differentiation factor 15 upregulated in osteocytic cells under hypoxia.

    PubMed

    Hinoi, Eiichi; Ochi, Hiroki; Takarada, Takeshi; Nakatani, Eri; Iezaki, Takashi; Nakajima, Hiroko; Fujita, Hiroyuki; Takahata, Yoshifumi; Hidano, Shinya; Kobayashi, Takashi; Takeda, Shu; Yoneda, Yukio

    2012-04-01

    Osteocytes are thought to play a role as a mechanical sensor through their communication network in bone. Although osteocytes are the most abundant cells in bone, little attention has been paid to their physiological and pathological functions in skeletogenesis. Here, we have attempted to delineate the pivotal functional role of osteocytes in regulation of bone remodeling under pathological conditions. We first found markedly increased osteoclastic differentiation by conditioned media (CM) from osteocytic MLO-Y4 cells previously exposed to hypoxia in vitro. Using microarray and real-time PCR analyses, we identified growth differentiation factor 15 (GDF15) as a key candidate factor secreted from osteocytes under hypoxia. Recombinant GDF15 significantly promoted osteoclastic differentiation in a concentration-dependent manner, with concomitant facilitation of phosphorylation of both p65 and inhibitory-κB in the presence of receptor activator of nuclear factor-κB ligand. To examine the possible functional significance of GDF15 in vivo, mice were subjected to ligation of the right femoral artery as a hypoxic model. A significant increase in GDF15 expression was specifically observed in tibias of the ligated limb but not in tibias of the normally perfused limb. Under these experimental conditions, in cancellous bone of proximal tibias in the ligated limb, a significant reduction was observed in bone volume, whereas a significant increase was seen in the extent of osteoclast surface/bone surface when determined by bone histomorphometric analysis. Finally, the anti-GDF15 antibody prevented bone loss through inhibiting osteoclastic activation in tibias from mice with femoral artery ligation in vivo, in addition to suppressing osteoclastic activity enhanced by CM from osteocytes exposed to hypoxia in vitro. These findings suggest that GDF15 could play a pivotal role in the pathogenesis of bone loss relevant to hypoxia through promotion of osteoclastogenesis after

  17. Application of Gas Dynamical Friction for Planetesimals. II. Evolution of Binary Planetesimals

    NASA Astrophysics Data System (ADS)

    Grishin, Evgeni; Perets, Hagai B.

    2016-04-01

    One of the first stages of planet formation is the growth of small planetesimals and their accumulation into large planetesimals and planetary embryos. This early stage occurs long before the dispersal of most of the gas from the protoplanetary disk. At this stage gas-planetesimal interactions play a key role in the dynamical evolution of single intermediate-mass planetesimals (mp ˜ 1021-1025 g) through gas dynamical friction (GDF). A significant fraction of all solar system planetesimals (asteroids and Kuiper-belt objects) are known to be binary planetesimals (BPs). Here, we explore the effects of GDF on the evolution of BPs embedded in a gaseous disk using an N-body code with a fiducial external force accounting for GDF. We find that GDF can induce binary mergers on timescales shorter than the disk lifetime for masses above mp ≳ 1022 g at 1 au, independent of the binary initial separation and eccentricity. Such mergers can affect the structure of merger-formed planetesimals, and the GDF-induced binary inspiral can play a role in the evolution of the planetesimal disk. In addition, binaries on eccentric orbits around the star may evolve in the supersonic regime, where the torque reverses and the binary expands, which would enhance the cross section for planetesimal encounters with the binary. Highly inclined binaries with small mass ratios, evolve due to the combined effects of Kozai-Lidov (KL) cycles with GDF which lead to chaotic evolution. Prograde binaries go through semi-regular KL evolution, while retrograde binaries frequently flip their inclination and ˜50% of them are destroyed.

  18. Differential Binding Activity of TGF-β Family Proteins to Select TGF-β Receptors.

    PubMed

    Khalil, Ashraf M; Dotimas, Hyna; Kahn, Julius; Lamerdin, Jane E; Hayes, David B; Gupta, Priyanka; Franti, Michael

    2016-09-01

    Growth differentiation factor-11 (GDF11) and myostatin (MSTN) are highly related transforming growth factor-β (TGF-β) ligands with 89% amino acid sequence homology. They have different biologic activities and diverse tissue distribution patterns. However, the activities of these ligands are indistinguishable in in vitro assays. SMAD2/3 signaling has been identified as the canonical pathway for GDF11 and MSTN, However, it remains unclear which receptor heterodimer and which antagonists preferentially mediate and regulate signaling. In this study, we investigated the initiation and regulation of GDF11 and MSTN signaling at the receptor level using a novel receptor dimerization detection technology. We used the dimerization platform to link early receptor binding events to intracellular downstream signaling. This approach was instrumental in revealing differential receptor binding activity within the TGF-β family. We verified the ActR2b/ALK5 heterodimer as the predominant receptor for GDF11- and MSTN-induced SMAD2/3 signaling. We also showed ALK7 specifically mediates activin-B signaling. We verified follistatin as a potent antagonist to neutralize both SMAD2/3 signaling and receptor dimerization. More remarkably, we showed that the two related antagonists, growth and differentiation factor-associated serum protein (GASP)-1 and GASP2, differentially regulate GDF11 (and MSTN) signaling. GASP1 blocks both receptor dimerization and downstream signaling. However, GASP2 blocks only downstream signaling without interference from receptor dimerization. Our data strongly suggest that physical binding of GDF11 (and MSTN) to both ActR2b and ALK5 receptors is required for initiation of signaling. PMID:27340210

  19. Lessons Learned from Natural and Industrial Analogues for Storage of Carbon Dioxide

    NASA Astrophysics Data System (ADS)

    Jeandel, E.; Battani, A.; Sarda, P.

    2009-04-01

    samples paradoxically exhibit high R/Ra ratios (between 1,39 and 3,96Ra), attesting to a dominant mantle-derived helium component. Thus, in such CO2-leaking sites, the origin of CO2 seems to be related to the addition of crustal- CO2, poor in helium, during gas migration. On the other hand, gases sampled in good containment sites exhibit lower R/Ra ratio (0,36-1,07Ra), still indicating a present but smaller mantle-derived helium component, and associated to a typical MORB CO2/3He ratio: these features highlight a dominant mantle source for the CO2 in these gases. Isotopic fractionation of noble gases appears also to be closely linked to the quality of the containment, since a mass-related isotopic fractionation of neon and argon has been observed in all the CO2-leaking sites. This enrichment in the lightest noble gas isotope can be interpreted as a geochemical footprint of the rapid gas migration toward surface. Second, a 2-years geochemical tracing experiment on a natural gas storage site exploited by the GDF SUEZ Company was performed. Gas sampling was done every month during both the injection (usually in summer) and withdrawal (usually in winter) periods. This monitoring test demonstrates the possibility to identify physico-chemical processes taking place in the reservoir at a human time scale. More specifically, the gases sampled at the producing wells exhibit mixing trends between the different injected gas end-members, depending on the sampling date and the location of the wells. A significant partitioning between water and the gas phase has also been identified and is apparently related to changes of the gas to water volume ratio during gas withdrawal. These two complementary studies proved the effectiveness of noble gases and carbon isotopes in terms of leak detection and as tracers of the CO2 behaviour, thus increasing interest in the proposed method and providing general information on its use. References: Marty, B. and Jambon, A., 1987. C/3He in volatile

  20. Basement structural control on Cretaceous pull-apart basins of the central Eastern Egypt Desert

    NASA Astrophysics Data System (ADS)

    McCaffrey, K.; El Kazzaz, Y.; Holdsworth, B.

    2006-12-01

    The present-day Red Sea / Gulf of Suez rift system is attributed to extensional block faulting with along-axis segmentation into sub-basins with different dip polarities. The northwestern margin of the Red Sea - Gulf of Suez rift system is exposed for about 400 km along the northwestern Red Sea coast near Quseir to the tip of the Gulf of Suez at Suez City. This area contains elements of the pre-Red Sea structural pattern which has been viewed in similar terms as one of fault-related basin formation. Four distinct depocenters (sub-basins) separated by complex accommodation zones are present containing 500-700m thick section ranging in age from the Late Cretaceous to the Middle Eocene. Each sub-basin is asymmetric, bounded on one side by a major NW-trending border fault system with large throws (3-6 km in general) with a dominant strata dip direction toward the border fault system. These basins are arranged in en echelon patterns and now form separate elongated ridges surrounded by basement rocks. Our study of the tectonic evolution of the central eastern section of the Gulf of Suez rift and the Northwestern Red Sea has focused on the interaction of pre-existing basement fabrics with the pre-Red Sea structural development. The study involved analysis of LandsatTM images and aerial photographs integrated with results from reconnaissance geological mapping. Our provisional results indicate that the Gebel Um Hammad/Duwi and Hammadat sub-basins were sited in pull-apart structures created by dextral reactivation of E-W to ENE-WSW trending basement fault zones. We show how the basin-bounding fault systems, lower order normal faults and folds in both hangingwall sequences and in basement are compatible with a Late Cretaceous to Early Eocene strike-slip regime. In contrast, the main Red Sea Gulf of Suez rift shows no evidence for strike-slip influence with the main boundary faults cutting across basement fabrics, however, as pointed out by previous authors, rift segmentation

  1. Vertically Aligned Nanoplate Particles Directed by Block Copolymer Domains for Anisotropic Properties

    NASA Astrophysics Data System (ADS)

    Krook, Nadia; Meth, Jeffrey; Murray, Christopher; Riggleman, Robert; Composto, Russell

    During common processing methods, anisotropic fillers in polymer nanocomposites align in the direction of flow, parallel to the surfaces, thus enhancing properties in the plane of the substrate. This research aims to create thin film nanocomposites with perpendicularly aligned anisotropic particles to improve properties in the out-of-plane direction. The demonstrated work explores vertical orientation of rare-earth fluoride nanoplates in lamellar-forming poly(styrene- b-methyl methacrylate) to establish a platform that controls the alignment of any planar particle. Currently, gadolinium fluoride (GdF3) rhombus nanoplates with the longest and shortest diagonal dimensions of ~30 nm and ~25 nm, respectively, have been specially synthesized with the potential to intercalate the block copolymer (BCP) domains. By employing a ternary brush blend layer to neutralize silicon substrates to both BCP domains, vertical lamellae orientation has been enabled with an optimum film thickness of ~110 nm. The GdF3 surfaces are chemically modified to drive the plates to a specific BCP domain. After surface modification, the dispersion of GdF3 in homopolymer will first be shown followed by morphology results from integrating GdF3 into the BCP using scanning and transmission electron microscopy.

  2. Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility — A Review

    PubMed Central

    de Castro, Fernanda Cavallari; Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde

    2016-01-01

    Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-β) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review. PMID:26954112

  3. Genome walk of an unknown upstream region of myostatin gene in Spanish goats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myostatin (MSTN) gene product also known as growth differentiation factor (GDF8) is a member of the TGF-ß family of secreted proteins. It is shown to be a negative regulator of muscle mass development. Mutations in the MSTN gene have been reported in mice, cattle and humans that lead to muscular hyp...

  4. Microbial degradation of isosaccharinic acid at high pH

    PubMed Central

    Bassil, Naji M; Bryan, Nicholas; Lloyd, Jonathan R

    2015-01-01

    Intermediate-level radioactive waste (ILW), which dominates the radioactive waste inventory in the United Kingdom on a volumetric basis, is proposed to be disposed of via a multibarrier deep geological disposal facility (GDF). ILW is a heterogeneous wasteform that contains substantial amounts of cellulosic material encased in concrete. Upon resaturation of the facility with groundwater, alkali conditions will dominate and will lead to the chemical degradation of cellulose, producing a substantial amount of organic co-contaminants, particularly isosaccharinic acid (ISA). ISA can form soluble complexes with radionuclides, thereby mobilising them and posing a potential threat to the surrounding environment or ‘far field'. Alkaliphilic microorganisms sampled from a legacy lime working site, which is an analogue for an ILW-GDF, were able to degrade ISA and couple this degradation to the reduction of electron acceptors that will dominate as the GDF progresses from an aerobic ‘open phase' through nitrate- and Fe(III)-reducing conditions post closure. Furthermore, pyrosequencing analyses showed that bacterial diversity declined as the reduction potential of the electron acceptor decreased and that more specialised organisms dominated under anaerobic conditions. These results imply that the microbial attenuation of ISA and comparable organic complexants, initially present or formed in situ, may play a role in reducing the mobility of radionuclides from an ILW-GDF, facilitating the reduction of undue pessimism in the long-term performance assessment of such facilities. PMID:25062127

  5. 40 CFR 63.11124 - What notifications must I submit and when?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... in § 63.13. (i) The name and address of the owner and the operator. (ii) The address (i.e., physical... and the operator. (ii) The address (i.e., physical location) of the GDF. (iii) A statement that the...)(2) of this subsection. (i) You operate a vapor balance system at your gasoline dispensing...

  6. VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5

    PubMed Central

    Szumska, Dorota; Pieles, Guido; Essalmani, Rachid; Bilski, Michal; Mesnard, Daniel; Kaur, Kulvinder; Franklyn, Angela; El Omari, Kamel; Jefferis, Joanna; Bentham, Jamie; Taylor, Jennifer M.; Schneider, Jurgen E.; Arnold, Sebastian J.; Johnson, Paul; Tymowska-Lalanne, Zuzanna; Stammers, Dave; Clarke, Kieran; Neubauer, Stefan; Morris, Andrew; Brown, Steve D.; Shaw-Smith, Charles; Cama, Armando; Capra, Valeria; Ragoussis, Jiannis; Constam, Daniel; Seidah, Nabil G.; Prat, Annik; Bhattacharya, Shoumo

    2008-01-01

    We have identified an ethylnitrosourea (ENU)-induced recessive mouse mutation (Vcc) with a pleiotropic phenotype that includes cardiac, tracheoesophageal, anorectal, anteroposterior patterning defects, exomphalos, hindlimb hypoplasia, a presacral mass, renal and palatal agenesis, and pulmonary hypoplasia. It results from a C470R mutation in the proprotein convertase PCSK5 (PC5/6). Compound mutants (Pcsk5Vcc/null) completely recapitulate the Pcsk5Vcc/Vcc phenotype, as does an epiblast-specific conditional deletion of Pcsk5. The C470R mutation ablates a disulfide bond in the P domain, and blocks export from the endoplasmic reticulum and proprotein convertase activity. We show that GDF11 is cleaved and activated by PCSK5A, but not by PCSK5A-C470R, and that Gdf11-deficient embryos, in addition to having anteroposterior patterning defects and renal and palatal agenesis, also have a presacral mass, anorectal malformation, and exomphalos. Pcsk5 mutation results in abnormal expression of several paralogous Hox genes (Hoxa, Hoxc, and Hoxd), and of Mnx1 (Hlxb9). These include known Gdf11 targets, and are necessary for caudal embryo development. We identified nonsynonymous mutations in PCSK5 in patients with VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb malformation OMIM 192350) and caudal regression syndrome, the phenotypic features of which resemble the mouse mutation. We propose that Pcsk5, at least in part via GDF11, coordinately regulates caudal Hox paralogs, to control anteroposterior patterning, nephrogenesis, skeletal, and anorectal development. PMID:18519639

  7. Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility - A Review.

    PubMed

    de Castro, Fernanda Cavallari; Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde

    2016-08-01

    Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-β) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review. PMID:26954112

  8. Transgenic overexpression of bone morphogenetic protein 11 propeptide in skeleton enhances bone formation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bone morphogenetic protein 11 (BMP11) is a key regulatory protein in skeletal development. BMP11 propeptide has been shown to antagonize GDF11 activity in vitro. To explore the role of BMP11 propeptide in skeletal formation in vivo, we generated transgenic mice with skeleton-specific overexpression...

  9. Growth differentiation factor 15 may protect the myocardium from no-reflow by inhibiting the inflammatory-like response that predominantly involves neutrophil infiltration

    PubMed Central

    ZHANG, MEI; PAN, KUNYING; LIU, QIANPING; ZHOU, XIN; JIANG, TIEMIN; LI, YUMING

    2016-01-01

    The aim of the current study was to investigate the time course of the expression of growth differentiation factor-15 (GDF-15) in rat ischemic myocardium with increasing durations of reperfusion, and to elucidate its physiopathological role in the no-reflow phenomenon. Wistar rats were randomly divided into ischemia reperfusion (I/R) and sham groups, and myocardial I/R was established by ligation of the left anterior descending coronary artery for 1 h followed by reperfusion for 2, 4, 6, 12, 24 h and 7 days whilst rats in the sham group were subjected to a sham operation. The expression levels of GDF-15 and ICAM-1 were measured, in addition to myeloperoxidase (MPO) activity. The myocardial anatomical no-reflow and infarction areas were assessed. The area at risk was not significantly different following various periods of reperfusion, while the infarct area and no-reflow area were significantly greater following 6 h of reperfusion (P<0.05). The mRNA and protein expression levels of GDF-15 were increased during the onset and development of no-reflow, and peaked following 24 h of reperfusion. MPO activity was reduced with increasing reperfusion duration, while ICAM-1 levels were increased. Hematoxylin and eosin staining demonstrated that myocardial neutrophil infiltration was significantly increased by I/R injury, in particular following 2, 4 and 6 h of reperfusion. GDF-15 expression levels were negatively correlated with MPO activity (r=−0.55, P<0.001), and the MPO activity was negatively correlated with the area of no-reflow (r=−0.46, P<0.01). By contrast, GDF-15 was significantly positively correlated with ICAM-1 levels (r=0.52, P<0.01), which additionally were demonstrated to be significantly positively associated with the size of the no-reflow area (r= 0.39, P<0.05). The current study demonstrated the time course effect of reperfusion on the expression of GDF-15 in the myocardial I/R rat model, with the shorter reperfusion times (6 h) resulting in

  10. Lineage Tracing of Resident Tendon Progenitor Cells during Growth and Natural Healing

    PubMed Central

    Dyment, Nathaniel A.; Hagiwara, Yusuke; Matthews, Brya G.; Li, Yingcui; Kalajzic, Ivo; Rowe, David W.

    2014-01-01

    Unlike during embryogenesis, the identity of tissue resident progenitor cells that contribute to postnatal tendon growth and natural healing is poorly characterized. Therefore, we utilized 1) an inducible Cre driven by alpha smooth muscle actin (SMACreERT2), that identifies mesenchymal progenitors, 2) a constitutively active Cre driven by growth and differentiation factor 5 (GDF5Cre), a critical regulator of joint condensation, in combination with 3) an Ai9 Cre reporter to permanently label SMA9 and GDF5-9 populations and their progeny. In growing mice, SMA9+ cells were found in peritendinous structures and scleraxis-positive (ScxGFP+) cells within the tendon midsubstance and myotendinous junction. The progenitors within the tendon midsubstance were transiently labeled as they displayed a 4-fold expansion from day 2 to day 21 but reduced to baseline levels by day 70. SMA9+ cells were not found within tendon entheses or ligaments in the knee, suggesting a different origin. In contrast to the SMA9 population, GDF5-9+ cells extended from the bone through the enthesis and into a portion of the tendon midsubstance. GDF5-9+ cells were also found throughout the length of the ligaments, indicating a significant variation in the progenitors that contribute to tendons and ligaments. Following tendon injury, SMA9+ paratenon cells were the main contributors to the healing response. SMA9+ cells extended over the defect space at 1 week and differentiated into ScxGFP+ cells at 2 weeks, which coincided with increased collagen signal in the paratenon bridge. Thus, SMA9-labeled cells represent a unique progenitor source that contributes to the tendon midsubstance, paratenon, and myotendinous junction during growth and natural healing, while GDF5 progenitors contribute to tendon enthesis and ligament development. Understanding the mechanisms that regulate the expansion and differentiation of these progenitors may prove crucial to improving future repair strategies. PMID:24759953

  11. Growth-differentiation factor-15, endoglin and N-terminal pro-brain natriuretic peptide induction in athletes participating in an ultramarathon foot race.

    PubMed

    Tchou, Isabelle; Margeli, Alexandra; Tsironi, Maria; Skenderi, Katerina; Barnet, Marc; Kanaka-Gantenbein, Christina; Papassotiriou, Ioannis; Beris, Photis

    2009-09-01

    We investigated the actions of growth-differentiation factor (GDF)-15, endoglin and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in 15 male athletes who participated in the ultradistance foot race of the 246 km 'Sparthathlon'. Measurements were performed before (phase I), at the end of the race (phase II) and 48 h post-race (phase III). GDF-15 and endoglin serum concentrations were determined with enzyme-linked immunosorbent assay and NT-pro-BNP plasma levels by electrochemiluminescence. GDF-15 levels were increased from phase I (563.9 +/- 57.1 pg ml(-1)) to phase II (2311.1 +/- 462.3 pg ml(-1)) and decreased at phase III (862.0 +/- 158.0 pg ml(-1)) (p < 0.0002). NT-pro-BNP levels followed a similar pattern to that of GDF-15 from 38.1 +/- 4.8 pg ml(-1) at phase I to 1280.6 +/- 259.0 pg ml(-1) at phase II and 89.8 +/- 13.6 pg ml(-1) at phase III (p < 0.0001) and at the same time points, endoglin levels were 4.7 +/- 0.2 ng ml(-1) at phase I, 5.8 +/- 0.2 ng ml(-1) at phase II and 4.3 +/- 0.2 ng ml(-1) at phase III (p < 0.002). These findings indicate that circulating GDF-15, endoglin and NT-pro-BNP levels reflect a transient endothelial dysfunction in these athletes who participated in a foot race consisting of continuous, prolonged and brisk exercise. PMID:19563304

  12. Stratified Whole Genome Linkage Analysis of Chiari Type I Malformation Implicates Known Klippel-Feil Syndrome Genes as Putative Disease Candidates

    PubMed Central

    Markunas, Christina A.; Soldano, Karen; Dunlap, Kaitlyn; Cope, Heidi; Asiimwe, Edgar; Stajich, Jeffrey; Enterline, David; Grant, Gerald; Fuchs, Herbert

    2013-01-01

    Chiari Type I Malformation (CMI) is characterized by displacement of the cerebellar tonsils below the base of the skull, resulting in significant neurologic morbidity. Although multiple lines of evidence support a genetic contribution to disease, no genes have been identified. We therefore conducted the largest whole genome linkage screen to date using 367 individuals from 66 families with at least two individuals presenting with nonsyndromic CMI with or without syringomyelia. Initial findings across all 66 families showed minimal evidence for linkage due to suspected genetic heterogeneity. In order to improve power to localize susceptibility genes, stratified linkage analyses were performed using clinical criteria to differentiate families based on etiologic factors. Families were stratified on the presence or absence of clinical features associated with connective tissue disorders (CTDs) since CMI and CTDs frequently co-occur and it has been proposed that CMI patients with CTDs represent a distinct class of patients with a different underlying disease mechanism. Stratified linkage analyses resulted in a marked increase in evidence of linkage to multiple genomic regions consistent with reduced genetic heterogeneity. Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of “CTD-negative” families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS). Interestingly, roughly 3–5% of CMI patients are diagnosed with KFS. In order to investigate the possibility that CMI and KFS are allelic, GDF3 and GDF6 were sequenced leading to the identification of a previously known KFS missense mutation and potential regulatory variants in GDF6. This study has demonstrated the value of reducing genetic heterogeneity by clinical stratification implicating several convincing biological candidates and further supporting the hypothesis that

  13. Investigations of TGF-β signaling in preantral follicles of female mice reveal differential roles for bone morphogenetic protein 15.

    PubMed

    Fenwick, Mark A; Mora, Jocelyn M; Mansour, Yosef T; Baithun, Christina; Franks, Stephen; Hardy, Kate

    2013-09-01

    Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are 2 closely related TGF-β ligands implicated as key regulators of follicle development and fertility. Animals harboring mutations of these factors often exhibit a blockage in follicle development beyond the primary stage and therefore little is known about the role of these ligands during subsequent (preantral) stages. Preantral follicles isolated from immature mice were cultured with combinations of BMP15, GDF9, and activin receptor-like kinase (ALK) inhibitors. Individually, GDF9 and BMP15 promoted follicle growth during the first 24 hours, whereas BMP15 subsequently (48-72 h) caused follicle shrinkage and atresia with increased granulosa cell apoptosis. Inhibition of ALK6 prevented the BMP15-induced reduction in follicle size and under basal conditions promoted a rapid increase in granulosa cell proliferation, suggesting BMP15 signals through ALK6, which in turn acts to restrain follicle growth. In the presence of GDF9, BMP15 no longer promoted atresia and in fact follicle growth was increased significantly more than with either ligand alone. This cooperative effect was accompanied by differential expression of Id1-3, Smad6-7, and Has2 and was blocked by the same ALK5 inhibitor used to block GDF9 signaling. Immunostaining for SMAD2/3 and SMAD1/5/8, representing the 2 main branches of TGF-β signaling, supported the fact that both canonical pathways have the potential to be active in growing follicles, whereas primordial follicles only express SMAD2/3. Overall results highlight differential effects of the 2 main TGF-β signaling pathways during preantral follicle growth. PMID:23782946

  14. The Nile River

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This image of the northern portion of the Nile River was captured by MISR's nadir camera on January 30, 2001 (Terra orbit 5956). The Nile is the longest river in the world, extending for about 6700 kilometers from its headwaters in the highlands of eastern Africa. At the apex of the fertile Nile River Delta is the Egyptian capital city of Cairo. To the west are the Great Pyramids of Giza. North of here the Nile branches into two distributaries, the Rosetta to the west and the Damietta to the east. Also visible in this image is the Suez Canal, a shipping waterway connecting Port Said on the Mediterranean Sea with the Gulf of Suez. The Gulf is an arm of the Red Sea, and is located on the righthand side of the picture. Image credit: NASA/GSFC/LaRC/JPL, MISR Team.

  15. Gamma ray spectrometry logs as a hydrocarbon indicator for clastic reservoir rocks in Egypt.

    PubMed

    Al-Alfy, I M; Nabih, M A; Eysa, E A

    2013-03-01

    Petroleum oil is an important source for the energy in the world. The Gulf of Suez, Nile Delta and South Valley are important regions for studying hydrocarbon potential in Egypt. A thorium normalization technique was applied on the sandstone reservoirs in the three regions to determine the hydrocarbon potentialities zones using the three spectrometric radioactive gamma ray-logs (eU, eTh and K% logs). The conventional well logs (gamma-ray, deep resistivity, shallow resistivity, neutron, density and sonic logs) are analyzed to determine the net pay zones in these wells. Indices derived from thorium normalized spectral logs indicate the hydrocarbon zones in petroleum reservoirs. The results of this technique in the three regions (Gulf of Suez, Nile Delta and South Valley) are in agreement with the results of the conventional well log analyses by ratios of 82%, 78% and 71% respectively. PMID:23306160

  16. Parasitic copepods from Egyptian Red Sea fishes: Bomolochidae Claus, 1875.

    PubMed

    El-Rashidy, Hoda Hassan; Boxshall, Geoffrey Allan

    2016-02-01

    Two species of parasitic copepods from the genus Bomolochus von Nordmann, 1832 (Cyclopoida: Bomolochidae) are redescribed in detail, based on material collected from the gills of Red Sea fishes. Host material was caught at El-tor, near Sharm El-Sheikh, and in the Gulf of Suez, Egypt. Both sexes of Bomolochus bellones Burmeister, 1835 were collected from the gills of a needlefish Tylosurus choram (Rüppell) caught in the Gulf of Suez. This is a new host record. The female is well characterised so only the male is described. Adult females of Bomolochus minus Lin & Ho, 2005 were obtained from the branchial cavities and gills of mojarra Gerres oyena (Forsskål). This species was known only from its original description in Taiwan, and this report constitutes a new host record and a significant range extension. Both parasite species are new records for Egyptian Red Sea waters. PMID:26790683

  17. Seasonal distribution of fleas infesting rodents in various Egyptian eco-geographical areas and their susceptibility to malathion.

    PubMed

    Allam, Kamilia A M; Shalaby, Afaf A; Ashour, Mahmoud A

    2002-08-01

    The rodent population and their ectoparasites especially fleas, in various Egyptian eco-geographical areas were studied It was noticed that flea infestation varied according to rodent species and to the bioclimatic conditions. High flea indices were recorded in certain seasons of the year. The flea index was above one during spring in the southern of Nile Delta and semi-arid coastal areas, in summer in northern coastal areas and in autumn in southern of Nile Delta. Susceptibility tests were conducted using the WHO diagnostic dose of malathion (5%) on three populations of fleas collected from Qualyobia, Suez and Beni-Suef Governorates. The results indicated that malathion (5%) was very effective on fleas collected from Beni-Suef and Suez, but there was an evidence of increased tolerance among flea population collected from Qualyobia Governorate. PMID:12214918

  18. Implementation of MASW and waveform inversion techniques for new seismic hazard estimation technique

    NASA Astrophysics Data System (ADS)

    el-aziz abd el-aal, abd; Kamal, heba

    2016-04-01

    In this contribution, an integrated multi-channel analysis of Surface Waves (MASW) technique is applied to explore the geotechnical parameters of subsurface layers at the Zafarana Wind Farm site. The study area includes many active fault systems along the Gulf of Suez that cause many moderate and large earthquakes. Overall, the seismic activity of the area has recently become better understood following the use of waveform inversion method and software to develop accurate focal mechanism solutions for recent recorded earthquakes around the studied area. These earthquakes resulted in major stress-drops in the Eastern Desert and the Gulf of Suez area. These findings have helped to reshape the understanding of the seismotectonic environment of the Gulf of Suez area, which is a perplexing tectonic domain. Based on the collected new information and data, this study uses new an extended stochastic technique to re-examine the seismic hazard for the Gulf of Suez region, particularly the wind turbine towers sites at Zafarana Wind Farm and its vicinity. The essential characteristics of the extended stochastic technique are to obtain and simulate ground motion in order to minimize future earthquake consequences. The first step of this technique is defining the seismic sources which mostly affect the study area. Then, the maximum expected magnitude is defined for each of these seismic sources. It is followed by estimating the ground motion using an empirical attenuation relationship. Finally, the site amplification is implemented in calculating the peak ground acceleration (PGA) at each site of interest. Key words: MASW, waveform inversion, extended stochastic technique, Zafarana Wind Farm

  19. The Sinai triple junction revisited

    NASA Astrophysics Data System (ADS)

    Courtillot, Vincent; Armijo, Rolando; Tapponnier, Paul

    1987-09-01

    This paper is a summary of a more detailed analysis of the kinematics of the Sinai triple junction (Courtillot et al., 1987). Accurate kinematic data are lacking along the Red Sea and they can be supplemented by bathymetric, topographic and geological data pertaining to the three arms of the entirely continental Sinai triple junction. Motions across the northern Red Sea and along the Gulf of Elat are an order of magnitude larger than across the Gulf of Suez. The direction of motion there remains a major uncertainty. A possible kinematic model is highlighted, in which right-lateral strike-slip motion and small pull-apart basins occur along the Gulf of Suez, in agreement with recent field observations in Egypt. Early Miocene is marked by major geodynamical changes all along the northern boundaries of the African and Indian plates. We suggest that rifting in the Arabian Sea, Gulf of Aden, Red Sea and Gulf of Suez was initiated at the end of the first phase of continental extrusion of Indochina, when the Tibetan plateau began to rise and spreading in the South China Sea came to a halt.

  20. Earthquakes focal mechanism and stress field pattern in the northeastern part of Egypt

    NASA Astrophysics Data System (ADS)

    Mohamed, Emad K.; Hassoup, A.; Abou Elenean, K. M.; Othman, Adel A. A.; Hamed, Diaa-Eldin M. K.

    2015-12-01

    Egypt is characterized by moderate size seismicity where earthquakes are distributed within several active regions. In the present study, we investigated the source mechanism of earthquakes using the digital waveform data recorded by the Egyptian National Seismic Network (ENSN) during the period from 2004 to 2008. The focal mechanisms are constructed with high reliability based on the polarity of the first motion of P-wave. These solutions are used to examine the mode of tectonic deformation and the present-day stress field pattern affecting on different tectonic provinces in the northern part of Egypt. The results demonstrate mainly a normal faulting mechanism with minor strike slip component generally trending parallel to the northern Red Sea, the Suez rift, Aqaba rift with their connection with the great rift system of the Red Sea and the Gulf of Suez and Cairo-Alexandria trend. The inversion technique scheme is used also in the present study for determining the regional stress field parameters for earthquake focal mechanism solutions based on the grid search method of Gephart and Forsyth (1984). The Results of the stress tensor using focal mechanisms of recent earthquakes show a prevailed tension stress field in N52°E, N41°E and N52°E for the northern Red Sea, Gulf of Suez and Gulf of Aqaba zone respectively.

  1. Curie depth map for Sinai Peninsula, Egypt deduced from the analysis of magnetic data

    NASA Astrophysics Data System (ADS)

    Aboud, Essam; Salem, Ahmed; Mekkawi, Mahmoud

    2011-06-01

    Sinai Peninsula is considered as a unique region in the world due to its geographical location, tectonic and thermal activities. It is located geographically at the crossroads of Europe, Asia, and Africa constituting a triple junction point between the three continents. It is also characterized by thermal manifestations represented by several hot springs with varied temperatures (30-70 °C). Most of these hot springs are located along the shoreline of the Gulf of Suez. In this study, we aim to map the Curie depth isotherm surface for Sinai Peninsula based on the analysis of ground magnetic data. Spectral analysis technique will be used to estimate the boundaries (top and bottom) of the magnetized crust. The depths obtained for the bottom of magnetized crust are assumed to correspond to Curie point depths where the magnetic layer loss its magnetization. Results of this study indicate that the shallow Curie depths (~ 15-18 km) are located at the southern part of Sinai Peninsula and along the shoreline of the Gulf of Suez and depths increase (22-25 km) towards the central and north western portions of Sinai Peninsula. The whole average Curie depth point of Sinai Peninsula is about 20 km. Generally, the shallow depths to Curie isotherm indicate that Sinai Peninsula is a promising area for further geothermal exploration particularly near the eastern side of the Gulf of Suez.

  2. Labor, nationalism, and imperialism in eastern Arabia: Britain, the Shaikhs, and the Gulf oil workers in Bahrain, Kuwait and Qatar, 1932-1956

    SciTech Connect

    Saleh, H.M.A.

    1991-01-01

    This study examines the lack of a noticeable indigenous labor movement in the contemporary Gulf Arab countries of Bahrain, Kuwait and Qatar; it focuses on the emergence, after the discovery of oil, of an industrial Gulf labor force, and on the evolution of the British policy towards oil and Gulf oil workers. The period examined begins with the discovery of oil in Bahrain in 1932 (the first such discovery on the Arab side of the Gulf), and ends with the Suez Crisis of 1956. The latter is a watershed event in Gulf history. It is argued that the Suez Crisis was in large part responsible for the long-term defeat of the indigenous labor movement in the Gulf. Attention is given to the parts played by the British Government of India, the Foreign Office, the local Shaikhs, the Gulf nationalists, and by the workers themselves. Policies towards workers passed through two different periods. In the first, 1932-1945, the Government of India had no direct interest in the Gulf labor situation; in the second, 1946-1956, the Foreign Office took increased interest in the welfare of local oil workers, primarily because of the importance of oil to reconstruction of the British economy after the war. However, the Suez Crisis in 1956 convinced the British to withdraw their support for the workers.

  3. [Beriberi, recurrent nutritional disease in a detention house in Côte-d'Ivoire].

    PubMed

    Aké-Tano, O; Konan, E Y; Tetchi, E O; Ekou, F K; Ekra, D; Coulibaly, A; Dagnan, N S

    2011-12-01

    As a re-emerging disease, beriberi caused by a lack of thiamine in food threatens more and more prisons in developing countries. Indeed in 2008, a beriberi epidemic occurred in a detention house of Côte-d'Ivoire called Maca. The goal of our retrospective investigation was to describe this epidemic in order to improve prisoners' health. The study related to 131 subjects, 64% of cases affected (N = 205). The total rate of beriberi attack was estimated at 38.6‰. The mean age was 33; all patients were male and they were detained in "Batiment C" (70.2%), synonymous with heavy punishment. They spent about 28.1 month in Maca. The clinical symptoms were neurological signs (swarming: 41%) and cardiovascular signs (dyspnoea: 42%, thoracic pain: 35%). Half of the patients (51%) presented oedemas of the lower limbs. The rate of healing was about 97% when patients followed treatment. Providing good nutrition to the prisoners and the distribution of vitamin complements will avoid other epidemics. PMID:21336653

  4. Personalized risk assessment of heart failure patients: more perspectives from transforming growth factor super-family members.

    PubMed

    Goletti, S; Gruson, D

    2015-03-30

    More personalized risk assessment of patients with heart failure (HF) is important to develop more tailored based care and for a better allocation of resources. The measurement of biomarkers is now part of the standards of care and is important for the sub-phenotyping of HF patients to demonstrate the activation of pathophysiological pathways engaged in the worsening of HF. The sub-phenotyping of patients can lead therefore to a more personalized selection of the treatment. Several members of the transforming growth factor β (TGF-β) super-family, such as myostatin, activin A, GDF-15 and GDF-11, are involved in cardiac remodeling and the evaluation of their circulating levels might provide new insights to the course of the disease and also to guide prognostication and therapeutic selection of HF patients. PMID:25260834

  5. Non-Invasive Biomarkers for Duchenne Muscular Dystrophy and Carrier Detection.

    PubMed

    Anaya-Segura, Monica Alejandra; García-Martínez, Froylan Arturo; Montes-Almanza, Luis Angel; Díaz, Benjamín-Gomez; Avila-Ramírez, Guillermina; Alvarez-Maya, Ikuri; Coral-Vazquez, Ramón Mauricio; Mondragón-Terán, Paul; Escobar-Cedillo, Rosa Elena; García-Calderón, Noemí; Vazquez-Cardenas, Norma Alejandra; García, Silvia; López-Hernandez, Luz Berenice

    2015-01-01

    Non-invasive biological indicators of the absence/presence or progress of the disease that could be used to support diagnosis and to evaluate the effectiveness of treatment are of utmost importance in Duchenne Muscular Dystrophy (DMD). This neuromuscular disorder affects male children, causing weakness and disability, whereas female relatives are at risk of being carriers of the disease. A biomarker with both high sensitivity and specificity for accurate prediction is preferred. Until now creatine kinase (CK) levels have been used for DMD diagnosis but these fail to assess disease progression. Herein we examined the potential applicability of serum levels of matrix metalloproteinase 9 and matrix metalloproteinase 2, tissue inhibitor of metalloproteinases 1, myostatin (GDF-8) and follistatin (FSTN) as non-invasive biomarkers to distinguish between DMD steroid naïve patients and healthy controls of similar age and also for carrier detection. Our data suggest that serum levels of MMP-9, GDF-8 and FSTN are useful to discriminate DMD from controls (p < 0.05), to correlate with some neuromuscular assessments for DMD, and also to differentiate between Becker muscular dystrophy (BMD) and Limb-girdle muscular dystrophy (LGMD) patients. In DMD individuals under steroid treatment, GDF-8 levels increased as FSTN levels decreased, resembling the proportions of these proteins in healthy controls and also the baseline ratio of patients without steroids. GDF-8 and FSTN serum levels were also useful for carrier detection (p < 0.05). Longitudinal studies with larger cohorts are necessary to confirm that these molecules correlate with disease progression. The biomarkers presented herein could potentially outperform CK levels for carrier detection and also harbor potential for monitoring disease progression. PMID:26091074

  6. MO-G-BRF-07: Optical Characterization of Novel Terbium-Doped Nanophosphors Excited by Clinical Electron and Photon Beams for Potential Use in Molecular Imaging Or Photodynamic Therapy

    SciTech Connect

    Darafsheh, A; Paik, T; Tenuto, M; Najmr, S; Friedberg, J; Murray, C; Finlay, J

    2014-06-15

    Purpose: Optical properties of terbium (Tb3+)-doped gadolinium trifluoride (GdF3) nanoplates irradiated by electron and photon beams were investigated for their potential as optical probes. The contribution of induced Cerenkov radiation in exciting the nanophosphors was investigated as well. Methods: The emission spectra of Terbium-doped GdF3 dispersed in hexane, embedded in tissue mimicking phantoms were collected by an optical fiber connected to a CCD-coupled spectrograph, while the samples were irradiated by a medical linear accelerator with electron beams of energies 6, 9, 12, 16, and 20 MeV or X-ray beams of energies of 6, and 15 MV. The contribution of induced Cerenkov radiation in exciting the nanophosphores was investigated in a dedicated experimental apparatus through optical isolation of the samples and also by using 125 kVp X-ray beams whose energy is below the threshold for generating Cerenkov radiation in that medium. Results: Terbium-doped GdF3 nanoplates show characteristic cathodoluminescence emission peaks at 488, 543, 586, and 619 nm, which are responsible for the characteristic f-f transition of terbium ion. In a series of experiments, the contribution of Cerenkov radiation in the luminescence of such nanophosphors was ruled out. Conclusion: We have characterized the optical properties of Terbium-doped GdF3 nanoplates. Such nanocrystals with emission tunability and high surface area that facilitates attachment with targeting reagents are promising in situ light source candidates for molecular imaging or exciting a photosensitizer for ultralow fluence photodynamic therapy. This work is supported by the Department of Radiation Oncology at the University of Pennsylvania, the American Cancer Society through IRG-78-002-28, and the University of Pennsylvania's Nano/Bio Interface Center through NSEC DMR08-32802.

  7. BMP Receptor Signaling Is Required for Postnatal Maintenance of Articular Cartilage

    PubMed Central

    2004-01-01

    Articular cartilage plays an essential role in health and mobility, but is frequently damaged or lost in millions of people that develop arthritis. The molecular mechanisms that create and maintain this thin layer of cartilage that covers the surface of bones in joint regions are poorly understood, in part because tools to manipulate gene expression specifically in this tissue have not been available. Here we use regulatory information from the mouse Gdf5 gene (a bone morphogenetic protein [BMP] family member) to develop new mouse lines that can be used to either activate or inactivate genes specifically in developing joints. Expression of Cre recombinase from Gdf5 bacterial artificial chromosome clones leads to specific activation or inactivation of floxed target genes in developing joints, including early joint interzones, adult articular cartilage, and the joint capsule. We have used this system to test the role of BMP receptor signaling in joint development. Mice with null mutations in Bmpr1a are known to die early in embryogenesis with multiple defects. However, combining a floxed Bmpr1a allele with the Gdf5-Cre driver bypasses this embryonic lethality, and leads to birth and postnatal development of mice missing the Bmpr1a gene in articular regions. Most joints in the body form normally in the absence of Bmpr1a receptor function. However, articular cartilage within the joints gradually wears away in receptor-deficient mice after birth in a process resembling human osteoarthritis. Gdf5-Cre mice provide a general system that can be used to test the role of genes in articular regions. BMP receptor signaling is required not only for early development and creation of multiple tissues, but also for ongoing maintenance of articular cartilage after birth. Genetic variation in the strength of BMP receptor signaling may be an important risk factor in human osteoarthritis, and treatments that mimic or augment BMP receptor signaling should be investigated as a possible

  8. Bone Morphogenetic Protein 15 in the Pro-Mature Complex Form Enhances Bovine Oocyte Developmental Competence

    PubMed Central

    Sudiman, Jaqueline; Sutton-McDowall, Melanie L.; Ritter, Lesley J.; White, Melissa A.; Mottershead, David G.; Thompson, Jeremy G.; Gilchrist, Robert B.

    2014-01-01

    Developmental competence of in vitro matured (IVM) oocytes needs to be improved and this can potentially be achieved by adding recombinant bone morphogenetic protein 15 (BMP15) or growth differentiation factor (GDF9) to IVM. The aim of this study was to determine the effect of a purified pro-mature complex form of recombinant human BMP15 versus the commercially available bioactive forms of BMP15 and GDF9 (both isolated mature regions) during IVM on bovine embryo development and metabolic activity. Bovine cumulus oocyte complexes (COCs) were matured in vitro in control medium or treated with 100 ng/ml pro-mature BMP15, mature BMP15 or mature GDF9 +/− FSH. Metabolic measures of glucose uptake and lactate production from COCs and autofluorescence of NAD(P)H, FAD and GSH were measured in oocytes after IVM. Following in vitro fertilisation and embryo culture, day 8 blastocysts were stained for cell numbers. COCs matured in medium +/− FSH containing pro-mature BMP15 displayed significantly improved blastocyst development (57.7±3.9%, 43.5±4.2%) compared to controls (43.3±2.4%, 28.9±3.7%) and to mature GDF9+FSH (36.1±3.0%). The mature form of BMP15 produced intermediate levels of blastocyst development; not significantly different to control or pro-mature BMP15 levels. Pro-mature BMP15 increased intra-oocyte NAD(P)H, and reduced glutathione (GSH) levels were increased by both forms of BMP15 in the absence of FSH. Exogenous BMP15 in its pro-mature form during IVM provides a functional source of oocyte-secreted factors to improve bovine blastocyst development. This form of BMP15 may prove useful for improving cattle and human artificial reproductive technologies. PMID:25058588

  9. Tectonic and climatic considerations for deep geological disposal of radioactive waste: A UK perspective.

    PubMed

    McEvoy, F M; Schofield, D I; Shaw, R P; Norris, S

    2016-11-15

    Identifying and evaluating the factors that might impact on the long-term integrity of a deep Geological Disposal Facility (GDF) and its surrounding geological and surface environment is central to developing a safety case for underground disposal of radioactive waste. The geological environment should be relatively stable and its behaviour adequately predictable so that scientifically sound evaluations of the long-term radiological safety of a GDF can be made. In considering this, it is necessary to take into account natural processes that could affect a GDF or modify its geological environment up to 1millionyears into the future. Key processes considered in this paper include those which result from plate tectonics, such as seismicity and volcanism, as well as climate-related processes, such as erosion, uplift and the effects of glaciation. Understanding the inherent variability of process rates, critical thresholds and likely potential influence of unpredictable perturbations represent significant challenges to predicting the natural environment. From a plate-tectonic perspective, a one million year time frame represents a very short segment of geological time and is largely below the current resolution of observation of past processes. Similarly, predicting climate system evolution on such time-scales, particularly beyond 200ka AP is highly uncertain, relying on estimating the extremes within which climate and related processes may vary with reasonable confidence. The paper highlights some of the challenges facing a deep geological disposal program in the UK to review understanding of the natural changes that may affect siting and design of a GDF. PMID:27457674

  10. Feasibility of investigating differential proteomic expression in depression: implications for biomarker development in mood disorders.

    PubMed

    Frye, M A; Nassan, M; Jenkins, G D; Kung, S; Veldic, M; Palmer, B A; Feeder, S E; Tye, S J; Choi, D S; Biernacka, J M

    2015-01-01

    The objective of this study was to determine whether proteomic profiling in serum samples can be utilized in identifying and differentiating mood disorders. A consecutive sample of patients with a confirmed diagnosis of unipolar (UP n=52) or bipolar depression (BP-I n=46, BP-II n=49) and controls (n=141) were recruited. A 7.5-ml blood sample was drawn for proteomic multiplex profiling of 320 proteins utilizing the Myriad RBM Discovery Multi-Analyte Profiling platform. After correcting for multiple testing and adjusting for covariates, growth differentiation factor 15 (GDF-15), hemopexin (HPX), hepsin (HPN), matrix metalloproteinase-7 (MMP-7), retinol-binding protein 4 (RBP-4) and transthyretin (TTR) all showed statistically significant differences among groups. In a series of three post hoc analyses correcting for multiple testing, MMP-7 was significantly different in mood disorder (BP-I+BP-II+UP) vs controls, MMP-7, GDF-15, HPN were significantly different in bipolar cases (BP-I+BP-II) vs controls, and GDF-15, HPX, HPN, RBP-4 and TTR proteins were all significantly different in BP-I vs controls. Good diagnostic accuracy (ROC-AUC⩾0.8) was obtained most notably for GDF-15, RBP-4 and TTR when comparing BP-I vs controls. While based on a small sample not adjusted for medication state, this discovery sample with a conservative method of correction suggests feasibility in using proteomic panels to assist in identifying and distinguishing mood disorders, in particular bipolar I disorder. Replication studies for confirmation, consideration of state vs trait serial assays to delineate proteomic expression of bipolar depression vs previous mania, and utility studies to assess proteomic expression profiling as an advanced decision making tool or companion diagnostic are encouraged. PMID:26645624

  11. Chlorinated and brominated organic contaminants in fish from Shanghai markets: a case study of human exposure.

    PubMed

    Qiu, Yanling; Strid, Anna; Bignert, Anders; Zhu, Zhiliang; Zhao, Jianfu; Athanasiadou, Maria; Athanassiadis, Ioannis; Bergman, Åke

    2012-10-01

    In the present study were two favorite edible fish species for local residents, i.e., mandarin fish and crawfish, collected from the Shanghai market and analyzed for selected organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), hexabromocyclododecane (HBCDD), polybrominated diphenyl ethers (PBDEs) and methoxylated PBDEs (MeO-PBDEs). Efforts were also made to identify the potential sources of these contaminants. Comparable concentrations of hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs) and HBCDD were found in muscle tissue of mandarin fish from Guangdong (GDF), the Pearl River Delta and from Taihu Lake (TLF), the Yangtze River Delta. Levels of chlordanes, PCBs and PBDEs were about one magnitude lower in TLF compared to GDF. The concentrations of OCPs in the butter-like gland of the crawfish (CFB) were 2-5 times of those in the crawfish muscle (CFM) while concentrations of PCBs, PBDEs and MeO-PBDEs were comparable. The different patterns and levels of chlorinated and brominated organohalogen contaminants seen in mandarin fish from GDF and TLF indicates that different types of chemicals might be used in the two delta regions. The present study also shows a good correlation between the concentrations of hexachlorobenzene (HCB) and pentachloroanisol (PCA) in fish for the first time. Fish consumption limits based on chemical contaminants with non-carcinogenic effects were calculated. The estimated maximum daily consumption limit for GDF, TLF, CFM and CFB were 1.5, 2.6, 3.7 and 0.08 kg, respectively, indicating no significant risk regarding the persistent organic pollutants measured in the present study. PMID:22749935

  12. A Tale from TGF-β Superfamily for Thymus Ontogeny and Function

    PubMed Central

    Jurberg, Arnon Dias; Vasconcelos-Fontes, Larissa; Cotta-de-Almeida, Vinícius

    2015-01-01

    Multiple signaling pathways control every aspect of cell behavior, organ formation, and tissue homeostasis throughout the lifespan of any individual. This review takes an ontogenetic view focused on the large superfamily of TGF-β/bone morphogenetic protein ligands to address thymus morphogenesis and function in T cell differentiation. Recent findings on a role of GDF11 for reversing aging-related phenotypes are also discussed. PMID:26441956

  13. Synovial joint morphogenesis requires the chondrogenic action of Sox5 and Sox6 in growth plate and articular cartilage

    PubMed Central

    Dy, Peter; Smits, Patrick; Silvester, Amber; Penzo-Méndez, Alfredo; Dumitriu, Bogdan; Han, Yu; de la Motte, Carol A.; Kingsley, David M.; Lefebvre, Véronique

    2010-01-01

    The mechanisms underlying synovial joint development remain poorly understood. Here we use complete and cell-specific gene inactivation to identify the roles of the redundant chondrogenic transcription factors Sox5 and Sox6 in this process. We show that joint development aborts early in complete mutants (Sox5−/−6−/−). Gdf5 and Wnt9a expression is punctual in articular progenitor cells, but Sox9 downregulation and cell condensation in joint interzones are late. Joint cell differentiation is unsuccessful, regardless of lineage, and cavitation fails. Sox5 and Sox6 restricted expression to chondrocytes in wild-type embryos and continued Erg expression and weak Ihh expression in Sox5−/−6−/− growth plates suggest that growth plate failure contribute to this Sox5−/−6−/− joint morphogenesis block. Sox5/6 inactivation in specified joint cells and chondrocytes (Sox5fl/fl6fl/flCol2Cre) also results in a joint morphogenesis block, whereas Sox5/6 inactivation in specified joint cells only (Sox5fl/fl6fl/flGdf5Cre) results in milder joint defects and normal growth plates. Sox5fl/fl6fl/flGdf5Cre articular chondrocytes remain undifferentiated, as shown by continued Gdf5 expression and pancartilaginous gene downregulation. Along with Prg4 downregulation, these defects likely account for joint tissue overgrowth and incomplete cavitation in adult mice. Together, these data suggest that synovial joint morphogenesis relies on essential roles for Sox5/6 in promoting both growth plate and articular chondrocyte differentiation. PMID:20206616

  14. Potent Paracrine Effects of human induced Pluripotent Stem Cell-derived Mesenchymal Stem Cells Attenuate Doxorubicin-induced Cardiomyopathy

    PubMed Central

    Zhang, Yuelin; Liang, Xiaoting; Liao, Songyan; Wang, Weixin; Wang, Junwen; Li, Xiang; Ding, Yue; Liang, Yingmin; Gao, Fei; Yang, Mo; Fu, Qingling; Xu, Aimin; Chai, Yuet-Hung; He, Jia; Tse, Hung-Fat; Lian, Qizhou

    2015-01-01

    Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can protect cardiomyocytes against anthracycline-induced cardiomyopathy (AIC) through paracrine effects. Nonetheless the paracrine effects of human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) on AIC are poorly understood. In vitro studies reveal that doxorubicin (Dox)-induced reactive oxidative stress (ROS) generation and cell apoptosis in neonatal rat cardiomyocytes (NRCMs) are significantly reduced when treated with conditioned medium harvested from BM-MSCs (BM-MSCs-CdM) or iPSC-MSCs (iPSC-MSCs-CdM). Compared with BM-MSCs-CdM, NRCMs treated with iPSC-MSCs-CdM exhibit significantly less ROS and cell apoptosis in a dose-dependent manner. Transplantation of BM-MSCs-CdM or iPSC-MSCs-CdM into mice with AIC remarkably attenuated left ventricular (LV) dysfunction and dilatation. Compared with BM-MSCs-CdM, iPSC-MSCs-CdM treatment showed better alleviation of heart failure, less cardiomyocyte apoptosis and fibrosis. Analysis of common and distinct cytokines revealed that macrophage migration inhibitory factor (MIF) and growth differentiation factor-15 (GDF-15) were uniquely overpresented in iPSC-MSC-CdM. Immunodepletion of MIF and GDF-15 in iPSC-MSCs-CdM dramatically decreased cardioprotection. Injection of GDF-15/MIF cytokines could partially reverse Dox-induced heart dysfunction. We suggest that the potent paracrine effects of iPSC-MSCs provide novel “cell-free” therapeutic cardioprotection against AIC, and that MIF and GDF-15 in iPSC-MSCs-CdM are critical for these enhanced cardioprotective effects. PMID:26057572

  15. Growth differentiation factor 6 derived from mesenchymal stem/stromal cells reduces age-related functional deterioration in multiple tissues

    PubMed Central

    Hisamatsu, Daisuke; Ohno-Oishi, Michiko; Nakamura, Shiho; Mabuchi, Yo; Naka-Kaneda, Hayato

    2016-01-01

    The senescence-associated secretory phenotype (SASP) has attracted attention as a mechanism that connects cellular senescence to tissue dysfunction, and specific SASP factors have been identified as systemic pro-aging factors. However, little is known about the age-dependent changes in the secretory properties of stem cells. Young, but not old, mesenchymal stem/stromal cells (MSCs) are a well-known source of critical regenerative factors, but the identity of these factors remains elusive. In this study, we identified growth differentiation factor 6 (Gdf6; also known as Bmp13 and CDMP-2) as a regenerative factor secreted from young MSCs. The expression of specific secretory factors, including Gdf6, was regulated by the microRNA (miRNA) miR-17, whose expression declined with age. Upregulation of Gdf6 restored the osteogenic capacity of old MSCs in vitro and exerted positive effects in vivo on aging-associated pathologies such as reduced lymphopoiesis, insufficient muscle repair, reduced numbers of neural progenitors in the brain, and chronic inflammation. Our results suggest that manipulation of miRNA could enable control of the SASP, and that regenerative factors derived from certain types of young cells could be used to treat geriatric diseases. PMID:27311402

  16. Ror2 signaling is required for local upregulation of GFD6 and activation of BMP signaling at the neural plate border.

    PubMed

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

    2016-09-01

    The receptor tyrosine kinase Ror2 is a major Wnt receptor that activates β-catenin-independent signaling and plays a conserved role in the regulation of convergent extension movements and planar cell polarity in vertebrates. Mutations in the ROR2 gene cause recessive Robinow syndrome in humans, a short-limbed dwarfism associated with craniofacial malformations. Here, we show that Ror2 is required for local upregulation of gdf6 at the neural plate border in Xenopus embryos. Ror2 morphant embryos fail to upregulate neural plate border genes and show defects in the induction of neural crest cell fate. These embryos lack the spatially restricted activation of BMP signaling at the neural plate border at early neurula stages, which is required for neural crest induction. Ror2-dependent planar cell polarity signaling is required in the dorsolateral marginal zone during gastrulation indirectly to upregulate the BMP ligand Gdf6 at the neural plate border and Gdf6 is sufficient to rescue neural plate border specification in Ror2 morphant embryos. Thereby, Ror2 links Wnt/planar cell polarity signaling to BMP signaling in neural plate border specification and neural crest induction. PMID:27578181

  17. Effect of Human Ovarian Tissue Vitrification/Warming on the Expression of Genes Related to Folliculogenesis

    PubMed Central

    Shams Mofarahe, Zahra; Ghaffari Novin, Marefat; Jafarabadi, Mina; Salehnia, Mojdeh; Noroozian, Mohsen; Ghorbanmehr, Nassim

    2015-01-01

    Background: Ovarian tissue cryopreservation is an alternative strategy to preserve the fertility of women predicted to undergo premature ovarian failure. This study was designed to evaluate the expression of folliculogenesis-related genes, including factor in the germline alpha (FIGLA), growth differentiation factor-9 (GDF-9), follicle-stimulating hormone receptor (FSHR), and KIT LIGAND after vitrification/warming of human ovarian tissue. Methods: Human ovarian tissue samples were collected from five transsexual women. In the laboratory, the ovarian medullary part was removed by a surgical blade, and the cortical tissue was cut into small pieces. Some pieces were vitrified and warmed and the others were considered as non-vitrified group (control). Follicular normality was assessed with morphological observation by a light microscope, and the expression of FIGLA, KIT LIGAND, GDF-9,, and FSHR genes was examined using real-time RT-PCR in both the vitrified and non-vitrified groups. Results: Overall, 85% of the follicles preserved their normal morphologic feature after warming. The percentage of normal follicles and the expression of FIGLA, KIT LIGAND, GDF-9, and FSHR genes were similar in both vitrified and non-vitrified groups (P > 0.05). Conclusion: Vitrification/warming of human ovarian tissue had no remarkable effect on the expression of folliculogenesis-related genes. PMID:26175108

  18. A Boolean Function for Neural Induction Reveals a Critical Role of Direct Intercellular Interactions in Patterning the Ectoderm of the Ascidian Embryo.

    PubMed

    Ohta, Naoyuki; Waki, Kana; Mochizuki, Atsushi; Satou, Yutaka

    2015-12-01

    A complex system of multiple signaling molecules often produce differential gene expression patterns in animal embryos. In the ascidian embryo, four signaling ligands, Ephrin-A.d (Efna.d), Fgf9/16/20, Admp, and Gdf1/3-r, coordinately induce Otx expression in the neural lineage at the 32-cell stage. However, it has not been determined whether differential inputs of all of these signaling pathways are really necessary. It is possible that differential activation of one of these signaling pathways is sufficient and the remaining signaling pathways are activated in all cells at similar levels. To address this question, we developed a parameter-free method for determining a Boolean function for Otx expression in the present study. We treated activities of signaling pathways as Boolean values, and we also took all possible patterns of signaling gradients into consideration. We successfully determined a Boolean function that explains Otx expression in the animal hemisphere of wild-type and morphant embryos at the 32-cell stage. This Boolean function was not inconsistent with three sensing patterns, which represented whether or not individual cells received sufficient amounts of the signaling molecules. These sensing patterns all indicated that differential expression of Otx in the neural lineage is primarily determined by Efna.d, but not by differential inputs of Fgf9/16/20, Admp, and Gdf1/3-r signaling. To confirm this hypothesis experimentally, we simultaneously knocked-down Admp, Gdf1/3-r, and Fgf9/16/20, and treated this triple morphant with recombinant bFGF and BMP4 proteins, which mimic Fgf9/16/20 and Admp/Gdf1/3-r activity, respectively. Although no differential inputs of Admp, Gdf1/3-r and Fgf9/16/20 signaling were expected under this experimental condition, Otx was expressed specifically in the neural lineage. Thus, direct cell-cell interactions through Efna.d play a critical role in patterning the ectoderm of the early ascidian embryo. PMID:26714026

  19. Correlation consistent basis sets for lanthanides: The atoms La-Lu.

    PubMed

    Lu, Qing; Peterson, Kirk A

    2016-08-01

    Using the 3rd-order Douglas-Kroll-Hess (DKH3) Hamiltonian, all-electron correlation consistent basis sets of double-, triple-, and quadruple-zeta quality have been developed for the lanthanide elements La through Lu. Basis sets designed for the recovery of valence correlation (defined here as 4f5s5p5d6s), cc-pVnZ-DK3, and outer-core correlation (valence + 4s4p4d), cc-pwCVnZ-DK3, are reported (n = D, T, and Q). Systematic convergence of both Hartree-Fock and correlation energies towards their respective complete basis set (CBS) limits are observed. Benchmark calculations of the first three ionization potentials (IPs) of La through Lu are reported at the DKH3 coupled cluster singles and doubles with perturbative triples, CCSD(T), level of theory, including effects of correlation down through the 4s electrons. Spin-orbit coupling is treated at the 2-component HF level. After extrapolation to the CBS limit, the average errors with respect to experiment were just 0.52, 1.14, and 4.24 kcal/mol for the 1st, 2nd, and 3rd IPs, respectively, compared to the average experimental uncertainties of 0.03, 1.78, and 2.65 kcal/mol, respectively. The new basis sets are also used in CCSD(T) benchmark calculations of the equilibrium geometries, atomization energies, and heats of formation for Gd2, GdF, and GdF3. Except for the equilibrium geometry and harmonic frequency of GdF, which are accurately known from experiment, all other calculated quantities represent significant improvements compared to the existing experimental quantities. With estimated uncertainties of about ±3 kcal/mol, the 0 K atomization energies (298 K heats of formation) are calculated to be (all in kcal/mol): 33.2 (160.1) for Gd2, 151.7 (-36.6) for GdF, and 447.1 (-295.2) for GdF3. PMID:27497543

  20. Correlation consistent basis sets for lanthanides: The atoms La-Lu

    NASA Astrophysics Data System (ADS)

    Lu, Qing; Peterson, Kirk A.

    2016-08-01

    Using the 3rd-order Douglas-Kroll-Hess (DKH3) Hamiltonian, all-electron correlation consistent basis sets of double-, triple-, and quadruple-zeta quality have been developed for the lanthanide elements La through Lu. Basis sets designed for the recovery of valence correlation (defined here as 4f5s5p5d6s), cc-pVnZ-DK3, and outer-core correlation (valence + 4s4p4d), cc-pwCVnZ-DK3, are reported (n = D, T, and Q). Systematic convergence of both Hartree-Fock and correlation energies towards their respective complete basis set (CBS) limits are observed. Benchmark calculations of the first three ionization potentials (IPs) of La through Lu are reported at the DKH3 coupled cluster singles and doubles with perturbative triples, CCSD(T), level of theory, including effects of correlation down through the 4s electrons. Spin-orbit coupling is treated at the 2-component HF level. After extrapolation to the CBS limit, the average errors with respect to experiment were just 0.52, 1.14, and 4.24 kcal/mol for the 1st, 2nd, and 3rd IPs, respectively, compared to the average experimental uncertainties of 0.03, 1.78, and 2.65 kcal/mol, respectively. The new basis sets are also used in CCSD(T) benchmark calculations of the equilibrium geometries, atomization energies, and heats of formation for Gd2, GdF, and GdF3. Except for the equilibrium geometry and harmonic frequency of GdF, which are accurately known from experiment, all other calculated quantities represent significant improvements compared to the existing experimental quantities. With estimated uncertainties of about ±3 kcal/mol, the 0 K atomization energies (298 K heats of formation) are calculated to be (all in kcal/mol): 33.2 (160.1) for Gd2, 151.7 (-36.6) for GdF, and 447.1 (-295.2) for GdF3.

  1. A Boolean Function for Neural Induction Reveals a Critical Role of Direct Intercellular Interactions in Patterning the Ectoderm of the Ascidian Embryo

    PubMed Central

    Mochizuki, Atsushi; Satou, Yutaka

    2015-01-01

    A complex system of multiple signaling molecules often produce differential gene expression patterns in animal embryos. In the ascidian embryo, four signaling ligands, Ephrin-A.d (Efna.d), Fgf9/16/20, Admp, and Gdf1/3-r, coordinately induce Otx expression in the neural lineage at the 32-cell stage. However, it has not been determined whether differential inputs of all of these signaling pathways are really necessary. It is possible that differential activation of one of these signaling pathways is sufficient and the remaining signaling pathways are activated in all cells at similar levels. To address this question, we developed a parameter-free method for determining a Boolean function for Otx expression in the present study. We treated activities of signaling pathways as Boolean values, and we also took all possible patterns of signaling gradients into consideration. We successfully determined a Boolean function that explains Otx expression in the animal hemisphere of wild-type and morphant embryos at the 32-cell stage. This Boolean function was not inconsistent with three sensing patterns, which represented whether or not individual cells received sufficient amounts of the signaling molecules. These sensing patterns all indicated that differential expression of Otx in the neural lineage is primarily determined by Efna.d, but not by differential inputs of Fgf9/16/20, Admp, and Gdf1/3-r signaling. To confirm this hypothesis experimentally, we simultaneously knocked-down Admp, Gdf1/3-r, and Fgf9/16/20, and treated this triple morphant with recombinant bFGF and BMP4 proteins, which mimic Fgf9/16/20 and Admp/Gdf1/3-r activity, respectively. Although no differential inputs of Admp, Gdf1/3-r and Fgf9/16/20 signaling were expected under this experimental condition, Otx was expressed specifically in the neural lineage. Thus, direct cell–cell interactions through Efna.d play a critical role in patterning the ectoderm of the early ascidian embryo. PMID:26714026

  2. Effects of growth factors on the proliferation of human keratinocytes and fibroblasts in vitro.

    PubMed

    Kim, D S; Korting, H C; Schäfer-Korting, M

    1998-01-01

    Growth/differentiation factor-5 (GDF-5) is a new member of the transforming growth factor-beta (TGF-beta) superfamily of multifunctional peptide growth factors that appear to mediate many key events in cell growth and development. The effects of GDF-5 and other growth factors (epidermal growth factor, EGF; TGF-beta 1) on the proliferation of human keratinocytes and fibroblasts compared with desoximetasone and calcipotriol have been investigated. The proliferation rate was determined by a hemocytometer, MTT assay and the incorporation of [3H]-thymidine. Moreover, cell cycle analyses were performed and the influence on interleukin-1 alpha (IL-1 alpha) production in keratinocytes was measured by enzyme-linked immunosorbent assay (ELISA) because of its pronounced proinflammatory effect. In keratinocytes, GDF-5 stimulated cell proliferation to a minor extent. The drug already proved to be effective at very low concentrations (0.1 ng/ml). Growth stimulatory effects with EGF have been observed only in keratinocyte basal medium (KBM), but not in keratinocyte growth medium (KGM). TGF-beta 1 markedly inhibited the proliferation of keratinocytes at concentrations > 1 ng/ml. Calcipotriol and desoximetasone also showed a dose-dependent cell growth inhibition in epidermal cell cultures. IL-1 alpha synthesis was greatly suppressed by calcipotriol 10(-8)-10(-6) M. EGF at 10 ng/ml, in contrast, strongly stimulated IL-1 alpha production. Neither GDF-5 nor TGF-beta 1 had a significant effect on IL-1 alpha production in keratinocyte monolayer cultures. In fibroblasts, GDF-5 induced very weak antiproliferative effects. Calcipotriol and desoximetasone also inhibited cell growth in fibroblast cultures whereas proliferation and DNA synthesis were strongly stimulated by 1 ng/ml EGF. There was, however, a contradiction between TGF-beta 1 results on fibroblasts. Whereas TGF-beta 1 increased proliferation in cell number determination and in the thymidine incorporation assay, MTT assays showed

  3. Tectonic framework of northeast Egypt and its bearing on hydrocarbon exploration

    SciTech Connect

    Khalil, M.; Moustafa, A.R.

    1995-08-01

    Detailed structural study of northern and central Sinai, the northern Eastern Desert, and the northern Gulf of Suez clarified the tectonic framework of northeast Egypt. This framework is related to the movements between the African Plate and the Eurasian and Arabian Plates. Late Cretaceous folding and thrusting in response to oblique convergence between the African and Eurasian Plates formed NE-ENE oriented, doubly plunging, en echelon folds of the northern Egypt fold belt. This fold belt is well exposed in northern Sinai and a few other places but is concealed under younger sediments in the other parts of northern Egypt. Younger folding of local importance is related to dextral slip on the Themed Fault (Central Sinai) in post Middle Eocene-pre Miocene time. Early Miocene rifting of the Afro-Arabian Plate led to the opening of the Suez rift and deposition of significant syn-rift facies. Half grabens and tilted fault blocks dominate the rift. Slightly tilted fault blocks characterize the competent Middle Eocene limestones of the Eastern Desert south of the Cairo-Suez road but north of this road, Middle Eocene rocks are locally dragged on nearby E-W and NW-SE oriented faults forming fault-drag folds. Ductile Upper Eocene and Miocene rocks are also folded about gentle NW-SE oriented doubly plunging folds. The different stages of tectonic activity in northern Egypt contributed to the development of different types of structural traps as well as different source, reservoir, and cap rocks. The sedimentary history of the region indicates well developed marine sediments of Jurassic, Cretaceous, Eocene, and Miocene ages. Basin development in structurally low areas provided good sites for hydrocarbon generation and maturation.

  4. Seawater Polluted with Highly Concentrated Polycyclic Aromatic Hydrocarbons Suppresses Osteoblastic Activity in the Scales of Goldfish, Carassius auratus.

    PubMed

    Suzuki, Nobuo; Sato, Masayuki; Nassar, Hossam F; Abdel-Gawad, Fagr Kh; Bassem, Samah M; Yachiguchi, Koji; Tabuchi, Yoshiaki; Endo, Masato; Sekiguchi, Toshio; Urata, Makoto; Hattori, Atsuhiko; Mishima, Hiroyuki; Shimasaki, Youhei; Oshima, Yuji; Hong, Chun-Sang; Makino, Fumiya; Tang, Ning; Toriba, Akira; Hayakawa, Kazuichi

    2016-08-01

    We have developed an original in vitro bioassay using teleost scale, that has osteoclasts, osteoblasts, and bone matrix as each marker: alkaline phosphatase (ALP) for osteoblasts and tartrate-resistant acid phosphatase (TRAP) for osteoclasts. Using this scale in vitro bioassay, we examined the effects of seawater polluted with highly concentrated polycyclic aromatic hydrocarbons (PAHs) and nitro-polycyclic aromatic hydrocarbons (NPAHs) on osteoblastic and osteoclastic activities in the present study. Polluted seawater was collected from two sites (the Alexandria site on the Mediterranean Sea and the Suez Canal site on the Red Sea). Total levels of PAHs in the seawater from the Alexandria and Suez Canal sites were 1364.59 and 992.56 ng/l, respectively. We were able to detect NPAHs in both seawater samples. Total levels of NPAHs were detected in the seawater of the Alexandria site (12.749 ng/l) and the Suez Canal site (3.914 ng/l). Each sample of polluted seawater was added to culture medium at dilution rates of 50, 100, and 500, and incubated with the goldfish scales for 6 hrs. Thereafter, ALP and TRAP activities were measured. ALP activity was significantly suppressed by both polluted seawater samples diluted at least 500 times, but TRAP activity did not change. In addition, mRNA expressions of osteoblastic markers (ALP, osteocalcin, and the receptor activator of the NF-κB ligand) decreased significantly, as did the ALP enzyme activity. In fact, ALP activity decreased on treatment with PAHs and NPAHs. We conclude that seawater polluted with highly concentrated PAHs and NPAHs influences bone metabolism in teleosts. PMID:27498800

  5. Nile River Delta, Egypt

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The Nile River Delta of Egypt (30.0N, 31.0E) irrigated by the Nile River and its many distributaries, is some of the richest farm land in the world and home to some 45 million people, over half of Egypt's population. The capital city of Cairo is at the apex of the delta. Just across the river from Cairo can be seen the ancient three big pyramids and sphinx at Giza and the Suez Canal is just to the right of the delta.

  6. Nile Delta, Egypt

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The Nile Delta of Egypt (30.0N, 31.0E) irrigated by the Nile River and its many distributaries, is some of the richest farm land in the world and home to some 45 million people, over half of Egypt's population of 57 million. The capital city of Cairo is at the apex of the delta in the middle of the scene. Across the river from Cairo can be seen the three big pyramids and sphinx at Giza and the Suez Canal is just to the right of the delta.

  7. Economic diplomacy. The political dynamics of oil leverage

    SciTech Connect

    Daoudi, M.S.; Dajani, M.S.

    1985-01-01

    This study probes the 1973-1974 Arab oil embargo, detailing its history, the motivations that caused it and its ripple effect on world politics and the international economic order. The authors examine the interruption of oil supplies to Western Europe during the 1956 Suez Canal crisis, the growing momentum of Arab oil leverage beginning with the First Arab Petroleum Congress in 1959, the decline of the oil companies' domination of the petroleum industry, and the Arab political environment between the 1967 Arab defeat and the 1973 Arab oil embargo. The book concludes with a discussion of the lessons to be learned from the recent embargoes.

  8. Egyptian exploration: background, models, and future potential

    SciTech Connect

    Kanes, W.H.; Abdine, S.

    1983-03-01

    Egypt has proven to be an area with excelllnt exploration potential. Recent discoveries in the Western Desert tilted fault blocks are leading to a reevaluation of new play concepts based on an east-west Tethyan rift structure model. Facies favorable to hydrocarbon accumulation are associated with shallow-water marine depositional environments. Production has not been great on a per-well basis, but fields have consistently out-produced the original recoverable reserve estimates. The Gulf of Suez lies within the rift between North Africa and Arabia-Sinai. It remains a major producing area with production from sandstones which range in age from Carboniferous to Cretaceous. The Upper Cretaceous and Lower Tertiary carbonates are potentially attractive zones, as are the Miocene clastics and carbonates. Miocene marls and Upper Cretaceous shales are source rocks, and thermal maturation can be directly related to continental rifting with the oil window most attractive in the southern third of the Gulf of Suez. Structural style is strongly rift-influenced with tilted and locally eroded hosts prevalent. The central gulf has a general eastern dip, whereas the northern and southern areas have a regional westward dip. This has had a direct influence in isolating some major oil fields and has adversely affected reflection seismic surveys. Exploration has been difficult because of excessive Miocene and younger salt thicknesses. With increasingly refined technology, attractive targets now are being delineated in the hitherto unexplored lows between horsts within the gulf.

  9. Factors governing the deep ventilation of the Red Sea

    NASA Astrophysics Data System (ADS)

    Papadopoulos, Vassilis P.; Zhan, Peng; Sofianos, Sarantis S.; Raitsos, Dionysios E.; Qurban, Mohammed; Abualnaja, Yasser; Bower, Amy; Kontoyiannis, Harilaos; Pavlidou, Alexandra; Asharaf, T. T. Mohamed; Zarokanellos, Nikolaos; Hoteit, Ibrahim

    2015-11-01

    A variety of data based on hydrographic measurements, satellite observations, reanalysis databases, and meteorological observations are used to explore the interannual variability and factors governing the deep water formation in the northern Red Sea. Historical and recent hydrographic data consistently indicate that the ventilation of the near-bottom layer in the Red Sea is a robust feature of the thermohaline circulation. Dense water capable to reach the bottom layers of the Red Sea can be regularly produced mostly inside the Gulfs of Aqaba and Suez. Occasionally, during colder than usual winters, deep water formation may also take place over coastal areas in the northernmost end of the open Red Sea just outside the Gulfs of Aqaba and Suez. However, the origin as well as the amount of deep waters exhibit considerable interannual variability depending not only on atmospheric forcing but also on the water circulation over the northern Red Sea. Analysis of several recent winters shows that the strength of the cyclonic gyre prevailing in the northernmost part of the basin can effectively influence the sea surface temperature (SST) and intensify or moderate the winter surface cooling. Upwelling associated with periods of persistent gyre circulation lowers the SST over the northernmost part of the Red Sea and can produce colder than normal winter SST even without extreme heat loss by the sea surface. In addition, the occasional persistence of the cyclonic gyre feeds the surface layers of the northern Red Sea with nutrients, considerably increasing the phytoplankton biomass.

  10. The Red Sea Basin Province: Sudr-Nubia(!) and Maqna(!) Petroleum Systems

    USGS Publications Warehouse

    Lindquist, Sandra J.

    1999-01-01

    The Sudr-Nubia(!) oil-prone total petroleum system dominates the densely explored Gulf of Suez part of the rifted Red Sea Basin Province. Upper Cretaceous to Eocene source rocks, primarily the Senonian Sudr Formation, are organic-rich, areally uniform marine carbonates that have generated known ultimate recoverable reserves exceeding 11 BBOE. The name Nubia is used for sandstone reservoirs with a wide range of poorly constrained, pre-rift geologic ages ranging from Early Paleozoic to Early Cretaceous. Syn- and post-rift Tertiary reservoirs, especially the Kareem Formation, also contain significant reserves. Partly overlapping Sudr-Nubia(!) is the areally larger and geochemically distinct, oil-and-gas-prone Maqna(!) total petroleum system within the southern Gulf of Suez basin and the sparsely explored remaining Red Sea basin. Known ultimate recoverable reserves are 50-100 MMBOE and more than 900 MMBOE, respectively, in those areas. Both the source and reservoir rocks in this petroleum system are Tertiary, dominantly Miocene, in age. Maqna(!) has the greater potential for future resource development.

  11. Influence of BMP-2 on early follicular development and mRNA expression of oocyte specific genes in bovine preantral follicles cultured in vitro.

    PubMed

    Rossi, Rodrigo O D S; da Cunha, Ellen V; Portela, Antonia M L R; Passos, José R S; Costa, José J N; Silva, Anderson W B; Saraiva, Márcia V A; Peixoto, Christina A; Donato, Mariana A M; van den Hurk, Robert; Silva, José R V

    2016-03-01

    This study evaluates the effect of different concentrations (0, 10, 50 and 100ng/mL) of bone morphogenetic protein-2 (BMP-2) on primordial and secondary follicle development. It also investigates the effects of FSH and BMP-2 on the growth, morphology, ultrastructure and expression of mRNA for GDF9, NLRP5 and NPM2 genes in secondary follicles cultured for 18 days. The presence of BMP-2 at all tested concentrations increased the development of primordial follicles in vitro, but the highest concentration of BMP-2 (100 ng/mL) reduced the percentage of normal follicles when compared with tissues cultured with 10 ng/mL BMP-2. During culture of secondary follicles, in contrast to higher concentrations (50 or 100 ng/mL), 10 ng/mL BMP-2 kept the morphology of follicles during initial stages of in vitro culture. This concentration of BMP-2 also benefits maintenance of the ultrastructure of 18-day cultured follicles. The presence of both BMP-2 and FSH in culture medium resulted in a significant (P<0.05) increase in follicular diameter after 18 days of culture. However, both FSH and BMP-2 reduced follicular mRNA expression of GDF9 and NLRP5 when compared to follicles cultured in media containing only FSH. In combination with FSH, BMP-2 reduced the mRNA levels of NPM2, when compared to follicles cultured in control medium. It is concluded from these data that 10 ng/mL BMP-2 promotes the growth of primordial in vitro and it helps to maintain the ultrastructure of secondary follicles, while FSH is more important for better expression of follicular markers like GDF9 and NLRP5. PMID:26435174

  12. Inflammatory biomarkers predicting prognosis in patients with acute dyspnea☆☆☆★

    PubMed Central

    Wiklund, Karolin; Gränsbo, Klas; Lund, Nathalie; Peyman, Marjaneh; Tegner, Lena; Toni-Bengtsson, Maria; Wieloch, Mattias; Melander, Olle

    2016-01-01

    Objective/Purpose The objective was to identify inflammatory biomarkers that predict risk of 90-day mortality in patients with acute dyspnea. Method We analyzed 25 inflammatory biomarkers, in plasma, in 407 adult patients admitted to the emergency department (ED) with acute dyspnea and related them to risk of 90-day mortality using Cox proportional hazard models adjusted for age, sex, oxygen saturation, respiratory rate, C-reactive protein, and Medical Emergency Triage and Treatment System–Adult score. Results Fifty patients (12%) died within 90 day from admission. Two strong and independent biomarker signals were detected: The hazard ratio (95% confidence interval) for 90-day mortality per 1-SD increment of interleukin-8 (IL-8) was 2.20 (1.67-2.90) (P = 2.5 × 10− 8) and for growth differentiation factor–15 (GDF-15) was 3.45 (2.18-5.45) (P = 1.3 × 10− 7) A Biomarker Mortality Risk Score (BMRS) summing standardized and weighted values of IL-8 and GDF-15 revealed that of patients belonging to quartile 1 (Q1) of the BMRS, only 1 patient died, whereas 32 patients died among those belonging to quartile 4. Each 1-SD increment of the BMRS was associated with a hazard ratio of 3.79 (2.50-5.73) (P = 2 × 10− 10) for 90-day mortality, and the point estimate was 13 times higher in Q4 as compared with Q1 of the BMRS (Ptrend over quartiles = 2 × 10− 6). Conclusion Interleukin-8 and GDF-15 are strongly and independently related to risk of 90-day mortality in unselected patients admitted to the ED because of acute dyspnea, suggesting that they may guide first-line physicians at the ED in risk assessment which in turn could lead to more accurate level of care and treatment intensity. PMID:26740417

  13. Atmospheric Aerosols in the Guánica Dry Forest

    NASA Astrophysics Data System (ADS)

    Colón-Cresp, L. J.; Mayol-Bracero, O. L.; Formenti, P.; Mazzei, F.

    2009-05-01

    Aerosols posses a substantial influence over the development and alteration of climate dynamics on the Caribbean. Among the principal sources of particulate matter that influence this region are the North African desert area, from which dust particles are usually transported by the trade winds, and anthropogenic activities that involve the combustion of fossil fuel. These types of aerosols have the potential to alter forests, among other multiple environments. This study focuses on the effects this type of aerosols can exert on Guánica's Dry Forest (GDF) in Puerto Rico. The GDF is one of the most intact mature dry forests in the Caribbean, is a place that has been chosen as the Atlantic Neotropical core site in the National Ecological Observatory Network (NEON), and is an UNESCO Man and Biosphere Reserve. To chemically characterize the aerosol inputs to the GDF, aerosol samples were collected using Stacked-Filter Units. Samples were analyzed using a thermal-optical analyzer (EC/OC analyzer) to determine the concentrations of organic and elemental carbon. X-ray Fluorescence (XRF) and Inductively coupled plasma (ICP) were also used to determine the elemental concentrations of different ions species. Preliminary ICP results showed the presence of Al, Na, Mg, Fe, and Ca in higher concentrations in the coarse than in the fine fraction, suggesting the influence of mineral dust. This was confirmed by back trajectory analyses using the NOAA HYSPLIT model. The EC/OC analyses showed low organic carbon concentrations during African dust events, which was expected since African dust particles are mainly inorganic. Elemental Carbon concentrations were also very low, showing that the study site had little anthropogenic influence. Results related to the elemental composition as determined using XRF and ICP analyses will also be presented at the meeting.

  14. Neonatal exposure to xenoestrogens impairs the ovarian response to gonadotropin treatment in lambs.

    PubMed

    Rivera, Oscar E; Varayoud, Jorgelina; Rodríguez, Horacio A; Santamaría, Clarisa G; Bosquiazzo, Verónica L; Osti, Mario; Belmonte, Norberto M; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2015-06-01

    Bisphenol A (BPA) and diethylstilbestrol (DES) are xenoestrogens, which have been associated with altered effects on reproduction. We hypothesized that neonatal xenoestrogen exposure affects the ovarian functionality in lambs. Thus, we evaluated the ovarian response to exogenous ovine FSH (oFSH) administered from postnatal day 30 (PND30) to PND32 in female lambs previously exposed to low doses of DES or BPA (BPA50: 50 μg/kg per day, BPA0.5: 0.5 μg/kg per day) from PND1 to PND14. We determined: i) follicular growth, ii) circulating levels of 17β-estradiol (E2), iii) steroid receptors (estrogen receptor alpha, estrogen receptor beta, and androgen receptor (AR)) and atresia, and iv) mRNA expression levels of the ovarian bone morphogenetic protein (BMPs) system (BMP6, BMP15, BMPR1B, and GDF9) and FSH receptor (FSHR). Lambs neonatally exposed to DES or BPA showed an impaired ovarian response to oFSH with a lower number of follicles ≥2 mm in diameter together with a lower number of atretic follicles and no increase in E2 serum levels in response to oFSH treatment. In addition, AR induction by oFSH was disrupted in granulosa and theca cells of lambs exposed to DES or BPA. An increase in GDF9 mRNA expression levels was observed in oFSH-primed lambs previously treated with DES or BPA50. In contrast, a decrease in BMPR1B was observed in BPA0.5-postnatally exposed lambs. The modifications in AR, GDF9, and BMPR1B may be associated with the altered ovarian function due to neonatal xenoestrogen exposure in response to an exogenous gonadotropin stimulus. These alterations may be the pathophysiological basis of subfertility syndrome in adulthood. PMID:25778539

  15. Anoxic Biodegradation of Isosaccharinic Acids at Alkaline pH by Natural Microbial Communities

    PubMed Central

    Rout, Simon P.; Charles, Christopher J.; Doulgeris, Charalampos; McCarthy, Alan J.; Rooks, Dave J.; Loughnane, J. Paul; Laws, Andrew P.; Humphreys, Paul N.

    2015-01-01

    One design concept for the long-term management of the UK’s intermediate level radioactive wastes (ILW) is disposal to a cementitious geological disposal facility (GDF). Under the alkaline (10.013.0) anoxic conditions expected within a GDF, cellulosic wastes will undergo chemical hydrolysis. The resulting cellulose degradation products (CDP) are dominated by α- and β-isosaccharinic acids (ISA), which present an organic carbon source that may enable subsequent microbial colonisation of a GDF. Microcosms established from neutral, near-surface sediments demonstrated complete ISA degradation under methanogenic conditions up to pH 10.0. Degradation decreased as pH increased, with β-ISA fermentation more heavily influenced than α-ISA. This reduction in degradation rate was accompanied by a shift in microbial population away from organisms related to Clostridium sporosphaeroides to a more diverse Clostridial community. The increase in pH to 10.0 saw an increase in detection of Alcaligenes aquatilis and a dominance of hydrogenotrophic methanogens within the Archaeal population. Methane was generated up to pH 10.0 with acetate accumulation at higher pH values reflecting a reduced detection of acetoclastic methanogens. An increase in pH to 11.0 resulted in the accumulation of ISA, the absence of methanogenesis and the loss of biomass from the system. This study is the first to demonstrate methanogenesis from ISA by near surface microbial communities not previously exposed to these compounds up to and including pH 10.0. PMID:26367005

  16. Retinoic acid receptor gamma-induced misregulation of chondrogenesis in the murine limb bud in vitro.

    PubMed

    Galdones, Eugene; Hales, Barbara F

    2008-11-01

    Vitamin A derivatives modulate gene expression through retinoic acid and rexinoid receptor (RAR/RXR) heterodimers and are indispensable for limb development. Of particular interest, RARgamma is highly expressed in cartilage, a target affected following retinoid-induced limb insult. The goal of this study was to examine how selective activation of RARgamma affects limb development. Forelimbs from E12.5 CD-1 mice were cultured for 6 days in the presence of all-trans RA (pan-RAR agonist; 0.1 or 1.0 microM) or BMS-189961 (BMS961, RARgamma-selective agonist; 0.01 or 0.1 microM) and limb morphology assessed. Untreated limbs developed normal cartilage elements whereas pan-RAR or RARgamma agonist-treated limbs exhibited reductive effects on chondrogenesis. Retinoid activity was assessed using RAREbeta2 (retinoic acid response element beta2)-lacZ reporter limbs; after 3 h of treatment, both drugs increased retinoid activity proximally. To elucidate the expression profiles of a subset of genes important for development, limbs were cultured for 3 h and cRNA hybridized to osteogenesis-focused microarrays. Two genes, matrix GLA protein (Mgp; chondrogenesis inhibitor) and growth differentiation factor-10 (Gdf10/Bmp3b) were induced by RA and BMS-189961. Real-time PCR was done to validate our results and whole mount in situ hybridizations against Mgp and Gdf10 localized their upregulation to areas of cartilage and programmed cell death, respectively. Thus, our results illustrate the importance of RARgamma in mediating the retinoid-induced upregulation of Mgp and Gdf10; determining their roles in chondrogenesis and cell death will help further unravel mechanisms underlying retinoid teratogenicity. PMID:18703560

  17. Evolutionary genetics and implications of small size and twinning in callitrichine primates

    PubMed Central

    Harris, R. Alan; Tardif, Suzette D.; Vinar, Tomas; Wildman, Derek E.; Rutherford, Julienne N.; Rogers, Jeffrey; Worley, Kim C.; Aagaard, Kjersti M.

    2014-01-01

    New World monkeys (NWMs) are characterized by an extensive size range, with clawed NWMs (subfamily Callitrichinae, or callitrichines) such as the common marmoset manifesting diminutive size and unique reproductive adaptations. Perhaps the most notable of these adaptations is their propensity toward multiple gestations (i.e., dichorionic twins and trichorionic triplets). Indeed, with the exception of Goeldi’s monkey (Callimico), callitrichine singleton pregnancies rarely occur. Multiple gestations seem to have coevolved with a suite of reproductive adaptations, including hematopoetic chimerism of siblings, suppression of reproduction in nondominant females, and cooperative alloparenting. The sequencing of the common marmoset (Callithrix jacchus) genome offers the opportunity to explore the genetic basis of these unusual traits within this primate lineage. In this study, we hypothesized that genetic changes arising during callitrichine evolution resulted in multiple ovulated ova with each cycle, and that these changes triggered adaptations that minimized complications common to multiple gestations in other primates, including humans. Callitrichine-specific nonsynonymous substitutions were identified in GDF9, BMP15, BMP4, and WFIKKN1. WFIKKN1, a multidomain protease inhibitor that binds growth factors and bone morphogenetic proteins, has nonsynonymous changes found exclusively in common marmosets and other tested callitrichine species that twin. In the one callitrichine species that does not produce twins (Callimico), this change has reverted back to the ancestral (nontwinning) primate sequence. Polymorphisms in GDF9 occur among human cohorts with a propensity for dizygotic twins, and polymorphisms in GDF9 and BMP15 are associated with twinning in sheep. We postulate that positive selection affected NWM growth patterns, with callitrichine miniaturization coevolving with a series of reproductive adaptations. PMID:24379383

  18. Evolutionary genetics and implications of small size and twinning in callitrichine primates.

    PubMed

    Harris, R Alan; Tardif, Suzette D; Vinar, Tomas; Wildman, Derek E; Rutherford, Julienne N; Rogers, Jeffrey; Worley, Kim C; Aagaard, Kjersti M

    2014-01-28

    New World monkeys (NWMs) are characterized by an extensive size range, with clawed NWMs (subfamily Callitrichinae, or callitrichines) such as the common marmoset manifesting diminutive size and unique reproductive adaptations. Perhaps the most notable of these adaptations is their propensity toward multiple gestations (i.e., dichorionic twins and trichorionic triplets). Indeed, with the exception of Goeldi's monkey (Callimico), callitrichine singleton pregnancies rarely occur. Multiple gestations seem to have coevolved with a suite of reproductive adaptations, including hematopoetic chimerism of siblings, suppression of reproduction in nondominant females, and cooperative alloparenting. The sequencing of the common marmoset (Callithrix jacchus) genome offers the opportunity to explore the genetic basis of these unusual traits within this primate lineage. In this study, we hypothesized that genetic changes arising during callitrichine evolution resulted in multiple ovulated ova with each cycle, and that these changes triggered adaptations that minimized complications common to multiple gestations in other primates, including humans. Callitrichine-specific nonsynonymous substitutions were identified in GDF9, BMP15, BMP4, and WFIKKN1. WFIKKN1, a multidomain protease inhibitor that binds growth factors and bone morphogenetic proteins, has nonsynonymous changes found exclusively in common marmosets and other tested callitrichine species that twin. In the one callitrichine species that does not produce twins (Callimico), this change has reverted back to the ancestral (nontwinning) primate sequence. Polymorphisms in GDF9 occur among human cohorts with a propensity for dizygotic twins, and polymorphisms in GDF9 and BMP15 are associated with twinning in sheep. We postulate that positive selection affected NWM growth patterns, with callitrichine miniaturization coevolving with a series of reproductive adaptations. PMID:24379383

  19. Effects of Zusanli and Ashi Acupoint Electroacupuncture on Repair of Skeletal Muscle and Neuromuscular Junction in a Rabbit Gastrocnemius Contusion Model

    PubMed Central

    Yu, Zhan-ge; Wang, Rong-guo; Xiao, Cheng; Zhao, Jun-yun; Shen, Qian; Liu, Shou-yao; Xu, Qian-wei; Zhang, Qing-xi; Wang, Yun-ting

    2016-01-01

    Objective. To explore the effects of electroacupuncture (EA) at ST36 (EA-ST36) and at Ashi acupoints (EA-Ashi) on skeletal muscle repair. Methods. Seventy-five rabbits were randomly divided into five groups: normal, contusion, EA-Ashi, EA-ST36, and EA at Ashi acupoints and ST36 (EA-AS). EA (0.4 mA, 2 Hz, 15 min) was applied after an acute gastrocnemius contusion. The morphology of myofibers and neuromuscular junctions (NMJs) and expressions of growth differentiation factor-8 (GDF-8), acetylcholinesterase (AChE), Neuregulin 1 (NGR1), and muscle-specific kinase (MuSK) were assessed 7, 14, and 28 days after contusion. Results. Compared with that in contusion group, there was an increase in the following respective parameters in treatment groups: the number and diameter of myofibers, the mean staining area, and continuities of NMJs. A comparison of EA-Ashi and EA-ST36 groups indicated that average myofiber diameter, mean staining area of NMJs, and expressions of AChE and NRG1 were higher in EA-Ashi group, whereas expression of GDF-8 decreased on day 7. However, increases in myofiber numbers, expressions of MuSK and AChE, as well as decreases in GDF-8 expression, and the discontinuities were observed in EA-ST36 group on the 28th day. Conclusion. Both EA-ST36 and EA-Ashi promoted myofiber regeneration and restoration of NMJs. EA-Ashi was more effective at earlier stages, whereas EA-ST36 played a more important role at later stages. PMID:27190536

  20. Real-Time Gamma Imaging of Technetium Transport through Natural and Engineered Porous Materials for Radioactive Waste Disposal

    PubMed Central

    2013-01-01

    We present a novel methodology for determining the transport of technetium-99m, a γ-emitting metastable isomer of 99Tc, through quartz sand and porous media relevant to the disposal of nuclear waste in a geological disposal facility (GDF). Quartz sand is utilized as a model medium, and the applicability of the methodology to determine radionuclide transport in engineered backfill cement is explored using the UK GDF candidate backfill cement, Nirex Reference Vault Backfill (NRVB), in a model system. Two-dimensional distributions in 99mTc activity were collected at millimeter-resolution using decay-corrected gamma camera images. Pulse-inputs of ∼20 MBq 99mTc were introduced into short (<10 cm) water-saturated columns at a constant flow of 0.33 mL min–1. Changes in calibrated mass distribution of 99mTc at 30 s intervals, over a period of several hours, were quantified by spatial moments analysis. Transport parameters were fitted to the experimental data using a one-dimensional convection–dispersion equation, yielding transport properties for this radionuclide in a model GDF environment. These data demonstrate that 99Tc in the pertechnetate form (Tc(VII)O4–) does not sorb to cement backfill during transport under model conditions, resulting in closely conservative transport behavior. This methodology represents a quantitative development of radiotracer imaging and offers the opportunity to conveniently and rapidly characterize transport of gamma-emitting isotopes in opaque media, relevant to the geological disposal of nuclear waste and potentially to a wide variety of other subsurface environments. PMID:24147650

  1. Identification of Pathways Mediating Growth Differentiation Factor5-Induced Tenogenic Differentiation in Human Bone Marrow Stromal Cells

    PubMed Central

    Tan, Sik-Loo; Ahmad, Tunku Sara; Ng, Wuey-Min; Azlina, Amir Abbas; Azhar, Mahmood Merican; Selvaratnam, Lakshmi; Kamarul, Tunku

    2015-01-01

    To date, the molecular signalling mechanisms which regulate growth factors-induced MSCs tenogenic differentiation remain largely unknown. Therefore, a study to determine the global gene expression profile of tenogenic differentiation in human bone marrow stromal cells (hMSCs) using growth differentiation factor 5 (GDF5) was conducted. Microarray analyses were conducted on hMSCs cultures supplemented with 100 ng/ml of GDF5 and compared to undifferentiated hMSCs and adult tenocytes. Results of QuantiGene® Plex assay support the use and interpretation of the inferred gene expression profiles and pathways information. From the 27,216 genes assessed, 873 genes (3.21% of the overall human transcriptome) were significantly altered during the tenogenic differentiation process (corrected p<0.05). The genes identified as potentially associated with tenogenic differentiation were ARHGAP29, CCL2, integrin alpha 8 and neurofilament medium polypeptides. These genes, were mainly associated with cytoskeleton reorganization (stress fibers formation) signaling. Pathway analysis demonstrated the potential molecular pathways involved in tenogenic differentiation were: cytoskeleton reorganization related i.e. keratin filament signaling and activin A signaling; cell adhesion related i.e. chemokine and adhesion signaling; and extracellular matrix related i.e. arachidonic acid production signaling. Further investigation using atomic force microscopy and confocal laser scanning microscopy demonstrated apparent cytoskeleton reorganization in GDF5-induced hMSCs suggesting that cytoskeleton reorganization signaling is an important event involved in tenogenic differentiation. Besides, a reduced nucleostemin expression observed suggested a lower cell proliferation rate in hMSCs undergoing tenogenic differentiation. Understanding and elucidating the tenogenic differentiation signalling pathways are important for future optimization of tenogenic hMSCs for functional tendon cell-based therapy and

  2. Non-Gaussian Diffusion Imaging for Enhanced Contrast of Brain Tissue Affected by Ischemic Stroke

    PubMed Central

    Geffroy, Françoise; Le Bihan, Denis; Shah, N. Jon

    2014-01-01

    Recent diffusion MRI studies of stroke in humans and animals have shown that the quantitative parameters characterising the degree of non-Gaussianity of the diffusion process are much more sensitive to ischemic changes than the apparent diffusion coefficient (ADC) considered so far as the “gold standard”. The observed changes exceeded that of the ADC by a remarkable factor of 2 to 3. These studies were based on the novel non-Gaussian methods, such as diffusion kurtosis imaging (DKI) and log-normal distribution function imaging (LNDFI). As shown in our previous work investigating the animal stroke model, a combined analysis using two methods, DKI and LNDFI provides valuable complimentary information. In the present work, we report the application of three non-Gaussian diffusion models to quantify the deviations from the Gaussian behaviour in stroke induced by transient middle cerebral artery occlusion in rat brains: the gamma-distribution function (GDF), the stretched exponential model (SEM), and the biexponential model. The main goal was to compare the sensitivity of various non-Gaussian metrics to ischemic changes and to investigate if a combined application of several models will provide added value in the assessment of stroke. We have shown that two models, GDF and SEM, exhibit a better performance than the conventional method and allow for a significantly enhanced visualization of lesions. Furthermore, we showed that valuable information regarding spatial properties of stroke lesions can be obtained. In particular, we observed a stratified cortex structure in the lesions that were well visible in the maps of the GDF and SEM metrics, but poorly distinguishable in the ADC-maps. Our results provided evidence that cortical layers tend to be differently affected by ischemic processes. PMID:24586610

  3. Involvement of the KIT/KITL signaling pathway in 4-vinylcyclohexene diepoxide-induced ovarian follicle loss in rats.

    PubMed

    Fernandez, Shannon M; Keating, Aileen F; Christian, Patricia J; Sen, Nivedita; Hoying, James B; Brooks, Heddwen L; Hoyer, Patricia B

    2008-08-01

    Repeated daily dosing of rats with the occupational chemical 4-vinylcyclohexene diepoxide (VCD) depletes the ovary of primordial and primary follicles through an increase in the natural process of atresia. Additionally, in vitro exposure of Postnatal Day 4 (PND 4) rat ovaries to VCD causes similar follicular depletion. This study was designed to investigate survival signaling pathways that may be associated with VCD-induced ovotoxicity in small preantral follicles. Female Fischer 344 rats (PND 28) were dosed daily (80 mg/kg/day VCD i.p.; 12 days in vivo), and PND 4 ovaries were cultured (VCD 20 or 30 microM; 8 days in vitro). Microarray analysis identified a subset of 14 genes whose expression was increased or decreased by VCD in both experiments (i.e., via both exposure routes). Particularly, the analysis showed that relative to controls, VCD did not affect mRNA expression of growth and differentiation factor 9 (Gdf9), whereas there were decreases in mRNA encoding bone morphogenic protein receptor 1a (Bmpr1a) and Kit. To confirm findings from microarray, the genes Gdf9, Bmpr1a, and Kit were further examined. When growth factors associated with these pathways were added to ovarian cultures during VCD exposure, GDF9 and BMP4 had no effect on VCD-induced ovotoxicity; however, KITL attenuated this follicle loss. Additionally, there was a decrease in Kit and an increase in Kitl expression (mRNA and protein) following VCD exposure, relative to control. These results support that VCD compromises KIT/KITL signaling, which is critical for follicular survival in primordial and primary follicles. PMID:18448842

  4. Anoxic Biodegradation of Isosaccharinic Acids at Alkaline pH by Natural Microbial Communities.

    PubMed

    Rout, Simon P; Charles, Christopher J; Doulgeris, Charalampos; McCarthy, Alan J; Rooks, Dave J; Loughnane, J Paul; Laws, Andrew P; Humphreys, Paul N

    2015-01-01

    One design concept for the long-term management of the UK's intermediate level radioactive wastes (ILW) is disposal to a cementitious geological disposal facility (GDF). Under the alkaline (10.013.0) anoxic conditions expected within a GDF, cellulosic wastes will undergo chemical hydrolysis. The resulting cellulose degradation products (CDP) are dominated by α- and β-isosaccharinic acids (ISA), which present an organic carbon source that may enable subsequent microbial colonisation of a GDF. Microcosms established from neutral, near-surface sediments demonstrated complete ISA degradation under methanogenic conditions up to pH 10.0. Degradation decreased as pH increased, with β-ISA fermentation more heavily influenced than α-ISA. This reduction in degradation rate was accompanied by a shift in microbial population away from organisms related to Clostridium sporosphaeroides to a more diverse Clostridial community. The increase in pH to 10.0 saw an increase in detection of Alcaligenes aquatilis and a dominance of hydrogenotrophic methanogens within the Archaeal population. Methane was generated up to pH 10.0 with acetate accumulation at higher pH values reflecting a reduced detection of acetoclastic methanogens. An increase in pH to 11.0 resulted in the accumulation of ISA, the absence of methanogenesis and the loss of biomass from the system. This study is the first to demonstrate methanogenesis from ISA by near surface microbial communities not previously exposed to these compounds up to and including pH 10.0. PMID:26367005

  5. Deep 2mm Surveys with GISMO : Searching for submillimeter galaxies at the highest redshifts

    NASA Astrophysics Data System (ADS)

    Staguhn, Johannes Gunter; Kovacs, Attila; Karim, Alexander; Arendt, Richard; Benford, Dominic J.; Decarli, Roberto; Dwek, Eli; Fixsen, Dale; Gene, Hilton; Irwin, Kent; Moseley, S. Harvey; Sharp, Elmer; Walter, Fabian; Edward, Wollack

    2015-08-01

    The GISMO 2 mm camera at the IRAM 30m telescope has been available to the astronomical community for years through the semi-annual IRAM call for proposals. The 2 mm band is in particular well suited to trace the first dusty galaxies in the universe, since their redshifted SEDs peak close to GISMO's observing frequency, whereas the medium redshift galaxy foreground is almost invisible in this band. This effect makes GISMO's deep field observations a valuable complement, rather than a redundancy, to the HERSCHEL far-infrared and sub-mm surveys. Two survey projects aiming at obtaining 2mm galaxy number counts are at the core of GISMO’s science. Simple models predict an appreciable number of galaxies detected in these surveys to be be at very high redshifts (z~5-6 and above) with intrinsic luminosities of a few 10^12 L_sol.The first of these projects is the GISMO Deep Field (GDF) survey, which is centered on the Hubble Deep Field North. This survey by now has reached the confusion limit (we measure a confusion noise of 60 microJy). Our detailed statistical analysis of the GDF data provides a solid estimate of the expected rate of false detections among those source identifications. Furthermore, numerical simulations were used, to estimate the "completeness" of our set of extracted sources. A comparison of our observations with model predictions shows that our results are in good agreement with galaxy count models.The second survey covers a ~ 1/4 square degree region in the COSMOS field, in which by now we have obtained sufficient sensitivity to extract statistically relevant galaxy number counts, and by using auxiliary data, redshift distributions. We will present first results that complement those obtained in the deeper GDF.

  6. The `advanced DIR-MCFC development' project, an overview

    NASA Astrophysics Data System (ADS)

    Kortbeek, P. J.; Ottervanger, R.

    An overview is given of the approach and mid-term status of the joint European `Advanced DIR-MCFC Development' project, in which BCN, BG plc, GDF, ECN, Stork, Schelde and Sydkraft co-operate. Hospitals are identified as an attractive initial market for cogeneration direct internal reforming-molten carbonate fuel cell (DIR-MCFC) systems in the size of 400 kWe. Innovative system and stack design concepts are being developed for this application. The `SMARTER' system, based on DIR stacks, combines high electric efficiency and a wide operational window with optimal system simplicity and low cost.

  7. Similar cellular migration patterns from niches in intervertebral disc and in knee-joint regions detected by in situ labeling: an experimental study in the New Zealand white rabbit

    PubMed Central

    2013-01-01

    Introduction Potential stem cell niches (SNs) were recently reported in intervertebral discs (IVDs) and knee joints (KJs) in different mammals (located adjacent to the epiphyseal plate; EP). The aim here was to examine further possible cellular migration and migration directions of cells originating from niches possibly involved in regeneration of cartilaginous tissues in the IVD and in the KJ regions in adult mammals. Methods In total, 33 rabbits were used in studies A through C. A. IVD cells were sorted; fluorescence-activated cell sorting (FACS) by size (forward scatter; ≤10 μm or >10 μm or GDF5+ cells (anti-GDF5 antibody). Sorted cells, labeled with cell tracer (carboxyfluorescein-diacetate-succinimidyl ester; CDFA-SE) were applied on IVD explants in vitro. Migrating cells/distance was evaluated by fluorescence- and confocal-microscopy (FC). B. DNA labeling was performed with BrdU (oral administration). Animals were killed (14 to 56 days), KJs collected, and BrdU+ cells visualized with immunohistochemistry (IHC)/anti-BrdU antibody in SN and articular cartilage (AC). C. Cell tracer: (Fe-nanoparticles: Endorem) were injected into SNs of IVDs (LI-LV) and KJs (tibia). Animals were killed after 2 to 6 weeks. Fe-labeled cells were traced by ferric-iron staining (Prussian blue reaction; Mallory method). Results A. GDF5+ cells and ≤10-μm cells displayed the best migration capability in IVD explants. GDF5+ cells were detected at a tissue depth of 1,300 μm (16 days). B. BrdU+ cells were observed in early time points in niches of KJs, and at later time points in AC, indicating a gradual migration of cells. C. Fe+ cells were detected in IVDs; in annulus fibrosus (AF) in 11 of 12 animals and in nucleus pulposus (NP) in two of 12 animals. In AC (tibia), Fe+ cells were detected in six of 12 animals. In the potential migration route (PMR), from niches toward the IVD, Fe+ cells (three of 12 animals) and in PMR toward AC (KJs) (six of 12 animals) were detected

  8. Revisiting Seafloor-Spreading in the Red Sea: Basement Nature, Transforms and Ocean-Continent Boundary

    NASA Astrophysics Data System (ADS)

    Tapponnier, P.; Dyment, J.; Zinger, M. A.; Franken, D.; Afifi, A. M.; Wyllie, A.; Ali, H. G.; Hanbal, I.

    2013-12-01

    A new marine geophysical survey on the Saudi Arabian side of the Red Sea confirms early inferences that ~ 2/3 of the eastern Red Sea is floored by oceanic crust. Most seismic profiles south of 24°N show a strongly reflective, landward-deepening volcanic basement up to ~ 100 km east of the axial ridge, beneath thick evaporitic deposits. This position of the Ocean-Continent Boundary (OCB) is consistent with gravity measurements. The low amplitudes and long wavelengths of magnetic anomalies older than Chrons 1-3 can be accounted for by low-pass filtering due to thick sediments. Seafloor-spreading throughout the Red Sea started around 15 Ma, as in the western Gulf of Aden. Its onset was coeval with the activation of the Aqaba/Levant transform and short-cutting of the Gulf of Suez. The main difference between the southern and northern Red Sea lies not in the nature of the crust but in the direction and modulus of the plate motion rate. The ~ 30° counterclockwise strike change and halving of the spreading rate (~ 16 to ~ 8 mm/yr) between the Hermil (17°N) and Suez triple junctions results in a shift from slow (≈ North Atlantic) to highly oblique, ultra-slow (≈ Southwest Indian) ridge type. The obliquity of spreading in the central and northern basins is taken up by transform discontinuities that stop ~ 40 km short of the coastline, at the OCB. Three large transform fault systems (Jeddah, Zabargad, El Akhawein) nucleated as continental transfer faults reactivating NNE-trending Proterozoic shear zones. The former two systems divide the Red Sea into three main basins. Between ~15 and ~5 Ma, for about 10 million years, thick evaporites were deposited directly on top of oceanic crust in deep water, as the depositional environment, modulated by climate, became restricted by the Suez and Afar/Bab-el-Mandeb volcano-tectonic 'flood-gates.' The presence of these thick deposits (up to ~ 8 km) suffices to account for the difference between the Red Sea and the Gulf of Aden

  9. Genetic Contribution to the Development of Radiographic Knee Osteoarthritis in a Population Presenting with Nonacute Knee Symptoms a Decade Earlier

    PubMed Central

    Huétink, Kasper; van der Voort, Paul; Bloem, Johan L.; Nelissen, Rob G. H. H.; Meulenbelt, Ingrid

    2016-01-01

    This study examined the contribution of the osteoarthritis (OA) susceptibility genes ASPN, GDF5, DIO2, and the 7q22 region to the development of radiographic knee OA in patients with a mean age of 40.6 ± 7.9 years (standard deviation) and who suffered from nonacute knee complaints a decade earlier. Dose–response associations of four single nucleotide polymorphisms(SNPs) in the susceptibility genes were determined by comparing 36 patients who showed the development of OA on radiographs (Kellgren and Lawrence score ≥1) with 88 patients having normal cartilage with no development of OA on radiographs. Multivariate logistic regression analysis including the variables such as age, gender, body mass index, and reported knee trauma was performed. A dose–response association of DIO2 SNP rs225014: odds ratio (OR) 2.3, 95% confidence interval (CI) 1.1–4.5 (P = 0.019) and GDF5 SNP rs143383: OR 2.0, 95% CI 1.1–3.8 (P = 0.031) was observed with knee OA development. The ASPN and 7q22 SNPs were not associated with OA development. PMID:27158223

  10. Toward the development of transcriptional biodosimetry for the identification of irradiated individuals and assessment of absorbed radiation dose.

    PubMed

    Brzóska, Kamil; Kruszewski, Marcin

    2015-08-01

    The most frequently used and the best established method of biological dosimetry at present is the dicentric chromosome assay, which is poorly suitable for a mass casualties scenario. This gives rise to the need for the development of new, high-throughput assays for rapid identification of the subjects exposed to ionizing radiation. In the present study, we tested the usefulness of gene expression analysis in blood cells for biological dosimetry. Human peripheral blood from three healthy donors was X-irradiated with doses of 0 (control), 0.6, and 2 Gy. The mRNA level of 16 genes (ATF3, BAX, BBC3, BCL2, CDKN1A, DDB2, FDXR, GADD45A, GDF15, MDM2, PLK3, SERPINE1, SESN2, TNFRSF10B, TNFSF4, and VWCE) was assessed by reverse transcription quantitative PCR 6, 12, 24, and 48 h after exposure with ITFG1 and DPM1 used as a reference genes. The panel of radiation-responsive genes was selected comprising GADD45A, CDKN1A, BAX, BBC3, DDB2, TNFSF4, GDF15, and FDXR. Cluster analysis showed that ΔC t values of the selected genes contained sufficient information to allow discrimination between irradiated and non-irradiated blood samples. The samples were clearly grouped according to the absorbed doses of radiation and not to the time interval after irradiation or to the blood donor. PMID:25972268

  11. The oncogene EVI1 enhances transcriptional and biological responses of human myeloid cells to all-trans retinoic acid

    PubMed Central

    Steinmetz, Birgit; Hackl, Hubert; Slabáková, Eva; Schwarzinger, Ilse; Smějová, Monika; Spittler, Andreas; Arbesu, Itziar; Shehata, Medhat; Souček, Karel; Wieser, Rotraud

    2014-01-01

    The product of the ecotropic virus integration site 1 (EVI1) gene, whose overexpression is associated with a poor prognosis in myeloid leukemias and some epithelial tumors, regulates gene transcription both through direct DNA binding and through modulation of the activity of other sequence specific transcription factors. Previous results from our laboratory have shown that EVI1 influenced transcription regulation in response to the myeloid differentiation inducing agent, all-trans retinoic acid (ATRA), in a dual manner: it enhanced ATRA induced transcription of the RARβ gene, but repressed the ATRA induction of the EVI1 gene itself. In the present study, we asked whether EVI1 would modulate the ATRA regulation of a larger number of genes, as well as biological responses to this agent, in human myeloid cells. U937 and HL-60 cells ectopically expressing EVI1 through retroviral transduction were subjected to microarray based gene expression analysis, and to assays measuring cellular proliferation, differentiation, and apoptosis. These experiments showed that EVI1 modulated the ATRA response of several dozens of genes, and in fact reinforced it in the vast majority of cases. A particularly strong synergy between EVI1 and ATRA was observed for GDF15, which codes for a member of the TGF-β superfamily of cytokines. In line with the gene expression results, EVI1 enhanced cell cycle arrest, differentiation, and apoptosis in response to ATRA, and knockdown of GDF15 counteracted some of these effects. The potential clinical implications of these findings are discussed. PMID:25486480

  12. The transcription factor Pitx2 positions the embryonic axis and regulates twinning

    PubMed Central

    Torlopp, Angela; Khan, Mohsin A F; Oliveira, Nidia M M; Lekk, Ingrid; Soto-Jiménez, Luz Mayela; Sosinsky, Alona; Stern, Claudio D

    2014-01-01

    Embryonic polarity of invertebrates, amphibians and fish is specified largely by maternal determinants, which fixes cell fates early in development. In contrast, amniote embryos remain plastic and can form multiple individuals until gastrulation. How is their polarity determined? In the chick embryo, the earliest known factor is cVg1 (homologous to mammalian growth differentiation factor 1, GDF1), a transforming growth factor beta (TGFβ) signal expressed posteriorly before gastrulation. A molecular screen to find upstream regulators of cVg1 in normal embryos and in embryos manipulated to form twins now uncovers the transcription factor Pitx2 as a candidate. We show that Pitx2 is essential for axis formation, and that it acts as a direct regulator of cVg1 expression by binding to enhancers within neighbouring genes. Pitx2, Vg1/GDF1 and Nodal are also key actors in left–right asymmetry, suggesting that the same ancient polarity determination mechanism has been co-opted to different functions during evolution. DOI: http://dx.doi.org/10.7554/eLife.03743.001 PMID:25496870

  13. Stokes Emission inGdF3:Nd3+Nanoparticles for Bioimaging Probe

    PubMed Central

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

    2014-01-01

    There is an 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 yield (QY) measurements in powder, poly maleic anhydride- alt-1- octadicene (PMAO) coated powder and colloidal solutions have been investigated. QY measurements have revealed that downconversion(Stokes emission)QY in an average 5 ± 2 nm sized GdF3: 1% Nd3+colloidalNPs are 2000 times higher than efficient upconversion (UC) particles NaYF4: 20 % Er/ 2% Yb of same size. Furthermore, the utility of these NIR emitting nanoparticles forbioimagingprobe has been demonstrated by confocal imaging and spectroscopic study. PMID:24336743

  14. Synthesis and characterization of a BaGdF5:Tb glass ceramic as a nanocomposite scintillator for x-ray imaging.

    PubMed

    Lee, Gyuhyon; Struebing, Christian; Wagner, Brent; Summers, Christopher; Ding, Yong; Bryant, Alex; Thadhani, Naresh; Shedlock, Daniel; Star-Lack, Josh; Kang, Zhitao

    2016-05-20

    Transparent glass ceramics with embedded light-emitting nanocrystals show great potential as low-cost nanocomposite scintillators in comparison to single crystal and transparent ceramic scintillators. In this study, cubic structure BaGdF5:Tb nanocrystals embedded in an aluminosilicate glass matrix are reported for potential high performance MeV imaging applications. Scintillator samples with systematically varied compositions were prepared by a simple conventional melt-quenching method followed by annealing. Optical, structural and scintillation properties were characterized to guide the design and optimization of selected material systems, aiming at the development of a system with higher crystal volume and larger crystal size for improved luminosity. It is observed that enhanced scintillation performance was achieved by tuning the glass matrix composition and using GdF3 in the raw materials, which served as a nucleation agent. A 26% improvement in light output was observed from a BaGdF5:Tb glass ceramic with addition of GdF3. PMID:27044066

  15. Transcriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies

    PubMed Central

    2014-01-01

    Background Mutations in the gene encoding thymidine kinase 2 (TK2) result in the myopathic form of mitochondrial DNA depletion syndrome which is a mitochondrial encephalomyopathy presenting in children. In order to unveil some of the mechanisms involved in this pathology and to identify potential biomarkers and therapeutic targets we have investigated the gene expression profile of human skeletal muscle deficient for TK2 using cDNA microarrays. Results We have analysed the whole transcriptome of skeletal muscle from patients with TK2 mutations and compared it to normal muscle and to muscle from patients with other mitochondrial myopathies. We have identified a set of over 700 genes which are differentially expressed in TK2 deficient muscle. Bioinformatics analysis reveals important changes in muscle metabolism, in particular, in glucose and glycogen utilisation, and activation of the starvation response which affects aminoacid and lipid metabolism. We have identified those transcriptional regulators which are likely to be responsible for the observed changes in gene expression. Conclusion Our data point towards the tumor suppressor p53 as the regulator at the centre of a network of genes which are responsible for a coordinated response to TK2 mutations which involves inflammation, activation of muscle cell death by apoptosis and induction of growth and differentiation factor 15 (GDF-15) in muscle and serum. We propose that GDF-15 may represent a potential novel biomarker for mitochondrial dysfunction although further studies are required. PMID:24484525

  16. The oncogene EVI1 enhances transcriptional and biological responses of human myeloid cells to all-trans retinoic acid.

    PubMed

    Steinmetz, Birgit; Hackl, Hubert; Slabáková, Eva; Schwarzinger, Ilse; Smějová, Monika; Spittler, Andreas; Arbesu, Itziar; Shehata, Medhat; Souček, Karel; Wieser, Rotraud

    2014-01-01

    The product of the ecotropic virus integration site 1 (EVI1) gene, whose overexpression is associated with a poor prognosis in myeloid leukemias and some epithelial tumors, regulates gene transcription both through direct DNA binding and through modulation of the activity of other sequence specific transcription factors. Previous results from our laboratory have shown that EVI1 influenced transcription regulation in response to the myeloid differentiation inducing agent, all-trans retinoic acid (ATRA), in a dual manner: it enhanced ATRA induced transcription of the RARβ gene, but repressed the ATRA induction of the EVI1 gene itself. In the present study, we asked whether EVI1 would modulate the ATRA regulation of a larger number of genes, as well as biological responses to this agent, in human myeloid cells. U937 and HL-60 cells ectopically expressing EVI1 through retroviral transduction were subjected to microarray based gene expression analysis, and to assays measuring cellular proliferation, differentiation, and apoptosis. These experiments showed that EVI1 modulated the ATRA response of several dozens of genes, and in fact reinforced it in the vast majority of cases. A particularly strong synergy between EVI1 and ATRA was observed for GDF15, which codes for a member of the TGF-β superfamily of cytokines. In line with the gene expression results, EVI1 enhanced cell cycle arrest, differentiation, and apoptosis in response to ATRA, and knockdown of GDF15 counteracted some of these effects. The potential clinical implications of these findings are discussed. PMID:25486480

  17. The enrichment of an alkaliphilic biofilm consortia capable of the anaerobic degradation of isosaccharinic acid from cellulosic materials incubated within an anthropogenic, hyperalkaline environment

    PubMed Central

    Charles, C. J.; Rout, S. P.; Garratt, E. J.; Patel, K.; Laws, A. P.; Humphreys, P. N.

    2015-01-01

    Anthropogenic hyperalkaline sites provide an environment that is analogous to proposed cementitious geological disposal facilities (GDF) for radioactive waste. Under anoxic, alkaline conditions cellulosic wastes will hydrolyze to a range of cellulose degradation products (CDP) dominated by isosaccharinic acids (ISA). In order to investigate the potential for microbial activity in a cementitious GDF, cellulose samples were incubated in the alkaline (∼pH 12), anaerobic zone of a lime kiln waste site. Following retrieval, these samples had undergone partial alkaline hydrolysis and were colonized by a Clostridia-dominated biofilm community, where hydrogenotrophic, alkaliphilic methanogens were also present. When these samples were used to establish an alkaline CDP fed microcosm, the community shifted away from Clostridia, methanogens became undetectable and a flocculate community dominated by Alishewanella sp. established. These flocs were composed of bacteria embedded in polysaccharides and proteins stabilized by extracellular DNA. This community was able to degrade all forms of ISA with >60% of the carbon flow being channelled into extracellular polymeric substance (EPS) production. This study demonstrated that alkaliphilic microbial communities can degrade the CDP associated with some radioactive waste disposal concepts at pH 11. These communities divert significant amounts of degradable carbon to EPS formation, suggesting that EPS has a central role in the protection of these communities from hyperalkaline conditions. PMID:26195600

  18. The enrichment of an alkaliphilic biofilm consortia capable of the anaerobic degradation of isosaccharinic acid from cellulosic materials incubated within an anthropogenic, hyperalkaline environment.

    PubMed

    Charles, C J; Rout, S P; Garratt, E J; Patel, K; Laws, A P; Humphreys, P N

    2015-08-01

    Anthropogenic hyperalkaline sites provide an environment that is analogous to proposed cementitious geological disposal facilities (GDF) for radioactive waste. Under anoxic, alkaline conditions cellulosic wastes will hydrolyze to a range of cellulose degradation products (CDP) dominated by isosaccharinic acids (ISA). In order to investigate the potential for microbial activity in a cementitious GDF, cellulose samples were incubated in the alkaline (∼pH 12), anaerobic zone of a lime kiln waste site. Following retrieval, these samples had undergone partial alkaline hydrolysis and were colonized by a Clostridia-dominated biofilm community, where hydrogenotrophic, alkaliphilic methanogens were also present. When these samples were used to establish an alkaline CDP fed microcosm, the community shifted away from Clostridia, methanogens became undetectable and a flocculate community dominated by Alishewanella sp. established. These flocs were composed of bacteria embedded in polysaccharides and proteins stabilized by extracellular DNA. This community was able to degrade all forms of ISA with >60% of the carbon flow being channelled into extracellular polymeric substance (EPS) production. This study demonstrated that alkaliphilic microbial communities can degrade the CDP associated with some radioactive waste disposal concepts at pH 11. These communities divert significant amounts of degradable carbon to EPS formation, suggesting that EPS has a central role in the protection of these communities from hyperalkaline conditions. PMID:26195600

  19. PEGylated Carbon Nanocapsule: A Universal Reactor and Carrier for In Vivo Delivery of Hydrophobic and Hydrophilic Nanoparticles.

    PubMed

    Rammohan, Amritha; Mishra, Gargi; Mahaling, Binapani; Tayal, Lokesh; Mukhopadhyay, Ahana; Gambhir, Sanjay; Sharma, Ashutosh; Sivakumar, Sri

    2016-01-13

    We have developed PEGylated mesoporous carbon nanocapsule as a universal nanoreactor and carrier for the delivery of highly crystalline hydrophobic/hydrophilic nanoparticles (NPs) which shows superior biocompatibility, dispersion in body fluids, good biodistribution and NPs independent cellular uptake mechanism. The hydrophobic/hydrophilic NPs without surface modification were synthesized in situ inside the cavities of mesoporous carbon capsules (200-850 nm). Stable and inert nature of carbon capsules in a wide range of reaction conditions like high temperature and harsh solvents, make it suitable for being used as nano/microreactors for the syntheses of a variety of NPs for bioimaging applications, such as NaYF4:Eu(3+)(5%), LaVO4:Eu(3+)(10%), GdVO4:Eu(3+)(10%), Y2O3:Eu(3+)(5%), GdF3:Tb(3+)(10%), Mo, Pt, Pd, Au, and Ag. Multiple types of NPs (Y2O3:Eu(3+)(5%) (hydrophobic) and GdF3:Tb(3+)(10%) (hydrophilic)) were coloaded inside the carbon capsules to create a multimodal agent for magneto-fluorescence imaging. Our in vivo study clearly suggests that carbon capsules have biodistribution in many organs including liver, heart, spleen, lungs, blood pool, and muscles. PMID:26646711

  20. Multiscale seismic attributes: source-corrected wavelet response and application to high-resolution seismic data

    NASA Astrophysics Data System (ADS)

    Ker, Stephan; Le Gonidec, Yves; Gibert, Dominique

    2012-09-01

    A wavelet-based method was presented in a previous work to introduce multiscale seismic attributes for high-resolution seismic data. Because of the limited frequency bandwidth of the seismic source, we observed distortions in the seismic attributes based on the wavelet response of the subsurface discontinuities (Le Gonidec et al.). In this paper, we go further in the seismic source-correction by considering Lévy alpha-stable distributions introduced in the formalism of the continuous wavelet transform (CWT). The wavelets are Gaussian derivative functions (GDF), characterized by a derivative order. We show that a high-resolution seismic source, after a classical signature processing, can be taken into account with a GDF. We demonstrate that in the framework of the Born approximation, the CWT of a seismic trace involving such a finite frequency bandwidth can be made equivalent to the CWT of the impulse response of the subsurface and is defined for a reduced range of dilations. We apply the method for the SYSIF seismic device (Marsset et al.; Ker et al.) and show that the source-corrections allow to define seismic attributes for layer thicknesses in the range [24; 115 cm]. We present the analysis for two seismic reflectors identified on a SYSIF profile, and we show that the source-corrected multiscale analysis quantifies their complex geometries.

  1. Generation and periodontal differentiation of human gingival fibroblasts-derived integration-free induced pluripotent stem cells.

    PubMed

    Yin, Xiaohui; Li, Yang; Li, Jingwen; Li, Peng; Liu, Yinan; Wen, Jinhua; Luan, Qingxian

    2016-05-01

    Induced pluripotent stem cells (iPSCs) have been recognized as a promising cell source for periodontal tissue regeneration. However, the conventional virus-based reprogramming approach is associated with a high risk of genetic mutation and limits their therapeutic utility. Here, we successfully generated iPSCs from readily accessible human gingival fibroblasts (hGFs) through an integration-free and feeder-free approach via delivery of reprogramming factors of Oct4, Sox2, Klf4, L-myc, Lin28 and TP53 shRNA with episomal plasmid vectors. The iPSCs presented similar morphology and proliferation characteristics as embryonic stem cells (ESCs), and expressed pluripotent markers including Oct4, Tra181, Nanog and SSEA-4. Additionally, these cells maintained a normal karyotype and showed decreased CpG methylation ratio in the promoter regions of Oct4 and Nanog. In vivo teratoma formation assay revealed the development of tissues representative of three germ layers, confirming the acquisition of pluripotency. Furthermore, treatment of the iPSCs in vitro with enamel matrix derivative (EMD) or growth/differentiation factor-5 (GDF-5) significantly up-regulated the expression of periodontal tissue markers associated with bone, periodontal ligament and cementum respectively. Taken together, our data demonstrate that hGFs are a valuable cell source for generating integration-free iPSCs, which could be sequentially induced toward periodontal cells under the treatment of EMD and GDF-5. PMID:26456649

  2. Synthesis and characterization of a BaGdF5:Tb glass ceramic as a nanocomposite scintillator for x-ray imaging

    NASA Astrophysics Data System (ADS)

    Lee, Gyuhyon; Struebing, Christian; Wagner, Brent; Summers, Christopher; Ding, Yong; Bryant, Alex; Thadhani, Naresh; Shedlock, Daniel; Star-Lack, Josh; Kang, Zhitao

    2016-05-01

    Transparent glass ceramics with embedded light-emitting nanocrystals show great potential as low-cost nanocomposite scintillators in comparison to single crystal and transparent ceramic scintillators. In this study, cubic structure BaGdF5:Tb nanocrystals embedded in an aluminosilicate glass matrix are reported for potential high performance MeV imaging applications. Scintillator samples with systematically varied compositions were prepared by a simple conventional melt-quenching method followed by annealing. Optical, structural and scintillation properties were characterized to guide the design and optimization of selected material systems, aiming at the development of a system with higher crystal volume and larger crystal size for improved luminosity. It is observed that enhanced scintillation performance was achieved by tuning the glass matrix composition and using GdF3 in the raw materials, which served as a nucleation agent. A 26% improvement in light output was observed from a BaGdF5:Tb glass ceramic with addition of GdF3.

  3. 2D magnetotelluric imaging of the Anqing-Guichi ore district, Yangtze metallogenic belt, eastern China: An insight into the crustal structure and tectonic units

    NASA Astrophysics Data System (ADS)

    Chen, Xiangbin; Yan, Jiayong

    2016-08-01

    Two parallel NW-trending magnetotelluric (MT) profiles were placed perpendicularly to the main structures of the Anqing-Guichi ore district, one of the seven ore districts in the middle-lower Yangtze River metallogenic belt of eastern China. In October-December 2013, the MT data acquisition was carried out at 117 sites with 0.5-1 km site spacing. The MT data has a good quality in the frequency range between 320 and 0.01 Hz. The dimensionality analysis and 2D resistivity inversion results indicate that: (1) the deep of the ore district with three-dimensional structural characteristics, but two-dimensional structural characteristics for shallow; (2) there is a clear correlation between resistivity and the main geological units of the ore district, as well as correlation with mapped surface faults; (3) the Gandan deep fault (GDF) and Jiangnan deep fault (JNF) extend from the surface to 10 km deep, with dip of NW45°, and dip angles larger than 60°. A series of NE-trending acidic intrusive rocks were controlled by the GDF.

  4. The transcription factor Pitx2 positions the embryonic axis and regulates twinning.

    PubMed

    Torlopp, Angela; Khan, Mohsin A F; Oliveira, Nidia M M; Lekk, Ingrid; Soto-Jiménez, Luz Mayela; Sosinsky, Alona; Stern, Claudio D

    2014-01-01

    Embryonic polarity of invertebrates, amphibians and fish is specified largely by maternal determinants, which fixes cell fates early in development. In contrast, amniote embryos remain plastic and can form multiple individuals until gastrulation. How is their polarity determined? In the chick embryo, the earliest known factor is cVg1 (homologous to mammalian growth differentiation factor 1, GDF1), a transforming growth factor beta (TGFβ) signal expressed posteriorly before gastrulation. A molecular screen to find upstream regulators of cVg1 in normal embryos and in embryos manipulated to form twins now uncovers the transcription factor Pitx2 as a candidate. We show that Pitx2 is essential for axis formation, and that it acts as a direct regulator of cVg1 expression by binding to enhancers within neighbouring genes. Pitx2, Vg1/GDF1 and Nodal are also key actors in left-right asymmetry, suggesting that the same ancient polarity determination mechanism has been co-opted to different functions during evolution. PMID:25496870

  5. Single nucleotide polymorphisms in premature ovarian failure-associated genes in a Chinese Hui population

    PubMed Central

    MA, LILI; CHEN, YAN; MEI, SI; LIU, CHUNLIAN; MA, XIAOHONG; LI, YONGLI; JIANG, YINZHI; HA, LINGXIA; XU, XIAN

    2015-01-01

    Premature ovarian failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles in individuals <40 years old, and is a major cause of infertility in females. Genetic factors are considered to be responsible for the development of POF, however, the exact pathogenesis remains to be elucidated in the majority of cases. In the present study, the single nucleotide polymorphisms (SNPs) of growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), inhibin βB (INHBB) and follicle stimulating hormone receptor (FSHR) genes were investigated, and their association with POF in a Chinese Hui population of the Ningxia Hui Autonomous Region in western China was evaluated. Peripheral blood samples were collected from 63 patients diagnosed with POF (POF group) and 58 normal control individuals (control group), from which the genomic DNA was isolated. The GDF9, BMP15, INHBB and FSHR genes were amplified using polymerase chain reaction assays, and their SNPs were determined by sequencing. In the four SNPs identified across the GDF9 loci, D57Y (169G>T), rs1049127 (546G>A), rs254286 (447C>T) and rs254285 (969C>G), the frequencies of the 546G>A genotype and allele A were significantly higher in the POF group, compared with the normal control group (34.92, vs. 6.90%; P<0.05 and 19.05, vs. 3.23%; P<0.05, repsectively), while no significant differences were observed in the occur rence of the c.447C>T and c.969C>G mutations between the two groups (60.32, vs. 50% and 50.79, vs. 55.17%, repsectively). The c.169G>T mutation within the GDF9 gene was only detected in two patients with POF, and the mutation did not occur in the normal control group. A total of three SNPs were detected within the BMP15 gene, including rs3810682 (−9C>G), rs79377927 (788_789insTCT) and rs17003221 (852C>T), and no significant differences were observed in the frequencies of the 9C>G and 852C>T genotypes between the POF and control groups (7.94, vs. 6.90% and 4

  6. Analyse des interactions energetiques entre un arena et son systeme de refrigeration

    NASA Astrophysics Data System (ADS)

    Seghouani, Lotfi

    La presente these s'inscrit dans le cadre d'un projet strategique sur les arenas finance par le CRSNG (Conseil de Recherche en Sciences Naturelles et en Genie du Canada) qui a pour but principal le developpement d'un outil numerique capable d'estimer et d'optimiser la consommation d'energie dans les arenas et curlings. Notre travail s'inscrit comme une suite a un travail deja realise par DAOUD et coll. (2006, 2007) qui a developpe un modele 3D (AIM) en regime transitoire de l'arena Camilien Houde a Montreal et qui calcule les flux de chaleur a travers l'enveloppe du batiment ainsi que les distributions de temperatures et d'humidite durant une annee meteorologique typique. En particulier, il calcule les flux de chaleur a travers la couche de glace dus a la convection, la radiation et la condensation. Dans un premier temps nous avons developpe un modele de la structure sous la glace (BIM) qui tient compte de sa geometrie 3D, des differentes couches, de l'effet transitoire, des gains de chaleur du sol en dessous et autour de l'arena etudie ainsi que de la temperature d'entree de la saumure dans la dalle de beton. Par la suite le BIM a ete couple le AIM. Dans la deuxieme etape, nous avons developpe un modele du systeme de refrigeration (REFSYS) en regime quasi-permanent pour l'arena etudie sur la base d'une combinaison de relations thermodynamiques, de correlations de transfert de chaleur et de relations elaborees a partir de donnees disponibles dans le catalogue du manufacturier. Enfin le couplage final entre l'AIM +BIM et le REFSYS a ete effectue sous l'interface du logiciel TRNSYS. Plusieurs etudes parametriques on ete entreprises pour evaluer les effets du climat, de la temperature de la saumure, de l'epaisseur de la glace, etc. sur la consommation energetique de l'arena. Aussi, quelques strategies pour diminuer cette consommation ont ete etudiees. Le considerable potentiel de recuperation de chaleur au niveau des condenseurs qui peut reduire l'energie requise par

  7. Heat flow in eastern Egypt - The thermal signature of a continental breakup

    NASA Technical Reports Server (NTRS)

    Morgan, P.; Boulos, F. K.; Hennin, S. F.; El-Sherif, A. A.; El-Sayed, A. A.

    1985-01-01

    Data on the heat flow in eastern Egypt were collected to provide information related to the mode and the mechanism of the Red Sea opening. The data indicate a general increase in heat flow towards the Red Sea (75-100 mW/sq m in a zone within 40 km of the coast compared with 35-55 mW/sq m inland). Moderately high heat flow (about 70 mW/sq m) was found for the Gulf of Suez. Heat production data indicate that the coastal thermal anomaly is not primarily related to crustal radiogenic heat production. Possible causes of the anomaly (one of which could be a high mantle heat flow causing a lithospheric thinning centered beneath the Red Sea) are discussed.

  8. Alien bryozoans in the eastern Mediterranean Sea--new records from the coast of Lebanon.

    PubMed

    Harmelin, Jean-Georges

    2014-01-01

    The Levant Basin (SE Mediterranean) is the most exposed to the introduction of non-indigenous species. The current assessment of exotic bryozoans present along the coast of Lebanon has been completed by the recording of fourteen cheilostome species (one cryptogenic) collected by diving in 17 localities (2-42 m). This set of exotic bryozoans comprises ten genera, including four (Akatopora Davis, 1934, Drepanophora Harmer, 1957, Mucropetraliella Stach, 1936 and Predanophora Tilbrook, 2006) not previously reported in the Mediterranean, while Celleporaria is the most successful extra-Mediterranean genus with four species in the survey collection. A new Celleporina species, C. bitari n. sp., also collected in the Red Sea, is described. Although lessepsian migration through the Suez Canal is the main pathway for exotic bryozoans in this region, the geographic origin of some species suggests that shipping through Gibraltar Strait is also responsible to a large extent. PMID:25544525

  9. Energy efficiency in membrane bioreactors.

    PubMed

    Barillon, B; Martin Ruel, S; Langlais, C; Lazarova, V

    2013-01-01

    Energy consumption remains the key factor for the optimisation of the performance of membrane bioreactors (MBRs). This paper presents the results of the detailed energy audits of six full-scale MBRs operated by Suez Environnement in France, Spain and the USA based on on-site energy measurement and analysis of plant operation parameters and treatment performance. Specific energy consumption is compared for two different MBR configurations (flat sheet and hollow fibre membranes) and for plants with different design, loads and operation parameters. The aim of this project was to understand how the energy is consumed in MBR facilities and under which operating conditions, in order to finally provide guidelines and recommended practices for optimisation of MBR operation and design to reduce energy consumption and environmental impacts. PMID:23787304

  10. Subsidence in the northeastern nile delta: rapid rates, possible causes, and consequences.

    PubMed

    Stanley, D J

    1988-04-22

    Holocene fluvial and marine deposits have accumulated in a graben-like structure on the northeastern margin of the Nile delta. This part of the delta, which includes Lake Manzala, Port Said, and the northern Suez Canal, has subsided rapidly at rates of up to 0.5 centimeter per year since about 7500 years ago. This subsidence has diverted at last four major distributaries of the Nile River into this region. The combined effects of continued subsidence and sea level rise may flood a large part of the northern delta plain by as much as 1 meter by the year 2100. The impact of continued subsidence, now occurring when sediment input along the coast has been sharply reduced because of the Aswan High Dam, is likely to be substantial, particularly in the Port Said area and as far inland as south of Lake Manzala. PMID:17784071

  11. Regional geothermal exploration in Egypt

    NASA Technical Reports Server (NTRS)

    Morgan, P.; Boulos, F. K.; Swanberg, C. A.

    1983-01-01

    A study is presented of the evaluation of the potential geothermal resources of Egypt using a thermal gradient/heat flow technique and a groundwater temperature/chemistry technique. Existing oil well bottom-hole temperature data, as well as subsurface temperature measurements in existing boreholes, were employed for the thermal gradient/heat flow investigation before special thermal gradient holes were drilled. The geographic range of the direct subsurface thermal measurements was extended by employing groundwater temperature and chemistry data. Results show the presence of a regional thermal high along the eastern margin of Egypt with a local thermal anomaly in this zone. It is suggested that the sandstones of the Nubian Formation may be a suitable reservoir for geothermal fluids. These findings indicate that temperatures of 150 C or higher may be found in this reservoir in the Gulf of Suez and Red Sea coastal zones where it lies at a depth of 4 km and deeper.

  12. Elemental analysis of Egyptian crude oils by INAA using rabbit irradiation system at ETRR-2 reactor.

    PubMed

    El-Khayatt, A M

    2010-12-01

    Instrumental neutron activation analysis (INAA) using rabbit irradiation system at ETRR-2 reactor was utilized to analyze some elements namely Na, Mg, Al, Cl, V, Mn, In, and Br in four different crude petroleum samples from different oil fields in the Suez-Gulf region of Egypt. The INAA was performed by four different standardization methods. Namely absolute, single comparator based on effective cross section concept, single comparator based on k(0,Au) factors, and that based on k(0,ic) factors defined versus any suitable internal comparator method. A FORTRAN computer program was written to calculate the extracted concentrations by these methods. A reasonable agreement between the obtained results was noticed. PMID:20692177

  13. Geophysical and seismo-tectonic evolution in Dahshure area, SW Cairo-Egypt

    NASA Astrophysics Data System (ADS)

    Mekkawi, Mahmoud; Abdel Aziz, Khiry; Mohamed, Abuela; Elbuieb, Mustafa

    2016-04-01

    The study of seismic hazard assessment around greater Cairo-Egypt is very important due to condense population (more than 20 million) in that area. Although, Egypt is characterized by low seismic activity. The seismotectonic zones and high activity are occurred along the Gulf of Aqaba-Dead Sea transform, the Northern Red Sea triple junction point, Aswan, Dahshur, and Cairo-Suez District . In this study, earthquake catalogue (up to 2015) of all seismo-tectonic zones in Egypt and its surroundings are used. Beside the seismicity analysis, gravity and magnetic maps of Dahshur area are analyses for tracing active subsurface faults that are responsible of earthquakes activity. The surface geology and subsurface faults are used to evaluate the tectonic framework in the area under study. Also, The seismicity maps, focal depths and seismic hazards values are calculated. Keyword: Seismo-tectonic, seismic hazards assessment, potential fields, Greater Cairo-Egypt

  14. Slim-hole drilling and innovation enable the development of the October Nezzazat, a marginal field in Egypt

    SciTech Connect

    Hassan, I.; Mansy, A.; Cook, B.S.; Leggett, R.B.

    1995-11-01

    The Gulf of Suez Petroleum Company (GUPCO) has recently used ``slim-hole`` drilling technology to enhance the economics of developing a marginal field by significantly reducing drilling and development costs. Drilling costs have been reduced by approximately 20%. risks have also increased with slim-hole technology, but are within manageable levels. In order to ensure a deep point of injection is maintained, small but difficult-to-fish gas-lift equipment has been installed inside of a 5-inch production liner. To date, no corrosion has been observed in the October field which would weaken the slim-hole bottomhole assembly and prevent future recovery of the packer and tubing. Sidetrack flexibility has also been reduced with the smaller tubulars.

  15. Active seeps, investment climate draw interest to Uganda

    SciTech Connect

    Patton, D.K.; Kashambuzi, R.; Rubondo, E.N.T.

    1995-05-01

    Production has not been established in Uganda, but the hydrocarbon generating capacity of its rift basin is clearly evident. Reports of oil seeps date to 1925 to observations by Wayland; who relates 52 hydrocarbon occurrences in and around Lake Albert. Although not all remain active, nine oil seeps in the rift basin are confirmed active at present. The Albertine graben, a part of the East African rift system, dominates the geology of Uganda. Other, larger basins of similar evolution in Africa include the Sirte basin and the Gulf of Suez basin. These prolific basins account for one third of Africa`s total reserves. The paper describes the geologic setting, reservoirs, source rocks, geologic seals, structures, exploration history, licenses available, and fiscal terms.

  16. STS-56 view of freeflying SPARTAN-201 and Earth observation of Nile River,Egypt

    NASA Technical Reports Server (NTRS)

    1993-01-01

    During STS-56, the Shuttle Pointed Autonomous Research Tool for Astronomy 201 (SPARTAN-201), a freeflying payload, is captured as it orbits the Earth above the Nile River Valley in Egypt. This synoptic view taken aboard Discovery, Orbiter Vehicle (OV) 103, reveals the landscapes of the Sinai and the Gulf of Suez on the left and the Qatara Depression on the right. The Nile River Valley and the base of the delta feature are in the center. The leaf-like appearance of El Fayum is clearly seen. The city of Cairo is also easily recognized at the base of the delta. SPARTAN-201 was later captured by OV-103's remote manipulator system (RMS) and returned to Earth with the astronaut crew.

  17. Fault reactivation control on normal fault growth: an experimental study

    NASA Astrophysics Data System (ADS)

    Bellahsen, Nicolas; Daniel, Jean Marc

    2005-04-01

    Field studies frequently emphasize how fault reactivation is involved in the deformation of the upper crust. However, this phenomenon is generally neglected (except in inversion models) in analogue and numerical models performed to study fault network growth. Using sand/silicon analogue models, we show how pre-existing discontinuities can control the geometry and evolution of a younger fault network. The models show that the reactivation of pre-existing discontinuities and their orientation control: (i) the evolution of the main fault orientation distribution through time, (ii) the geometry of relay fault zones, (iii) the geometry of small scale faulting, and (iv) the geometry and location of fault-controlled basins and depocenters. These results are in good agreement with natural fault networks observed in both the Gulf of Suez and Lake Tanganyika. They demonstrate that heterogeneities such as pre-existing faults should be included in models designed to understand the behavior and the tectonic evolution of sedimentary basins.

  18. An extended stochastic method for seismic hazard estimation

    NASA Astrophysics Data System (ADS)

    Abd el-aal, A. K.; El-Eraki, M. A.; Mostafa, S. I.

    2015-12-01

    In this contribution, we developed an extended stochastic technique for seismic hazard assessment purposes. This technique depends on the hypothesis of stochastic technique of Boore (2003) "Simulation of ground motion using the stochastic method. Appl. Geophy. 160:635-676". The essential characteristics of extended stochastic technique are to obtain and simulate ground motion in order to minimize future earthquake consequences. The first step of this technique is defining the seismic sources which mostly affect the study area. Then, the maximum expected magnitude is defined for each of these seismic sources. It is followed by estimating the ground motion using an empirical attenuation relationship. Finally, the site amplification is implemented in calculating the peak ground acceleration (PGA) at each site of interest. We tested and applied this developed technique at Cairo, Suez, Port Said, Ismailia, Zagazig and Damietta cities to predict the ground motion. Also, it is applied at Cairo, Zagazig and Damietta cities to estimate the maximum peak ground acceleration at actual soil conditions. In addition, 0.5, 1, 5, 10 and 20 % damping median response spectra are estimated using the extended stochastic simulation technique. The calculated highest acceleration values at bedrock conditions are found at Suez city with a value of 44 cm s-2. However, these acceleration values decrease towards the north of the study area to reach 14.1 cm s-2 at Damietta city. This comes in agreement with the results of previous studies of seismic hazards in northern Egypt and is found to be comparable. This work can be used for seismic risk mitigation and earthquake engineering purposes.

  19. The Red Sea/Gulf of Aden hydrocarbon potential reassessment

    SciTech Connect

    Beydoun, Z.R. )

    1991-08-01

    Samples from most of the 85 exploration wells drilled in the Red Sea and Gulf of Aden, made available to the UNDP/World Bank Red Sea/Gulf of Aden Regional Hydrocarbon Study Project by the participating states were examined for biostratigraphy and source rock geochemistry. Major tectonic elements segment both basins, but in the Gulf of Aden this is less evident as the drift stage is more advanced; additionally, the Red Sea exhibits asymmetry in crustal composition. All this has influenced the location and development of major sediment depocenters and delta fans. Major Neogeon syn-rift and post-rift (Miocene-Pliocene) lithostratigraphic units are correlatable from the petroliferous Gulf of Suez over the Red Sea: pre-rift (Paleogene and older) and syn-rift/post-rift (Oligocene-Miocene/Pliocene) units correlate well across the Gulf of Aden (middle Oligocene) to the southern Red Sea (upper Oligocene) to the northern Red Sea/Gulf of Suez (lower Miocene). Source-rich intervals are present in the mega-sequence of the pre-rift and syn/post-rift packages. Three undeveloped gas and condensate discoveries and a gas blowout plus numerous oil seepages in the Red Sea, and a black oil discovery in the Gulf of Aden are testimony to hydrocarbon generation and entrapment. Although a higher geothermal gradient is present in the southern Red Sea, modeling of the entire basin (rather than in segments) indicates that, contrary to conventional wisdom, the region is neither too hot nor all gas prone, but it possesses the geological parameters conducive to the generation, expulsion, and trapping of significant amount of oil and gas.

  20. Structural influence on hydrocarbon entrapment in the northwestern Red Sea, Egypt

    SciTech Connect

    Salah, M.G.; Alsharhan, A.S.

    1996-01-01

    The northwestern part of the Egyptian Red Sea has attracted the attention of many geologists because it lies at the triple junction of the main rifts between the Red Sea, the Gulf of Aqaba, and Gulf of Suez. The geometry of the fault system in this area of the basin clearly indicates an extensional setting. The area has a southwestward regional dip, and it has experienced more extension than the rest of the Gulf of Suez. Six tectonic stages, different in their stress history, sedimentary fill, and depositional setting, are recognized for the northwestern Red Sea: (1) Cambrian to early Cretaceous stage; (2) late Cretaceous to Oligocene stage; (3) early Miocene stage; (4) early to middle Miocene stage; (5) middle to late Miocene stage; and (6) post-Miocene stage. Magnetic, gravity, seismic, surface, and subsurface data from the northwestern Red Sea delineate several elongate structural highs separated by elongate troughs. Both highs and troughs have the same northwest-southeast direction as the clysmic trend. Some of the highs are dissected by cross elements that trend northeast-southwest and east-north-east-west-southwest and laterally offset these highs. The tectonic framework of the northwestern sector of the Red Sea had a significant influence on hydrocarbon generation, migration, and accumulation. The evidence for this influence includes the following: (1) the troughs form the main source kitchens where the Precambrian basement rocks are present at depths exceeding 4877 in (e.g., Gemsa Trough); (2) the magnitude of throw on the clysmic fault is critical in the entrapment mechanisms; (3) the cross elements play a major role in the hydrocarbon migration and accumulation because they truncate the extension of most of the oil fields and form their bounding faults; and (4) all the discovered oil fields in the study area are structural and/or combination traps and show good matches to the magnetic anomalies.

  1. New constraints on the Nubia-Sinai-Dead Sea fault crustal motion

    NASA Astrophysics Data System (ADS)

    Saleh, Mohamed; Becker, Matthias

    2015-05-01

    The subduction between Nubia and Eurasia and activities along the Red Sea, Gulf of Suez and Gulf of Aqaba may control the surface deformation in the north-eastern corner of the African continent. Using very few GPS stations in the Egyptian region, previous studies indicate northward motion of northern Nubia with respect to Eurasia of about 5 mm/yr (McClusky et al., 2000; Reilinger et al., 2006; Mahmoud et al., 2005). In order to constrain better the movement rate of northern Nubia and interaction between Nubia, Eurasia and Arabia plates, we are using for the first time 16 permanent GPS stations in combination with 47 non-permanent stations covering Egypt for the period 2006-2012. This paper extends the previous study (Saleh and Becker, 2013) by processing in addition to the Egyptian stations 86 permanent stations belonging to three different tectonic plates. This led to a considerably better coverage of the Sinai-Dead Sea region. This work intends to be the first comprehensive analysis of the permanent stations in combination with the various campaign data in selected regions of special interest in Egypt. The GPS sites show a relative motion between Nubia and Eurasia of about 6.5 ± 1 mm/yr, which increased toward the Hellenic trench, 8.2 ± 0.8 mm/yr in Sinai peninsula, 14.2 ± 1.4 mm/yr in the north of Arabian plate and 22.3 ± 0.7 mm/yr in eastern and central Turkey. The strain computation indicates high strain rates, where the deformation is strongly localized along the Dead Sea fault, and low to moderate strain rate in the Gulf of Suez and southern Sinai.

  2. Salt weathering in Egyptian limestone after laboratory simulations with continuous flow of salt solutions at different temperatures

    NASA Astrophysics Data System (ADS)

    Aly, Nevin; Gomez-Heras, Miguel; Hamed, Ayman; Alvarez de Buergo, Monica

    2013-04-01

    weathering in Egyptian limestone after laboratory simulations with continuous flow of salt solutions at different temperatures Nevin Aly Mohamed (1), Miguel Gomez - Heras(2), Ayman Hamed Ahmed (1), and Monica Alvarez de Buergo(2). (1) Faculty of Pet. & Min. Engineering- Suez Canal University, Suez, Egypt, (2) Instituto de Geociencias (CSIC-UCM) Madrid. Spain. Limestone is one of the most frequent building stones in Egypt and is used since the time of ancient Egyptians and salt weathering is one of the main threats to its conservation. Most of the limestone used in historical monuments in Cairo is a biomicrite extracted from the Mid-Eocene Mokattam Group. During this work, cylindrical samples (2.4 cm diameter and approx. 4.8 cm length) were subjected, in a purpose-made simulation chamber, to simulated laboratory weathering tests with fixed salt concentration (10% weight NaCl solution), at different temperatures, which were kept constant throughout each test (10, 20, 30, 40 oC). During each test, salt solutions flowed continuously imbibing samples by capilarity. Humidity within the simulation chamber was reduced using silica gel to keep it low and constant to increase evaporation rate. Temperature, humidity inside the simulation chamber and samples weight were digitally monitored during each test. Results show the advantages of the proposed experimental methodology using a continuous flow of salt solutions and shed light on the effect of temperature on the dynamics of salt crystallization on and within samples. Research funded by mission sector of high education ministry, Egypt and Geomateriales S2009/MAT-1629.

  3. Gravity observations at Sinai Peninsula and its geophysical and geodetic applications

    NASA Astrophysics Data System (ADS)

    Fathy, Karem; Zahran, K. H.; Radwan, Anwar H.; Sabet, Hassan S.; Hamed, Diaa

    2013-12-01

    South Sinai is an interesting region from both tectonic and seismological settings. Tectonically, Sinai Peninsula is strongly dominated by its active boundaries due to its location at the triple junction among the Gulf of Suez rift, the Aqaba-Levant transform fault and the Red Sea Rift. Moreover, reported seismological activities along the three tectonic boundaries indicate its continuous activities. It is thus of great interest to delineate the subsurface geological structure responsible of its tectonic settings and its relation to the seismological activity. Therefore, terrestrial gravity observation has been carried out to figure out the sub-surface structure representing its tectonic settings. On the other hand, the location of Sinai Peninsula between Gulf of Suez, Gulf of Aqepa and Red Sea has made the satellite altimetry data an optimum tool to determine the Gravity sources on the marine regions bounding the Sinai region. Finally, temporal gravity variation of the GRACE satellite mission, launched in 2003 gives the opportunity to monitor its temporal gravity variation on regional scale. Temporal gravity variation from GRACE demonstrates any possible mass redistribution along the pounding tectonic settings and its relation to seismicity. Observed gravity map shows significant gravity anomalies attributed to tectonic and seismicity. Satellite altimetry and gravity data are considered to be a valuable source of data to determine the offshore subsurface structure. Temporal gravity variations from GRACE shows important zones of mass redistribution attributed to its new tectonics and its relation to the seismological activities. Integrating all available data sheds more light on the geodynamic behavior of the selected region and its relation to the seismic activities.

  4. Natural discharge : a key to sustainable utilization of fossil groundwater.

    SciTech Connect

    Sultan, M.; Yan, E.; Sturchio, N.; Wagdy, A.; Abdel Gelil, K.; Becker, R.; Manocha, N.; Milewski, A.; Environmental Science Division; Western Michigan Univ.; Univ. of Illinois at Chicago; Cairo Univ.; Ministry of Water Resources and Irrigagion

    2007-01-01

    Rising demands for fresh water supplies in arid lands are leading to excessive exploitation and unsustainable mining of non-renewable fossil groundwater. Using the Nubian Aquifer of Saharan Africa as a test site, we demonstrate an integrated approach to identify areas of discharge that could have gone undetected, and to model extraction that is sustained by natural discharge. Using isotopic and geochemical analyses along with field and remote sensing data we show that discharge of the Nubian Aquifer is occurring on a larger scale, primarily through deep-seated fault systems, and that ascending groundwater discharges into relatively thick alluvial aquifers proximal to the fault complex that defines the River Nile and the Gulf of Suez. We develop a hydrologic model to assess the discharge and to constrain sustainable extraction in the Asyuti area along the River Nile and to demonstrate a replicable model for similar reservoirs. A two-dimensional groundwater flow model was constructed and calibrated against head data from 19 wells. Results point to a significant contribution to the Asyuti groundwater system from rising Nubian groundwater (3.19 x 10{sup 7} m{sup 3}/yr: 75% of incoming flow) and a modest contribution (1.08 x 10{sup 7} m{sup 3}/yr: 25% of incoming flow) from surface runoff. Approximately 2.5 x 10{sup 7} m{sup 3}/yr of groundwater could be used in a sustainable manner in Asyuti. Assuming geologic settings and discharge rates similar to those at Asyuti, we estimate that 70 x 10{sup 7} m{sup 3}/yr of groundwater may be available for sustainable development in similar settings around the River Nile and the Gulf of Suez.

  5. Survival of high latitude fringing corals in extreme temperatures: Red Sea oceanography

    NASA Astrophysics Data System (ADS)

    Moustafa, M. Z.; Moustafa, M. S.; Moustafa, Z. D.; Moustafa, S. E.

    2014-04-01

    This multi-year study set out to establish a comprehensive knowledgebase for a fringing coral reef in the Gulf of Suez, while also investigating the link between coral reef survivability and the extreme environmental conditions present in the region. The Gulf of Suez is a narrow branch of the northern Red Sea for which all forms of environmental and scientific data are severely lacking. Monitoring oceanographic and meteorological data provides evidence of both seasonal variability and interannual variability in this region, and may reveal correlations between reef health and prevailing climate conditions. Specifically, this research sought to document the environmental conditions under which Zaki's Reef, a small fringing coral reef (29.5°N and 32.4°E) that lies at the northernmost limit of tropical reefs worldwide, is able to survive, in order to determine how extreme the conditions are. Results of observed seawater temperature revealed that coral species at Zaki's Reef regularly experience 2-4 °C and 10-15 °C daily and seasonal temperature variations, respectively. Seawater temperature monthly means reached a minimum of 14 °C in February and a maximum of 33 °C in August. Monthly mean sea surface temperature climatology obtained from satellite measurements was comparable to observed seawater temperatures, while annual air and seawater temperature means were identical at 22 °C. Observed seawater temperatures exceeded established coral bleaching thresholds for extended periods of time, suggesting that coral species at this location may have developed a mechanism to cope with such extreme temperatures. Further scrutiny of these species and the mechanisms by which they are able to thrive is recommended.

  6. Exploration and assessment of the geothermal resources in the Hammam Faraun hot spring, Sinai Peninsula, Egypt

    NASA Astrophysics Data System (ADS)

    Zaher, Mohamed Abdel; Saibi, Hakim; Nishijima, Jun; Fujimitsu, Yasuhiro; Mesbah, Hany; Ehara, Sachio

    2012-02-01

    The tectonic position of Egypt in the northeastern corner of the African continent suggests that it may possess significant geothermal resources, especially along its eastern margin. The most promising areas for geothermal development in the northwest Red Sea-Gulf of Suez rift system are located where the eastern shore of the Gulf of Suez is characterized by superficial thermal manifestations, including a cluster of hot springs with varied temperatures. Magnetotelluric and gravity-reconnaissance surveys were carried out over the geothermal region of Hammam Faraun to determine the subsurface electric resistivity and the densities that are related to rock units. These surveys were conducted along profiles. One-dimensional (1D) and two-dimensional (2D) inversion model techniques were applied on the MT data, integrating the 2D inversion of gravity data. The objectives of these surveys were to determine and parameterize the subsurface source of the Hammam Faraun hot spring and to determine the origin of this spring. Based on this data, a conceptual model and numerical simulation were made of the geothermal area of Hammam Faraun. The numerical simulation succeeded in determining the characteristics of the heat sources beneath the Hammam Faraun hot spring and showed that the hot spring originates from a high heat flow and deep ground water circulation in the subsurface reservoir that are controlled by faults. These studies were followed by an assessment of the geothermal potential for electric generation from the Hammam Faraun hot spring. The value of the estimated potential is 28.34 MW, as the reservoir is assumed to be only 500 m thick. This value would be enough for the desalination of water for both human and agricultural consumption.

  7. Testicular cell-conditioned medium supports embryonic stem cell differentiation toward germ lineage and to spermatocyte- and oocyte-like cells.

    PubMed

    Shah, Syed M; Saini, Neha; Singh, Manoj K; Manik, Radheysham; Singla, Suresh K; Palta, Prabhat; Chauhan, Manmohan S

    2016-08-01

    Testicular cells are believed to secrete various growth factors that activate signaling pathways finally leading to gametogenesis. In vitro gametogenesis is an obscure but paramountly important task primarily because of paucity of the precursor cells and first trimester gonadal tissues. To overcome these limitations for development of in vitro gametes, the present study was designed to induce differentiation of buffalo embryonic stem (ES) cells into germ lineage cells on stimulation by testicular cell-conditioned medium (TCM), on the basis of the assumption that ES cells have the intrinsic property to differentiate into any cell type and TCM would provide the necessary growth factors for differentiation toward germ cell lineage. For this purpose, buffalo ES cells were differentiated as embryoid bodies (EB) in floating cultures and as monolayer adherent cultures in different doses (10%, 20%, and 40%) of TCM for different culture intervals (4, 8, and 14 days), to identify the optimum dose-and-time period. We observed that 40% TCM dose induces highest expression of primordial germ cell-specific (DAZL, VASA, and PLZF), meiotic (SYCP3, MLH1, TNP1/2, and PRM2), spermatocyte-specific (BOULE and TEKT1), and oocyte-specific genes (GDF9 and ZP2/3) for a culture period of 14 days under both floating and adherent differentiation. Immunocytochemical analysis of EBs and adherent cultures revealed presence of primordial germ cell markers (c-KIT, DAZL, and VASA), meiotic markers (SYCP3, MLH1 and PROTAMINE1), spermatocyte markers (ACROSIN and HAPRIN), and oocyte markers (GDF9 and ZP4), indicating progression into post-meiotic gametogenesis. The detection of germ cell-specific proteins in Day 14 EBs like VASA, GDF9, and ZP4 by Western blotting further confirmed germ lineage differentiation. The significantly lower (P < 0.05) concentration of 5-methyl-2-deoxycytidine in optimally differentiated EBs is suggestive of the process of methylation erasure. Oocyte-like structures

  8. Biologic Agents for Periodontal Regeneration and Implant Site Development.

    PubMed

    Suárez-López Del Amo, Fernando; Monje, Alberto; Padial-Molina, Miguel; Tang, ZhiHui; Wang, Hom-Lay

    2015-01-01

    The advancement of molecular mediators or biologic agents has increased tremendously during the last decade in periodontology and dental implantology. Implant site development and reconstruction of the lost periodontium represent main fields in which these molecular mediators have been employed and investigated. Different growth factors trigger different reactions in the tissues of the periodontium at various cellular levels. Proliferation, migration, and differentiation constitute the main target areas of these molecular mediators. It was the purpose of this comprehensive review to describe the origin and rationale, evidence, and the most current understanding of the following biologic agents: Recombinant Human Platelet-Derived Growth Factor-BB (rhPDGF-BB), Enamel Matrix Derivate (EMD), Platelet-Rich Plasma (PRP) and Platelet-Rich Fibrin (PRF), Recombinant Human Fibroblast Growth Factor-2 (rhFGF-2), Bone Morphogenic Proteins (BMPs, BMP-2 and BMP-7), Teriparatide PTH, and Growth Differential Factor-5 (GDF-5). PMID:26509173

  9. Genetics of osteoarthritis.

    PubMed

    Rodriguez-Fontenla, Cristina; Gonzalez, Antonio

    2015-01-01

    Osteoarthritis (OA) is a complex disease caused by the interaction of multiple genetic and environmental factors. This review focuses on the studies that have contributed to the discovery of genetic susceptibility factors in OA. The most relevant associations discovered until now are discussed in detail: GDF-5, 7q22 locus, MCF2L, DOT1L, NCOA3 and also some important findings from the arcOGEN study. Moreover, the different approaches that can be used to minimize the specific problems of the study of OA genetics are discussed. These include the study of microsatellites, phenotype standardization and other methods such as meta-analysis of GWAS and gene-based analysis. It is expected that these new approaches contribute to finding new susceptibility genetic factors for OA. PMID:24992825

  10. Small-signal model parameter extraction for AlGaN/GaN HEMT

    NASA Astrophysics Data System (ADS)

    Le, Yu; Yingkui, Zheng; Sheng, Zhang; Lei, Pang; Ke, Wei; Xiaohua, Ma

    2016-03-01

    A new 22-element small signal equivalent circuit model for the AlGaN/GaN high electron mobility transistor (HEMT) is presented. Compared with the traditional equivalent circuit model, the gate forward and breakdown conductions (G gsf and G gdf) are introduced into the new model to characterize the gate leakage current. Additionally, for the new gate-connected field plate and the source-connected field plate of the device, an improved method for extracting the parasitic capacitances is proposed, which can be applied to the small-signal extraction for an asymmetric device. To verify the model, S-parameters are obtained from the modeling and measurements. The good agreement between the measured and the simulated results indicate that this model is accurate, stable and comparatively clear in physical significance.

  11. Validation of AIRS Retrievals of CO2 via Comparison to In Situ Measurements

    NASA Technical Reports Server (NTRS)

    Olsen, Edward T.; Chahine, Moustafa T.; Chen, Luke L.; Jiang, Xun; Pagano, Thomas S.; Yung, Yuk L.

    2008-01-01

    Topics include AIRS on Aqua, 2002-present with discussion about continued operation to 2011 and beyond and background, including spectrum, weighting functions, and initialization; comparison with aircraft and FTIR measurements in Masueda (CONTRAIL) JAL flask measurements, Park Falls, WI FTIR, Bremen, GDF, and Spitsbergen, Norway; AIRS retrievals over addition FTIR sites in Darwin, AU and Lauder, NZ; and mid-tropospheric carbon dioxide weather and contribution from major surface sources. Slide titles include typical AIRS infrared spectrum, AIRS sensitivity for retrieving CO2 profiles, independence of CO2 solution with respect to the initial guess, available in situ measurements for validation and comparison, comparison of collocated V1.5x AIRS CO2 (N_coll greater than or equal to 9) with INTEX-NA and SPURT;

  12. Insights into Sex Chromosome Evolution and Aging from the Genome of a Short-Lived Fish.

    PubMed

    Reichwald, Kathrin; Petzold, Andreas; Koch, Philipp; Downie, Bryan R; Hartmann, Nils; Pietsch, Stefan; Baumgart, Mario; Chalopin, Domitille; Felder, Marius; Bens, Martin; Sahm, Arne; Szafranski, Karol; Taudien, Stefan; Groth, Marco; Arisi, Ivan; Weise, Anja; Bhatt, Samarth S; Sharma, Virag; Kraus, Johann M; Schmid, Florian; Priebe, Steffen; Liehr, Thomas; Görlach, Matthias; Than, Manuel E; Hiller, Michael; Kestler, Hans A; Volff, Jean-Nicolas; Schartl, Manfred; Cellerino, Alessandro; Englert, Christoph; Platzer, Matthias

    2015-12-01

    The killifish Nothobranchius furzeri is the shortest-lived vertebrate that can be bred in the laboratory. Its rapid growth, early sexual maturation, fast aging, and arrested embryonic development (diapause) make it an attractive model organism in biomedical research. Here, we report a draft sequence of its genome that allowed us to uncover an intra-species Y chromosome polymorphism representing-in real time-different stages of sex chromosome formation that display features of early mammalian XY evolution "in action." Our data suggest that gdf6Y, encoding a TGF-β family growth factor, is the master sex-determining gene in N. furzeri. Moreover, we observed genomic clustering of aging-related genes, identified genes under positive selection, and revealed significant similarities of gene expression profiles between diapause and aging, particularly for genes controlling cell cycle and translation. The annotated genome sequence is provided as an online resource (http://www.nothobranchius.info/NFINgb). PMID:26638077

  13. Biologic Agents for Periodontal Regeneration and Implant Site Development

    PubMed Central

    Suárez-López del Amo, Fernando; Monje, Alberto; Padial-Molina, Miguel; Tang, ZhiHui; Wang, Hom-Lay

    2015-01-01

    The advancement of molecular mediators or biologic agents has increased tremendously during the last decade in periodontology and dental implantology. Implant site development and reconstruction of the lost periodontium represent main fields in which these molecular mediators have been employed and investigated. Different growth factors trigger different reactions in the tissues of the periodontium at various cellular levels. Proliferation, migration, and differentiation constitute the main target areas of these molecular mediators. It was the purpose of this comprehensive review to describe the origin and rationale, evidence, and the most current understanding of the following biologic agents: Recombinant Human Platelet-Derived Growth Factor-BB (rhPDGF-BB), Enamel Matrix Derivate (EMD), Platelet-Rich Plasma (PRP) and Platelet-Rich Fibrin (PRF), Recombinant Human Fibroblast Growth Factor-2 (rhFGF-2), Bone Morphogenic Proteins (BMPs, BMP-2 and BMP-7), Teriparatide PTH, and Growth Differential Factor-5 (GDF-5). PMID:26509173

  14. Identification of genome-wide selection signatures in the Limousin beef cattle breed.

    PubMed

    Gurgul, A; Szmatoła, T; Ropka-Molik, K; Jasielczuk, I; Pawlina, K; Semik, E; Bugno-Poniewierska, M

    2016-08-01

    The study is aimed at identifying selection footprints within the genome of Limousin cattle. With the use of Extended Haplotype Homozygosity test, supplemented with correction for variation in recombination rates across the genome, we created map of selection footprints and detected 173 significant (p < 0.01) core haplotypes being potentially under positive selection. Within these regions, a number of candidate genes associated inter alia with skeletal muscle growth (GDF15, BMP7, BMP4 and TGFB3) or postmortem proteolysis and meat maturation (CAPN1 and CAPN5) were annotated. Noticeable clusters of selection footprints were detected on chromosomes 1, 4, 8 and 14, which are known to carry several quantitative trait loci for growth traits and meat quality. The study provides information about the genes and metabolic pathways potentially modified under the influence of directional selection, aimed at improving beef production characteristics in Limousin cattle. PMID:26611546

  15. Spectroscopic investigation and hydrogen-bonding analysis of triazinones.

    PubMed

    Dhas, Devadhas Arul; Joe, Isaac Hubert; Roy, Solomon Dawn Dharma; Balachandran, Sreedharan

    2012-08-01

    NIR FT-Raman, FTIR and UV-vis spectra of the herbicide metamitron were recorded and analyzed. The aromaticities, equilibrium geometries, bonding features, electrostatic potentials, and harmonic vibrational wavenumbers of the monomers and dimers of triazinone derivatives were also investigated with the aid of BLYP/6-311 G(df, p) density functional theory. Features in the vibrational spectra were assigned with the aid of the VEDA.4 program. The calculated results were a good match to the experimental data obtained from FTIR, Raman, and electronic absorption spectra. Mulliken population analysis was performed on the atomic charges and the HOMO-LUMO energies were also calculated. NBO analysis highlighted the intra- and intermolecular N-H…O and C-H…O hydrogen bonds in the crystal structures of the triazinones. The solvent effect was calculated using time-dependent density functional theory in combination with the polarizable continuum model. PMID:22350295

  16. Development of advanced concepts for DIR-MCFC cogeneration applications in the European Market

    SciTech Connect

    Kortbeek, P.J.; Ottervanger, R.G.; Dicks, A.L.

    1996-12-31

    Early 1996 a three year (1996 - 1998) joint European project was launched under the name {open_quote}Advanced DIR-MCFC Development{close_quote}, aiming at the development of Direct Internal Reforming (DIR) Molten Carbonate Fuel Cell (MCFC) systems for cogeneration applications for the European market. In this project participate: Brandstofcel Nederland BV (BCN), British Gas pic (BG), Gaz de France (GDF), Netherlands Energy Research foundation (ECN), Stork, Royal Schelde and Sydkraft AB. The European Fuel Cell User Group (EFCUG) supports the project as an advisory board. Whereas the US and Japanese programmes are aimed at large-scale demonstrations of the MCFC technology, this project focusses on the development of concepts and technology, required for MCFC systems that will be competative on the cogeneration market. The project partners provide the essential expertise: from end-user, system engineering, stack development up to fundamental material research.

  17. Development of an Environmental Safety Case for a Geological Disposal Facility in the UK

    NASA Astrophysics Data System (ADS)

    Bailey, L.; Clark, H.; Wellstead, M.

    2012-04-01

    Geological disposal is the UK policy for the long-term management of higher activity radioactive waste. The Radioactive Waste Management Directorate (RWMD) of the Nuclear Decommissioning Authority (NDA) has been given the responsibility for implementing geological disposal. The implementation process is founded on the principles of voluntarism and partnership and the UK Government has set in place a process that encourages communities to participate in the siting process. Developing an environmental safety case (ESC) that gives confidence that a geological disposal facility (GDF) for higher activity radioactive wastes will remain passively safe for hundreds of thousands of years after the facility has been closed, and is no longer actively maintained, is an important and challenging part of the programme to implement geological disposal. Our approach for building confidence in long-term safety is to use multiple barriers to isolate and contain the wastes and to explain our confidence in the performance of these barriers by developing a multi-factor safety case. We will develop a safety case based on varied and different lines of reasoning, including both quantitative aspects and qualitative arguments. We will use a range of safety arguments to support the ESC, drawing on underpinning science and engineering. We have published a generic ESC (that is not specific to any site or disposal facility design) that considers the long-term safety of illustrative generic disposal facility design examples in stylised geological environments. This generic ESC explains how engineered and natural barriers can work together to isolate and contain the radioactivity in the wastes. The safety arguments in the generic ESC are supported by calculations using a simple model that is illustrative of a broad range of disposal facility designs and geological environments. The generic ESC provides a benchmark enabling us to undertake disposability assessments for waste packages, without

  18. Cell reprogramming. Histone chaperone ASF1A is required for maintenance of pluripotency and cellular reprogramming.

    PubMed

    Gonzalez-Muñoz, Elena; Arboleda-Estudillo, Yohanna; Otu, Hasan H; Cibelli, Jose B

    2014-08-15

    Unfertilized oocytes have the intrinsic capacity to remodel sperm and the nuclei of somatic cells. The discoveries that cells can change their phenotype from differentiated to embryonic state using oocytes or specific transcription factors have been recognized as two major breakthroughs in the biomedical field. Here, we show that ASF1A, a histone-remodeling chaperone specifically enriched in the metaphase II human oocyte, is necessary for reprogramming of human adult dermal fibroblasts (hADFs) into undifferentiated induced pluripotent stem cell. We also show that overexpression of just ASF1A and OCT4 in hADFs exposed to the oocyte-specific paracrine growth factor GDF9 can reprogram hADFs into pluripotent cells. Our Report underscores the importance of studying the unfertilized MII oocyte as a means to understand the molecular pathways governing somatic cell reprogramming. PMID:25035411

  19. Comparison of different NaGdF4:Eu3+ synthesis routes and their influence on its structural and luminescent properties

    NASA Astrophysics Data System (ADS)

    Karbowiak, Mirosław; Mech, Agnieszka; Bednarkiewicz, Artur; Stręk, Wiesław; Kępiński, Leszek

    2005-06-01

    Eu3+:NaGdF4 samples were obtained via co-precipitation in aqueous solution (CP), reversed micelle (RM) method, reaction between solid GdF3 and NaF solution (SR) as well as a solid-state reaction at high temperatures (SS). The synthesised materials were characterised using X-ray powder diffractometry, TEM microscopy, infrared spectroscopy and TGA analysis. For discussion of optical properties excitation and emission spectra were recorded and emission decay times were measured. The CP and RM methods allow to obtain powders with crystallite size of ∼10 nm, which may be smoothly increased to about 1 μm during post-fabrication heat treatment. Differences in structural and especially in optical properties of phosphors prepared by different techniques are emphasised and applicability of wet-chemistry routes for synthesis of fluoride powders is argued.

  20. Quality Control Systems in Cardiac Aging

    PubMed Central

    Quarles, Ellen K; Dai, Dao-Fu; Tocchi, Autumn; Basisty, Nathan; Gitari, Lemuel; Rabinovitch, Peter S

    2015-01-01

    Cardiac aging is an intrinsic process that results in impaired cardiac function, along with cellular and molecular changes. These degenerative changes are intimately associated with quality control mechanisms. This review provides a general overview of the clinical and cellular changes which manifest in cardiac aging, and the quality control mechanisms involved in maintaining homeostasis and retarding aging. These mechanisms include autophagy, ubiquitin-mediated turnover, apoptosis, mitochondrial quality control and cardiac matrix homeostasis. Finally, we discuss aging interventions that have been observed to impact cardiac health outcomes. These include caloric restriction, rapamycin, resveratrol, GDF11, mitochondrial antioxidants and cardiolipin-targeted therapeutics. A greater understanding of the quality control mechanisms that promote cardiac homeostasis will help to understand the benefits of these interventions, and hopefully lead to further improved therapeutic modalities. PMID:25702865

  1. [Gd-doped natural thenardite: Eu photoluminescence properties of europium].

    PubMed

    Guzaliayi, Juman; Tuerxun, Aidilibike; Aizitiaili, Abulizi; Aierken, Sidike

    2012-06-01

    The authors prepared Na2SO4: Eu, Gd, and Na2Gd2 (SO4)4: Eu phosphors by heating, the mixed powder of GdF3, EuF3 and natural mirabilite with muffle furnace at 1 000 degrees C for 30 min and continually heating it with microwave at 750 degrees C for 10 min. With increasing the concentrations of Gd ion, the 610 nm emission intensity due to Eu3+ was strengthened. Gd3+ probably formed a bridge between substrate and the activator so that the energy is able to be transferred efficiently. The luminescence intensity, along with colorimetric purity, reaches the top with 21 mol% Gd3+ doping in the thenardite (Na2SO4: Eu) lattices, eventually coming up the quenching effects of concentration. PMID:22870627

  2. Atypical molecular profile for joint development in the avian costal joint.

    PubMed

    Winslow, B B; Burke, A C

    2010-10-01

    Development of synovial joints involves generation of cartilaginous anlagen, formation of interzones between cartilage anlagen, and cavitation of interzones to produce fluid filled cavities. Interzone development is not fully understood, but interzones are thought to develop from skeletogenic cells that are inhibited from further chondrogenic development by a cascade of gene expression including Wnt and Bmp family members. We examined the development of the rarely studied avian costal joint to better understand mechanisms of joint development. The costal joint is found within ribs, is morphologically similar to the metatarsophalangeal joint, and undergoes cavitation in a similar manner. In contrast to other interzones, Wnt14/9a, Gdf5, Chordin, Barx1, and Bapx1 are absent from the costal joint interzone, consistent with the absence of active β-catenin and phosphorylated Smad 1/5/8. However Autotaxin and Noggin are expressed. The molecular profile of the costal joint suggests there are alternative mechanisms of interzone development. PMID:20730871

  3. Ultraviolet-to-visible downconversion luminescence in solgel oxyfluoride glass ceramics containing Eu³⁺:GdF₃ nanocrystals.

    PubMed

    Szpikowska-Sroka, Barbara; Zur, Lidia; Czoik, Rozalia; Goryczka, Tomasz; Ządło, Maria; Pisarski, Wojciech A

    2014-06-01

    GdF3 nanocrystals doped with Eu3+ ions in oxyfluoride glass ceramics were prepared by a solgel method. The structural properties were examined by x-ray diffraction measurements. The effects of gadolinium codoping on europium emission in the prepared solgel glasses and glass ceramics have been studied. The emission bands originating from the 5D0 state of Eu3+ ions are enhanced under excitation of Gd3+ ions by 273 nm line. The electric dipole 5D0→7F2 transitions were dominant in the samples before heat treatment, whereas magnetic dipole 5D0→7F1 transitions had a higher probability in the samples after annealing. The luminescence lifetime for the 5D0 level of Eu3+ ions in the samples after excitation at 273 nm is long lived in comparison to excitation at 393 nm and increased to 190%. Energy transfer from Gd3+ to Eu3+ was observed. PMID:24876007

  4. Synthesis, characterization and vibrational properties of p-fluorosulfinylaniline

    NASA Astrophysics Data System (ADS)

    Páez Jerez, Ana L.; Flores Antognini, Andrea; Cutin, Edgardo H.; Robles, Norma L.

    2015-02-01

    The reaction of p-fluoroaniline and SOCl2 rendered p-fluorosulfinylaniline in good yield. The obtained dark yellowish liquid compound was characterized by NMR, UV-visible, FT-IR and Raman spectroscopies. The observed features were consistent with the existence of only one conformer, belonging to the CS symmetry group. A tentative assignment of the vibrational modes was performed on the basis of experimental spectra and quantum chemical calculations at different levels of theory (B3LYP and MP2 with 6-31+G(d), 6-311+G(d) and 6-311+G(df) basis sets). The conformational and vibrational properties of p-fluorosulfinylaniline were in good agreement with experimental data reported for other substituted sulfinylanilines and p-halogenanilines.

  5. Synthesis, characterization and vibrational properties of p-fluorosulfinylaniline.

    PubMed

    Páez Jerez, Ana L; Flores Antognini, Andrea; Cutin, Edgardo H; Robles, Norma L

    2015-02-25

    The reaction of p-fluoroaniline and SOCl2 rendered p-fluorosulfinylaniline in good yield. The obtained dark yellowish liquid compound was characterized by NMR, UV-visible, FT-IR and Raman spectroscopies. The observed features were consistent with the existence of only one conformer, belonging to the CS symmetry group. A tentative assignment of the vibrational modes was performed on the basis of experimental spectra and quantum chemical calculations at different levels of theory (B3LYP and MP2 with 6-31+G(d), 6-311+G(d) and 6-311+G(df) basis sets). The conformational and vibrational properties of p-fluorosulfinylaniline were in good agreement with experimental data reported for other substituted sulfinylanilines and p-halogenanilines. PMID:25228038

  6. Lefty Blocks a Subset of TGFβ Signals by Antagonizing EGF-CFC Coreceptors

    PubMed Central

    2004-01-01

    Members of the EGF-CFC family play essential roles in embryonic development and have been implicated in tumorigenesis. The TGFβ signals Nodal and Vg1/GDF1, but not Activin, require EGF-CFC coreceptors to activate Activin receptors. We report that the TGFβ signaling antagonist Lefty also acts through an EGF-CFC-dependent mechanism. Lefty inhibits Nodal and Vg1 signaling, but not Activin signaling. Lefty genetically interacts with EGF-CFC proteins and competes with Nodal for binding to these coreceptors. Chimeras between Activin and Nodal or Vg1 identify a 14 amino acid region that confers independence from EGF-CFC coreceptors and resistance to Lefty. These results indicate that coreceptors are targets for both TGFβ agonists and antagonists and suggest that subtle sequence variations in TGFβ signals result in greater ligand diversity. PMID:14966532

  7. Mechanochemical preparation of nanocrystalline NaYF4:Gd3+/Yb3+/Tm3+: An efficient upconversion phosphor

    NASA Astrophysics Data System (ADS)

    Zhang, Jun; Riesen, Hans

    2015-11-01

    We report on a mechanochemical preparation route for NaYF4:Gd3+/Yb3+/Tm3+ nanoparticles by ball-milling NaF, YF3, GdF3, YbF3 and TmF3 at room temperature. An analysis by XRD and TEM demonstrates that the resulting materials are mainly (∼88% after 4 h ball-milling) in the hexagonal phase and are on the nanoscale with an average crystallite size of ∼20 nm. The prepared nanoparticles display efficient upconversion emission; upon excitation by a 980 nm laser diode, bright visible blue light emission can be observed. However, in accord with previous results, the strongest emission is observed in the NIR at 800 nm.

  8. Combinatorial Analysis of Growth Factors Reveals the Contribution of Bone Morphogenetic Proteins to Chondrogenic Differentiation of Human Periosteal Cells.

    PubMed

    Mendes, Luis Filipe; Tam, Wai Long; Chai, Yoke Chin; Geris, Liesbet; Luyten, Frank P; Roberts, Scott J

    2016-05-01

    Successful application of cell-based strategies in cartilage and bone tissue engineering has been hampered by the lack of robust protocols to efficiently differentiate mesenchymal stem cells into the chondrogenic lineage. The development of chemically defined culture media supplemented with growth factors (GFs) has been proposed as a way to overcome this limitation. In this work, we applied a fractional design of experiment (DoE) strategy to screen the effect of multiple GFs (BMP2, BMP6, GDF5, TGF-β1, and FGF2) on chondrogenic differentiation of human periosteum-derived mesenchymal stem cells (hPDCs) in vitro. In a micromass culture (μMass) system, BMP2 had a positive effect on glycosaminoglycan deposition at day 7 (p < 0.001), which in combination with BMP6 synergistically enhanced cartilage-like tissue formation that displayed in vitro mineralization capacity at day 14 (p < 0.001). Gene expression of μMasses cultured for 7 days with a medium formulation supplemented with 100 ng/mL of BMP2 and BMP6 and a low concentration of GDF5, TGF-β1, and FGF2 showed increased expression of Sox9 (1.7-fold) and the matrix molecules aggrecan (7-fold increase) and COL2A1 (40-fold increase) compared to nonstimulated control μMasses. The DoE analysis indicated that in GF combinations, BMP2 was the strongest effector for chondrogenic differentiation of hPDCs. When transplanted ectopically in nude mice, the in vitro-differentiated μMasses showed maintenance of the cartilaginous phenotype after 4 weeks in vivo. This study indicates the power of using the DoE approach for the creation of new medium formulations for skeletal tissue engineering approaches. PMID:27018617

  9. Indications of that migration of stem cells is influenced by the extra cellular matrix architecture in the mammalian intervertebral disk region.

    PubMed

    Henriksson, H Barreto; Papadimitriou, N; Tschernitz, S; Svala, E; Skioldebrand, E; Windahl, S; Junevik, K; Brisby, H

    2015-10-01

    Disk-degeneration is believed a major cause for lumbar pain. Previously, potential stem cell niches in the intervertebral disk (IVD) region, located adjacent to epiphyseal plate, was reported. The aim of the study was to examine migration of mesenchymal stem cells (MSCs), extracellular matrix (ECM) architecture in a potential cellular migration route (CMR; area located between the niche and IVD) and in the IVD in non-degenerated lapine- and in human degenerated IVD tissues. Human MSCs (n=3), human degenerated IVD tissues (n=10) and lapine IVDs (n=10) were collected. The samples were examined by immunohistochemistry for stem cell markers; CD90, OCT3/4, pre-chondrocytic marker; GDF5, catabolic markers; MMP9, MMP13, inflammatory marker; IL1R, cellular migration markers; SNAI1, SNAI2, adhesion markers; β1-INTEGRIN and DDR2. In addition, gene-expression analyses (Real time PCR) were performed on additional samples. Further, time lapse studies were performed with hMSCs cultured on aligned COLL-I-fibers-coated glass-slides in DMEM-LG, 10% human serum containing fibroblast growth factor (bFGF). Presence of stem cells (CD90+, OCT3/4+), pre-chondocytic cells (GDF5+) and cells positive for migration markers (SNAI1+, SNAI2+), catabolic markers (MMP9+, MMP13+), inflammatory marker (IL1R+), adhesion markers (DDR2+, B1-INTEGRIN+) were detected (gene- and protein level) in investigated CMR and IVD regions. In the time lapse studies, MSCs alignment and protrusions were observed orientated in the same direction as collagen fibers. Results display influence of ECM collagen architecture and collagen fiber spatial direction on migration of stem cells. The results can be useful when developing tissue-engineering strategies for disk-degeneration. PMID:26337726

  10. The Inhibitory Core of the Myostatin Prodomain: Its Interaction with Both Type I and II Membrane Receptors, and Potential to Treat Muscle Atrophy.

    PubMed

    Ohsawa, Yutaka; Takayama, Kentaro; Nishimatsu, Shin-ichiro; Okada, Tadashi; Fujino, Masahiro; Fukai, Yuta; Murakami, Tatsufumi; Hagiwara, Hiroki; Itoh, Fumiko; Tsuchida, Kunihiro; Hayashi, Yoshio; Sunada, Yoshihide

    2015-01-01

    Myostatin, a muscle-specific transforming growth factor-β (TGF-β), negatively regulates skeletal muscle mass. The N-terminal prodomain of myostatin noncovalently binds to and suppresses the C-terminal mature domain (ligand) as an inactive circulating complex. However, which region of the myostatin prodomain is required to inhibit the biological activity of myostatin has remained unknown. We identified a 29-amino acid region that inhibited myostatin-induced transcriptional activity by 79% compared with the full-length prodomain. This inhibitory core resides near the N-terminus of the prodomain and includes an α-helix that is evolutionarily conserved among other TGF-β family members, but suppresses activation of myostatin and growth and differentiation factor 11 (GDF11) that share identical membrane receptors. Interestingly, the inhibitory core co-localized and co-immunoprecipitated with not only the ligand, but also its type I and type II membrane receptors. Deletion of the inhibitory core in the full-length prodomain removed all capacity for suppression of myostatin. A synthetic peptide corresponding to the inhibitory core (p29) ameliorates impaired myoblast differentiation induced by myostatin and GDF11, but not activin or TGF-β1. Moreover, intramuscular injection of p29 alleviated muscle atrophy and decreased the absolute force in caveolin 3-deficient limb-girdle muscular dystrophy 1C model mice. The injection suppressed activation of myostatin signaling and restored the decreased numbers of muscle precursor cells caused by caveolin 3 deficiency. Our findings indicate a novel concept for this newly identified inhibitory core of the prodomain of myostatin: that it not only suppresses the ligand, but also prevents two distinct membrane receptors from binding to the ligand. This study provides a strong rationale for the use of p29 in the amelioration of skeletal muscle atrophy in various clinical settings. PMID:26226340

  11. TGF-β signaling in insects regulates metamorphosis via juvenile hormone biosynthesis

    PubMed Central

    Ishimaru, Yoshiyasu; Tomonari, Sayuri; Matsuoka, Yuji; Watanabe, Takahito; Miyawaki, Katsuyuki; Bando, Tetsuya; Tomioka, Kenji; Ohuchi, Hideyo; Noji, Sumihare; Mito, Taro

    2016-01-01

    Although butterflies undergo a dramatic morphological transformation from larva to adult via a pupal stage (holometamorphosis), crickets undergo a metamorphosis from nymph to adult without formation of a pupa (hemimetamorphosis). Despite these differences, both processes are regulated by common mechanisms that involve 20-hydroxyecdysone (20E) and juvenile hormone (JH). JH regulates many aspects of insect physiology, such as development, reproduction, diapause, and metamorphosis. Consequently, strict regulation of JH levels is crucial throughout an insect’s life cycle. However, it remains unclear how JH synthesis is regulated. Here, we report that in the corpora allata of the cricket, Gryllus bimaculatus, Myoglianin (Gb’Myo), a homolog of Drosophila Myoglianin/vertebrate GDF8/11, is involved in the down-regulation of JH production by suppressing the expression of a gene encoding JH acid O-methyltransferase, Gb’jhamt. In contrast, JH production is up-regulated by Decapentaplegic (Gb’Dpp) and Glass-bottom boat/60A (Gb’Gbb) signaling that occurs as part of the transcriptional activation of Gb’jhamt. Gb’Myo defines the nature of each developmental transition by regulating JH titer and the interactions between JH and 20E. When Gb’myo expression is suppressed, the activation of Gb’jhamt expression and secretion of 20E induce molting, thereby leading to the next instar before the last nymphal instar. Conversely, high Gb’myo expression induces metamorphosis during the last nymphal instar through the cessation of JH synthesis. Gb’myo also regulates final insect size. Because Myo/GDF8/11 and Dpp/bone morphogenetic protein (BMP)2/4-Gbb/BMP5–8 are conserved in both invertebrates and vertebrates, the present findings provide common regulatory mechanisms for endocrine control of animal development. PMID:27140602

  12. Genomic screening identifies novel linkages and provides further evidence for a role of MYH9 in nonsyndromic cleft lip and palate

    PubMed Central

    Chiquet, Brett T; Hashmi, Syed S; Henry, Robin; Burt, Amber; Mulliken, John B; Stal, Samuel; Bray, Molly; Blanton, Susan H; Hecht, Jacqueline T

    2009-01-01

    Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth anomaly that requires prolonged multidisciplinary rehabilitation. Although variation in several genes has been identified as contributing to NSCLP, most of the genetic susceptibility loci have yet to be defined. To identify additional contributory genes, a high-throughput genomic scan was performed using the Illumina Linkage IVb Panel platform. We genotyped 6008 SNPs in nine non-Hispanic white NSCLP multiplex families and a single large African-American NSCLP multiplex family. Fourteen chromosomal regions were identified with LOD>1.5, including six regions not previously reported. Analysis of the data from the African-American and non-Hispanic white families revealed two likely chromosomal regions: 8q21.3–24.12 and 22q12.2–12.3 with LOD scores of 2.98 and 2.66, respectively. On the basis of biological function, syndecan 2 (SDC2) and growth differentiation factor 6 (GDF6) in 8q21.3–24.12 and myosin heavy-chain 9, non-muscle (MYH9) in 22q12.2–12.3 were selected as candidate genes. Association analyses from these genes yielded marginally significant P-values for SNPs in SDC2 and GDF6 (0.01≤P<0.05). Evidence for an altered transmission was found for four MYH9 SNPs (P<0.01). SNP rs1002246 exhibited altered transmission by all analytic methods. However, analysis of two SNP MYH9 haplotypes did not identify a single high-risk haplotype. Our results confirm a previous report that 8q21.3–24.12 may harbor a clefting gene and identify 22q12.2–12.3 as a new candidate region that contains MYH9. Most importantly, we confirm the previous report of an association with MYH9. PMID:18716610

  13. Genomic screening identifies novel linkages and provides further evidence for a role of MYH9 in nonsyndromic cleft lip and palate.

    PubMed

    Chiquet, Brett T; Hashmi, Syed S; Henry, Robin; Burt, Amber; Mulliken, John B; Stal, Samuel; Bray, Molly; Blanton, Susan H; Hecht, Jacqueline T

    2009-02-01

    Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth anomaly that requires prolonged multidisciplinary rehabilitation. Although variation in several genes has been identified as contributing to NSCLP, most of the genetic susceptibility loci have yet to be defined. To identify additional contributory genes, a high-throughput genomic scan was performed using the Illumina Linkage IVb Panel platform. We genotyped 6008 SNPs in nine non-Hispanic white NSCLP multiplex families and a single large African-American NSCLP multiplex family. Fourteen chromosomal regions were identified with LOD>1.5, including six regions not previously reported. Analysis of the data from the African-American and non-Hispanic white families revealed two likely chromosomal regions: 8q21.3-24.12 and 22q12.2-12.3 with LOD scores of 2.98 and 2.66, respectively. On the basis of biological function, syndecan 2 (SDC2) and growth differentiation factor 6 (GDF6) in 8q21.3-24.12 and myosin heavy-chain 9, non-muscle (MYH9) in 22q12.2-12.3 were selected as candidate genes. Association analyses from these genes yielded marginally significant P-values for SNPs in SDC2 and GDF6 (0.01

  14. TP53inp1 Gene Is Implicated in Early Radiation Response in Human Fibroblast Cells.

    PubMed

    Sándor, Nikolett; Schilling-Tóth, Boglárka; Kis, Enikő; Fodor, Lili; Mucsányi, Fruzsina; Sáfrány, Géza; Hegyesi, Hargita

    2015-01-01

    Tumor protein 53-induced nuclear protein-1 (TP53inp1) is expressed by activation via p53 and p73. The purpose of our study was to investigate the role of TP53inp1 in response of fibroblasts to ionizing radiation. γ-Ray radiation dose-dependently induces the expression of TP53inp1 in human immortalized fibroblast (F11hT) cells. Stable silencing of TP53inp1 was done via lentiviral transfection of shRNA in F11hT cells. After irradiation the clonogenic survival of TP53inp1 knockdown (F11hT-shTP) cells was compared to cells transfected with non-targeting (NT) shRNA. Radiation-induced senescence was measured by SA-β-Gal staining and autophagy was detected by Acridine Orange dye and microtubule-associated protein-1 light chain 3 (LC3B) immunostaining. The expression of TP53inp1, GDF-15, and CDKN1A and alterations in radiation induced mitochondrial DNA deletions were evaluated by qPCR. TP53inp1 was required for radiation (IR) induced maximal elevation of CDKN1A and GDF-15 expressions. Mitochondrial DNA deletions were increased and autophagy was deregulated following irradiation in the absence of TP53inp1. Finally, we showed that silencing of TP53inp1 enhances the radiation sensitivity of fibroblast cells. These data suggest functional roles for TP53inp1 in radiation-induced autophagy and survival. Taken together, we suppose that silencing of TP53inp1 leads radiation induced autophagy impairment and induces accumulation of damaged mitochondria in primary human fibroblasts. PMID:26512655

  15. Induced Autoimmunity against Gonadal Proteins Affects Gonadal Development in Juvenile Zebrafish

    PubMed Central

    Presslauer, Christopher; Nagasawa, Kazue; Dahle, Dalia; Babiak, Joanna; Fernandes, Jorge M. O.; Babiak, Igor

    2014-01-01

    A method to mitigate or possibly eliminate reproduction in farmed fish is highly demanded. The existing approaches have certain applicative limitations. So far, no immunization strategies affecting gonadal development in juvenile animals have been developed. We hypothesized that autoimmune mechanisms, occurring spontaneously in a number of diseases, could be induced by targeted immunization. We have asked whether the immunization against specific targets in a juvenile zebrafish gonad will produce an autoimmune response, and, consequently, disturbance in gonadal development. Gonadal soma-derived factor (Gsdf), growth differentiation factor (Gdf9), and lymphocyte antigen 75 (Cd205/Ly75), all essential for early gonad development, were targeted with 5 immunization tests. Zebrafish (n = 329) were injected at 6 weeks post fertilization, a booster injection was applied 15 days later, and fish were sampled at 30 days. We localized transcripts encoding targeted proteins by in situ hybridization, quantified expression of immune-, apoptosis-, and gonad-related genes with quantitative real-time PCR, and performed gonadal histology and whole-mount immunohistochemistry for Bcl2-interacting-killer (Bik) pro-apoptotic protein. The treatments resulted in an autoimmune reaction, gonad developmental retardation, intensive apoptosis, cell atresia, and disturbed transcript production. Testes were remarkably underdeveloped after anti-Gsdf treatments. Anti-Gdf9 treatments promoted apoptosis in testes and abnormal development of ovaries. Anti-Cd205 treatment stimulated a strong immune response in both sexes, resulting in oocyte atresia and strong apoptosis in supporting somatic cells. The effect of immunization was FSH-independent. Furthermore, immunization against germ cell proteins disturbed somatic supporting cell development. This is the first report to demonstrate that targeted autoimmunity can disturb gonadal development in a juvenile fish. It shows a straightforward potential

  16. TGF-β signaling in insects regulates metamorphosis via juvenile hormone biosynthesis.

    PubMed

    Ishimaru, Yoshiyasu; Tomonari, Sayuri; Matsuoka, Yuji; Watanabe, Takahito; Miyawaki, Katsuyuki; Bando, Tetsuya; Tomioka, Kenji; Ohuchi, Hideyo; Noji, Sumihare; Mito, Taro

    2016-05-17

    Although butterflies undergo a dramatic morphological transformation from larva to adult via a pupal stage (holometamorphosis), crickets undergo a metamorphosis from nymph to adult without formation of a pupa (hemimetamorphosis). Despite these differences, both processes are regulated by common mechanisms that involve 20-hydroxyecdysone (20E) and juvenile hormone (JH). JH regulates many aspects of insect physiology, such as development, reproduction, diapause, and metamorphosis. Consequently, strict regulation of JH levels is crucial throughout an insect's life cycle. However, it remains unclear how JH synthesis is regulated. Here, we report that in the corpora allata of the cricket, Gryllus bimaculatus, Myoglianin (Gb'Myo), a homolog of Drosophila Myoglianin/vertebrate GDF8/11, is involved in the down-regulation of JH production by suppressing the expression of a gene encoding JH acid O-methyltransferase, Gb'jhamt In contrast, JH production is up-regulated by Decapentaplegic (Gb'Dpp) and Glass-bottom boat/60A (Gb'Gbb) signaling that occurs as part of the transcriptional activation of Gb'jhamt Gb'Myo defines the nature of each developmental transition by regulating JH titer and the interactions between JH and 20E. When Gb'myo expression is suppressed, the activation of Gb'jhamt expression and secretion of 20E induce molting, thereby leading to the next instar before the last nymphal instar. Conversely, high Gb'myo expression induces metamorphosis during the last nymphal instar through the cessation of JH synthesis. Gb'myo also regulates final insect size. Because Myo/GDF8/11 and Dpp/bone morphogenetic protein (BMP)2/4-Gbb/BMP5-8 are conserved in both invertebrates and vertebrates, the present findings provide common regulatory mechanisms for endocrine control of animal development. PMID:27140602

  17. Masticatory HyperMuscularity is not related to Reduced Cranial Volume in Myostatin-Knockout Mice

    PubMed Central

    Cray, James; Kneib, Jared; Vecchione, Lisa; Byron, Craig; Cooper, Gregory M.; Losee, Joseph E.; Siegel, Michael I.; Hamrick, Mark W.; Sciote, James J.; Mooney, Mark P.

    2013-01-01

    It has been suggested recently that masticatory muscle size reduction in humans resulted in greater encephalization through decreased compressive forces on the cranial vault. Following this logic, if masticatory muscle size were increased, then a reduction in brain growth should also occur. The present study was designed to test this hypothesis using a myostatin (GDF-8) knockout mouse model. Myostatin is a negative regulator of skeletal muscle growth, and individuals lacking this gene show significant hypermuscularity. Sixty-two (32 wild-type and 30 GDF-8 −/− knockout), 1, 28, 56 and 180 day old CD-1 mice were used. Body and masseter muscle weights were collected following dissection and standardized lateral and dorsoventral cephalographs were obtained. Cephalometric landmarks were identified on the radiographs and cranial volume was calculated. Mean differences were assessed using a two-way ANOVA. KO mice had significantly greater body and masseter weights beginning at 28 days compared to WT controls. No significant differences in cranial volumes were noted between KO and WT. Muscle weight was not significantly correlated with cranial volume in 1, 28, or 180 day old mice. Muscle weights exhibited a positive correlation with cranial volume at 56 days. Results demonstrate that masticatory hypermuscularity is not associated with reduced cranial volume. In contrast, there is abundant data demonstrating the opposite, brain growth determines cranial vault growth and masticatory apparatus only affects ectocranial morphology. The results presented here do not support the hypothesis that a reduction in masticatory musculature relaxed compressive forces on the cranial vault allowing for greater encephalization. PMID:21618442

  18. Evidence of the Generation of Isosaccharinic Acids and Their Subsequent Degradation by Local Microbial Consortia within Hyper-Alkaline Contaminated Soils, with Relevance to Intermediate Level Radioactive Waste Disposal

    PubMed Central

    Rout, Simon P.; Charles, Christopher J.; Garratt, Eva J.; Laws, Andrew P.; Gunn, John; Humphreys, Paul N.

    2015-01-01

    The contamination of surface environments with hydroxide rich wastes leads to the formation of high pH (>11.0) soil profiles. One such site is a legacy lime works at Harpur Hill, Derbyshire where soil profile indicated in-situ pH values up to pH 12. Soil and porewater profiles around the site indicated clear evidence of the presence of the α and β stereoisomers of isosaccharinic acid (ISA) resulting from the anoxic, alkaline degradation of cellulosic material. ISAs are of particular interest with regards to the disposal of cellulosic materials contained within the intermediate level waste (ILW) inventory of the United Kingdom, where they may influence radionuclide mobility via complexation events occurring within a geological disposal facility (GDF) concept. The mixing of uncontaminated soils with the alkaline leachate of the site resulted in ISA generation, where the rate of generation in-situ is likely to be dependent upon the prevailing temperature of the soil. Microbial consortia present in the uncontaminated soil were capable of surviving conditions imposed by the alkaline leachate and demonstrated the ability to utilise ISAs as a carbon source. Leachate-contaminated soil was sub-cultured in a cellulose degradation product driven microcosm operating at pH 11, the consortia present were capable of the degradation of ISAs and the generation of methane from the resultant H2/CO2 produced from fermentation processes. Following microbial community analysis, fermentation processes appear to be predominated by Clostridia from the genus Alkaliphilus sp, with methanogenesis being attributed to Methanobacterium and Methanomassiliicoccus sp. The study is the first to identify the generation of ISA within an anthropogenic environment and advocates the notion that microbial activity within an ILW-GDF is likely to influence the impact of ISAs upon radionuclide migration. PMID:25748643

  19. Comparison of SUMO fusion technology with traditional gene fusion systems: enhanced expression and solubility with SUMO.

    PubMed

    Marblestone, Jeffrey G; Edavettal, Suzanne C; Lim, Yiting; Lim, Peter; Zuo, Xun; Butt, Tauseef R

    2006-01-01

    Despite the availability of numerous gene fusion systems, recombinant protein expression in Escherichia coli remains difficult. Establishing the best fusion partner for difficult-to-express proteins remains empirical. To determine which fusion tags are best suited for difficult-to-express proteins, a comparative analysis of the newly described SUMO fusion system with a variety of commonly used fusion systems was completed. For this study, three model proteins, enhanced green fluorescent protein (eGFP), matrix metalloprotease-13 (MMP13), and myostatin (growth differentiating factor-8, GDF8), were fused to the C termini of maltose-binding protein (MBP), glutathione S-transferase (GST), thioredoxin (TRX), NUS A, ubiquitin (Ub), and SUMO tags. These constructs were expressed in E. coli and evaluated for expression and solubility. As expected, the fusion tags varied in their ability to produce tractable quantities of soluble eGFP, MMP13, and GDF8. SUMO and NUS A fusions enhanced expression and solubility of recombinant proteins most dramatically. The ease at which SUMO and NUS A fusion tags were removed from their partner proteins was then determined. SUMO fusions are cleaved by the natural SUMO protease, while an AcTEV protease site had to be engineered between NUS A and its partner protein. A kinetic analysis showed that the SUMO and AcTEV proteases had similar KM values, but SUMO protease had a 25-fold higher kcat than AcTEV protease, indicating a more catalytically efficient enzyme. Taken together, these results demonstrate that SUMO is superior to commonly used fusion tags in enhancing expression and solubility with the distinction of generating recombinant protein with native sequences. PMID:16322573

  20. Stem cells derived from human first-trimester umbilical cord have the potential to differentiate into oocyte-like cells in vitro

    PubMed Central

    HU, XIANG; LU, HUA; CAO, SHENG; DENG, YAN-LI; LI, QI-JIA; WAN, QIAN; YIE, SHANG-MIAN

    2015-01-01

    Compared to stem cells derived from human term umbilical cord, stem cells derived from human first-trimester umbilical cord (hFTUC) exhibit a significantly greater proliferative potential, and more efficiency in terms of their in vitro differentiation. In the present study, we investigated whether hFTUC-derived stem cells are able to differentiate into germ cells. The hFTUC-derived stem cells were first isolated, expanded and then cultured in differentiation medium containing human follicular fluid, follicle-stimulating hormone (FSH)/luteinizing hormone (LH) and estradiol for 24 days. During the period of induction, a subpopulation of the cultured cells appeared that had a morphological resemblance to primordial germ cells (PGCs) and cumulus-oocyte complex (COC)-like cells, and oocyte-like cells (OLCs). The PGC-like cells expressed specific markers indicative of germ cell formation such as octamer-binding transcription factor 4 (OCT4), stage-specific embryonic antigen 1 (SSEA1), B lymphocyte-induced maturation protein-1 (BLIMP1), PR domain containing 14 (PRDM14), transcription factor AP-2 gamma (TFAP2C), VASA, STELLA, deleted in azoospermia-like (DAZL) and interferon-induced transmembrane protein 3 (IFITM3). The OLCs, which contained a single germinal vesicle, expressed oocyte-specific markers, such as synaptonemal complex protein 3 (SCP3), growth/differentiation factor-9 (GDF9), GDF9B and zona pellucida (ZP)1, ZP2 and ZP3. The COC-like cells secreted estradiol, vascular endothelial growth factor and leukemia inhibitory factor. Thus, our findings suggest that hFTUC-derived stem cells have an intrinsic ability to differentiate into OLCs, which may provide an in vitro model for the identification of factors involved in germ cell formation and differentiation. PMID:25760093

  1. The Inhibitory Core of the Myostatin Prodomain: Its Interaction with Both Type I and II Membrane Receptors, and Potential to Treat Muscle Atrophy

    PubMed Central

    Ohsawa, Yutaka; Takayama, Kentaro; Nishimatsu, Shin-ichiro; Okada, Tadashi; Fujino, Masahiro; Fukai, Yuta; Murakami, Tatsufumi; Hagiwara, Hiroki; Itoh, Fumiko; Tsuchida, Kunihiro; Hayashi, Yoshio; Sunada, Yoshihide

    2015-01-01

    Myostatin, a muscle-specific transforming growth factor-β (TGF-β), negatively regulates skeletal muscle mass. The N-terminal prodomain of myostatin noncovalently binds to and suppresses the C-terminal mature domain (ligand) as an inactive circulating complex. However, which region of the myostatin prodomain is required to inhibit the biological activity of myostatin has remained unknown. We identified a 29-amino acid region that inhibited myostatin-induced transcriptional activity by 79% compared with the full-length prodomain. This inhibitory core resides near the N-terminus of the prodomain and includes an α-helix that is evolutionarily conserved among other TGF-β family members, but suppresses activation of myostatin and growth and differentiation factor 11 (GDF11) that share identical membrane receptors. Interestingly, the inhibitory core co-localized and co-immunoprecipitated with not only the ligand, but also its type I and type II membrane receptors. Deletion of the inhibitory core in the full-length prodomain removed all capacity for suppression of myostatin. A synthetic peptide corresponding to the inhibitory core (p29) ameliorates impaired myoblast differentiation induced by myostatin and GDF11, but not activin or TGF-β1. Moreover, intramuscular injection of p29 alleviated muscle atrophy and decreased the absolute force in caveolin 3-deficient limb-girdle muscular dystrophy 1C model mice. The injection suppressed activation of myostatin signaling and restored the decreased numbers of muscle precursor cells caused by caveolin 3 deficiency. Our findings indicate a novel concept for this newly identified inhibitory core of the prodomain of myostatin: that it not only suppresses the ligand, but also prevents two distinct membrane receptors from binding to the ligand. This study provides a strong rationale for the use of p29 in the amelioration of skeletal muscle atrophy in various clinical settings. PMID:26226340

  2. Evidence of the generation of isosaccharinic acids and their subsequent degradation by local microbial consortia within hyper-alkaline contaminated soils, with relevance to intermediate level radioactive waste disposal.

    PubMed

    Rout, Simon P; Charles, Christopher J; Garratt, Eva J; Laws, Andrew P; Gunn, John; Humphreys, Paul N

    2015-01-01

    The contamination of surface environments with hydroxide rich wastes leads to the formation of high pH (>11.0) soil profiles. One such site is a legacy lime works at Harpur Hill, Derbyshire where soil profile indicated in-situ pH values up to pH 12. Soil and porewater profiles around the site indicated clear evidence of the presence of the α and β stereoisomers of isosaccharinic acid (ISA) resulting from the anoxic, alkaline degradation of cellulosic material. ISAs are of particular interest with regards to the disposal of cellulosic materials contained within the intermediate level waste (ILW) inventory of the United Kingdom, where they may influence radionuclide mobility via complexation events occurring within a geological disposal facility (GDF) concept. The mixing of uncontaminated soils with the alkaline leachate of the site resulted in ISA generation, where the rate of generation in-situ is likely to be dependent upon the prevailing temperature of the soil. Microbial consortia present in the uncontaminated soil were capable of surviving conditions imposed by the alkaline leachate and demonstrated the ability to utilise ISAs as a carbon source. Leachate-contaminated soil was sub-cultured in a cellulose degradation product driven microcosm operating at pH 11, the consortia present were capable of the degradation of ISAs and the generation of methane from the resultant H2/CO2 produced from fermentation processes. Following microbial community analysis, fermentation processes appear to be predominated by Clostridia from the genus Alkaliphilus sp, with methanogenesis being attributed to Methanobacterium and Methanomassiliicoccus sp. The study is the first to identify the generation of ISA within an anthropogenic environment and advocates the notion that microbial activity within an ILW-GDF is likely to influence the impact of ISAs upon radionuclide migration. PMID:25748643

  3. Quantifying (12/13)CH(4) migration and fate following sub-surface release to an agricultural soil.

    PubMed

    Shaw, G; Atkinson, B; Meredith, W; Snape, C; Steven, M; Hoch, A; Lever, D

    2014-07-01

    Following gas generation in a Geological Disposal Facility (GDF), (14)C-containing gases could migrate through the geosphere, eventually diffusing into soils at the Earth's surface. This paper reports summary results from laboratory and field experiments to obtain information on the probable rates of a) diffusive transport and b) oxidation of (12/13)CH(4) (as a surrogate for (14)CH4) in a typical agricultural soil in the UK. Rates of CH(4) oxidation were generally low in the field and undisturbed soil columns, though a re-packed column of homogenised topsoil oxidised ambient atmospheric CH(4) 20× faster than an undisturbed soil column. In contrast to low observed rates of CH(4) oxidation, the effective diffusion of CH(4) through the soil was rapid. Isotopically labelled CH(4) injected at a depth of 45 cm in the field diffused to the surface and exited the soil over a time period ranging from 8 to 24 h. The rate of CH(4) diffusion through the soil was increased by the presence of ryegrass roots which increased soil porosity and decreased water content. δ(13)C values for laboratory column soils after labelled CH(4) injection experiments showed no sign of residual (13)C, despite the extremely high δ(13)C values of the injected (12/13)CH(4). If laboratory observations are confirmed by measurements in field samples it can be concluded that the majority of (14)CH(4) from a GDF which enters a soil with low methanotrophic activity will be lost to the free atmosphere after diffusing rapidly through the soil column. PMID:23958331

  4. Smooth-Threshold Multivariate Genetic Prediction with Unbiased Model Selection.

    PubMed

    Ueki, Masao; Tamiya, Gen

    2016-04-01

    We develop a new genetic prediction method, smooth-threshold multivariate genetic prediction, using single nucleotide polymorphisms (SNPs) data in genome-wide association studies (GWASs). Our method consists of two stages. At the first stage, unlike the usual discontinuous SNP screening as used in the gene score method, our method continuously screens SNPs based on the output from standard univariate analysis for marginal association of each SNP. At the second stage, the predictive model is built by a generalized ridge regression simultaneously using the screened SNPs with SNP weight determined by the strength of marginal association. Continuous SNP screening by the smooth thresholding not only makes prediction stable but also leads to a closed form expression of generalized degrees of freedom (GDF). The GDF leads to the Stein's unbiased risk estimation (SURE), which enables data-dependent choice of optimal SNP screening cutoff without using cross-validation. Our method is very rapid because computationally expensive genome-wide scan is required only once in contrast to the penalized regression methods including lasso and elastic net. Simulation studies that mimic real GWAS data with quantitative and binary traits demonstrate that the proposed method outperforms the gene score method and genomic best linear unbiased prediction (GBLUP), and also shows comparable or sometimes improved performance with the lasso and elastic net being known to have good predictive ability but with heavy computational cost. Application to whole-genome sequencing (WGS) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) exhibits that the proposed method shows higher predictive power than the gene score and GBLUP methods. PMID:26947266

  5. Plio-Pleistocene extinctions and immigration credit reflected in the size-frequency distribution of Mediterranean marine bivalves

    NASA Astrophysics Data System (ADS)

    Nawrot, Rafal; Zuschin, Martin; Chattopadhyay, Devapriya

    2015-04-01

    Following the opening of the Suez Canal hundreds of Red Sea species have entered the Mediterranean Sea making it a global hot spot of marine bioinvasion. With the ongoing influx of the subtropical and tropical alien species and increasing sea surface temperatures, the Mediterranean biota is currently gaining a more tropical character and increasingly becoming a mixture of faunal stocks with different evolutionary histories. This susceptibility to invasion was suggested to reflect the presence of an empty ecological space left after decimation of incumbent warm-water fauna during Plio-Pleistocene climate fluctuations. As molluscs are among the most prolific immigrants, we test this hypothesis using data on taxonomic composition and body size of Pliocene Mediterranean bivalves derived from the literature sources and museum collections. The Pliocene inter-specific size-frequency distribution (SFD) is strikingly similar to the SFDs of the Recent Red Sea bivalve fauna, in spite of different biogeographic provenance and the absence of true reef ecosystems in the Pliocene of the Mediterranean region. In contrast, body-size patterns in both assemblages are significantly different from the present-day Mediterranean fauna characterized by smaller median and modal size. Our preliminary results suggest that the distinct shape of the modern Mediterranean SFD may reflect the selective nature of the late Piacenzian - Galesian (Late Pliocene - Early Pleistocene) extinctions pulses related to the onset of the Northern Hemisphere glaciations. These extinctions affected almost 40% of Pliocene species and were biased towards large-bodied taxa. They were not followed by re-immigration of warm-water species owing to the isolation from the tropical Atlantic biota by the cold upwelling along the NW coasts of Africa. The resulting invasion credit (sensu Jackson & Sax, 2010) is currently being paid by the Red Sea bivalves colonizing the Mediterranean Sea through the Suez Canal. Successful

  6. Remote sensing, planform, and facies analysis of the Plain of Tineh, Egypt for the remains of the defunct Pelusiac River

    NASA Astrophysics Data System (ADS)

    Quintanar, Jessica; Khan, Shuhab D.; Fathy, Mohamed S.; Zalat, Abdel-Fattah A.

    2013-11-01

    The Pelusiac Branch was a distributary river in the Nile Delta that splits off from the main trunk of the Nile River as it flowed toward the Mediterranean. At approximately 25 A.D., it was chocked by sand and silt deposits from prograding beach accretion processes. The lower course of the river and its bifurcation point from the trunk of the Nile have been hypothesized based on ancient texts and maps, as well as previous research, but results have been inconsistent. Previous studies partly mapped the lower course of the Pelusiac River in the Plain of Tineh, east of the Suez Canal, but rapid urbanization related to the inauguration of the Peace Canal mega-irrigation project has covered any trace of the linear feature reported by these previous studies. The present study used multispectral remote sensing data of GeoEYE-1 and Landsat-TM to locate and accurately map the course of the defunct Pelusiac River within the Plain of Tineh. Remote sensing analysis identified a linear feature that is 135 m wide at its maximum and approximately 13 km long. It extends from the Pelusium ruins to the Suez Canal, just north of the Peace Canal. This remotely located linear feature corresponds to the path of the Pelusiac River during Roman times. Planform geomorphology was applied to determine the hydrological regime and paleodischarge of the river prior to becoming defunct. Planform analysis derived a bankfull paleodischarge value of ~ 5700 m3 s- 1 and an average discharge of 650 m3 s- 1, using the reach average for the interpreted Pelusiac River. The derived values show a river distributary similar in discharge to the modern dammed Damietta river. Field work completed in April of 2012 derived four sedimentary lithofacies of the upper formation on the plain that included pro-delta, delta-front and delta-plain depositional environments. Diatom and fossil mollusk samples were also identified that support coastal beach and lagoonal environments of deposition. Measured section columns

  7. Sinai Peninsula, Shaded Relief and Colored Height

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The Sinai Peninsula, located between Africa and Asia, is a result of those two continents pulling apart from each other. Earth's crust is cracking, stretching, and lowering along the two northern branches of the Red Sea, namely the Gulf of Suez, seen here on the west (left), and the Gulf of Aqaba, seen to the east (right). This color-coded shaded relief image shows the triangular nature of the peninsula, with the coast of the Mediterranean Sea forming the northern side of the triangle. The Suez Canal can be seen as the narrow vertical blue line in the upper left connecting the Red Sea to the Mediterranean.

    The peninsula is divided into three distinct parts; the northern region consisting chiefly of sandstone, plains and hills, the central area dominated by the Tih Plateau, and the mountainous southern region where towering peaks abound. Much of the Sinai is deeply dissected by river valleys, or wadis, that eroded during an earlier geologic period and break the surface of the plateau into a series of detached massifs with a few scattered oases.

    Two visualization methods were combined to produce the image: shading and color coding of topographic height. The shade image was derived by computing topographic slope in the northwest-southeast direction, so that northwest slopes appear bright and southeast slopes appear dark. Color coding is directly related to topographic height, with green at the lower elevations, rising through yellow and tan, to white at the highest elevations.

    Elevation data used in this image were acquired by the Shuttle Radar Topography Mission aboard the Space Shuttle Endeavour, launched on Feb. 11, 2000. SRTM used the same radar instrument that comprised the Spaceborne Imaging Radar-C/X-Band Synthetic Aperture Radar (SIR-C/X-SAR) that flew twice on the Space Shuttle Endeavour in 1994. SRTM was designed to collect 3-D measurements of the Earth's surface. To collect the 3-D data, engineers added a 60-meter (approximately 200-foot

  8. [Migrations and economic and social change in Egypt].

    PubMed

    Ged, A

    1985-01-01

    The inexistence in the Arab world of institutions to facilitate development led Egypt to adopt the infitah, a policy of economic opening which is not a voluntarist economic strategy but rather is intended to create a climate favorable to a more capitalistic orientation for individuals with access to petroleum income. Egypt's gross national product grew by 4.6%/year in the dozen years through 1965, but thereafter growth was sluggish or even negative. After 1967 the choices of the dominant economic classes were oriented toward liberalism, and the arrival of Sadat allowed this orientation to prevail even before the infitah. The various measures of the infitah were designed to promote investment, reactivate the private sector, and reorganize the public sector. Most of the specific projects approved through 1978 were in the tertiary sector, they did little to stimulate further development, and the total number of jobs created was relatively insignificant. The transformation of the Egyptian economy is due not so much to the infitah as to 4 other elements: oil, income from the Suez canal, tourism, and emigration. At present petroleum represents 30% of Egypt's exports, the Suez canal will probably bring in $1.5 billion annually in coming years, and tourism brought in $1 billion in 1984, but in terms of economic and social impact on the total population emigration is much more important. The number of emigrants increased from 100,000 in 1973 to over 3 million in 1984 and the extent of their remittances increased from $184 million in 1973 to nearly $4 billion at present. Serious shortages of skilled and unskilled labor have been created by the departure of 10-15% of the overall labor force and a higher proportion for some skilled professions. The number of workers in construction more than doubled from 1971-79, while 10% of the agricultural labor force departed. Agricultural wages increased by an average of 7.1% in these years as agricultural workers were attracted to the

  9. Regional consequences of a biotic interchange: insights from the Lessepsian invasion

    NASA Astrophysics Data System (ADS)

    Nawrot, Rafal; Albano, Paolo G.; Chattopadhyay, Devapriya; Zuschin, Martin

    2016-04-01

    The fossil record provides ample evidence of large-scale biotic interchanges and their pervasive effects on regional biotas, but mechanisms controlling such events are difficult to decipher in deep time. Massive invasion of Indo-Pacific species into the Mediterranean Sea triggered by the opening of the Suez Canal offers a unique opportunity to examine the ecological consequences of breaking down biogeographic barriers. We developed an extensive database of taxonomic composition, body size and ecological characteristics of the Red Sea and Mediterranean bivalve fauna in order to link biotic selectivity of the invasion process with its effects on the recipient biota. Shallow-water occurrence and presence outside the tropical zone in other regions are the strongest predictors of the successful transition through the Suez Canal. Subsequent establishment of alien species in the Mediterranean Sea correlates with early arrival and preference for hard substrates. Finally, large-bodied species and hard-bottom dwellers are over-represented among the invasive aliens that have reached the spread stage and impose a strong impact on native communities. Although body size is important only at the last invasion stage, alien species are significantly larger compared to native Mediterranean bivalves. This reflects biogeographic difference in the body-size distributions of the source and recipient species pools related to the recent geological history of the Mediterranean Sea. Contrary to the general expectations on the effects of temperature on average body size, continued warming of the Mediterranean Sea accelerates the entry of tropical aliens and thus indirectly leads to increase in the proportion of large-bodied species in local communities and the regional biota. Invasion-driven shifts in species composition are stronger in hard-substrate communities, which host a smaller pool of incumbent species and are more susceptible to the establishment of newcomers. Analogous differences

  10. Seismotectonics of the Sinai subplate - the eastern Mediterranean region

    NASA Astrophysics Data System (ADS)

    Salamon, Amos; Hofstetter, Avraham; Garfunkel, Zvi; Ron, Hagai

    2003-10-01

    We define the Sinai subplate, from a seismotectonic perspective, as a distinct component in the plate tectonics of the eastern Mediterranean region. This is based on the tectonic characteristics of a comprehensive listing of all ML>= 4 recorded seismicity in the region during the 20th century, on newly calculated and recalculated fault plane mechanisms of first P-wave arrivals and on published solutions based on waveform inversion of broad-band data. The low seismicity level and scarcity of strong events in the region required a thorough search for useful data and a careful examination of the reliability of the focal solutions. We gathered all available records of first P-wave onsets from the ISS and ISC Bulletins and the local seismic networks. Altogether, we were able to calculate 48 new focal mechanisms and 33 recalculated ones of events that occurred during the years 1940-1992. With the increasing number of teleseismic and regional broad-band stations in the later years, we added 37 solutions based on teleseismic and regional waveform inversions of events that occurred during 1977-2001. These mechanisms enabled us to examine the seismotectonic character of the Sinai subplate. The strike and rake directions of the calculated mechanisms usually reflect the geometry and the large-scale type of deformation observed along the boundaries of the Sinai subplate-the Dead Sea Transform, the Cypriot Arc convergent zone and the Suez Rift. Nevertheless, along each of these boundaries we found anomalous solutions that attest to the complexity of the deformation processes along plate margins. Earthquakes along the Dead Sea Transform exhibit mainly sinistral transtension and transpression, reflecting its leaky manner and local change in the transform geometry. The presence of other unexpected mechanisms near the transform, however, reflects the heterogeneous deformation it induces around. As expected, thrust mechanisms along the Cypriot Arc mirror its convergent nature and

  11. A.E. Nordenski and the auroral oval

    NASA Astrophysics Data System (ADS)

    Nygrén, Tuomo; Silén, Johan

    In 1857, Adold Erik Nordenskiöld (1832-1901), a Finnish geographer and mineralogist, was forced to withdraw from his position at the University of Helsinki because of a conflict with the czarist officials in Finland. He then moved to Sweden, where he became one of the most celebrated explorers of his time. Most famous of his polar expeditions was the discovery of the Northeast Passage. Nordenskiöld made his voyage in the wooden steamship Vega in 1878-79.Vega started its voyage on June 22, 1878, and was directed in a course around Scandinavia and along the Siberian coast toward Bering Strait. Nordenskiöld's plan was to reach the Pacific Ocean during the summer months, but this was hindered by unfavorable ice conditions. At the end of September the sea was blocked by ice fields, and the Vega had to pass the winter on the northern coast of the Chukchi Peninsula (67°4‧49″N, 173°23‧2″W)—exasperatingly close to the open waters of Bering Strait. The ship could not set sail any sooner than the following July when the sea was free again. After visiting Japan, China, and Ceylon, the Vega passed through the Suez Canal and finally, on April 24, 1880, arrived at Stockholm.

  12. Oil and gas developments in North Africa in 1983

    SciTech Connect

    Nicod, M.A.

    1984-10-01

    Petroleum rights in the 6 countries (Algeria, Egypt, Libya, Morocco, Sudan, and Tunisia) covered by this paper amounted to 1,821,966 km/sup 2/ at the end of 1983, an 11% decrease from the 2,044,851 km/sup 2/ at the end of 1982. This decrease is mostly due to relinquishments in Sudan. Onshore seismic activity decreased in all countries except Sudan, where it slightly increased. Marine seismic activity increased by 85%, mostly due to significant efforts in Morocco and Egypt. Exploration drilling activity increased with 179 wildcats completed in 1983 compared to 166 in 1982. The success rate was 44.7% compared to 36% in 1982. No discoveries were made in Morocco. No new hydrocarbon province was discovered in 1983. Development drilling sharply increased in Egypt and remained at about the same levels in the other countries as in 1982. In Sudan, Chevron started in late September the first development drilling operations in Unity field. Oil production, with a daily average of 2,872,000 bbl, was at the same level as in 1982. In Egypt, 7 new fields went on-stream in the Gulf of Suez, 2 in the Western Desert, and 1 in the Eastern Desert. One field was put on-stream in Libya and 4 in Tunisia. Utilized gas production probably remained at the same level as in 1982 (2000 mmcf/day). 9 figures, 28 tables.

  13. Tectonic paleostress fields in the southwestern part of Jordan: New insights from the fault slip data in the southeastern flank of the Dead Sea Fault Zone

    NASA Astrophysics Data System (ADS)

    Radaideh, Omar M. A.; Melichar, Rostislav

    2015-09-01

    A new approach for paleostress analysis, using the nine-dimensional space fault slip inversion method, was performed in the southeastern flank of the Jordan-Dead Sea Fault. Five major tectonic episodes with different kinematics were successfully detected from the inversion of a new fault slip data, which thereby caused reactivation of inherited crustal structures and established new ones. These episodes prevailed since Late Cretaceous times, and their chronological constraints were established essentially from the stratigraphic ages of the affected rocks and the crosscutting relationships of successive striae locally observed on the fault planes. During the Late Cretaceous to late Eocene, the area was under a compressional/strike-slip stress regime with a ~E-W trending σ1. At Oligocene, a strike-slip stress regime with NW-SE striking σ1 occurred. Both compression regimes correspond to the so-called Syrian Arc Deformation that gave rise to distinctive folds in Jordan and its surrounding areas. An extension with ~N-S to NE-SW trending σ3 followed the late Oligocene compression event and took place during Miocene time, most probably linked to the opening of the Red Sea-Suez Rift. Late Cenozoic tectonics show the occurrence of two successive compressions, NW-SE then both NE-SW and ~N-S, which generally reflect a continental collisional setting between the Arabian and Eurasian plates.

  14. Molecular Evidence for Lessepsian Invasion of Soritids (Larger Symbiont Bearing Benthic Foraminifera)

    PubMed Central

    Apothéloz-Perret-Gentil, Laure; Pawlowski, Jan; Abdu, Uri; Almogi-Labin, Ahuva; Hyams-Kaphzan, Orit; Bakhrat, Anna; Abramovich, Sigal

    2013-01-01

    The Mediterranean Sea is considered as one of the hotspots of marine bioinvasions, largely due to the influx of tropical species migrating through the Suez Canal, so-called Lessepsian migrants. Several cases of Lessepsian migration have been documented recently, however, little is known about the ecological characteristics of the migrating species and their aptitude to colonize the new areas. This study focused on Red Sea soritids, larger symbiont-bearing benthic foraminifera (LBF) that are indicative of tropical and subtropical environments and were recently found in the Israeli coast of the Eastern Mediterranean. We combined molecular phylogenetic analyses of soritids and their algal symbionts as well as network analysis of Sorites orbiculus Forskål to compare populations from the Gulf of Elat (northern Red Sea) and from a known hotspot in Shikmona (northern Israel) that consists of a single population of S. orbiculus. Our phylogenetic analyses show that all specimens found in Shikmona are genetically identical to a population of S. orbiculus living on a similar shallow water pebbles habitat in the Gulf of Elat. Our analyses also show that the symbionts found in Shikmona and Elat soritids belong to the Symbiodinium clade F5, which is common in the Red Sea and also present in the Indian Ocean and Caribbean Sea. Our study therefore provides the first genetic and ecological evidences that indicate that modern population of soritids found on the Mediterranean coast of Israel is probably Lessepsian, and is less likely the descendant of a native ancient Mediterranean species. PMID:24204936

  15. Egyptian Red Sea petroleum geology and regional geophysical evaluation

    SciTech Connect

    Ahmed, Y.H.; Shalaan, A.A.; Zaki, H.A. )

    1991-08-01

    The World Bank-executed Red Sea/Gulf of Aden Regional Hydrocarbon Study Project was organized to synthesize data on the Red Sea and Gulf of Aden basins. The primary objectives were to encourage increased hydrocarbon exploration techniques basin wide, and to train national geoscientists in exploration techniques. The study was carried out be task forces for each participating country, working in Cairo under the supervision of World Bank technical personnel. In addition, biostratigraphic, paleoenvironmental, and lithostratigraphic analyses by Robertson Group and geochemical studies and BEICIP were carried out on well cuttings and core samples. The study of the Egyptian Red Sea was based on public-domain exploration data, published information, and data released by operating companies. This included reports, sections, and wireline logs from 13 well, samples from ten wells for biostratigraphic analysis, and samples from eight wells for geochemical analysis. Interpretation was carried out on 4,350 line-km of seismic data selected from a grid of 19,000 line-km of data. Four horizons were identified on a regional basis, including the sea floor, top, and near base of middle to upper Miocene evaporites, and approximate acoustic basement. The results show that the Egyptian Red Sea is similar to the better known, productive Gulf of Suez in many respects, including overall tectonic evolution and structural style, present geothermal gradients, and Miocene to Holocene stratigraphic sequence. Based in part on this similarity, the Egyptian Red Sea appears to contain the necessary elements for an attractive petroleum potential.

  16. Sudanese Gulf of Aden petroleum geology and regional geophysical evaluation

    SciTech Connect

    Osman, E.; Rahman, B.A.; Abdella, H.E.M.; Ali, A.O. )

    1991-08-01

    The World Bank-executed Red Sea/Gulf of Aden Regional Hydrocarbon Study Project was organized to synthesize data on the Red Sea and Gulf of Aden basins. The primary objectives were to encourage increased hydrocarbon exploration activity within the project area by applying recent exploration techniques basin wide, and to train national geoscientists in exploration techniques. The study of the Sudanese Red Sea was based on public-domain exploration data, published information, and data released by operating companies. The results show that the Sudanese, Red Sea is similar to the better known, productive Gulf of Suez. In many respects, including the overall tectonic evolution, the structural style,a nd Miocene-to-Holocene stratigraphic sequence. A major difference involves the development of thick depocenters of Pliocene-Holocene super-evaporite sediments, in part controlled by offsets in the topographic rift shoulder of the basin, which result in large paleodrainage basins that supplied sediment to the basin. The sediments in these depocenters are thick enough, and geothermal gradients sufficiently high, to suggest the possibility of significant hydrocarbon generation in the depocenters. This is supported by important super-evaporite hydrocarbon shows in the Tokar Delta area of southern Sudanese Red Sea. Outside of the Pliocene-Holocene depocenters, conditions appear favorable for an attractive hydrocarbon potential in subevaporite units.

  17. STS-56 Earth observation of the northeastern Nile Delta

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-56 Earth observation of the northeastern Nile Delta was photographed from the Earth-orbiting Discovery, Orbiter Vehicle (OV) 103. The branch of the Nile featured in the frame is Daimietta. The Suez Canal marks the boundary of the Nile Delta agriculture and the Sinai Desert to the right. Lake Masada, the dark waterlogged area to the west (left) of Port Said is becoming more saline as the Aswan Dam has reduced sediment downstream. This sediment reduction, according to NASA scientists studying the STS-56 photography, has resulted in increased coastal erosion and the intrusion of a salt-water lens to the ground water, particularly in the northeastern portions of the delta. Center pivot irrigation fields are located along either side of the Ramses Canal, which connects the Daimietta Nile with Great Bitter Lake. This canal has been re-dug three or four times in the past 3,000 years. Historians note that the canal's most famous use was as the departure point of the fleet of Pharaoh Necho.

  18. Tectonic evolution of the Palmyra zone, Syria

    SciTech Connect

    O'Keefe, F.X.; Sengor, A.M.C. )

    1988-08-01

    The Palmyra foldbelt extends approximately 350 km northeast from its intersection with the Dead Sea transform near Damascus. The surface expression of this feature is a southeast-verging fold-and-thrust belt that brings rocks as old as Triassic to the surface in fault contact with Upper Cretaceous and Tertiary rocks. The palmyra region is first recognized as a subsiding trough from at least Triassic and possibly Permian time through middle Tertiary. This subsidence increases south-westward, reaching a reported maximum of 6 km of sediment north of Damascus, and is related to right-lateral motion along the eastern margin of the opening southern branch of the Neotethys sea as the Cimmerian continent moved northward away from northeast AFrica during Permian-Triassic time. Extension and subsidence continued through the Jurassic and Cretaceous, interrupted by uplift and erosion from Late Jurassic to Early Cretaceous in the northeastern part of the zone. Compression and inversion of the Palmyra zone begin during Miocene time with the initiation of left-lateral displacement on the Dead Sea transform system related to the continued opening of the Red Sea and the failure of the Gulf of Suez rift system. Approximately 105 km of offset are reported for the Dead Sea transform along the Jordan-Israel border segment, while 60 km are reported in Syria north of Lebanon. The Palmyra foldbelt accommodates this discrepancy through oblique shortening, possibly utilizing pre-existing extensional fault systems.

  19. Graben hydrocarbon occurrences and structural style

    SciTech Connect

    Harding, T.P.

    1984-03-01

    Major hydrocarbon occurrences, types of traps, and structural styles have been synthesized from the Sirte basin, the Suez and Viking grabens, and from other normal faulted regions. Hydrocarbons occur in a stacked succession of one or more basins: pregraben, graben fill, and interior sag. Preservation of pregraben accumulations depends on late initiation of crustal arching and limitation of uplift to the graben shoulders. Furthermore, a stable pregraben tectonic environment is required to ensure internal continuity of subsequent fault-block closures. Hydrocarbon traps in the pregraben and graben-fill sediments are primarily dependent on the multidirectional orientation of normal faults, tilting of fault blocks, and, in many cases, flexing or erosion parallel with block edges. The fault pattern is dominated by longitudinal faults subparallel with the graben axis and, secondarily, by oblique faults. The direction and degree of block rotation are influenced by fault profile (planar or listric), degree of extension, fault pattern (doglegs, junctions, terminations), downwarping of the subsequent sag basin, and isostatic adjustment between large blocks.

  20. North African petroleum geology: regional structure and stratigraphic overview of a hydrocarbon-rich cratonic area

    SciTech Connect

    O'Connor, T.E.; Kanes, W.H.

    1985-02-01

    North Africa, including Sinai, contains some of the most important hydrocarbon-producing basins in the world. The North African Symposium is devoted to examining the exploration potential of the North African margin in light of the most recent and promising exploration discoveries. The geologic variety of the region is extraordinary and can challenge any exploration philosophy. Of primary interest are the Sirte basin of Libya, which has produced several billion barrels of oil, and the Gulf of Suez, a narrow, evaporite-capped trough with five fields that will produce more than 5 billion bbl. Both are extensional basins with minimal lateral movement and with good source rocks in direct proximity to reservoirs. Structural models of these basins give firm leads for future exploration. More difficult to evaluate are the Tethyan realm basins of the northern Sinai, and the Western Desert of Egypt, the Cyrenaican Platform of Libya, and the Tunisia-Sicily shelf area, where there are only limited subsurface data. These basins are extensional in origin also, but have been influenced by lateral tectonics. Favorable reservoirs exist, but source rocks have been a problem locally. Structural models with strong stratigraphic response offer several favorable play concepts. The Paleozoic Ghadames basin in Libya, Tunisia, and Algeria has the least complex structural history, and production appears to be limited to small structures. A series of stratigraphic models indicates additional areas with exploration potential. The Paleozoic megabasin of Morocco, with its downfaulted Triassic grabens, remains an untested but attractive area.

  1. North African geology: exploration matrix for potential major hydrocarbon discoveries

    SciTech Connect

    Kanes, W.H.; O'Connor, T.E.

    1985-02-01

    Based on results and models presented previously, it is possible to consider an exploration matrix that examines the 5 basic exploration parameters: source, reservoir, timing, structure, and seal. This matrix indicates that even those basins that have had marginal exploration successes, including the Paleozoic megabasin and downfaulted Triassic grabens of Morocco, the Cyrenaican platform of Libya, and the Tunisia-Sicily shelf, have untested plays. The exploration matrix also suggests these high-risk areas could change significantly, if one of the 5 basic matrix parameters is upgraded or if adjustments in political or financial risk are made. The Sirte basin and the Gulf of Suez, 2 of the more intensely explored areas, also present attractive matrix prospects, particularly with deeper Nubian beds or with the very shallow Tertiary sections. The Ghadames basin of Libya and Tunisia shows some potential, but its evaluation responds strongly to stratigraphic and external nongeologic matrix variations based on degree of risk exposure to be assumed. Of greatest risk in the matrix are the very deep Moroccan Paleozoic clastic plays and the Jurassic of Sinai. However, recent discoveries may upgrade these untested frontier areas. Based on the matrix generated by the data presented at a North African Petroleum Geology symposium, significant hydrocarbon accumulations are yet to be found. The remaining questions are: where in the matrix does each individual company wish to place its exploration capital and how much should be the risk exposure.

  2. Genomic signatures of rapid adaptive evolution in the bluespotted cornetfish, a Mediterranean Lessepsian invader.

    PubMed

    Bernardi, Giacomo; Azzurro, Ernesto; Golani, Daniel; Miller, Michael Ryan

    2016-07-01

    Biological invasions are increasingly creating ecological and economical problems both on land and in aquatic environments. For over a century, the Mediterranean Sea has steadily been invaded by Indian Ocean/Red Sea species (called Lessepsian invaders) via the Suez Canal, with a current estimate of ~450 species. The bluespotted cornetfish, Fistularia commersonii, considered a 'Lessepsian sprinter', entered the Mediterranean in 2000 and by 2007 had spread through the entire basin from Israel to Spain. The situation is unique and interesting both because of its unprecedented rapidity and by the fact that it took this species c. 130 years to immigrate into the Mediterranean. Using genome scans, with restriction site-associated DNA (RAD) sequencing, we evaluated neutral and selected genomic regions for Mediterranean vs. Red Sea cornetfish individuals. We found that few fixed neutral changes were detectable among populations. However, almost half of the genes associated with the 47 outlier loci (potentially under selection) were related to disease resistance and osmoregulation. Due to the short time elapsed from the beginning of the invasion to our sampling, we interpret these changes as signatures of rapid adaptation that may be explained by several mechanisms including preadaptation and strong local selection. Such genomic regions are therefore good candidates to further study their role in invasion success. PMID:27162055

  3. Late Cretaceous multicolored shales and phosphatic sedimentary rocks in Egypt

    SciTech Connect

    Glenn, C.R.; Garrison, R.E.; Arthur, M.A.

    1983-03-01

    Upper Cretaceous transitional fluvial to marine variegated shale (upper Nubia Formation) and the fully marine Duwi (phosphate) Formation occur as thin, widespread, shallow-marine deposits in an east-west-trending belt spanning the lower-middle latitudes of Egypt. On a larger scale, the phosphoritic rocks in Egypt represent but a small portion of a laterally extensive Middle Eastern-North African phosphogenic province of Upper Cretaceous-Lower Tertiary age that accounts for accumulation of minable marine phosphate in excess of 70 billion tons. Phosphorites, porcelanites/cherts, organic carbon-rich shales, glauconitic sandstones, and bioclastic and fine-grained carbonate rocks variously reflect major hemipelagic and shallow-water carbonate sedimentation. Biosiliceous hemipelagic deposits, now diagenetically altered to procelanite and chert, reflect low energy depositional conditions that were periodically interrupted by high energy, possibly storm-induced currents and/or down-slope redeposition. Both dark shales and porcelanites locally contain abundant organic matter and are commonly finely laminated. Porcelanites and black shales are phosphatic, containing phosphatic grains identical, morphologically and chemically, to those found in associated phosphorites, and are probably the source from which the phosphorites were derived. The organic carbon-rich shales of the Duwi Formation appear to be quite laterally extensive and may, depending on thermal maturity, represent potential hydrocarbon source rocks in other portions of the region (e.g., Western Desert, Gulf of Suez), where they are more deeply buried.

  4. Depositional environments and sequence architecture of the Raha and Abu Qada formations (Cenomanian-Turonian), west central Sinai, Egypt

    NASA Astrophysics Data System (ADS)

    Anan, Tarek I.; El-Shahat, Adam; Genedi, Adel; Grammer, Michael

    2013-06-01

    Cenomanian-Turonian deposits are important reservoirs for many oil fields in the Western Desert and the Gulf of Suez region of Egypt. Study of the Raha and Abu Qada formations (Cenomanian-Turonian), from five dip-oriented outcrop locations in west central Sinai; indicates deposition of a mixed siliciclastic-carbonate system on a ramp setting. The inner ramp facies (bivalve and benthonic foraminiferal wackestone) grades northward to the mid ramp facies (echinoderm calcisphere packstone, and oyster floatstone), and outer ramp facies (planktonic foraminiferal wackestone and calcisphere wackestone). The two studied formations comprise one second-order depositional sequence (duration of approximately 10 Million years). This large scale sequence includes four third-order depositional sequences, three of which are observed in the Raha Formation, with the other one recorded in the Abu Qada Formation. Because west central Sinai was tectonically stable during the Cenomanian and Turonian, the main factor controlling the lateral and vertical distribution of facies tracts is likely due to changes in the relative sea level. The Cenomanian-Turonian boundary event is known as the largest oceanic anoxic event during the Cretaceous. This global event has been documented in three of the studied sections. The recorded δ13C excursions range from +3.04‰ to +5.24‰. These high positive excursions in δ13C are associated with highly negative values of δ18O (values range from -6.01‰ to -1.38‰).

  5. Diagenetic control of reservoir quality of Araba and Naqua diagenetic quartzarenites (Cambrian), Gebel Araba-Qabeliat, Southwest Sinai, Egypt

    SciTech Connect

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

    1991-03-01

    Sandstones of the marine Lower Cambrian Araba Formation and the overlying fluvial Upper Cambrian( ) Naqus Formation in Gebel Araba-Qabeliat, southwest Sinai (the eastern side of the Gulf of Suez) were studied to evaluate the major factors controlling potential hydrocarbon reservoir quality. The formations have a composite thickness of 873 m and overlie Precambrian granite and metamorphic rocks and underlie Cretaceous marine strata. The framework composition of both sandstones is almost entirely quartz with trace amounts of muscovite, K-feldspar, and heavy minerals. Up to 21.5% oversize pores, some filled with younger cements, attest to extensive dissolution loss of detrital grains, chiefly feldspar. Because the final mineralogical maturation of these quartzarenites was through diagenesis, they are diagenetic quartzarenites. Following deposition, the introduction of thin coatings of infiltered clay was followed by the precipitation of 6.3% unhomogeneously distributed quartz cement. Some outcrop samples contain pore-occluding gypsum cement or mixtures of gypsum and halite cement. Sr{sup 87}/Sr{sup 86} ratios of seven samples of gypsum cement have values (0.7077 to 0.7083) that are equal to Miocene and slightly younger seawater. These Cambrian sandstones have excellent reservoir potential (mean thin section porosity = 25.7%) because they contained few ductile grains to enhance compaction, and they developed significant amounts of secondary pores by both dissolution of calcite cement and unstable detrital grains. Kaolinite and dickite are potential problems for hydrocarbon production in some beds.

  6. Fracture types detected in eastern Mediterranean reservoirs (Turkey and Egypt)

    SciTech Connect

    Nurmi, R.; Taha, M.

    1988-08-01

    Most of Turkey's reservoirs are in the fractured Cretaceous Mardin Formation; however, new possibilities in fractured Paleozoic sandstones are being sought. The dominant fractures are fold related and are found on the northern flanks of the asymmetrical anticlines. The strike of these fractures is perpendicular to bedding planes and parallel to dip. There are fewer tear-fault-related and crestal-position fractures, but these may have a greater vertical extent. Fractures are present in all the producing areas of Egypt except the Nile delta. Basement fractures associated with shear zones in the southern Gulf of Suez have become an important exploration target. Fracture orientations are related to the major shear orientations except where later folding and faulting have caused structural rotation. The development of Zeit Bay field has shown that fractured basement rock can constitute a significant reservoir. The fracture reservoirs in northern Sinai and the Western Desert are in Cretaceous and Jurassic limestones and/or dolomitic limestones. The major shear fractures are parallel to the northwest-north-northwest compressive stresses that formed the reservoir structures; however, local fold- and fault-related fractures are also present.

  7. Truth and consequences: the bioinvasion of the Mediterranean Sea.

    PubMed

    Galil, Bella Sarah

    2012-09-01

    Over 660 alien marine multicellular species have been recorded in the Mediterranean Sea, with many establishing viable populations and subsequently dispersing from their points of entry. A brief overview is presented of the current state of knowledge of bioinvasions in the Mediterranean Sea, with particular attention paid to gelatinous invasive species. A database of alien species records was used to characterize their identity, pattern of expansion and native region, and to discuss the relative importance of different taxa and vectors in the various regions of the sea. The temporal and spatial spread of 4 alien scyphozoans and 2 alien ctenophores is outlined. Although thermophilic species constitute the majority of Mediterranean aliens, Erythrean aliens are predominant in the east, with shipping and mariculture being mainly responsible for introductions in the northwest. The propagule pressure driving the Erythrean invasion is powerful in the establishment and spread of alien species in the eastern Mediterranean. The implications of the enlargement of the Suez Canal, reflecting patterns in global trade and economy, are briefly discussed. Finally, as alien species inventories play a pivotal role in informing regional policy and management decisions and identifying resource priorities, the scientific community is called upon to pay particular attention to their accuracy and veracity. PMID:22938526

  8. A Change of Heart? British Policies towards Tubercular Refugees during 1959 World Refugee Year.

    PubMed

    Taylor, Becky

    2015-01-01

    This article looks at Britain's response to the World Refugee Year (1959-60), and in particular the government's decision to allow entry to refugees with tuberculosis and other chronic illnesses. In doing so, it broke the practice established by the 1920 Aliens' Order which had barred entry to immigrants with a range of medical conditions. This article uses the entry of these sick refugees as an opportunity to explore whether government policy represented as much of a shift in attitude and practice as contemporary accounts suggested. It argues for the importance of setting the reception of tubercular and other 'disabled' refugees in 1959-61 in its very particular historical context, showing it was a case less of the government thinking differently about refugees, and more of how, in a post-Suez context, the government felt obliged to take into account international and public opinion. The work builds on and adds to the growing literature surrounding refugees and disease. It also places the episode within the specificity of the post-war changing epidemiological climate; the creation of the National Health Service; and the welfare state more broadly. In looking at the role of refugee organizations in the Year, the article also contributes to debates over the place of voluntary agencies within British society. PMID:26411063

  9. The tectonic evolution of Red Sea and Gulf of Aden

    SciTech Connect

    Allen, R.B. ); Sikander, A.H. ); Abouzakhm, A.G.

    1991-08-01

    The Red Sea and Gulf of Aden, formed by rifting of the Arabian plate away from Africa, have been the subjects of numerous studies since the 1960s. Geophysical and geological data gathered during hydrocarbon exploration by several companies are being synthesized as part of the World Bank-executed Red Sea/Gulf of Aden Regional Hydrocarbon Study Project. This synthesis provides an opportunity to study the regional variation in tectonic history and structural style within the two basins, particularly toward the basin margins, where data coverage is most complete and a thinner sedimentary cover allows more reliable interpretation of deeper horizons. Based on this data, most of the Red Sea shows a similar tectonic history to that of the Gulf of Suez. Widespread normal faulting developed contemporaneous with deposition of a dominantly clastic sequence of Oligocene( ) to middle Miocene age. The faulting often dies out within or below thick middle to upper Miocene evaporite deposits with only few faults affecting the younger units. The Gulf of Aden, on the other hand, shows a strong contrast between largely west-northwest-east-southeast oriented extensional structures on land, and generally more east-west oriented extensional structures on the continental shelves and slopes. The onshore extensional structures oriented oblique to the coast, and approximately perpendicular to transform fault trends in the oceanic crust of the central Gulf of Aden. This contrast is extensional structure orientations has important implications for the tectonic evolution of the Gulf of Aden.

  10. Indications of marine bioinvasion from network theory. An analysis of the global cargo ship network

    NASA Astrophysics Data System (ADS)

    Kölzsch, A.; Blasius, B.

    2011-12-01

    The transport of huge amounts of small aquatic organisms in the ballast tanks and at the hull of large cargo ships leads to ever increasing rates of marine bioinvasion. In this study, we apply a network theoretic approach to examine the introduction of invasive species into new ports by global shipping. This is the first stage of the invasion process where it is still possible to intervene with regulating measures. We compile a selection of widely used and newly developed network properties and apply these to analyse the structure and spread characteristics of the directed and weighted global cargo ship network (GCSN). Our results reveal that the GCSN is highly efficient, shows small world characteristics and is positive assortative, indicating that quick spread of invasive organisms between ports is likely. The GCSN shows strong community structure and contains two large communities, the Atlantic and Pacific trading groups. Ports that appear as connector hubs and are of high centralities are the Suez and Panama Canal, Singapore and Shanghai. Furthermore, from robustness analyses and the network's percolation behaviour, we evaluate differences of onboard and in-port ballast water treatment, set them into context with previous studies and advise bioinvasion management strategies.

  11. Evaluation of the Role of Postnatal Ambroxol in the Prevention and Treatment of Respiratory Distress Syndrome in Preterm Neonates

    PubMed Central

    Elsayed, Hesham F; Elkhaiouby, Muhammed I; Elsharkawey, Sunia M; Elnemr, Muna A

    2006-01-01

    Objective: to study the effect of the postnatal administration of Ambroxol in the prevention of respiratory distress syndrome in preterm neonates at risk and on the severity of the disease in those neonates already suffering from it. Methods: the study was a randomized clinical trial performed on 120 preterm neonates admitted to the neonatal unit of the Suez Canal University Hospital, Egypt, with gestational age of 28 to 34 weeks. It was performed in the period from September 2001 through March 2003. Half of the enrolled neonates received intravenous ambroxol (20 mg/kg/d), while the control group received the routine management of prematurity and a placebo. Results: Ambroxol decreased the incidence of Respiratory Distress Syndrome (RDS), improved the gas exchange, and decreased Continious Positive Airway pressure (CPAP) pressure, the length of mechanical ventilation and also the mortality rate. Conclusion: the study concluded that Ambroxol reduced the incidence of this disease in preterm neonates at risk of developing it, and improved the clinical course of RDS. PMID:21748134

  12. Seismic hazard studies in Egypt

    NASA Astrophysics Data System (ADS)

    Mohamed, Abuo El-Ela A.; El-Hadidy, M.; Deif, A.; Abou Elenean, K.

    2012-12-01

    The study of earthquake activity and seismic hazard assessment of Egypt is very important due to the great and rapid spreading of large investments in national projects, especially the nuclear power plant that will be held in the northern part of Egypt. Although Egypt is characterized by low seismicity, it has experienced occurring of damaging earthquake effect through its history. The seismotectonic sitting of Egypt suggests that large earthquakes are possible particularly along the Gulf of Aqaba-Dead Sea transform, the Subduction zone along the Hellenic and Cyprean Arcs, and the Northern Red Sea triple junction point. In addition some inland significant sources at Aswan, Dahshour, and Cairo-Suez District should be considered. The seismic hazard for Egypt is calculated utilizing a probabilistic approach (for a grid of 0.5° × 0.5°) within a logic-tree framework. Alternative seismogenic models and ground motion scaling relationships are selected to account for the epistemic uncertainty. Seismic hazard values on rock were calculated to create contour maps for four ground motion spectral periods and for different return periods. In addition, the uniform hazard spectra for rock sites for different 25 periods, and the probabilistic hazard curves for Cairo, and Alexandria cities are graphed. The peak ground acceleration (PGA) values were found close to the Gulf of Aqaba and it was about 220 gal for 475 year return period. While the lowest (PGA) values were detected in the western part of the western desert and it is less than 25 gal.

  13. Detection of ground deformation over Sharm El-Sheikh-Ras Nasrani coastal zone, South Sinai (Egypt), by using time series SAR interferometry

    NASA Astrophysics Data System (ADS)

    Seleem, Tarek A.; Parcharidis, Issaak; Foumelis, Michael; Kourkouli, Penelope

    2011-03-01

    The investigation area is located in the most southern part of Sinai Peninsula boarded from the west by the Gulf of Suez and from the east by the Gulf of Aqaba. The present study concerns the application of stacking and persistent scattering of SAR interferometry in order to monitor ground deformation in the southern part of Sharm El-Shiekh area. The specific techniques were applied in order to reduce the influence of atmospheric effects on the ground deformation estimates. For this purpose a total number of 26 ENVISAT ASAR scenes covering the period between 2003 and 2009 were processed and analyzed. Interferometric processing results show both patterns of uplift and downlift in the study area. Specifically an area along the coastline with a N-S direction, corresponding to the build up zone of Sharm El-Sheikh, shows annual average subsidence rates between 5 and 7 mm/yr along the line of sight (LOS). On the contrary, Sharm El-Maya, an inner zone, parallel to the above subsided area; shows maximum slant range uplift of 5 mm/yr. The obtained results of both stacking and persistent scattering indicate that the ground deformation in Sharm El-Sheikh-Ras Nasrani coastal zone is attributed to several effecting factors compromising water pumping, lithology, seismicity, and possible active fracture. The contribution of all these factors is discussed in the context.

  14. Impact of wastewater reuse on cobalt status in Egyptian environment.

    PubMed

    Abdel-Sabour, M F

    2003-05-01

    Cobalt is used in the manufacture of alloys, catalysts in the petroleum industry, catalytic converters, and paint pigments. Thus the potential for Co releases into the environment is highly increased. Use of waste sludges and sewage effluent to fertilize and irrigate soils has also increased soil Co concentrations. Total cobalt contents of alluvial delta soil of Egypt show considerable variation ranging from 13.1 to 64.7 ppm. The impact of either wastewater irrigation or industrial activities on soil total Co was obvious due to accumulation of organic matter and solid waste in the surface soil samples. Food crops and vegetables should not be grown on soil highly contaminated by Co. It is noteworthy that the delayed neutron activation analysis (DNAA) technique could be used successfully for total Co determination due to its high sensitivity. It is quit clearly that dust samples of Cairo City contains higher Co level, as compared to Suez Canal Region (Ismailia, Port Said an El-Sues cities). The high values in Cairo City may be due to the existence of industries around the city and the intensive traffic. To minimize Co environmental hazards, waste effluents should be treated on site. Thus, levels of potentially toxic Co needs to be continuously monitored and should be removed during several treatment processes before the disposal of these wastes. PMID:12938992

  15. The strokes that killed Churchill, Roosevelt, and Stalin.

    PubMed

    Ali, Rohaid; Connolly, Ian D; Li, Amy; Choudhri, Omar A; Pendharkar, Arjun V; Steinberg, Gary K

    2016-07-01

    From February 4 to 11, 1945, President Franklin D. Roosevelt of the United States, Soviet Union Premier Joseph Stalin, and British Prime Minister Winston Churchill met near Yalta in Crimea to discuss how post-World War II (WWII) Europe should be organized. Within 2 decades of this conference, all 3 men had died. President Roosevelt died 2 months after the Yalta Conference due to a hemorrhagic stroke. Premier Stalin died 8 years later, also due to a hemorrhagic stroke. Finally, Prime Minister Churchill died 20 years after the conference because of complications due to stroke. At the time of Yalta, these 3 men were the leaders of the most powerful countries in the world. The subsequent deterioration of their health and eventual death had varying degrees of historical significance. Churchill's illness forced him to resign as British prime minister, and the events that unfolded immediately after his resignation included Britain's mismanagement of the Egyptian Suez Crisis and also a period of mistrust with the United States. Furthermore, Roosevelt was still president and Stalin was still premier at their times of passing, so their deaths carried huge political ramifications not only for their respective countries but also for international relations. The early death of Roosevelt, in particular, may have exacerbated post-WWII miscommunication between America and the Soviet Union-miscommunication that may have helped precipitate the Cold War. PMID:27364260

  16. Tendon proper- and peritenon-derived progenitor cells have unique tenogenic properties

    PubMed Central

    2014-01-01

    Introduction Multipotent progenitor populations exist within the tendon proper and peritenon of the Achilles tendon. Progenitor populations derived from the tendon proper and peritenon are enriched with distinct cell types that are distinguished by expression of markers of tendon and vascular or pericyte origins, respectively. The objective of this study was to discern the unique tenogenic properties of tendon proper- and peritenon-derived progenitors within an in vitro model. We hypothesized that progenitors from each region contribute differently to tendon formation; thus, when incorporated into a regenerative model, progenitors from each region will respond uniquely. Moreover, we hypothesized that cell populations like progenitors were capable of stimulating tenogenic differentiation, so we generated conditioned media from these cell types to analyze their stimulatory potentials. Methods Isolated progenitors were seeded within fibrinogen/thrombin gel-based constructs with or without supplementation with recombinant growth/differentiation factor-5 (GDF5). Early and late in culture, gene expression of differentiation markers and matrix assembly genes was analyzed. Tendon construct ultrastructure was also compared after 45 days. Moreover, conditioned media from tendon proper-derived progenitors, peritenon-derived progenitors, or tenocytes was applied to each of the three cell types to determine paracrine stimulatory effects of the factors secreted from each of the respective cell types. Results The cell orientation, extracellular domain and fibril organization of constructs were comparable to embryonic tendon. The tendon proper-derived progenitors produced a more tendon-like construct than the peritenon-derived progenitors. Seeded tendon proper-derived progenitors expressed greater levels of tenogenic markers and matrix assembly genes, relative to peritenon-derived progenitors. However, GDF5 supplementation improved expression of matrix assembly genes in peritenon

  17. New insights into BMP-7 mediated osteoblastic differentiation of primary human mesenchymal stem cells.

    PubMed

    Lavery, Karen; Hawley, Sara; Swain, Pamela; Rooney, Robert; Falb, Dean; Alaoui-Ismaili, Moulay Hicham

    2009-07-01

    Bone Morphogenetic Proteins (BMPs) are members of the TGF-beta superfamily of growth factors. Several BMPs exhibit osteoinductive bioactivities, and are critical for bone formation in both developing and mature skeletal systems. BMP-7 (OP-1) is currently used clinically in revision of posterolateral spine fusions and long bone non-unions. The current study characterizes BMP-7 induced gene expression during early osteoblastic differentiation of human mesenchymal stem cells (hMSC). Primary hMSC were treated with BMP-7 for 24 or 120 h and gene expression across the entire human genome was evaluated using Affymetrix HG-U133 Plus 2.0 Arrays. 955 probe sets representing 655 genes and 95 ESTs were identified as differentially expressed and were organized into three major expression profiles (Profiles A, B and C) by hierarchical clustering. Genes from each profile were classified according to biochemical pathway analyses. Profile A, representing genes upregulated by BMP-7, revealed strong enrichment for established osteogenic marker genes, as well as several genes with undefined roles in osteoblast function, including MFI2, HAS3, ADAMTS9, HEY1, DIO2 and FGFR3. A functional screen using siRNA suggested roles for MFI2, HEY1 and DIO2 in osteoblastic differentiation of hMSC. Profile B contained genes transiently downregulated by BMP-7, including numerous genes associated with cell cycle regulation. Follow-up studies confirmed that BMP-7 attenuates cell cycle progression and cell proliferation during early osteoblastic differentiation. Profile C, comprised of genes continuously downregulated by BMP-7, exhibited strong enrichment for genes associated with chemokine/cytokine activity. Inhibitory effects of BMP-7 on cytokine secretion were verified by analysis of enriched culture media. Potent downregulation of CHI3L1, a potential biomarker for numerous joint diseases, was also observed in Profile C. A focused evaluation of BMP, GDF and BMP inhibitor expression elucidated feedback

  18. Melatonin enhances the in vitro maturation and developmental potential of bovine oocytes denuded of the cumulus oophorus.

    PubMed

    Zhao, Xue-Ming; Min, Jiang-Tao; Du, Wei-Hua; Hao, Hai-Sheng; Liu, Yan; Qin, Tong; Wang, Dong; Zhu, Hua-Bin

    2015-08-01

    This study was designed to determine the effect of melatonin on the in vitro maturation (IVM) and developmental potential of bovine oocytes denuded of the cumulus oophorus (DOs). DOs were cultured alone (DOs) or with 10-9 M melatonin (DOs + MT), cumulus-oocyte complexes (COCs) were cultured without melatonin as the control. After IVM, meiosis II (MII) rates of DOs, and reactive oxygen species (ROS) levels, apoptotic rates and parthenogenetic blastocyst rates of MII oocytes were determined. The relative expression of ATP synthase F0 Subunit 6 and 8 (ATP6 and ATP8), bone morphogenetic protein 15 (BMP-15) and growth differentiation factor 9 (GDF-9) mRNA in MII oocytes and IFN-tau (IFN-τ), Na+/K+-ATPase, catenin-beta like 1 (CTNNBL1) and AQP3 mRNA in parthenogenetic blastocysts were quantified using real-time polymerase chain reaction (PCR). The results showed that: (1) melatonin significantly increased the MII rate of DOs (65.67 ± 3.59 % vs. 82.29 ± 3.92%; P < 0.05), decreased the ROS level (4.83 ± 0.42 counts per second (c.p.s) vs. 3.78 ± 0.29 c.p.s; P < 0.05) and apoptotic rate (36.99 ± 3.62 % vs. 21.88 ± 2.08 %; P < 0.05) and moderated the reduction of relative mRNA levels of ATP6, ATP8, BMP-15 and GDF-9 caused by oocyte denudation; (2) melatonin significantly increased the developmental rate (24.17 ± 3.54 % vs. 35.26 ± 4.87%; P < 0.05), and expression levels of IFN-τ, Na+/K+-ATPase, CTNNBL1 and AQP3 mRNA of blastocyst. These results indicated that melatonin significantly improved the IVM quality of DOs, leading to an increased parthenogenetic blastocyst formation rate and quality. PMID:24869483

  19. Follicle-restricted compartmentalization of transforming growth factor beta superfamily ligands in the feline ovary.

    PubMed

    Bristol, Sarah K; Woodruff, Teresa K

    2004-03-01

    Ovarian follicular development, follicle selection, and the process of ovulation remain poorly understood in most species. Throughout reproductive life, follicle fate is balanced between growth and apoptosis. These opposing forces are controlled by numerous endocrine, paracrine, and autocrine factors, including the ligands represented by the transforming growth factor beta (TGFbeta) superfamily. TGFbeta, activin, inhibin, bone morphometric protein (BMP), and growth differentiation factor 9 (GDF-9) are present in the ovary of many animals; however, no comprehensive analysis of the localization of each ligand or its receptors and intracellular signaling molecules during folliculogenesis has been done. The domestic cat is an ideal model for studying ovarian follicle dynamics due to an abundance of all follicle populations, including primordial stage, and the amount of readily available tissue following routine animal spaying. Additionally, knowledge of the factors involved in feline follicular development could make an important impact on in vitro maturation/in vitro fertilization (IVM/IVF) success for endangered feline species. Thus, the presence and position of TGFbeta superfamily members within the feline ovary have been evaluated in all stages of follicular development by immunolocalization. The cat inhibin alpha subunit protein is present in all follicle stages but increases in intensity within the mural granulosa cells in large antral follicles. The inhibin betaA and betaB subunit proteins, in addition to the activin type I (ActRIB) and activin type II receptor (ActRIIB), are produced in primordial and primary follicle granulosa cells. Additionally, inhibin betaA subunit is detected in the theca cells from secondary through large antral follicle size classes. GDF-9 is restricted to the oocyte of preantral and antral follicles, whereas the type II BMP receptor (BMP-RII) protein is predominantly localized to primordial- and primary-stage follicles. TGFbeta1, 2

  20. Effect of oocyte-secreted factors on porcine in vitro maturation, cumulus expansion and developmental competence of parthenotes.

    PubMed

    Gomez, Ma Ninia L; Kang, Jung Taek; Koo, Ok Jae; Kim, Su Jin; Kwon, Dae Kee; Park, Sol Ji; Atikuzzaman, Mohammad; Hong, So Gun; Jang, Goo; Lee, Byeong Chun

    2012-05-01

    The oocyte is known from recent studies in the mouse, cow, sheep and human to be a central regulator of follicular cell function. However, in the pig, little information is known about the regulation of cumulus expansion by oocyte-secreted factors and oocyte quality. We investigated the possible effects of oocyte-secreted factors during in vitro maturation on cumulus expansion and on porcine oocytes as judged by subsequent embryonic development after parthenogenetic activation. Cumulus-oocyte complexes (COC) from antral follicles of pig ovaries collected from a local abattoir were divided into control and treatment groups and were cultured in tissue culture medium 199 supplemented with follicle-stimulating hormone. Treatment groups consisted of increasing numbers of denuded oocytes (DO) co-cultured with COC (at ratios of COC to DO of 1:1, 1:2, 1:3, 1:4 and 1:5). After incubation for 44 h, cumulus expansion and maturation rates were assessed and oocytes were activated parthenogenetically. Cumulus expansion in the 1 COC:4 DO and 1 COC:5 DO groups was low and altered because full dispersion of the outer layer did not occur. Cell viability was not affected, as measured by the automated cell counter, but scanning electron microscopy revealed only a scanty extracellular matrix. Blastocyst rate was significantly higher in the 1 COC:4 DO (34.4%) and in the 1 COC:5 DO (34.9%) groups (p < 0.05) when compared with other groups. Maturation rate, cleavage rate and total cell number showed no significant difference between control and treatment groups. Amplification by reverse transcription polymerase chain reaction (RT-PCR) showed up-regulation of growth differentiation factor 9 (GDF9) in the cumulus cells in the 1 COC:4 DO group at 44 h. We conclude that denuded porcine oocytes could improve the maturation of COC as evidenced by increased blastocyst development in the 1 COC:4 DO, even though cumulus expansion was poor. This improvement could be a result of the GDF9 up

  1. A gene expression map of the larval Xenopus laevis head reveals developmental changes underlying the evolution of new skeletal elements.

    PubMed

    Square, Tyler; Jandzik, David; Cattell, Maria; Coe, Alex; Doherty, Jacob; Medeiros, Daniel Meulemans

    2015-01-15

    The morphology of the vertebrate head skeleton is highly plastic, with the number, size, shape, and position of its components varying dramatically between groups. While this evolutionary flexibility has been key to vertebrate success, its developmental and genetic bases are poorly understood. The larval head skeleton of the frog Xenopus laevis possesses a unique combination of ancestral tetrapod features and anuran-specific novelties. We built a detailed gene expression map of the head mesenchyme in X. laevis during early larval development, focusing on transcription factor families with known functions in vertebrate head skeleton development. This map was then compared to homologous gene expression in zebrafish, mouse, and shark embryos to identify conserved and evolutionarily flexible aspects of vertebrate head skeleton development. While we observed broad conservation of gene expression between X. laevis and other gnathostomes, we also identified several divergent features that correlate to lineage-specific novelties. We noted a conspicuous change in dlx1/2 and emx2 expression in the second pharyngeal arch, presaging the differentiation of the reduced dorsal hyoid arch skeletal element typical of modern anamniote tetrapods. In the first pharyngeal arch we observed a shift in the expression of the joint inhibitor barx1, and new expression of the joint marker gdf5, shortly before skeletal differentiation. This suggests that the anuran-specific infrarostral cartilage evolved by partitioning of Meckel's cartilage with a new paired joint. Taken together, these comparisons support a model in which early patterning mechanisms divide the vertebrate head mesenchyme into a highly conserved set of skeletal precursor populations. While subtle changes in this early patterning system can affect skeletal element size, they do not appear to underlie the evolution of new joints or cartilages. In contrast, later expression of the genes that regulate skeletal element

  2. Innovative 3D and 4D geological interpretation, modelling and visualisation techniques for subsurface characterisation of complex industrial sites - examples in the UK nuclear industry

    NASA Astrophysics Data System (ADS)

    Smith, Nicholas; Shevelan, John; Hodgetts, David; Head, William

    2013-04-01

    structural information. Detailed examination of these alongside numerous borehole logs and existing and new low-resolution geophysical data has allowed the creation of 3D geological interpretations and models, enabling the construction of 3D and 4D hydrogeological and contaminant transport models that are essential to environmental safety cases. Staying within the nuclear industry, geological characterisation issues may become even more prevalent in the UK's search for a location to build a geological disposal facility (GDF) for the disposal of its higher resolution radioactive waste. Here intrusive investigations would typically involve the drilling of boreholes, yet intrusion needs to be kept to a minimum. However, we show how innovative laser-based digital data gathering techniques which are currently being employed in the development of 3D structural models of crystalline rocks, are likely to be vital to the geological characterisation of the deep subsurface at potential UK locations for a GDF whilst keeping intrusion to a minimum.

  3. Mineralogical Evidence for the Palaeohydrogeological Stability of a Deep Groundwater System in Fractured Rock, in West Cumbria, Northwest England

    NASA Astrophysics Data System (ADS)

    Milodowski, A. E.; Gillespie, M. R.; Chenery, S. R. N.; Naden, J.; Shaw, R. P.

    2014-12-01

    An important requirement of the safety assessment for a geological disposal facility (GDF) for radioactive waste is to be able to demonstrate the long-term chemical stability of the groundwater system at repository depth over the long period of time during which the waste will be a hazard, typically up to one million years. Of particular concern in the UK is the potential for oxidising groundwater to penetrate to repository depth during periods of glaciation, thereby increasing the mobility of some transuranic radionuclides.Between 1990 and 1998, United Kingdom Nirex Limited carried out geological investigations into the suitability of a potential site in the Sellafield area of NW England, for a GDF for L/ILW. As part of these investigations, detailed petrological analysis of fracture mineralisation in 23 deep boreholes identified a complex sequence of mineralisation events referred to as ME1-ME9. The distribution of the ME9 calcite mineralisation correlates closely with present-day groundwater flows. The ME9 calcite has been studied in more detail to understand the evolution of the deep groundwater system. The morphology and growth zoning characteristics of the calcites reflects the groundwater chemistry. Freshwater calcites display c-axis flattened to equant crystals, and are non-ferroan and strongly zoned with Mn-rich and Mn-free bands. Deeper saline-zone calcites display c-axis elongated crystals, with high Mn:Fe and low Mn:Fe growth zones. Calcite in the transition zone between the saline and fresh groundwater display saline-type cores overgrown by freshwater-type calcite, indicating a small depression of the position of the transition zone during the growth of the calcites. Sr isotope ratios and fluid inclusion chemistry confirm a link between ME9 calcite and the present regional groundwater system. Modelling of the oxygen isotope data indicates that some growth zones in the ME9 calcite precipitated from groundwater potentially containing a significant

  4. Expression profiling and Ingenuity biological function analyses of interleukin-6- versus nerve growth factor-stimulated PC12 cells

    PubMed Central

    Kunz, Dieter; Walker, Gaby; Bedoucha, Marc; Certa, Ulrich; März-Weiss, Pia; Dimitriades-Schmutz, Beatrice; Otten, Uwe

    2009-01-01

    Background The major goal of the study was to compare the genetic programs utilized by the neuropoietic cytokine Interleukin-6 (IL-6) and the neurotrophin (NT) Nerve Growth Factor (NGF) for neuronal differentiation. Results The designer cytokine Hyper-IL-6 in which IL-6 is covalently linked to its soluble receptor s-IL-6R as well as NGF were used to stimulate PC12 cells for 24 hours. Changes in gene expression levels were monitored using Affymetrix GeneChip technology. We found different expression for 130 genes in IL-6- and 102 genes in NGF-treated PC12 cells as compared to unstimulated controls. The gene set shared by both stimuli comprises only 16 genes. A key step is upregulation of growth factors and functionally related external molecules known to play important roles in neuronal differentiation. In particular, IL-6 enhances gene expression of regenerating islet-derived 3 alpha (REG3A; 1084-fold), regenerating islet-derived 3 beta (REG3B/PAPI; 672-fold), growth differentiation factor 15 (GDF15; 80-fold), platelet-derived growth factor alpha (PDGFA; 69-fold), growth hormone releasing hormone (GHRH; 30-fold), adenylate cyclase activating polypeptide (PACAP; 20-fold) and hepatocyte growth factor (HGF; 5-fold). NGF recruits GDF15 (131-fold), transforming growth factor beta 1 (TGFB1; 101-fold) and brain-derived neurotrophic factor (BDNF; 89-fold). Both stimuli activate growth-associated protein 43 (GAP-43) indicating that PC12 cells undergo substantial neuronal differentiation. Moreover, IL-6 activates the transcription factors retinoic acid receptor alpha (RARA; 20-fold) and early growth response 1 (Egr1/Zif268; 3-fold) known to play key roles in neuronal differentiation. Ingenuity biological function analysis revealed that completely different repertoires of molecules are recruited to exert the same biological functions in neuronal differentiation. Major sub-categories include cellular growth and differentiation, cell migration, chemotaxis, cell adhesion, small

  5. Mesenchymal stem cells preserve neonatal right ventricular function in a porcine model of pressure overload.

    PubMed

    Wehman, Brody; Sharma, Sudhish; Pietris, Nicholas; Mishra, Rachana; Siddiqui, Osama T; Bigham, Grace; Li, Tieluo; Aiello, Emily; Murthi, Sarah; Pittenger, Mark; Griffith, Bartley; Kaushal, Sunjay

    2016-06-01

    Limited therapies exist for patients with congenital heart disease (CHD) who develop right ventricular (RV) dysfunction. Bone marrow-derived mesenchymal stem cells (MSCs) have not been evaluated in a preclinical model of pressure overload, which simulates the pathophysiology relevant to many forms of CHD. A neonatal swine model of RV pressure overload was utilized to test the hypothesis that MSCs preserve RV function and attenuate ventricular remodeling. Immunosuppressed Yorkshire swine underwent pulmonary artery banding to induce RV dysfunction. After 30 min, human MSCs (1 million cells, n = 5) or placebo (n = 5) were injected intramyocardially into the RV free wall. Serial transthoracic echocardiography monitored RV functional indices including 2D myocardial strain analysis. Four weeks postinjection, the MSC-treated myocardium had a smaller increase in RV end-diastolic area, end-systolic area, and tricuspid vena contracta width (P < 0.01), increased RV fractional area of change, and improved myocardial strain mechanics relative to placebo (P < 0.01). The MSC-treated myocardium demonstrated enhanced neovessel formation (P < 0.0001), superior recruitment of endogenous c-kit+ cardiac stem cells to the RV (P < 0.0001) and increased proliferation of cardiomyocytes (P = 0.0009) and endothelial cells (P < 0.0001). Hypertrophic changes in the RV were more pronounced in the placebo group, as evidenced by greater wall thickness by echocardiography (P = 0.008), increased cardiomyocyte cross-sectional area (P = 0.001), and increased expression of hypertrophy-related genes, including brain natriuretic peptide, β-myosin heavy chain and myosin light chain. Additionally, MSC-treated myocardium demonstrated increased expression of the antihypertrophy secreted factor, growth differentiation factor 15 (GDF15), and its downstream effector, SMAD 2/3, in cultured neonatal rat cardiomyocytes and in the porcine RV myocardium. This is the first report of the use of MSCs as a therapeutic

  6. The Hippo/MST Pathway Member SAV1 Plays a Suppressive Role in Development of the Prehierarchical Follicles in Hen Ovary.

    PubMed

    Lyu, Zhichao; Qin, Ning; Tyasi, Thobela Louis; Zhu, Hongyan; Liu, Dehui; Yuan, Shuguo; Xu, Rifu

    2016-01-01

    The Hippo/MST signaling pathway is a critical player in controlling cell proliferation, self-renewal, differentiation, and apoptosis of most tissues and organs in diverse species. Previous studies have shown that Salvador homolog 1 (SAV1), a scaffolding protein which functions in the signaling system is expressed in mammalian ovaries and play a vital role in governing the follicle development. But the exact biological effects of chicken SAV1 in prehierarchical follicle development remain poorly understood. In the present study, we demonstrated that the SAV1 protein is predominantly expressed in the oocytes and undifferentiated granulosa cells in the various sized prehierarchical follicles of hen ovary, and the endogenous expression level of SAV1 mRNA appears down-regulated from the primordial follicles to the largest preovulatory follicles (F2-F1) by immunohistochemistry and real-time RT-PCR, respectively. Moreover, we found the intracellular SAV1 physically interacts with each of the pathway members, including STK4/MST1, STK3/MST2, LATS1 and MOB2 using western blotting. And SAV1 significantly promotes the phosphorylation of LATS1 induced by the kinase of STK4 or STK3 in vitro. Furthermore, SAV1 knockdown by small interfering RNA (siRNA) significantly increased proliferation of granulosa cells from the prehierarchical follicles (6-8 mm in diameter) by BrdU-incorporation assay, in which the expression levels of GDF9, StAR and FSHR mRNA was notably enhanced. Meanwhile, these findings were consolidated by the data of SAV1 overexpression. Taken together, the present results revealed that SAV1 can inhibit proliferation of the granulosa cells whereby the expression levels of GDF9, StAR and FSHR mRNA were negatively regulated. Accordingly, SAV1, as a member of the hippo/MST signaling pathway plays a suppressive role in ovarian follicle development by promoting phosphorylation and activity of the downstream LATS1, may consequently lead to prevention of the follicle

  7. The Hippo/MST Pathway Member SAV1 Plays a Suppressive Role in Development of the Prehierarchical Follicles in Hen Ovary

    PubMed Central

    Tyasi, Thobela Louis; Zhu, Hongyan; Liu, Dehui; Yuan, Shuguo; Xu, Rifu

    2016-01-01

    The Hippo/MST signaling pathway is a critical player in controlling cell proliferation, self-renewal, differentiation, and apoptosis of most tissues and organs in diverse species. Previous studies have shown that Salvador homolog 1 (SAV1), a scaffolding protein which functions in the signaling system is expressed in mammalian ovaries and play a vital role in governing the follicle development. But the exact biological effects of chicken SAV1 in prehierarchical follicle development remain poorly understood. In the present study, we demonstrated that the SAV1 protein is predominantly expressed in the oocytes and undifferentiated granulosa cells in the various sized prehierarchical follicles of hen ovary, and the endogenous expression level of SAV1 mRNA appears down-regulated from the primordial follicles to the largest preovulatory follicles (F2-F1) by immunohistochemistry and real-time RT-PCR, respectively. Moreover, we found the intracellular SAV1 physically interacts with each of the pathway members, including STK4/MST1, STK3/MST2, LATS1 and MOB2 using western blotting. And SAV1 significantly promotes the phosphorylation of LATS1 induced by the kinase of STK4 or STK3 in vitro. Furthermore, SAV1 knockdown by small interfering RNA (siRNA) significantly increased proliferation of granulosa cells from the prehierarchical follicles (6–8 mm in diameter) by BrdU-incorporation assay, in which the expression levels of GDF9, StAR and FSHR mRNA was notably enhanced. Meanwhile, these findings were consolidated by the data of SAV1 overexpression. Taken together, the present results revealed that SAV1 can inhibit proliferation of the granulosa cells whereby the expression levels of GDF9, StAR and FSHR mRNA were negatively regulated. Accordingly, SAV1, as a member of the hippo/MST signaling pathway plays a suppressive role in ovarian follicle development by promoting phosphorylation and activity of the downstream LATS1, may consequently lead to prevention of the follicle

  8. The Infertility of Repeat-Breeder Cows During Summer Is Associated with Decreased Mitochondrial DNA and Increased Expression of Mitochondrial and Apoptotic Genes in Oocytes.

    PubMed

    Ferreira, Roberta Machado; Chiaratti, Marcos Roberto; Macabelli, Carolina Habermann; Rodrigues, Carlos Alberto; Ferraz, Márcio Leão; Watanabe, Yeda Fumie; Smith, Lawrence Charles; Meirelles, Flávio Vieira; Baruselli, Pietro Sampaio

    2016-03-01

    Oocyte quality is known to be a major cause of infertility in repeat-breeder (RB) and heat-stressed dairy cows. However, the mechanisms by which RB oocytes become less capable of supporting embryo development remain largely unknown. Thus, the aim of this study was to investigate whether the decreased oocyte competence of RB cows (RBs) during summer is associated with an altered gene expression profile and a decrease in mitochondrial DNA (mtDNA) copy number. Therefore, oocytes collected from heifers, non-RBs in peak lactation (PLs), and RBs were used to evaluate mtDNA amounts as well as the expression levels of genes associated with the mitochondria (MT-CO1,NRF1,POLG,POLG2,PPARGC1A, andTFAM), apoptosis (BAX,BCL2, andITM2B), and oocyte maturation (BMP15,FGF8,FGF10,FGF16,FGF17, andGDF9). The oocytes retrieved from RBs during winter contained over eight times more mtDNA than those retrieved from RBs during summer. They also contained significantly less mtDNA than oocytes retrieved from heifers and PLs during summer. Moreover, the expression of mitochondria- (NRF1,POLG,POLG2,PPARGC1A, andTFAM) and apoptosis-related (BAXandITM2B) genes, as well as ofGDF9, in RB oocytes collected during summer was significantly greater than that in oocytes collected from heifers and PLs during the same season. In oocytes from heifers and PLs, the expression levels of these genes were lower in those collected during summer compared with winter, but this difference was not observed in oocytes collected from RBs. Altogether, these data provide evidence of altered gene expression and reduced mtDNA copy number in the oocytes collected from RBs during summer. This indicates a loss of fertility in RBs during summer, which might be caused by a possible mitochondrial dysfunction associated with a greater chance of oocytes to undergo apoptosis. PMID:26843447

  9. BMP treatment of C3H10T1/2 mesenchymal stem cells induces both chondrogenesis and osteogenesis.

    PubMed

    Shea, Colleen M; Edgar, Cory M; Einhorn, Thomas A; Gerstenfeld, Louis C

    2003-12-15

    The molecular mechanisms by which bone morphogenetic proteins (BMPs) promote skeletal cell differentiation were investigated in the murine mesenchymal stem cell line C3H10T1/2. Both BMP-7 and BMP-2 induced C3H10T1/2 cells to undergo a sequential pattern of chondrogenic followed by osteogenic differentiation that was dependent on both the concentration and the continuous presence of BMP in the growth media. Differentiation was determined by the expression of chondrogenesis and osteogenesis associated matrix genes. Subsequent experiments using BMP-7 demonstrated that withdrawal of BMP from the growth media led to a complete loss of skeletal cell differentiation accompanied by adipogenic differentiation of these cells. Continuous treatment with BMP-7 increased the expression of Sox9, Msx 2, and c-fos during the periods of chondrogenic differentiation after which point their expression decreased. In contrast, Dlx 5 expression was induced by BMP-7 treatment and remained elevated throughout the time-course of skeletal cell differentiation. Runx2/Cbfa1 was not detected by ribonuclease protection assay (RPA) and did not appear to be induced by BMP-7. The sequential nature of differentiation of chondrocytic and osteoblastic cells and the necessity for continuous BMP treatment to maintain skeletal cell differentiation suggests that the maintenance of selective differentiation of the two skeletal cell lineages might be dependent on BMP-7-regulated expression of other morphogenetic factors. An examination of the expression of Wnt, transforming growth factor-beta (TGF-beta), and the hedgehog family of morphogens showed that Wnt 5b, Wnt 11, BMP-4, growth and differentiation factor-1 (GDF-1), Sonic hedgehog (Shh), and Indian hedgehog (Ihh) were endogenously expressed by C3H10T1/2 cells. Wnt 11, BMP-4, and GDF-1 expression were inhibited by BMP-7 treatment in a dose-dependent manner while Wnt 5b and Shh were selectively induced by BMP-7 during the period of chondrogenic

  10. Gravity and magnetic data across the Ghost Dance Fault in WT-2 Wash, Yucca Mountain, Nevada

    SciTech Connect

    Oliver, H.W.; Sikora, R.F.

    1994-12-31

    Detailed gravity and ground magnetic data were obtained in September 1993 along a 4,650 ft-long profile across the Ghost Dance Fault system in WT-2 Wash. Gravity stations were established every 150 feet along the profile. Total-field magnetic measurements made initially every 50 ft along the profile, then remade every 20 ft through the fault zone. These new data are part of a geologic and geophysical study of the Ghost Dance Fault (GDF) which includes detailed geologic mapping, seismic reflection, and some drilling including geologic and geophysical logging. The Ghost Dance Fault is the only through-going fault that has been identified within the potential repository for high-level radioactive waste at Yucca Mountain, Nevada. Preliminary gravity results show a distinct decrease of 0.1 to 0.2 mGal over a 600-ft-wide zone to the east of and including the mapped fault. The gravity decrease probably marks a zone of brecciation. Another fault-offset located about 2,000 ft to the east of the GDF was detected by seismic reflection data and is also marked by a distinct gravity low. The ground magnetic data show a 200-ft-wide magnetic low of about 400 nT centered about 100 ft east of the Ghost Dance Fault. The magnetic low probably marks a zone of brecciation within the normally polarized Topopah Spring Tuff, the top of which is about 170 ft below the surface, and which is known from drilling to extend to a depth of about 1,700 ft. Three-component magnetometer logging in drill hole WT-2 located about 2,700 ft east of the Ghost Dance Fault shows that the Topopah Spring Tuff is strongly polarized magnetically in this area, so that fault brecciation of a vertical zone within the Tuff could provide an average negative magnetic contrast of the 4 Am{sup {minus}1} needed to produce the 400 nT low observed at the surface.

  11. Dynamic activation of bone morphogenetic protein signaling in collagen-induced arthritis supports their role in joint homeostasis and disease

    PubMed Central

    Daans, Melina; Lories, Rik JU; Luyten, Frank P

    2008-01-01

    Introduction Rheumatoid arthritis is a chronic systemic autoimmune disease affecting peripheral joints and leading to loss of joint function. The severity and outcome of disease are dependent on the balance between inflammatory/destructive and homeostatic or repair pathways. Increasing evidence suggests a role for bone morphogenetic protein (BMP) signaling in joint homeostasis and disease. Methods Activation of BMP signaling in collagen-induced arthritis as a model of rheumatoid arthritis was studied by immunohistochemistry and Western blot for phosphorylated SMAD1/5 at different time points. Expression of different BMP ligands and noggin, a BMP antagonist, was determined on synovium and cartilage extracts of arthritic knees, at different time points, with quantitative polymerase chain reaction. At the protein level, BMP2 and BMP7 were studied with immunohistochemistry. Finally, the effect of anti-tumor necrosis factor-alpha (TNFα) treatment on the expression of BMP2, BMP7, and growth and differentiation factor-5 (GDF5) in synovium and cartilage of arthritic knees was investigated. Results A time-dependent activation of the BMP signaling pathway in collagen-induced arthritis was demonstrated with a dynamic and characteristic expression pattern of different BMP subfamily members in synovium and cartilage of arthritic knees. As severity increases, the activation of BMP signaling becomes more prominent in the invasive pannus tissue. BMP2 is present in cartilage and the hyperplastic lining layer. BMP7 is found in the sublining zone and inflammatory infiltrate. Treatment with etanercept slowed down progression of disease, but no change in expression of GDF5, BMP2, and BMP7 in synovium was found; in the cartilage, however, blocking of TNFα increased the expression of BMP7. Conclusions BMP signaling is dynamically activated in collagen-induced arthritis and is partly TNFα-independent. TNFα blocking increased the expression of BMP7 in the articular cartilage, possibly

  12. Investigating α-particle radiation damage in phyllosilicates using synchrotron microfocus-XRD/XAS: implications for geological disposal of nuclear waste

    NASA Astrophysics Data System (ADS)

    Bower, W. R.; Pearce, C. I.; Pimblott, S. M.; Haigh, S. J.; Mosselmans, J. F. W.; Pattrick, R. A. D.

    2014-12-01

    The response of mineral phases to the radiation fields that will be experienced in a geological disposal facility (GDF) for nuclear waste is poorly understood. Phyllosilicates are critical phases in a GDF with bentonite clay as the backfill of choice surrounding high level wastes in the engineered barrier, and clays and micas forming the most important reactive component of potential host rocks. It is essential that we understand changes in mineral properties and behaviour as a result of damage from both α and γ radiation over long timescales. Radiation damage has been demonstrated to affect the physical integrity and oxidation state1 of minerals which will also influence their ability to react with radionuclides. Using the University of Manchester's newly commissioned particle accelerator at the Dalton Cumbrian Facility, UK, model phyllosilicate minerals (e.g. biotite, chlorite) were irradiated with high energy (5MeV) alpha particles at controlled dose rates. This has been compared alongside radiation damage found in naturally formed 'radiohalos' - spherical areas of discolouration in minerals surrounding radioactive inclusions, resulting from alpha particle penetration, providing a natural analogue to study lattice damage under long term bombardment1,2. Both natural and artificially irradiated samples have been analysed using microfocus X-ray absorption spectroscopy and high resolution X-ray diffraction mapping on Beamline I18 at Diamond Light Source; samples were probed for redox changes and long/short range disorder. This was combined with lattice scale imaging of damage using HR-TEM (TitanTM Transmission Electron Microscope). The results show aberrations in lattice parameters as a result of irradiation, with multiple damage-induced 'domains' surrounded by amorphous regions. In the naturally damaged samples, neo-formed phyllosilicate phases are shown to be breakdown products of highly damaged regions. A clear reduction of the Fe(III) component has been

  13. Hepatic Fatty Acid Oxidation Restrains Systemic Catabolism during Starvation.

    PubMed

    Lee, Jieun; Choi, Joseph; Scafidi, Susanna; Wolfgang, Michael J

    2016-06-28

    The liver is critical for maintaining systemic energy balance during starvation. To understand the role of hepatic fatty acid β-oxidation on this process, we generated mice with a liver-specific knockout of carnitine palmitoyltransferase 2 (Cpt2(L-/-)), an obligate step in mitochondrial long-chain fatty acid β-oxidation. Fasting induced hepatic steatosis and serum dyslipidemia with an absence of circulating ketones, while blood glucose remained normal. Systemic energy homeostasis was largely maintained in fasting Cpt2(L-/-) mice by adaptations in hepatic and systemic oxidative gene expression mediated in part by Pparα target genes including procatabolic hepatokines Fgf21, Gdf15, and Igfbp1. Feeding a ketogenic diet to Cpt2(L-/-) mice resulted in severe hepatomegaly, liver damage, and death with a complete absence of adipose triglyceride stores. These data show that hepatic fatty acid oxidation is not required for survival during acute food deprivation but essential for constraining adipocyte lipolysis and regulating systemic catabolism when glucose is limiting. PMID:27320917

  14. Development of novel activin-targeted therapeutics.

    PubMed

    Chen, Justin L; Walton, Kelly L; Al-Musawi, Sara L; Kelly, Emily K; Qian, Hongwei; La, Mylinh; Lu, Louis; Lovrecz, George; Ziemann, Mark; Lazarus, Ross; El-Osta, Assam; Gregorevic, Paul; Harrison, Craig A

    2015-03-01

    Soluble activin type II receptors (ActRIIA/ActRIIB), via binding to diverse TGF-β proteins, can increase muscle and bone mass, correct anemia or protect against diet-induced obesity. While exciting, these multiple actions of soluble ActRIIA/IIB limit their therapeutic potential and highlight the need for new reagents that target specific ActRIIA/IIB ligands. Here, we modified the activin A and activin B prodomains, regions required for mature growth factor synthesis, to generate specific activin antagonists. Initially, the prodomains were fused to the Fc region of mouse IgG2A antibody and, subsequently, "fastener" residues (Lys(45), Tyr(96), His(97), and Ala(98); activin A numbering) that confer latency to other TGF-β proteins were incorporated. For the activin A prodomain, these modifications generated a reagent that potently (IC(50) 5 nmol/l) and specifically inhibited activin A signaling in vitro, and activin A-induced muscle wasting in vivo. Interestingly, the modified activin B prodomain inhibited both activin A and B signaling in vitro (IC(50) ~2 nmol/l) and in vivo, suggesting it could serve as a general activin antagonist. Importantly, unlike soluble ActRIIA/IIB, the modified prodomains did not inhibit myostatin or GDF-11 activity. To underscore the therapeutic utility of specifically antagonising activin signaling, we demonstrate that the modified activin prodomains promote significant increases in muscle mass. PMID:25399825

  15. Sarcopenia--The search for emerging biomarkers.

    PubMed

    Kalinkovich, Alexander; Livshits, Gregory

    2015-07-01

    Sarcopenia, an age-related decline in skeletal muscle mass and function, dramatically affects the life quality of elder people. In view of increasing life expectancy, sarcopenia renders a heavy burden on the health care system. However, although there is a consensus that sarcopenia is a multifactorial syndrome, its etiology, underlying mechanisms, and even definition remain poorly delineated, thus, preventing development of a precise treatment strategy. The main aim of our review is to critically analyze potential sarcopenia biomarkers in light of the molecular mechanisms of their involvement in sarcopenia pathogenesis. Normal muscle mass and function maintenance are proposed to be dependent on the dynamic balance between the positive regulators of muscle growth such as bone morphogenetic proteins (BMPs), brain-derived neurotrophic factor (BDNF), follistatin (FST) and irisin, and negative regulators including TGFβ, myostatin, activins A and B, and growth and differentiation factor-15 (GDF-15). We hypothesize that the shift in this balance to muscle growth inhibitors, along with increased expression of the C- terminal agrin fragment (CAF) associated with age-dependent neuromuscular junction (NMJ) dysfunction, as well as skeletal muscle-specific troponin T (sTnT), a key component of contractile machinery, is a main mechanism underlying sarcopenia pathogenesis. Thus, this review proposes and emphasizes that these molecules are the emerging sarcopenia biomarkers. PMID:25962896

  16. Geography of follicle formation in the embryonic mouse ovary impacts activation pattern during the first wave of folliculogenesis.

    PubMed

    Cordeiro, Marília H; Kim, So-Youn; Ebbert, Katherine; Duncan, Francesca E; Ramalho-Santos, João; Woodruff, Teresa K

    2015-10-01

    During embryonic development, mouse female germ cells enter meiosis in an anterior-to-posterior wave believed to be driven by retinoic acid. It has been proposed that ovarian follicle formation and activation follow the same general wave of meiotic progression; however, the precise anatomic specification of these processes has not been delineated. Here, we created a mouse line using Mvh, Gdf9, and Zp3 promoters to drive distinct temporal expression of three fluorescent proteins in the oocytes and to identify where the first follicle cohort develops. The fluorescent profile revealed that the first growing follicles consistently appeared in a specific region of the ovary, the anterior-dorsal region, which led us to analyze if meiotic onset occurred earlier in the dorsal ovarian region. Surprisingly, in addition to the anterior-to-posterior wave, we observed an early meiotic entry in the ventral region of the ovary. This additional anatomic stratification of meiosis contrasts with the localization of the initial follicle formation and activation in the dorsal region of the ovary. Therefore, our study suggests that the specification of cortical and medullar areas in the ventral and dorsal regions on the ovary, rather than the onset of meiosis, impacts where the first follicle activation event occurs. PMID:26246221

  17. Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity

    PubMed Central

    Verdeguer, Francisco; Soustek, Meghan S.; Hatting, Maximilian; Blättler, Sharon M.; McDonald, Devin; Barrow, Joeva J.

    2015-01-01

    Mitochondrial oxidative and thermogenic functions in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensates for partial deficiencies in this tissue and protects against obesity. Here, we show that the transcription factor Yin Yang 1 (YY1) in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins, including fibroblast growth factor 21 (FGF21), bone morphogenetic protein 8b (BMP8b), growth differentiation factor 15 (GDF15), angiopoietin-like 6 (Angptl6), neuromedin B, and nesfatin, linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity and exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight. PMID:26503783

  18. Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity.

    PubMed

    Verdeguer, Francisco; Soustek, Meghan S; Hatting, Maximilian; Blättler, Sharon M; McDonald, Devin; Barrow, Joeva J; Puigserver, Pere

    2016-01-01

    Mitochondrial oxidative and thermogenic functions in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensates for partial deficiencies in this tissue and protects against obesity. Here, we show that the transcription factor Yin Yang 1 (YY1) in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins, including fibroblast growth factor 21 (FGF21), bone morphogenetic protein 8b (BMP8b), growth differentiation factor 15 (GDF15), angiopoietin-like 6 (Angptl6), neuromedin B, and nesfatin, linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity and exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight. PMID:26503783

  19. IMP1 suppresses breast tumor growth and metastasis through the regulation of its target mRNAs

    PubMed Central

    Liu, Xin; Huang, Wenhe; Chen, Shaoying; Zhou, Yanchun; Li, Deling; Singer, Robert H.; Gu, Wei

    2016-01-01

    We have previously reported the ability of IMP1 in inhibiting proliferation and invasiveness of breast carcinoma cells in vitro. In the current study, we utilized a mouse xenograft model to further investigate the function of IMP1 in breast tumor progression and its underlying mechanism. We demonstrated that IMP1 expression significantly suppressed the growth of MDA231 cell-derived xenograft tumors and subsequent lung metastasis. Microarray analyses and differential gene expression identified handful mRNAs, many of which were involved in breast tumor-growth and metastasis. Further studies revealed that these mRNAs were directly interacted with the KH34 domain of IMP1 and this interaction post-transcriptionally regulated their corresponding protein expression. Either deletion of the KH34 domain of IMP1 or alteration of the expression of IMP1-bound mRNAs affected cell proliferation and tumor growth, producing the same phenotypes as IMP1 knockdown. Correlation of increased IMP1 expression with the reduced levels of its bound mRNAs, such as PTGS2, GDF15 and IGF-2 transcripts, was also observed in human breast tumors. Our studies provide insights into a molecular mechanism that the positive function of IMP1 to inhibit breast tumor growth and metastasis could be through the regulation of its target mRNAs. PMID:26910917

  20. DNA Methylation in Osteoarthritis

    PubMed Central

    den Hollander, Wouter; Meulenbelt, Ingrid

    2015-01-01

    Osteoarthritis (OA) is a prevalent disease of articular joints and primarily characterized by degradation and calcification of articular cartilage. Presently, no effective treatment other than pain relief exists and patients ultimately need to undergo replacement surgery of the affected joint. During disease progression articular chondrocytes, the single cell type present in articular cartilage, show altered transcriptional profiles and undergo phenotypic changes that resemble the terminal differentiation route apparent in growth plate chondrocytes. Hence, given its prominent function in both regulating gene expression and maintaining cellular phenotypes, DNA methylation of CpG dinucleotides is intensively studied in the context of OA. An increasing number of studies have been published that employed a targeted approach on genes known to play a role in OA pathophysiology. As of such, it has become clear that OA responsive DNA methylation changes seem to mediate disease associated aberrant gene expression. Furthermore, established OA susceptibility alleles such as GDF5 and DIO2 appear to confer OA risk via DNA methylation and respective pathophysiological expression changes. In more recent years, genome wide profiling of DNA methylation in OA affected articular cartilage has emerged as a powerful tool to address the epigenetic changes in their entirety, which has resulted in the identification of putative patient subgroups as well as generic OA associated pathways. PMID:27019616

  1. Eye development genes and known syndromes.

    PubMed

    Slavotinek, Anne M

    2011-12-01

    Anophthalmia and microphthalmia (A/M) are significant eye defects because they can have profound effects on visual acuity. A/M is associated with non-ocular abnormalities in an estimated 33-95% of cases and around 25% of patients have an underlying genetic syndrome that is diagnosable. Syndrome recognition is important for targeted molecular genetic testing, prognosis and for counseling regarding recurrence risks. This review provides clinical and molecular information for several of the commonest syndromes associated with A/M: Anophthalmia-Esophageal-Genital syndrome, caused by SOX2 mutations, Anophthalmia and pituitary abnormalities caused by OTX2 mutations, Matthew-Wood syndrome caused by STRA6 mutations, oculofaciocardiodental syndrome and Lenz microphthalmia caused by BCOR mutations, Microphthalmia Linear Skin pigmentation syndrome caused by HCCS mutations, Anophthalmia, pituitary abnormalities, polysyndactyly caused by BMP4 mutations and Waardenburg anophthalmia caused by mutations in SMOC1. In addition, we briefly discuss the ocular and extraocular phenotypes associated with several other important eye developmental genes, including GDF6, VSX2, RAX, SHH, SIX6 and PAX6. PMID:22005280

  2. Alpha 5 Integrin Mediates Osteoarthritic Changes in Mouse Knee Joints

    PubMed Central

    Candela, Maria Elena; Wang, Chao; Gunawardena, Aruni T.; Zhang, Kairui; Cantley, Leslie; Yasuhara, Rika; Usami, Yu; Francois, Noelle; Iwamoto, Masahiro; van der Flier, Arjan; Zhang, Yejia; Qin, Ling; Han, Lin; Enomoto-Iwamoto, Motomi

    2016-01-01

    Osteoarthritis (OA) is one of most common skeletal disorders and can affect synovial joints such as knee and ankle joints. α5 integrin, a major fibronectin receptor, is expressed in articular cartilage and has been demonstrated to play roles in synovial joint development and in the regulation of chondrocyte survival and matrix degradation in articular cartilage. We hypothesized that α5 integrin signaling is involved in pathogenesis of OA. To test this, we generated compound mice that conditionally ablate α5 integrin in the synovial joints using the Gdf5Cre system. The compound mice were born normally and had an overall appearance similar to the control mice. However, when the mutant mice received the OA surgery, they showed stronger resistance to osteoarthritic changes than the control. Specifically the mutant knee joints presented lower levels of cartilage matrix and structure loss and synovial changes and showed stronger biomechanical properties than the control knee joints. These findings indicate that α5 integrin may not be essential for synovial joint development but play a causative role in induction of osteoarthritic changes. PMID:27280771

  3. Bimodal Imaging Using Neodymium Doped Gadolinium Fluoride Nanocrystals with Near-Infrared to Near-Infrared Downconversion Luminescence and Magnetic Resonance Properties

    PubMed Central

    Mimun, L. Christopher; Ajithkumar, Gangadharan; Pokhrel, Madhab; Yust, Brian G.; Elliott, Zak G.; Pedraza, Francisco; Dhanale, Ashish; Tang, Liang; Lin, Ai-Ling; Dravid, Vinayak P.; Sardar, Dhiraj K

    2013-01-01

    Here we report the synthesis, characterization and application of a multifunctional surface functionalized GdF3:Nd3+ nanophosphor that exhibits efficient near infrared (NIR) fluorescence as well as magnetic properties, which can be utilized for bimodal imaging in medical applications. The nanoparticles are small with an average size of 5 nm and form stable colloids that last for several weeks without settling, enabling the use for several biomedical and photonic applications. Their excellent NIR properties, such as nearly 11 % quantum yield of the 1064 nm emission, make them ideal contrast agents and biomarkers for in vitro and in vivo NIR optical bioimaging. The nanophosphors which were coated with poly(maleic anhydride- alt-1-octadicene) (PMAO) were implemented in cellular imaging and show no significant cellular toxicity for concentrations up to 200 μg ml−1. Furthermore, the incorporation of Gd into the nanocrystalline structure supplies exceptional magnetic properties, making them ideal for use as magnetic resonance imaging (MRI) contrast agents. The utility of these NIR emitting nanoparticles in infrared bioimaging and as contrast agent in magnetic resonance imaging was demonstrated by confocal imaging, magnetic resonance and tissue experiments. PMID:25584192

  4. Enhanced Fluoride Over-coated Al Mirrors for FUV Space Astronomy

    NASA Astrophysics Data System (ADS)

    Quijada, Manuel; Rice, S.; Threat, F. T.; Del Hoyo, J. G.

    2014-01-01

    Astronomical observations in the Far Ultraviolet (FUV) spectral region are some of the more challenging due to the very distant and faint objects that are typically searched for in cosmic origin studies such as origin of large scale structure, the formation, evolution, and age of galaxies and the origin of stellar and planetary systems. These challenges are driving the need to improve the performance of optical coatings over a wide spectral range that would increase reflectance in mirrors and reduced absorption in dielectric filters used in optical telescope for FUV observations. This paper will present recent advances in reflectance performance for Al+MgF2 mirrors optimized for Lyman-alpha wavelength by performing the deposition of the MgF2 overcoat at elevated substrate temperatures. We will also present optical characterization of little studied rare-earth fluorides such as GdF3 and LuF3 that exhibit low-absorption over a wide wavelength range and could therefore be used as high refractive index alternatives for dielectric coatings at FUV wavelengths.

  5. Celecoxib downregulates CD133 expression through inhibition of the Wnt signaling pathway in colon cancer cells.

    PubMed

    Deng, Yanhong; Su, Qiao; Mo, Jianwen; Fu, Xinhui; Zhang, Yan; Lin, Edward H

    2013-02-01

    CD133-positive cancer stem cells in colon cancer are resistant to conventional chemotherapy. The aim of the present study was to investigate the effect of celecoxib, a COX-2 inhibitor, on CD133 expression in HT29 and DLD1 cells. HT29 and DLD1 cells were treated with celecoxib using different concentrations and duration. CD133 expression was detected by flow cytometry, Western blotting, immunofluorescence, and quantitative real-time PCR. Wnt signaling pathway activity was measured by luciferase assay and gene expression changes were monitored using microarray analysis. HT29 cells showed significantly decreasing levels of CD133 expression with increasing concentrations of or duration of exposure to celecoxib. CD133 mRNA relative expression in HT29 and DLD1 cells also decreased with drug exposure. Furthermore, Wnt activation in HT29 and DLD1 cells decreased with celecoxib treatment. Gene expression microarray showed stemness genes, including Lgr5, Oct4, Prominin-1, Prominin-2, CXCR4, E2F8, CDK-2, were downregulated and differentiation genes, including CEACAM5, GDF, ADFP, ICAM1, were upregulated. Our results show that CD133 expression was downregulated by celecoxib through inhibition of the Wnt signaling pathway, which may be lead to cell differentiation. PMID:23245395

  6. X-ray excited photoluminescence near the giant resonance in solid-solution Gd(1-x)Tb(x)OCl nanocrystals and their retention upon solvothermal topotactic transformation to Gd(1-x)Tb(x)F3.

    PubMed

    Waetzig, Gregory R; Horrocks, Gregory A; Jude, Joshua W; Zuin, Lucia; Banerjee, Sarbajit

    2016-01-14

    Design rules for X-ray phosphors are much less established as compared to their optically stimulated counterparts owing to the absence of a detailed understanding of sensitization mechanisms, activation pathways and recombination channels upon high-energy excitation. Here, we demonstrate a pronounced modulation of the X-ray excited photoluminescence of Tb(3+) centers upon excitation in proximity to the giant resonance of the host Gd(3+) ions in solid-solution Gd1-xTbxOCl nanocrystals prepared by a non-hydrolytic cross-coupling method. The strong suppression of X-ray excited optical luminescence at the giant resonance suggests a change in mechanism from multiple exciton generation to single thermal exciton formation and Auger decay processes. The solid-solution Gd1-xTbxOCl nanocrystals are further topotactically transformed with retention of a nine-coordinated cation environment to solid-solution Gd1-xTbxF3 nanocrystals upon solvothermal treatment with XeF2. The metastable hexagonal phase of GdF3 can be stabilized at room temperature through this topotactic approach and is transformed subsequently to the orthorhombic phase. The fluoride nanocrystals indicate an analogous but blue-shifted modulation of the X-ray excited optical luminescence of the Tb(3+) centers upon X-ray excitation near the giant resonance of the host Gd(3+) ions. PMID:26661920

  7. Effect of bexarotene on differentiation of glioblastoma multiforme compared with ATRA.

    PubMed

    Heo, Jin-Chul; Jung, Tae-Hoon; Lee, Sungjin; Kim, Hyun Young; Choi, Gildon; Jung, Myungeun; Jung, Daeyoung; Lee, Heung Kyoung; Lee, Jung-Ok; Park, Ji-Hwan; Hwang, Daehee; Seol, Ho Jun; Cho, Heeyeong

    2016-06-01

    Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor. Since differentiation can attenuate or halt the growth of tumor cells, an image-based phenotypic screening was performed to find out drugs inducing morphological differentiation of GBMs. Bexarotene, a selective retinoid X receptor agonist, showed strong inhibition of neurospheroidal colony formation and migration of cultured primary GBM cells. Bexarotene treatment reduced nestin expression, while significantly increasing glial fibrillary acidic protein (GFAP) expression. The effect of bexarotene on gene expression profile was compared with the activity of all-trans retinoic acid (ATRA), a well-known differentiation inducer. Both drugs largely altered the gene expression pattern into a tumor-ameliorating direction. These drugs increased the gene expression levels of Krüppel-like factor 9 (KLF9), regulator of G-protein signaling 4 (RGS4), growth differentiation factor 15 (GDF15), angiopoietin-like protein 4 (ANGPTL4), and lowered the level of chemokine receptor type 4 (CXCR4). However, transglutaminase 2 (TG2) induction, an adverse effect of ATRA, was much weaker in bexarotene treated primary GBM cells. Consistently, the TG2 enzymatic activity was negligibly affected by bexarotene treatment. It is important to control TG2 overexpression since its upregulation is correlated with tumor transformation and drug resistance. Bexarotene also showed in vivo tumoricidal effects in a GBM xenograft mouse model. Therefore, we suggest bexarotene as a more beneficial differentiation agent than ATRA for GBM. PMID:26957434

  8. Mouse Oocyte Control of Granulosa Cell Development and Function: Paracrine Regulation of Cumulus Cell Metabolism

    PubMed Central

    Su, You-Qiang; Sugiura, Koji; Eppig, John J.

    2009-01-01

    Bi-directional communication between oocytes and the companion granulosa cells is essential for the development and functions of both compartments. Oocytes are deficient in their ability to transport certain amino acids and in carrying out glycolysis and cholesterol biosynthesis, and require that cumulus cells provide them with the specific amino acids and the products in these metabolic pathways. Oocytes control metabolic activities in cumulus cells by promoting the expression of genes in cumulus cells encoding specific amino acid transporters and enzymes essential for the oocyte-deficient metabolic processes. Hence, oocytes outsource metabolic functions to cumulus cells to compensate for oocyte metabolic deficiencies. Oocyte control of granulosa cell metabolism may also participate in regulating the rate of follicular development in coordination with endocrine, paracrine and autocrine signals. Oocytes influence granulosa cell development mainly by secretion of paracrine factors although juxtacrine signals probably also participate. Key oocyte-derived paracine factors include growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) 15, and fibroblast growth factor 8B (FGF8B). PMID:19197803

  9. [Release of toxic agents from ceramic utensils].

    PubMed

    Herrmann, H J

    1978-01-01

    Under the influence of acidic agents, ceramic glazes and decorations for ceramics may release certain toxicants, especially lead and cadmium. Both elements are essential constituents of ceramic colours and glazes; their release to acidic foods is technologically unavoidable, but it may be minimized by the utilization of appropriate decoration agents and techniques. In most industrial countries, the release of toxicants from utensils is severely limited, the maximum permissible values and the methods of test and analysis being in part very different and not always in agreement with the demands and conditions of practice. The problems related to the release of toxicants from ceramic utensils are treated from the aspects of ceramics, test techniques, analytics, toxicology and food law, with special regard to the necessity for a well-balanced compromise between the justified hygienic demands of health protection and the actual technological possibi