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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. 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.

  6. 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

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... certificated under the system prescribed in 35 CFR part 135. (b) All vessels intending to transit the Suez... 46 Shipping 2 2010-10-01 2010-10-01 false Vessels transiting the Panama and Suez Canals. 69.7... MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS General § 69.7 Vessels transiting the Panama and Suez Canals....

  8. 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

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

    PubMed Central

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

    2016-01-01

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

  10. 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

  11. Reduced Expression of GDF-15 Is Associated With Atrophic Inflammatory Lesions of the Prostate

    PubMed Central

    Lambert, James R.; Whitson, Ramon J.; Iczkowski, Kenneth A.; La Rosa, Francisco G.; Smith, Maxwell L.; Wilson, R. Storey; Smith, Elizabeth E.; Torkko, Kathleen C.; Gari, Hamid H.; Lucia, M. Scott

    2015-01-01

    BACKGROUND Accumulating evidence suggests that chronic prostatic inflammation may lead to prostate cancer development. Growth differentiation factor-15 (GDF-15) is highly expressed in the prostate and has been associated with inflammation and tumorigenesis. METHODS To examine the relationship between GDF-15 and prostatic inflammation, GDF-15 expression was measured by immunohistochemical (IHC) staining in human prostatectomy specimens containing inflammation. The relationship between GDF-15 and specific inflammatory cells was determined using non-biased computer image analysis. To provide insight into a potential suppressive role for GDF-15 in inflammation, activation of inflammatory mediator nuclear factor of kappa B (NFκB) was measured in PC3 cells. RESULTS GDF-15 expression in luminal epithelial cells was decreased with increasing inflammation severity, suggesting an inverse association between GDF-15 and inflammation. Quantification of IHC staining by image analysis for GDF-15 and inflammatory cell markers revealed an inverse correlation between GDF-15 and CD3+, CD4+, CD8+, CD68+, and inos+ leukocytes. GDF-15 suppressed NFκB activity in luciferase reporter assays. Expression of the NFκB target, interleukin 8 (IL-8), was downregulated by GDF-15. CONCLUSIONS The inverse relationship between GDF-15 and inflammation demonstrates a novel expression pattern for GDF-15 in the human prostate and suppression of NFκB activity may shed light on a potential mechanism for this inverse correlation. PMID:25327758

  12. 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.

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. Growth differentiation factor 9 (GDF9) stimulates proliferation and inhibits steroidogenesis by bovine theca cells: influence of follicle size on responses to GDF9.

    PubMed

    Spicer, Leon J; Aad, Pauline Y; Allen, Dustin T; Mazerbourg, Sabine; Payne, Anita H; Hsueh, Aaron J

    2008-02-01

    Ovarian follicular development is controlled by numerous paracrine and endocrine regulators, including oocyte-derived growth differentiation factor 9 (GDF9), and a localized increase in bioavailable insulin-like growth factor 1 (IGF1). The effects of GDF9 on function of theca cells collected from small (3-6 mm) and large (8-22 mm) ovarian follicles were investigated. In small-follicle theca cells cultured in the presence of both LH and IGF1, GDF9 increased cell numbers and DNA synthesis, as measured by a (3)H-thymidine incorporation assay, and dose-dependently decreased both progesterone and androstenedione production. Theca cells from large follicles had little or no response to GDF9 in terms of cell proliferation or steroid production induced by IGF1. Small-follicle theca cell studies indicated that GDF9 decreased the abundance of LHR and CYP11A1 mRNA in theca cells, but had no effect on IGF1R, STAR, or CYP17A1 mRNA abundance or the percentage of cells staining for CYP17A1 proteins. GDF9 activated similar to mothers against decapentaplegics (SMAD) 2/3-induced CAGA promoter activity in transfected theca cells. Small-follicle theca cells had more ALK5 mRNA than large-follicle theca cells. Small-follicle granulosa cells appeared to have greater GDF9 mRNA abundance than large-follicle granulosa cells, but theca cells had no detectable GDF9 mRNA. We conclude that theca cells from small follicles are more responsive to GDF9 than those from large follicles and that GDF9 mRNA may be produced by granulosa cells in cattle. Because GDF9 increased theca cell proliferation and decreased theca cell steroidogenesis, oocyte- and granulosa cell-derived GDF9 may simultaneously promote theca cell proliferation and prevent premature differentiation of the theca interna during early follicle development.

  18. Expression of growth differentiation factor 9 (GDF9) and its receptor in adult cat testis.

    PubMed

    Zhao, Li; He, JunPing; Guo, QingYun; Wen, XueXue; Zhang, XueJing; Dong, ChangSheng

    2011-12-01

    Oocyte-secreted growth differentiation factor (GDF) 9 plays an essential role during follicle maturation through actions on granulosa cells. Despite its critical role in female reproduction, GDF9 expression, signalling and function are less well characterized during spermatogenesis. The purpose of this study was to investigate temporal and spatial expression and potential cellular targets of GDF9 in the adult cat testis. Our result confirmed that GDF9 is stage-specifically localized in the cytoplasm of round spermatids and pachytene spermatocytes of the cat seminiferous epithelium. In particular, activin receptor-like kinase (ALK) 5, the type I receptor of GDF9, is principally localized in the cytoplasm of round spermatids. Smad2/3, signal transducers for GDF9 signalling pathway, is mainly immunolocalized in the cytoplasm of germ cells, Sertoli cells and Leydig cells, but the expression in germ cells are weaker than in Sertoli cells. The expression pattern of ALK5 and Smad2/3 show that GDF9-ALK5-Smad2/3 may not be the only signalling pathway for testicular cell to respond to GDF9. Overall, our results demonstrate that GDF9 is a germ cell-specific factor in the adult cat testis, and that GDF9 regulates the tight junctions of Sertoli cells by paracrine secretion, and regulates the germ cells by autocrine secretion.

  19. Sea-level Variation Along the Suez Canal

    NASA Astrophysics Data System (ADS)

    Eid, F. M.; Sharaf El-Din, S. H.; Alam El-Din, K. A.

    1997-05-01

    The variation of sea level at 11 stations distributed along the Suez Canal was studied during the period from 1980 to 1986. The ranges of variation in daily mean sea level at Port Said and Port Tawfik are about 60 and 120 cm, respectively. The minimum range of daily variation is at Kantara (47 cm). The fluctuations of the monthly mean sea level between the two ends of the Suez Canal vary from one season to another. From July to December, the sea level at Port Said is higher than that at Port Tawfik, with the maximum difference (10·5 cm) in September. During the rest of the year, the mean sea level at Port Tawfik is higher than that at Port Said, with the maximum difference (31·5 cm) in March. The long-term variations of the annual mean sea level at both Port Said and Port Tawfik for the period from 1923 to 1986 showed a positive trend. The sea level at Port Said increased by about 27·8 cm century -1while it increased by only 9·1 cm century -1at Port Tawfik. This indicates that the difference between sea level at Port Said and Port Tawfik has decreased with time.

  20. Amino acid 72 of mouse and human GDF9 mature domain is responsible for altered homodimer bioactivities but has subtle effects on GDF9:BMP15 heterodimer activities.

    PubMed

    Peng, Jia; Wigglesworth, Karen; Rangarajan, Adithya; Eppig, John J; Thompson, Thomas B; Matzuk, Martin M

    2014-12-01

    Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-secreted paralogs of the transforming growth factor beta (TGFbeta) superfamily. In mammals, these two growth factors play critical roles in folliculogenesis. As previously reported, an arginine in the pre-helix loop of GDF5 defines the high binding specificity to its type 1 receptor. Interestingly, bioactive mouse GDF9 and human BMP15 share the conserved arginine in the pre-helix loop, but their low-activity counterparts (mouse BMP15 and human GDF9) have a glycine or a proline instead. To address the question of whether the arginine residue defines the different activities of GDF9 and BMP15 homodimers and their heterodimers in human and mouse, we used site-directed mutagenesis to change the species-specific residues in human and mouse proteins, and examined their activities in our in vitro assays. Although amino acid 72 of mature GDF9 is responsible for altered homodimer bioactivities, neither the corresponding BMP15 amino acid 62 nor the intact pre-helix loop is indispensable for BMP15 homodimer activity. However, amino acid 72 in GDF9 only has only subtle effects on GDF9:BMP15 heterodimer activity. Based on previous studies and our recent findings, we provide hypothetical models to understand the molecular mechanism to define activities of the homodimeric and heterodimeric ligands. The arginine residue in the pre-helix loop of GDF9 homodimer may prevent the inhibition from its pro-domain or directly alter receptor binding, but this residue in GDF9 does not significantly affect the heterodimer activity, because of suggested conformational changes during heterodimer formation.

  1. 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

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

    PubMed

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

    2016-01-01

    Growth differentiation factor 11 (GDF11) regulates cell growth and differentiation in both embryonic and adult tissues. Circulating GDF11 levels have recently been reported to be significantly lower in aging mice and restoration of GDF11 reversed age-related cardiac hypertrophy in old mice. Here, we evaluated the potential of serum levels of GDF11 as a circulating biomarker in dogs at different stages of heart failure, due to chronic mitral valve insufficiency (CMVI). We found no significant differences in serum GDF11 levels between dogs at different stages of CMVI-associated heart failure. Furthermore, the circulating levels of GDF11 did not correlate with age, body weight, echocardiographic variables, and the severity of CMVI-induced heart failure in dogs. PMID:26733738

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

    PubMed

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

    2016-04-01

    Growth differentiation factor 11 (GDF11) and myostatin (or GDF8) are closely related members of the transforming growth factor β superfamily and are often perceived to serve similar or overlapping roles. Yet, despite commonalities in protein sequence, receptor utilization and signaling, accumulating evidence suggests that these 2 ligands can have distinct functions in many situations. GDF11 is essential for mammalian development and has been suggested to regulate aging of multiple tissues, whereas myostatin is a well-described negative regulator of postnatal skeletal and cardiac muscle mass and modulates metabolic processes. In this review, we discuss the biochemical regulation of GDF11 and myostatin and their functions in the heart, skeletal muscle, and brain. We also highlight recent clinical findings with respect to a potential role for GDF11 and/or myostatin in humans with heart disease. Finally, we address key outstanding questions related to GDF11 and myostatin dynamics and signaling during development, growth, and aging. PMID:27034275

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

    PubMed

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

    2016-01-01

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

  5. The proregion of mouse BMP15 regulates the cooperative interactions of BMP15 and GDF9.

    PubMed

    McIntosh, C Joy; Lun, Stan; Lawrence, Steve; Western, Andrea H; McNatty, Kenneth P; Juengel, Jennifer L

    2008-11-01

    Bone morphogenetic protein 15 (BMP15) and growth and differentiation factor 9 (GDF9) are secreted by the mammalian oocyte and are essential for ovarian follicular development, ovulation, and fertility. However, the secreted forms of the BMP15 and GDF9 proteins and the nature of cooperative molecular interactions between BMP15 and GDF9 previously reported have not been fully characterized. In this study, we found that recombinant mouse BMP15 and GDF9 are secreted as cleaved mature and proregion proteins, with BMP15 also secreted as uncleaved promature protein. Noncovalent interactions were identified between the mature and proregion proteins of each growth factor. Moreover, GDF9 mature protein was found to coimmunoprecipitate with the BMP15 proregion, suggestive of a heteromeric association between BMP15 and GDF9. Mouse GDF9 was found to exist mostly as a dimer of mature protein, in both the presence and absence of BMP15. In contrast, BMP15 formed mostly multimers of proregion and mature protein when combined with GDF9, providing further evidence for heteromeric interaction. Mouse BMP15 was found to act cooperatively with GDF9 in a rat granulosa cell thymidine incorporation bioassay and to signal through the BMPR2 and ACVR1B/TGFBR1/ACVR1C receptor-mediated pathways. Immunoneutralization experiments using GDF9 mature protein antibody indicated that these cooperative interactions are species specific. Additionally, immunoneutralization with proregion antibodies highlighted the involvement of the BMP15 proregion in BMP15/GDF9 cooperative interactions. Taken together, these findings support a novel hypothesis where the extracellular cooperative interactions of recombinant mouse BMP15 and GDF9 are multimeric, involving the proregion of BMP15, and may well be species specific.

  6. Biogenic Films at the Mouth of the Suez Canal

    NASA Technical Reports Server (NTRS)

    2002-01-01

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

  7. 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.

  8. 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.

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

    PubMed Central

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

    2016-01-01

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

  10. Elevated GDF11 Is a Risk Factor for Age-Related Frailty and Disease in Humans.

    PubMed

    Glass, David J

    2016-07-12

    GDF11 was reported to decline with age and to have muscle and heart rejuvenating effects. These reports were disputed. A Cell Metabolism paper now shows that in human beings, GDF11 does not decline with age and is actually a risk factor for frailty and other morbidities (Schafer et al., 2016). PMID:27411004

  11. 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.

  12. 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

  13. Activation of latent human GDF9 by a single residue change (Gly 391 Arg) in the mature domain.

    PubMed

    Simpson, Courtney M; Stanton, Peter G; Walton, Kelly L; Chan, Karen L; Ritter, Lesley J; Gilchrist, Robert B; Harrison, Craig A

    2012-03-01

    Growth differentiation factor 9 (GDF9) controls granulosa cell growth and differentiation during early ovarian folliculogenesis and regulates cumulus cell function and ovulation rate in the later stages of this process. Similar to other TGF-β superfamily ligands, GDF9 is secreted from the oocyte in a noncovalent complex with its prodomain. In this study, we show that prodomain interactions differentially regulate the activity of GDF9 across species, such that murine (m) GDF9 is secreted in an active form, whereas human (h) GDF9 is latent. To understand this distinction, we used site-directed mutagenesis to introduce nonconserved mGDF9 residues into the pro- and mature domains of hGDF9. Activity-based screens of the resultant mutants indicated that a single mature domain residue (Gly(391)) confers latency to hGDF9. Gly(391) forms part of the type I receptor binding site on hGDF9, and this residue is present in all species except mouse, rat, hamster, galago, and possum, in which it is substituted with an arginine. In an adrenocortical cell luciferase assay, hGDF9 (Gly(391)Arg) had similar activity to mGDF9 (EC(50) 55 ng/ml vs. 28 ng/ml, respectively), whereas wild-type hGDF9 was inactive. hGDF9 (Gly(391)Arg) was also a potent stimulator of murine granulosa cell proliferation (EC(50) 52 ng/ml). An arginine at position 391 increases the affinity of GDF9 for its signaling receptors, enabling it to be secreted in an active form. This important species difference in the activation status of GDF9 may contribute to the variation observed in follicular development, ovulation rate, and fecundity between mammals.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. Bioactivity and prognostic significance of growth differentiation factor GDF15 secreted by bone marrow mesenchymal stem cells in multiple myeloma.

    PubMed

    Corre, Jill; Labat, Elodie; Espagnolle, Nicolas; Hébraud, Benjamin; Avet-Loiseau, Hervé; Roussel, Murielle; Huynh, Anne; Gadelorge, Mélanie; Cordelier, Pierre; Klein, Bernard; Moreau, Philippe; Facon, Thierry; Fournié, Jean-Jacques; Attal, Michel; Bourin, Philippe

    2012-03-15

    Overexpression of growth differentiation factor 15 (GDF15) by bone marrow mesenchymal stem cells occurs widely in patients with multiple myeloma, but the pathophysiologic effects of GDF15 in this setting remain undefined. GDF15 has been described in numerous solid tumors but never in hematologic malignancies. In this study, we report that GDF15 significantly increases survival of stroma-dependent multiple myeloma cells including primary multiple myeloma cells. In particular, GDF15 conferred resistance to melphalan, bortezomib, and to a lesser extent, lenalidomide in both stroma-dependent and stroma-independent multiple myeloma cells. Akt-dependent signaling was critical to mediate the effects of GDF15, whereas Src and extracellular signal-regulated kinase 1/2 signaling pathways were not involved. Given these results, we tested the clinical significance of plasma concentrations of GDF15 (pGDF15) in 131 patients with multiple myeloma and found that it correlated with disease prognosis. Specifically, patients with high levels of pGDF15 had lower probabilities of event-free and overall survival 30 months after diagnosis than patients with low pGDF15 levels. Our findings suggest that tumor microenvironment-derived GDF15 is a key survival and chemoprotective factor for multiple myeloma cells, which is pathophysiologically linked to both initial parameters of the disease as well as patient survival.

  19. 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

  20. 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

  1. GDF-15 and Hepcidin Levels in Nonanemic Patients with Impaired Glucose Tolerance

    PubMed Central

    Altinova, Alev Eroglu; Akturk, Mujde; Gulbahar, Ozlem; Arslan, Emre; Ors Sendogan, Damla; Yetkin, Ilhan; Toruner, Fusun Balos

    2016-01-01

    Aims. Growth Differentiation Factor-15 (GDF-15) has been suggested as one of the regulators of hepcidin, an important regulatory peptide for iron deposition. Current data is conflicting about the relationship between hepcidin and disorders of glucose metabolism. We aimed to investigate serum hepcidin and GDF-15 concentrations and their associations with each other, in nonanemic subjects with impaired glucose tolerance (IGT) in comparison with the nonanemic subjects with normal glucose tolerance (NGT). Methods. Thirty-seven subjects with IGT and 32 control subjects with NGT, who were age-, gender-, and body mass index- (BMI-) matched, were included in the study. Results. Serum GDF-15 levels were significantly higher in IGT compared to NGT. There were no differences in hepcidin, interleukin-6, and high sensitive C-reactive protein levels between the groups. We found a positive correlation between GDF-15 and hepcidin levels. There were also positive correlations between GDF-15 and age, uric acid, creatinine, and area under the curve for glucose (AUC-G). Hepcidin was correlated positively with ferritin levels. In the multiple regression analysis, GDF-15 concentrations were independently associated with age, uric acid, and AUC-G. Conclusions. Impaired glucose tolerance is associated with increased GDF-15 levels even in the absence of anemia, but the levels of hepcidin are not significantly altered in prediabetic state.

  2. 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

  3. 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

  4. GDF-15 and Hepcidin Levels in Nonanemic Patients with Impaired Glucose Tolerance

    PubMed Central

    Altinova, Alev Eroglu; Akturk, Mujde; Gulbahar, Ozlem; Arslan, Emre; Ors Sendogan, Damla; Yetkin, Ilhan; Toruner, Fusun Balos

    2016-01-01

    Aims. Growth Differentiation Factor-15 (GDF-15) has been suggested as one of the regulators of hepcidin, an important regulatory peptide for iron deposition. Current data is conflicting about the relationship between hepcidin and disorders of glucose metabolism. We aimed to investigate serum hepcidin and GDF-15 concentrations and their associations with each other, in nonanemic subjects with impaired glucose tolerance (IGT) in comparison with the nonanemic subjects with normal glucose tolerance (NGT). Methods. Thirty-seven subjects with IGT and 32 control subjects with NGT, who were age-, gender-, and body mass index- (BMI-) matched, were included in the study. Results. Serum GDF-15 levels were significantly higher in IGT compared to NGT. There were no differences in hepcidin, interleukin-6, and high sensitive C-reactive protein levels between the groups. We found a positive correlation between GDF-15 and hepcidin levels. There were also positive correlations between GDF-15 and age, uric acid, creatinine, and area under the curve for glucose (AUC-G). Hepcidin was correlated positively with ferritin levels. In the multiple regression analysis, GDF-15 concentrations were independently associated with age, uric acid, and AUC-G. Conclusions. Impaired glucose tolerance is associated with increased GDF-15 levels even in the absence of anemia, but the levels of hepcidin are not significantly altered in prediabetic state. PMID:27642607

  5. A deletion mutation in GDF9 in sisters with spontaneous DZ twins.

    PubMed

    Montgomery, Grant W; Zhao, Zhen Zhen; Marsh, Anna J; Mayne, Renee; Treloar, Susan A; James, Michael; Martin, Nicholas G; Boomsma, Dorret I; Duffy, David L

    2004-12-01

    A loss of function mutation in growth differentiation factor 9 (GDF9) in sheep causes increased ovulation rate and infertility in a dosage-sensitive manner. Spontaneous dizygotic (DZ) twinning in the human is under genetic control and women with a history of DZ twinning have an increased incidence of multiple follicle growth and multiple ovulation. We sequenced the GDF9 coding region in DNA samples from 20 women with DZ twins and identified a four-base pair deletion in GDF9 in two sisters with twins from one family. We screened a further 429 families and did not find the loss of function mutation in any other families. We genotyped eight single nucleotide polymorphisms across the GDF9 locus in 379 families with two sisters who have both given birth to spontaneous DZ twins (1527 individuals) and 226 triad families with mothers of twins and their parents (723 individuals). Using case control analysis and the transmission disequilibrium test we found no evidence for association between common variants in GDF9 and twinning in the families. We conclude that rare mutations in GDF9 may influence twinning, but twinning frequency is not associated with common variation in GDF9.

  6. 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

  7. 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

  8. Human Adaptive Evolution at Myostatin (GDF8), a Regulator of Muscle Growth

    PubMed Central

    Saunders, Matthew A. ; Good, Jeffrey M. ; Lawrence, Elizabeth C. ; Ferrell, Robert E. ; Li, Wen-Hsiung ; Nachman, Michael W. 

    2006-01-01

    Myostatin (GDF8) is a negative regulator of muscle growth in mammals, and loss-of-function mutations are associated with increased skeletal-muscle mass in mice, cattle, and humans. Here, we show that positive natural selection has acted on human nucleotide variation at GDF8, since the observed ratio of nonsynonymous:synonymous changes among humans is significantly greater than expected under the neutral model and is strikingly different from patterns observed across mammalian orders. Furthermore, extended haplotypes around GDF8 suggest that two amino acid variants have been subject to recent positive selection. Both mutations are rare among non-Africans yet are at frequencies of up to 31% in sub-Saharan Africans. These signatures of selection at the molecular level suggest that human variation at GDF8 is associated with functional differences. PMID:17186467

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

    PubMed Central

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

    2016-01-01

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

  10. GDF9 modulates the reproductive and tumor phenotype of female inha-null mice.

    PubMed

    Myers, Michelle; Mansouri-Attia, Nadera; James, Rebecca; Peng, Jia; Pangas, Stephanie A

    2013-04-01

    Intraovarian factors play important roles in coordinating germ cell and somatic cell growth in the ovary. Prior to the onset of gonadotropin stimulation and reproductive cyclicity, follicle development is dependent upon locally produced growth factors, such as the transforming growth factor beta family members inhibin, activin, and GDF9. In the absence of inhibin in prepubertal mice (Inha(-/-)), there are marked alterations in preantral follicle growth, but no evidence of ovarian tumors characteristic of adult Inha-null mice. To ascertain the contribution of GDF9 to the Inha-null phenotype, we analyzed folliculogenesis in postnatal Inha Gdf9 double knockout mice. Deletion of Gdf9 from Inha(-/-) rescues the initial growth defects found at early follicle stages in Inha(-/-) ovaries, but surprisingly enhances the onset of pretumor lesions. The normalization of growth dynamics between granulosa cells and oocytes of Inha Gdf9 double knockout mice is also accompanied by a reduction in levels of the activin/inhibin beta B subunit, Inhbb, which is upregulated in Inha(-/-) ovaries. However, at later ages, Inha Gdf9 double knockout ovaries are similar to Inha(-/-) ovaries, and show upregulation of the activin/inhibin subunits and downregulation of the growth factor, kit ligand, thus resulting in a local environment that is growth-promoting for granulosa cells but growth-inhibitory for oocytes. These data suggest a sequential mechanism of action initiated by GDF9 in the Inha knockout mouse that promotes defective folliculogenesis. These studies thus provide a novel role for GDF9 in causing reproductive defects and suppressing tumor initiation in the Inha(-/-) mouse model.

  11. 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

  12. GDF9 as a candidate gene for prolificacy of Small Tail Han sheep.

    PubMed

    Chu, M X; Yang, J; Feng, T; Cao, G L; Fang, L; Di, R; Huang, D W; Tang, Q Q; Ma, Y H; Li, K; Li, N

    2011-11-01

    Growth differentiation factor 9 (GDF9) which controls the fecundity of Belclare, Cambridge, Santa Ines, Moghani, Ghezel and Thoka ewes was studied as a candidate gene for the prolificacy of Small Tail Han sheep. According to the sequence of ovine GDF9 gene, six pairs of primers were designed to detect single nucleotide polymorphisms of two exons of GDF9 gene in both high fecundity breed (Small Tail Han sheep) and low fecundity breed (Dorset sheep) by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Only the products amplified by primers 2-1 and 2-2 displayed polymorphisms. For primer 2-1, three genotypes (AA, AB and BB) were detected in both sheep breeds. Sequencing revealed one silent mutation (G477A) in exon 2 of GDF9 gene in the BB genotype in comparison with the AA, which was known as G3 mutation of GDF9 gene in Belclare and Cambridge ewes. The relationship of least squares means for litter size was AA > AB > BB in Small Tail Han sheep (P > 0.05). For primer 2-2, two genotypes (CC and CD) were detected in both sheep breeds. Sequencing revealed one novel single nucleotide mutation (G729T) in exon 2 of GDF9 gene in the CD genotype in comparison with the CC, which resulted in an amino acid change (Gln243His). The ewes with mutation heterozygous genotype CD had 0.77 (P < 0.01) lambs more than those with wild type CC in Small Tail Han sheep. These results preliminarily indicated that allele D of GDF9 gene was a potential genetic marker for improving litter size in Small Tail Han sheep.

  13. 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.

  14. Mouse GDF9 decreases KITL gene expression in human granulosa cells.

    PubMed

    Tuck, Astrud R; Mottershead, David G; Fernandes, Herman A; Norman, Robert J; Tilley, Wayne D; Robker, Rebecca L; Hickey, Theresa E

    2015-03-01

    Kit ligand (KITL) is an important granulosa cell-derived growth factor in ovarian folliculogenesis, but its expression and function in human granulosa cells are currently poorly understood. Based on studies performed in animal models, it was hypothesised that KITL gene expression in human granulosa cells is regulated by androgens and/or growth differentiation factor 9 (GDF9). We utilised two models of human granulosa cells, the KGN granulosa tumour cell line and cumulus granulosa cells obtained from preovulatory follicles of women undergoing assisted reproduction. Cells were treated with combinations of 5α-dihydrotestosterone (DHT), recombinant mouse GDF9, and the ALK4/5/7 inhibitor SB431542. KITL mRNA levels were measured by quantitative real-time PCR. No change in KITL mRNA expression was observed after DHT treatment under any experimental conditions, but GDF9 treatment resulted in a significant decrease in KITL mRNA levels in both KGN and cumulus cells. The effect of GDF9 was abolished by the addition of SB431542. These results indicate that KITL is not directly regulated by androgen signalling in human granulosa cells. Moreover, this study provides the first evidence that GDF9 negatively regulates KITL gene expression in human granulosa cells providing new information on the regulation of these important growth factors in the human ovary.

  15. Identification of novel missense mutations of GDF9 in Chinese women with polycystic ovary syndrome.

    PubMed

    Wang, Binbin; Zhou, Sirui; Wang, Jing; Liu, Jingjing; Ni, Feng; Yan, Jinting; Mu, Yuan; Cao, Yunxia; Ma, Xu

    2010-09-01

    The gene for growth differentiation factor 9 (GDF9) is expressed in human oocytes and has an important function in regulating early follicle growth and fertility. Polycystic ovary syndrome (PCOS) is one of the common defects that causes ovary dysfunction and is linked to aberrant processes in folliculogenesis. Previous studies have discovered several mutations in the screening of GDF9 in premature ovarian failure but none in PCOS. This current study focused on the mutational analysis of the coding region of GDF9 among 216 Chinese PCOS patients. Of the 10 different variants found in this study, five novel missense mutations in GDF9 were discovered namely c.15C>G, c.118T>G, c.133A>G, c.1025A>T and c.1275C>A. The above-mentioned mutations indicate GDF9 may be potentially associated with PCOS patients. As far as is known, this study is the first to provide evidence for such an association.

  16. 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

  17. 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

  18. The Role and Regulation of Gdf11 in Smad2 Activation During Tailbud Formation in The Xenopus Embryo

    PubMed Central

    Ho, Diana M.; Yeo, Chang-Yeol; Whitman, Malcolm

    2013-01-01

    A key role for phosphorylation of Smad2 by TGFß superfamily ligands in the axial patterning of early embryos is well established. The regulation and role of Smad2 signaling in post-neurula embryonic patterning, however, is less well understood. While a variety of TGFß superfamily ligands are implicated in various stages of anterior-posterior patterning, the ligand GDF11 has been shown to have a particular role in post-gastrula patterning in the mouse. Mouse GDF11 is specifically localized to the developing tail and is essential for normal posterior axial patterning. Mature GDF11 ligand is inhibited by its own prodomain, and extracellular proteolysis of this prodomain is thought to be necessary for GDF11 activity. The contribution of this proteolytic regulatory mechanism to Smad activation during embryogenesis in vivo, and to the development of posterior pattern, has not been characterized. We investigate here the role of Xenopus GDF11 in the activation of Smad2 during the development of tailbud stage embryos, and the role of this activation in larval development. We also demonstrate that the activity of BMP-1/Tolloid -like proteases is necessary for the normal GDF11-dependent activation of Smad2 phosphorylation during post-gastrula development. These data demonstrate that GDF11 has a central role in the activation of Smad2 phosphorylation in tailbud stage Xenopus embryos, and provide the first evidence that BMP-1/Tolloid-mediated prodomain cleavage is important for activation of GDF11 in vivo. PMID:20807570

  19. 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

  20. 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

  1. 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

  2. Amino Acid 72 of Mouse and Human GDF9 Mature Domain Is Responsible for Altered Homodimer Bioactivities but Has Subtle Effects on GDF9:BMP15 Heterodimer Activities1

    PubMed Central

    Peng, Jia; Wigglesworth, Karen; Rangarajan, Adithya; Eppig, John J.; Thompson, Thomas B.; Matzuk, Martin M.

    2014-01-01

    ABSTRACT Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-secreted paralogs of the transforming growth factor beta (TGFbeta) superfamily. In mammals, these two growth factors play critical roles in folliculogenesis. As previously reported, an arginine in the pre-helix loop of GDF5 defines the high binding specificity to its type 1 receptor. Interestingly, bioactive mouse GDF9 and human BMP15 share the conserved arginine in the pre-helix loop, but their low-activity counterparts (mouse BMP15 and human GDF9) have a glycine or a proline instead. To address the question of whether the arginine residue defines the different activities of GDF9 and BMP15 homodimers and their heterodimers in human and mouse, we used site-directed mutagenesis to change the species-specific residues in human and mouse proteins, and examined their activities in our in vitro assays. Although amino acid 72 of mature GDF9 is responsible for altered homodimer bioactivities, neither the corresponding BMP15 amino acid 62 nor the intact pre-helix loop is indispensable for BMP15 homodimer activity. However, amino acid 72 in GDF9 only has only subtle effects on GDF9:BMP15 heterodimer activity. Based on previous studies and our recent findings, we provide hypothetical models to understand the molecular mechanism to define activities of the homodimeric and heterodimeric ligands. The arginine residue in the pre-helix loop of GDF9 homodimer may prevent the inhibition from its pro-domain or directly alter receptor binding, but this residue in GDF9 does not significantly affect the heterodimer activity, because of suggested conformational changes during heterodimer formation. PMID:25253739

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

    SciTech Connect

    Perry, S.K.; Schamel, S.

    1985-01-01

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

  4. Signalling pathways mediating specific synergistic interactions between GDF9 and BMP15.

    PubMed

    Mottershead, David G; Ritter, Lesley J; Gilchrist, Robert B

    2012-03-01

    Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are two proteins selectively expressed in the oocyte which are essential for normal fertility. Both of these proteins are members of the transforming growth factor beta (TGF-β) superfamily and as such are produced as pre-proproteins, existing after proteolytic processing as a complex of the respective pro and mature regions. Previous work has shown that these two proteins interact both at the genetic and cellular signalling levels. In this study, our aim was to determine if the purified mature regions of GDF9 and BMP15 exhibit synergistic interactions on granulosa cells and to determine if such interactions are specific to these two proteins. We have used primary cultures of murine granulosa cells and [(3)H]-thymidine incorporation or transcriptional reporter assays as our readouts. We observed clear synergistic interactions between the mature regions of GDF9 and BMP15 when either DNA synthesis or SMAD3 signalling were examined. GDF9/BMP15 synergistic interactions were specific such that neither factor could be replaced by an analogous TGF-β superfamily member. The GDF9/BMP15 synergistic signalling response was inhibited by the SMAD2/3 phosphorylation inhibitor SB431542, as well as inhibition of the mitogen-activated protein kinase or rous sarcoma oncogene (SRC) signalling pathways, but not the nuclear factor kappa B pathway. In this study, we show that purified mature regions of GDF9 and BMP15 synergistically interact in a specific manner which is not dependent on the presence of a pro-region. This synergistic interaction is targeted at the SMAD3 pathway, and is dependent on ERK1/2 and SRC kinase signalling.

  5. Importance of the GDF9 signaling pathway on cumulus cell expansion and oocyte competency in sheep.

    PubMed

    Varnosfaderani, Sh Rouhollahi; Ostadhosseini, S; Hajian, M; Hosseini, S M; Khashouei, E Asadi; Abbasi, H; Hosseinnia, P; Nasr-Esfahani, M H

    2013-09-15

    Acquisition of developmental competency in cumulus oocyte complexes (COCs) is derived from endocrine hormones and oocyte secreted factors. The contribution of these factors in oocyte maturation and development is an active area of research. The objective of this research was to investigate whether growth differentiation factor 9 (GDF9) that is secreted by oocyte affects cumulus expansion and oocyte development in sheep. Immature ovine COCs were cultured in the presence of recombinant human GDF9 (rhGDF9), denuded oocytes, SB-431542, a specific inhibitor of activin-like kinase 4/5/7; or a combination of these factors. Routine in vitro maturation of COCs and denuded oocytes were used as external control samples. Cultured COCs were used for assessment of (1) cumulus expansion; (2) expression of cumulus-related transcripts including pentraxin 3, hyaluronan synthase 2 (HAS2), tumor necrosis factor alpha-induced protein 6, prostaglandin synthase 2, B-cell lymphoma 2 (BCL2), and Bcl2-associated X (BAX); and (3) yield and quality of embryo development. It was observed that cumulus expansion was not affected by any of these treatments. HAS2 mRNA expression confirmed this observation. In the presence of exogenous GDF9, cleavage rate was reduced, blastocyst rate did not differ from other groups, and trophectoderm cell number significantly increased. This suggests that exogenous GDF9 could improve embryo quality. It was also observed that oocyte secreted factors reduced proapoptotic BAX mRNA, and BCL2 mRNA expression was not significantly different from other groups. This study provides evidence that GDF9 signaling might have a minor influence on ovine cumulus expansion and oocyte development and that other signaling pathway(s) might have a dominant role.

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

    PubMed Central

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

    2015-01-01

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

  7. 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

  8. 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.

  9. GCNF-dependent repression of BMP-15 and GDF-9 mediates gamete regulation of female fertility

    PubMed Central

    Lan, Zi-Jian; Gu, Peili; Xu, Xueping; Jackson, Kathy J.; DeMayo, Francesco J.; O’Malley, Bert W.; Cooney, Austin J.

    2003-01-01

    To determine the function of germ cell nuclear factor (GCNF) in female reproduction, we generated an oocyte-specific GCNF knockout mouse model (GCNFfl/flZp3Cre+). These mice displayed hypofertility due to prolonged diestrus phase of the estrous cycle and aberrant steroidogenesis. These reproductive defects were secondary to a primary defect in the oocytes, in which expression of the paracrine transforming growth factor-β signaling molecules, bone morphogenetic protein 15 (BMP-15) and growth differentiation factor 9 (GDF-9), were up-regulated in GCNFfl/flZp3Cre+ females at diestrus. This was a direct effect of GCNF, as molecular studies showed that GCNF bound to DR0 elements within the BMP-15 and GDF-9 gene promoters and repressed their reporter activities. Consistent with these findings, abnormal double-oocyte follicles, indicative of aberrant BMP-15/GDF-9 expression, were observed in GCNFfl/flZp3Cre+ females. The Cre/loxP knockout of GCNF in the oocyte has uncovered a new regulatory pathway in ovarian function. Our results show that GCNF directly regulates paracrine communication between the oocyte and somatic cells by regulating the expression of BMP-15 and GDF-9, to affect female fertility. PMID:12912906

  10. Expression of growth differentiation factor 9 (GDF9), ALK5, and claudin-11 in adult alpaca testis.

    PubMed

    Guo, Qing Yun; Gao, Zhen Zhen; Zhao, Li; He, Jun Ping; Dong, Cheng Sheng

    2013-01-01

    Growth differentiation factor 9 (GDF9) is an oocyte-derived factor critical for folliculogenesis. Recently, in vitro data showed that GDF9 inhibited the localization of tight junction (TJ) proteins, suggesting that GDF9 could potentially regulate spermatogenesis in vivo, via inhibition of Sertoli cell TJ function. The purpose of the present study was to determine the expression and localization of GDF9, its receptor, ALK5, and its latent target protein, claudin-11 (one of TJ proteins) in adult alpaca testis using Western blot and immunohistochemistry. Western blotting results demonstrated that GDF9, ALK5 and claudin-11 were expressed in the adult alpaca testis. Immunohistochemistry revealed that GDF9 was expressed stage-specifically in the cytoplasm of pachytene spermatocytes and round spermatids of the adult alpaca seminiferous epithelium. Type I receptor, ALK5 was mainly localized in the cytoplasm of round spermatids and Leydig cells, and to a lesser extent in the cytoplasm of pachytene spermatocytes and Sertoli cells. Its latent target protein, claudin-11, was perpendicular or parallel to the basal lamina in the basal part of Sertoli cells. These results indicated that GDF9, as a paracrine and autocrine growth factor derived from round spermatids and pachytene spermatocytes, is involved in regulating spermatogenesis via action on germ cells or somatic cells (i.e. Leydig cells, Sertoli cells).

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

    PubMed

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

    2009-11-01

    Biovariability, reference change values (RCV), and index of individuality (IOI) have not been previously described for NT-proANP or GDF15. Also, the relation of changes of these markers to other clinical variables or biomarkers is unknown. In 41 patients with stable chronic systolic dysfunction, NT-proANP and GDF15 were measured alongside with clinical variables/markers comprising NT-proBNP, hsTnT, and hsCRP at four sampling intervals (2 weeks, 1-, 2-, 3-month intervals). At 2 weeks, 1-, 2-, and 3-month-follow-up, individual NT-proANP variations were 27.1, 22.5, 28.9, 15.6%, respectively, corresponding to RCVs of 53.2, 62.4, 80.2, and 43.2%, respectively. For GDF15, the respective individual variations were 6.8, 4.1, 5.5, 6.8%, corresponding to RCVs of 18.8, 11.5, 15.3 and 18.8%. Neither changes of NT-proANP or GDF15 correlated with changes in any of the clinical variables or biomarkers examined except for GDF15 with renal function. Baseline hormonal levels and clinical variables did not consistently influence the extent of change. The IOI was 0.19-0.35 according to interval for NT-proANP and 0.06-0.09 for GDF 15. In patients with CHF preselected for clinical stability changes of NT-proANP at intermediate follow-up do not correlate with changes in other variables; changes of GDF15 inversely correlate with renal function. The extent of change in both markers is not related to baseline hormonal levels or other baseline variables. RCVs are high for NT-proANP and low for GDF15, while inter-individual variation is high in GDF15 and intermediate in NT-proANP. PMID:19352585

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

    PubMed

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

    2009-11-01

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

  13. 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

  14. 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.

  15. 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.

  16. Uplift and subsidence of the Suez rift: Constraints from fission-track analysis and sediment backstripping

    SciTech Connect

    Steckler, M.S.; Omar, G.I.; Buck, W.R. )

    1988-08-01

    The Gulf of Suez is a Neogene rift that has evolved as one arm of the Sinai triple junction. The basement uplifts flanking the rift are larger than can be explained by uniform lithospheric extension. The timing of the regional heating required by the uplift has important implications for hydrocarbon maturation for the Gulf of Suez and rifts in general. The local geology indicates that the uplift did not predate rifting. Therefore, a regional subsidence and two-dimensional backstripping of the rift sediments were undertaken in conjunction with fission track analyses of the basement uplift. The initial rift deposits (Nukhul Formation) indicate slow extension during the earliest Miocene. The extension rate increased at the beginning of the deposition of the Rudeis Formation at approximately 19 Ma as the Gulf of Suez entered its main phase of rifting. By the end of the deposition of the Kareem Formation (approximately 14-15 Ma), most of the Africa-Arabia separation had transferred to the Gulf of Aqaba-Dead Sea transform. In order to determine the onset of the rift flank uplift relative to the rift history, 55 apatite fission track analyses were performed on samples from the basement of the eastern desert, on the western side of the rift. Apatite fission tracks record the thermal history of the samples for temperatures up to 125{degree}c. Apparent ages range from 382 to 11 Ma representing samples that have undergone various degrees of track annealing. Track length distributions clearly show the fading of tracks acquired prior to uplift in more deeply buried samples and the accumulation of long unannealed tracks subsequent to unroofing. The pattern of the track length vs. age distribution indicates that major uplift began simultaneously with the main phase of rifting at 19-20 Ma.

  17. 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

  18. Tectono-stratigraphic development of the Neogene Gulf of Suez rift basin

    SciTech Connect

    Richardson, M.; Arthur, M.A. )

    1988-08-01

    Subsidence analysis (backstripping) was carried out on a series of wells from the Gulf of Suez and northern Red Sea region of Egypt in order to examine the interplay between tectonic events, basin subsidence, sedimentation, and sea level changes in a young, developing ocean basin and continental margin. Using constraints on chronostratigraphy and paleodepth from various sources combined with stratigraphic and structural information from industry wells and other geophysical sources, it has been possible to compile the data necessary to perform geohistory analyses throughout the region.

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

    PubMed

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

    2015-10-01

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

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

    SciTech Connect

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

    1988-08-01

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

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

    PubMed

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

    2012-09-01

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

  2. Growth differentiation factor 9 (GDF9) forms an incoherent feed-forward loop modulating follicle-stimulating hormone β-subunit (FSHβ) gene expression.

    PubMed

    Choi, Soon Gang; Wang, Qian; Jia, Jingjing; Pincas, Hanna; Turgeon, Judith L; Sealfon, Stuart C

    2014-06-01

    Gonadotropin-releasing hormone (GnRH) is secreted in brief pulses from the hypothalamus and regulates follicle-stimulating hormone β-subunit (FSHβ) gene expression in pituitary gonadotropes in a frequency-sensitive manner. The mechanisms underlying its preferential and paradoxical induction of FSHβ by low frequency GnRH pulses are incompletely understood. Here, we identify growth differentiation factor 9 (GDF9) as a GnRH-suppressed autocrine inducer of FSHβ gene expression. GDF9 gene transcription and expression were preferentially decreased by high frequency GnRH pulses. GnRH regulation of GDF9 was concentration-dependent and involved ERK and PKA. GDF9 knockdown or immunoneutralization reduced FSHβ mRNA expression. Conversely, exogenous GDF9 induced FSHβ expression in immortalized gonadotropes and in mouse primary pituitary cells. GDF9 exposure increased FSH secretion in rat primary pituitary cells. GDF9 induced Smad2/3 phosphorylation, which was impeded by ALK5 knockdown and by activin receptor-like kinase (ALK) receptor inhibitor SB-505124, which also suppressed FSHβ expression. Smad2/3 knockdown indicated that FSHβ induction by GDF9 involved Smad2 and Smad3. FSHβ mRNA induction by GDF9 and GnRH was synergistic. We hypothesized that GDF9 contributes to a regulatory loop that tunes the GnRH frequency-response characteristics of the FSHβ gene. To test this, we determined the effects of GDF9 knockdown on FSHβ induction at different GnRH pulse frequencies using a parallel perifusion system. Reduction of GDF9 shifted the characteristic pattern of GnRH pulse frequency sensitivity. These results identify GDF9 as contributing to an incoherent feed-forward loop, comprising both intracellular and secreted components, that regulates FSHβ expression in response to activation of cell surface GnRH receptors.

  3. 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

  4. Mid-clysmic event, Gulf of Suez rotational deformation associated with a deep crustal detachment fault

    SciTech Connect

    Vigano, P.L.; Patton, T.L. )

    1988-08-01

    Dip relationships at the boundaries of three stratigraphic packages (one prerift and two synrift) in the Gulf of Suez suggest that the early stages of structural development in the Gulf of Suez can be subdivided into two phases. Synrift sediments deposited in the first phase of deformation (prerotation units) demonstrate only minor angular discordance with the underlying pre-Miocene (prerift stratigraphy). Synrift sediments deposited in the second phase of deformation (rotation units) show marked angular discordance and onlapping relationships with underlying units. The authors propose that the prerotation units were deposited during a period of basin-wide, generally vertical subsidence which was accommodated by slip on numerous, oppositely dipping normal faults. As subsidence continued, faults with similar dip directions began to work in unison and dominate the deformation of portions of the rift, causing faults with other orientations to play a lesser role or to become inactive. Minor rotations occurred during this phase of deformation. The rotational phase of deformation initiated as major faults propagated downward to and merged with a major detachment surface at depth. As extension continued, rotation of large, fault-bound blocks along deep seated listric faults resulted in the exposure and erosion of both pre-Miocene and prerotation units along the updip segments of the blocks. Sediments deposited during the rotational phase of deformation transgressed the backs of these rotated blocks and were laid down in angular discordance with the underlying units.

  5. [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.

  6. 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.

  7. 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.

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

    SciTech Connect

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

    1988-01-01

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

  9. [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

  10. GDF9 Mutation Analyses in 100 Chinese Women with Premature Ovarian Failure (POF)

    PubMed Central

    Zhao, Han; Qin, Yingying; Kovanci, Ertug; Simpson, Joe Leigh; Rajkovic, Aleksandar; Chen, Zi-Jiang

    2009-01-01

    We screened growth differentiation factor 9 (GDF9) coding regions for mutations in a Chinese sample of 100 women with premature ovarian failure (POF) and discovered 4 novel SNPs: c.436C>T (p.Arg146Cys), c.588A>C (silent), c.712A>G (p.Thr238Ala) and c.1283G>C (p.Ser428Thr). Non-synonymous SNPs c.436C>T and c.1283G>C were also detected in the control population. The c.712A>G perturbation results in a missense mutation (p.Thr238Ala) and was not present in any of 96 controls. Substitution of the hydrophobic amino acid residue alanine for hydrophilic threonine may disrupt GDF9 function. PMID:17482612

  11. Molecular characterization of gdf9 and bmp15 genes in rare minnow Gobiocypris rarus and their expression upon bisphenol A exposure in adult females.

    PubMed

    Zhang, Yingying; Yuan, Cong; Qin, Fang; Hu, Guojun; Wang, Zaizhao

    2014-08-10

    Growth differentiation factor 9 (Gdf9) and bone morphogenetic protein 15 (Bmp15) are members of transforming growth factor β (TGFβ) superfamily that plays important roles in regulating ovarian functions. We cloned the cDNAs of gdf9 and bmp15 in rare minnow Gobiocypris rarus. The full length cDNAs of gdf9 and bmp15 were 1999 and 1721 bp, encoding 431 and 384 amino acids respectively. They both contained conserved TGFβ superfamily domain, with six conserved cysteine residues. Tissue distribution showed that both gdf9 and bmp15 are highly expressed in the G. rarus ovary. Following bisphenol A (BPA) treatment, ovarian transcripts of gdf9 and bmp15 together with the gonadosomatic index and the ovarian histology were altered. It suggests that the altered gdf9 and bmp15 expression may play roles in the weight gain and abnormal development of the ovary following BPA exposure.

  12. Polymorphisms of caprine GDF9 gene and their association with litter size in Jining Grey goats.

    PubMed

    Feng, T; Geng, C X; Lang, X Z; Chu, M X; Cao, G L; Di, R; Fang, L; Chen, H Q; Liu, X L; Li, N

    2011-11-01

    The exons 1, 2 and flanking region of growth differentiation factor 9 (GDF9) gene in five randomly selected does of Jining Grey, Boer and Liaoning Cashmere goats were amplified and analyzed. Thirteen nucleotide differences were identified in GDF9 gene between sheep (AF078545) and goats. Four SNPs (G3288A in intron 1, G423A, A959C [Gln320Pro] and G1189A [Val397Ile] in exon 2) were detected in four goat breeds with different prolificacy, in which G3288A was a new SNP in goats. The results showed that loci 3288, 423 and 1189 in Boer goats, loci 3288 and 423 in Guizhou White goats, loci 423 and 1189 in Liaoning Cashmere goats were all in complete linkage disequilibrium (D' = 1, r (2) = 1), respectively. In moderate (Boer goat) and low prolificacy (Liaoning Cashmere goat) breeds, linkage analysis indicated that there were more fervent linkage disequilibrium among loci 3288, 423 and 1189 than high prolificacy (Jining Grey and Guizhou White goats) breeds. For the 959 locus, the genotype distribution showed obvious difference between high prolificacy breeds and moderate or low prolificacy breeds (P < 0.05 or P < 0.01). The Jining Grey goat does with genotype CC or AC had 0.81 (P < 0.01) or 0.63 (P < 0.01) kids more than those with genotype AA, respectively. The present study preliminarily showed an association between allele C at 959 locus of GDF9 gene and high litter size in Jining Grey goats. These results provide further evidence that the GDF9 gene may be significantly correlated with high prolificacy in goats.

  13. Polymorphism of BMPR1B, BMP15 and GDF9 fecundity genes in prolific Garole sheep.

    PubMed

    Polley, Shamik; De, Sachinandan; Brahma, Biswajit; Mukherjee, Ayan; Vinesh, P V; Batabyal, Subhasis; Arora, Jaspreet Singh; Pan, Subhransu; Samanta, Ashis Kumar; Datta, Tirtha Kumar; Goswami, Surender Lal

    2010-06-01

    Mutation studies in different prolific sheep breeds have shown that the transforming growth factor beta super family ligands viz. the growth differentiation factor 9 (GDF9/FecG), bone morphogenetic protein 15 (BMP15/FecX) and associated type I receptors, bone morphogenetic protein receptor (BMPR1B/FecB), are major determinant of ovulation rate and consequent increase in litter size. The Garole sheep is a highly prolific sheep breed of India. Characterization of fecundity genes in these animals could substantially improvise the breeding programme in these animals as well as other sheep breeds of the region. The present study was therefore designed with the objective of polymorphism study of fecundity genes in these prolific microsheep. A total of 11 point mutations were detected by polymerase chain reaction (PCR)-based method. A competitive technique called tetra-primer amplification refractory mutation system-PCR was adapted to type a total of ten points of two ovine fecundity genes (GDF9 and BMP15). The FecB locus of the BMPR1B gene and G1 locus of GDF9 gene were found to be polymorphic. In FecB locus, two genotypes, wild type (FecB(+)) and mutant (FecBB), were detected with allele frequencies of 0.39 and 0.61, respectively. At G1 locus, two genotypes, mutant (A) and wild types (G) were detected with allele frequencies of 0.18 and 0.82, respectively. This study reports Garole sheep as the fourth sheep breed after Belclare/Cambridge, Lacaune and Small-tailed Han sheep, where coexisting polymorphism has been found in two different fecundity genes (BMPRIB and GDF9 genes).

  14. Mutations in GDF5 Reveal a Key Residue Mediating BMP Inhibition by NOGGIN

    PubMed Central

    König, Jana; Reissner, Carsten; Stricker, Sigmar; Kuss, Pia; Haupt, Julia; Renninger, Stephanie; Nickel, Joachim; Sebald, Walter; Groppe, Jay C.; Plöger, Frank; Pohl, Jens; Schmidt-von Kegler, Mareen; Walther, Maria; Gassner, Ingmar; Rusu, Cristina; Janecke, Andreas R.; Dathe, Katarina; Mundlos, Stefan

    2009-01-01

    Signaling output of bone morphogenetic proteins (BMPs) is determined by two sets of opposing interactions, one with heterotetrameric complexes of cell surface receptors, the other with secreted antagonists that act as ligand traps. We identified two mutations (N445K,T) in patients with multiple synostosis syndrome (SYM1) in the BMP–related ligand GDF5. Functional studies of both mutants in chicken micromass culture demonstrated a gain of function caused by a resistance to the BMP–inhibitor NOGGIN and an altered signaling effect. Residue N445, situated within overlapping receptor and antagonist interfaces, is highly conserved among the BMP family with the exception of BMP9 and BMP10, in which it is substituted with lysine. Like the mutant GDF5, both BMPs are insensitive to NOGGIN and show a high chondrogenic activity. Ectopic expression of BMP9 or the GDF5 mutants resulted in massive induction of cartilage in an in vivo chick model presumably by bypassing the feedback inhibition imposed by endogenous NOGGIN. Swapping residues at the mutation site alone was not sufficient to render Bmp9 NOG-sensitive; however, successive introduction of two additional substitutions imparted high to total sensitivity on customized variants of Bmp9. In conclusion, we show a new mechanism for abnormal joint development that interferes with a naturally occurring regulatory mechanism of BMP signaling. PMID:19956691

  15. Identification of point mutations in exon 2 of GDF9 gene in Kermani sheep.

    PubMed

    Khodabakhshzadeh, R; Mohammadabadi, M R; Esmailizadeh, A K; Moradi Shahrebabak, H; Bordbar, F; Ansari Namin, S

    2016-01-01

    Screening the fertile ewes from national herds to detect the major genes for prolificacy is an effective way to create the fertile flocks. Growth differentiation factor (GDF) 9 is a member of the transforming growth factor β superfamily that is essential for folliculogenesis and female fertility. The aim of this study was to detect single nucleotide polymorphisms (SNPs) in exon 2 of GDF9 gene in Kermani sheep breed using PCR-SSCP. Genomic DNA was extracted from whole blood of collected samples using salting-out method. Whole exon 2 of GDF9 gene was amplified (634 bp and 647 bp fragments) using designed specific primers. The single stranded conformation polymorphism (SSCP) patterns of PCR products were studied using electrophoresis on acrylamide gel and silver-nitrate staining method. Finally, 4 banding patterns for the first primer pair and 4 banding patterns for the second primer pair were obtained. Also, indices of population genetic per SNP were calculated using Gen Alex 6.41 software. The sequencing results showed the presence of 3 mutations (SNP) (443, 477 and 721 positions) in the studied population. PMID:27487501

  16. Identification of point mutations in exon 2 of GDF9 gene in Kermani sheep.

    PubMed

    Khodabakhshzadeh, R; Mohammadabadi, M R; Esmailizadeh, A K; Moradi Shahrebabak, H; Bordbar, F; Ansari Namin, S

    2016-01-01

    Screening the fertile ewes from national herds to detect the major genes for prolificacy is an effective way to create the fertile flocks. Growth differentiation factor (GDF) 9 is a member of the transforming growth factor β superfamily that is essential for folliculogenesis and female fertility. The aim of this study was to detect single nucleotide polymorphisms (SNPs) in exon 2 of GDF9 gene in Kermani sheep breed using PCR-SSCP. Genomic DNA was extracted from whole blood of collected samples using salting-out method. Whole exon 2 of GDF9 gene was amplified (634 bp and 647 bp fragments) using designed specific primers. The single stranded conformation polymorphism (SSCP) patterns of PCR products were studied using electrophoresis on acrylamide gel and silver-nitrate staining method. Finally, 4 banding patterns for the first primer pair and 4 banding patterns for the second primer pair were obtained. Also, indices of population genetic per SNP were calculated using Gen Alex 6.41 software. The sequencing results showed the presence of 3 mutations (SNP) (443, 477 and 721 positions) in the studied population.

  17. 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

  18. Active immunization against the proregions of GDF9 or BMP15 alters ovulation rate and litter size in mice.

    PubMed

    McIntosh, C Joy; Lawrence, Steve; Smith, Peter; Juengel, Jennifer L; McNatty, Kenneth P

    2012-02-01

    The transforming growth factor β (TGFB) superfamily proteins bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), are essential for mammalian fertility. Recent in vitro evidence suggests that the proregions of mouse BMP15 and GDF9 interact with their mature proteins after secretion. In this study, we have actively immunized mice against these proregions to test the potential in vivo roles on fertility. Mice were immunized with either N- or C-terminus proregion peptides of BMP15 or GDF9, or a full-length GDF9 proregion protein, each conjugated to keyhole limpet hemocyanin (KLH). For each immunization group, ovaries were collected from ten mice for histology after immunization, while a further 20 mice were allowed to breed and litter sizes were counted. To link the ovulation and fertility data of these two experimental end points, mice were joined during the time period identified by histology as being the ovulatory period resulting in to the corpora lutea (CL) counted. Antibody titers in sera increased throughout the study period, with no cross-reactivity observed between BMP15 and GDF9 sera and antigens. Compared with KLH controls, mice immunized with the N-terminus BMP15 proregion peptide had ovaries with fewer CL (P<0.05) and produced smaller litters (P<0.05). In contrast, mice immunized with the full-length GDF9 proregion not only had more CL (P<0.01) but also had significantly smaller litter sizes (P<0.01). None of the treatments affected the number of antral follicles per ovary. These findings are consistent with the hypothesis that the proregions of BMP15 and GDF9, after secretion by the oocyte, have physiologically important roles in regulating ovulation rate and litter size in mice.

  19. Gulf of Suez-Rift basin stratigraphy: an interplay of subsidence and Eustatic sea level

    SciTech Connect

    Richardson, M.; Arthur, M.A.

    1987-05-01

    The Gulf of Suez and Red Sea rift basin underwent a period of rapid subsidence from the early Miocene to the Pliocene during which time a thick (up to 4 km) series of marine evaporites accumulated within the basin. The evaporitic sequence interfingers with carbonates and clastics over structural highs within and along the margins of the basin. Evaporite deposition was also interrupted basin wide by short periods of normal marine sedimentation. Timing and paleo-oceanographic aspects of evaporite deposition within the rift is controversial. A change over of marine source waters within the basin from the Mediterranean Sea to an opening of the rift to the Indian Ocean occurred sometime between the earliest Messinian and earliest Pliocene. Preliminary data suggests that anhydrites from this evaporite sequence retain original Miocene sea water Sr/sup 87//Sr/sup 86/ values which can be compared to Neogene strontium isotope versus time curves in order to further constrain the age of the nonfossiliferous evaporite group. This, combined with currently accepted biostratigraphies for the normal marine strata, enable us to refine rift stratigraphy in order to examine basin subsidence, evaporite accumulation rates, and the correlation of rift tectonics, sedimentation, and associated paleo-oceanographic events. Initial fragmentation and subsidence propagated from the south to the north in the Gulf of Suez during the Aquitanian to Burdigalian (20-25 Ma), and mixed clastic, carbonate, and evaporitic sediments (Nukhul Formation) up to 700 m thick were deposited in isolated subbasins within the rift. This episode was followed by renewed uplift of the rift shoulders, rapid subsidence, and increased clastic influx (late Rudeis Formation) during the Burdigalian (ca. 20-17 Ma).

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

    SciTech Connect

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

    1987-05-01

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

  1. 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

  2. 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

  3. Kinetics of GDF9 expression in buffalo oocytes during in vitro maturation and their associated development ability.

    PubMed

    Jain, Tripti; Jain, Asit; Kumar, Parveen; Goswami, S L; De, S; Singh, Dheer; Datta, T K

    2012-09-15

    The capacity of fully grown oocytes to regulate their own microenvironment by secreted paracrine factors contribute to their developmental competence. In spite of growing evidence about the vital role of Growth Differentiation Factor 9 (GDF9) in determination of oocyte developmental competence, there is insufficient information about time dependent behavior of its expression during in vitro maturation (IVM) to have definite understanding about at what time point during IVM it plays most crucial role. The study reports the kinetics of GDF9 expression under four different IVM supplement conditions in buffalo oocytes and their concomitant development rate up to blastocyst. Oocytes matured under an ideal media condition with all supplements and those cultured with only FSH resulted in significantly higher cumulus expansion, nuclear maturation, cleavage and blastocyst rates. GDF9 expression at both mRNA and protein levels at different time points of IVM revealed that magnitude of mRNA abundance at 8h of IVM was most important towards imparting development competence to buffalo oocytes. Appearance of GDF9 protein in maturing oocytes was found asynchronous with mRNA appearance in the time course of IVM suggesting possible posttranscriptional regulation of this gene under dynamic oocyte cumulus cell communication process. Abundance of mature GDF9 protein at 16 h was most consistently related with all oocyte development parameters.

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

    PubMed Central

    Sullivan, Aideen M; O'Keeffe, Gerard W

    2005-01-01

    Growth/differentiation factor-5 (GDF5) is a member of the transforming growth factor-β 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

  5. 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.

  6. Differential expression of GDF-9 and BMP- 15 during follicular development in canine ovaries evaluated by flow cytometry.

    PubMed

    Fernandez, Tomas; Palomino, Jaime; Parraguez, Victor H; Peralta, Oscar A; De los Reyes, Monica

    2016-04-01

    Growth differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP-15) play important functions in follicular and oocyte development in many species. This study evaluated the dynamic expression of GDF-9 and BMP-15 in canine follicles cells using flow cytometry analysis. Follicular cells were removed from three sizes of antral follicles (small, medium and large) from ovaries of bitches throughout the estrus cycle. Cells were incubated with anti-human GDF-9 polyclonal and anti-mouse BMP-15 monoclonal antibodies. A size and complexity discriminatory gate was used for the cytometryc analysis in the initial dot plot and, additionally, a CD45 marker for leukocyte and propidium iodide (PI) were used for erythrocyte and debris discrimination. The evidence corroborated the presence of both proteins in canine follicle cells, but these proteins were not expressed equally during follicular development. The results analyzed by ANOVA showed that GDF-9 expression decreased (P<0.05) during follicular growth in anestrus and proestrous/estrous, but increased in diestrus (P<0.05). The expression levels of BMP-15 rose (P<0.05) from small to medium sizes in anestrous without changing at diestrus. Small antral follicles expressed the highest values of GDF-9 at anestrus while only BMP-15 showed higher value in small antral follicles at proestrous-estrus compared to diestrus and anestrus. Both proteins decreased in proestrous/estrous (P<0.05) with increasing follicle size, registering the lowest levels in large follicles. The flow cytometric assay was able to assess GDF-9 and BMP-15 expression in canine follicular cells, showing that these proteins were differentially expressed during follicular development, possibly related to the special features of canine reproduction.

  7. Differential expression of GDF-9 and BMP- 15 during follicular development in canine ovaries evaluated by flow cytometry.

    PubMed

    Fernandez, Tomas; Palomino, Jaime; Parraguez, Victor H; Peralta, Oscar A; De los Reyes, Monica

    2016-04-01

    Growth differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP-15) play important functions in follicular and oocyte development in many species. This study evaluated the dynamic expression of GDF-9 and BMP-15 in canine follicles cells using flow cytometry analysis. Follicular cells were removed from three sizes of antral follicles (small, medium and large) from ovaries of bitches throughout the estrus cycle. Cells were incubated with anti-human GDF-9 polyclonal and anti-mouse BMP-15 monoclonal antibodies. A size and complexity discriminatory gate was used for the cytometryc analysis in the initial dot plot and, additionally, a CD45 marker for leukocyte and propidium iodide (PI) were used for erythrocyte and debris discrimination. The evidence corroborated the presence of both proteins in canine follicle cells, but these proteins were not expressed equally during follicular development. The results analyzed by ANOVA showed that GDF-9 expression decreased (P<0.05) during follicular growth in anestrus and proestrous/estrous, but increased in diestrus (P<0.05). The expression levels of BMP-15 rose (P<0.05) from small to medium sizes in anestrous without changing at diestrus. Small antral follicles expressed the highest values of GDF-9 at anestrus while only BMP-15 showed higher value in small antral follicles at proestrous-estrus compared to diestrus and anestrus. Both proteins decreased in proestrous/estrous (P<0.05) with increasing follicle size, registering the lowest levels in large follicles. The flow cytometric assay was able to assess GDF-9 and BMP-15 expression in canine follicular cells, showing that these proteins were differentially expressed during follicular development, possibly related to the special features of canine reproduction. PMID:26876149

  8. 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.

  9. 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

  10. Expression of growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), and BMP receptors in the ovaries of goats.

    PubMed

    Silva, J R V; van den Hurk, R; van Tol, H T A; Roelen, B A J; Figueiredo, J R

    2005-01-01

    The process of ovarian folliculogenesis is composed of proliferation and differentiation of the constitutive cells in developing follicles. In goats, relatively little information is available on the local factors that regulate this process. We studied the presence and distribution of growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), and BMP receptors types 2 (BMPR2), 1A (BMPR1A), and 1B (BMPR1B) in goat ovaries to find evidence for their possible roles in folliculogenesis. Ovaries of cyclic goats were collected and fixed in paraformaldehyde for immunohistochemical localization of GDF9 and BMP15 proteins or used to collect follicles and luteal tissue to study the mRNA expression of GDF9, BMP15, and BMP receptors using reverse transcriptase polymerase chain reaction (RT-PCR). GDF9 and BMP15 proteins were found in oocytes of all types of follicles and granulosa cells of primary, secondary, and antral but not primordial follicles. The mRNAs for GDF9, BMP15, BMPR2, BMPR1A, and BMPR1B were detected in primordial, primary, and secondary follicles as well as in oocyte and granulosa cells of antral follicles. Transcripts for BMPR2, BMPR1A, BMPR1B, and GDF9, and GDF9 protein were furthermore found in corpora lutea. It is concluded that the mRNAs and proteins of GDF9 and BMP15 and the mRNAs of BMP receptors are expressed in goat ovarian follicles at all stages of their development, and that they form a complex intrafollicular regulatory system during folliculogenesis. Expression of all BMP receptor mRNAs and GDF9 mRNA and protein in luteal tissue additionally points to a role of GDF9 in corpus luteum function.

  11. Signalling pathways involved in the cooperative effects of ovine and murine GDF9+BMP15-stimulated thymidine uptake by rat granulosa cells.

    PubMed

    Reader, Karen L; Heath, Derek A; Lun, Stan; McIntosh, C Joy; Western, Andrea H; Littlejohn, Roger P; McNatty, Kenneth P; Juengel, Jennifer L

    2011-07-01

    Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-secreted factors known to be involved in regulating the proliferation and differentiation of granulosa cells during follicular growth. The aims of this study were to determine the signalling pathways used by recombinant forms of murine and ovine GDF9 and BMP15 in combination (GDF9+BMP15) and the molecular complexes formed by combinations of these factors. Differences in the molecular forms of combinations of murine and ovine GDF9+BMP15 were observed by western blot analysis. Ovine GDF9+BMP15-stimulated (3)H-thymidine uptake was completely blocked by SMAD2/3 and nuclear factor-κB pathway inhibitors and partially blocked by a p38-mitogen-activated protein kinase (MAPK) inhibitor. Thymidine uptake by murine GDF9+BMP15 was reduced by the SMAD2/3 and extracellular signal-regulated kinase-MAPK pathway inhibitors and increased after addition of a c-Jun N-terminal kinase inhibitor. Stimulation of (3)H-thymidine uptake by GDF9+BMP15 from either species was not affected by the SMAD1/5/8 pathway inhibitor. In conclusion, both murine and ovine GDF9+BMP15-stimulated thymidine incorporation in rat granulosa cells was dependent on the SMAD2/3 signalling pathway but not the SMAD1/5/8 pathway. Divergence in the non-SMAD signalling pathways used by murine and ovine GDF9+BMP15 was also evident and may be due to the differences observed in the molecular complexes formed by these factors. These results are consistent with the hypothesis that the disparate cooperative functions of GDF9 and BMP15 in different species are mediated by divergent non-SMAD signalling pathways.

  12. 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.

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

    NASA Technical Reports Server (NTRS)

    Steckler, Michael S.; Omar, Gomaa I.

    1994-01-01

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

  14. Polymorphism of GDF9 gene and its association with litter size in goats.

    PubMed

    Chu, M X; Wu, Z H; Feng, T; Cao, G L; Fang, L; Di, R; Huang, D W; Li, X W; Li, N

    2011-08-01

    Growth differentiation factor 9 (GDF9) was studied as a candidate gene for high prolificacy in goats. The polymorphism of exon 1 and flanking of GDF9 gene was detected by PCR-SSCP in five goat breeds with different prolificacy. Three genotypes (AA, AB and BB) were detected in goat breeds joined and two silent mutations (c.183A>C and c.336C>T) were identified in comparison genotype AA with genotype BB. Heterozygous genotype AB and wild type BB were detected in all five goat breeds and homozygous genotype AA was only detected in Jining Grey goats. The frequencies of genotypes AA, AB and BB were 0.18, 0.42 and 0.40 in Jining Grey goats, respectively. The genotype distribution was different (P < 0.01) between high prolificacy breed (Jining Grey goat) and low prolificacy breeds (Boer, Wendeng Dairy, Liaoning Cashmere and Beijing native goats). The Jining Grey goat does with genotype AA and AB had 0.72 (P < 0.01) and 0.56 (P < 0.01) kids more than those with genotype BB, respectively. The does with genotype AA had 0.16 (P > 0.05) kids more than those with genotype AB. These indicated that the allele A may have certain correlation with prolificacy in Jining Grey goats.

  15. 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.

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

    PubMed

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

    2015-01-01

    1. Mutations in growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are significantly associated with reproductive performance in mammals and the objective of the present study was to identify polymorphic sites and elucidate the association between genotypes in BMP15 and GDF9 and egg production. 2. Polymorphisms in BMP15 exon1 and GDF9 exon2 were detected by DNA sequencing and PCR-RFLP. Three SNPs were detected in each of BMP15 (A111G, C231T and C34T) and GDF9 (G593A, T824C and C896T). C34T leads to the substitution of Leu by Phe, which was predicted to affect protein function. 3. Results of the association analysis indicated that C34T had an effect on total egg production at 300 d of age (EN) and age at first laying (AFE). G593A affected EN and both C231T and C896T influenced AFE. The TGC1TGC1 diplotype in BMP15 had the highest EN. 4. In conclusion, EN may be significantly improved by marker-assisted selection of the BMP15 genotypes in maternal lines of Shaobo hens. PMID:25735815

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

    PubMed

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

    2015-01-01

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

  18. Polymorphism identification in goat GNRH1 and GDF9 genes and their association analysis with litter size.

    PubMed

    An, X P; Hou, J X; Zhao, H B; Li, G; Bai, L; Peng, J Y; M Yan, Q; Song, Y X; Wang, J G; Cao, B Y

    2013-04-01

    This study investigated the polymorphisms of GNRH1 and GDF9 genes in 641 goats of three breeds: Xinong Saanen, Guanzhong and Boer. Two allelic variants were identified in the GNRH1 gene (JN645280:g.3548A>G and JN645281:g.3699G>A) and one allelic variant was found in the GDF9 gene (JN655693:g.4093G>A). Furthermore, g.4093G>A was a missense mutation (p.Val397Ile of GDF9). Results of an association analysis indicated that SNPs g.3548A>G and g.4093G>A had significant effects on litter size (P < 0.05). The combination genotypes of SNPs g.3548A>G, g.3699G>A and g.4093G>A also affected litter size with the C5 genotype having the highest litter size in the first, third, fourth and average parity. Hence, the biochemical and physiological functions, together with the results obtained in our investigation, suggest that the GNRH1 and GDF9 genes could serve as genetic markers for litter size in goat breeding.

  19. Characterization of NOBOX DNA binding specificity and its regulation of Gdf9 and Pou5f1 promoters.

    PubMed

    Choi, Youngsok; Rajkovic, Aleksandar

    2006-11-24

    Nobox (newborn ovary homeobox gene) deficiency disrupts early folliculogenesis and the expression of oocyte-specific genes in mice. Here, we identified several cis-acting sites, TAATTG, TAGTTG, and TAATTA as NOBOX DNA binding elements (NBEs) using a library of randomly generated oligonucleotides by cyclic amplification of sequence target assay and mutation analyses. We show that NOBOX preferentially binds to the NOBOX binding elements with high affinity. In addition, we found that promoter regions of mouse Pou5f1 and Gdf9 contain one (-426) and three NOBOX binding elements (-786, -967, and -1259), respectively. NOBOX binds to these putative NOBOX binding elements with high affinity and augmented transcriptional activity of luciferase reporter driven by mouse Pou5f1 and Gdf9 promoters containing the NOBOX binding elements. In chromatin immunoprecipitation assays, DNA sequences from Pou5f1 and Gdf9 promoters co-precipitated with anti-NOBOX antibody. These results suggest that NOBOX directly regulates the transcription of Pou5f1 and Gdf9 in oocytes during early folliculogenesis.

  20. 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.

  1. Miocene sandstone provenance relations in the Gulf of Suez: Insights into synrift unroofing and uplift history

    SciTech Connect

    Evans, A.L. )

    1990-09-01

    Time-compositional relations inferred from point counts of 46 upper Oligocene to middle Miocene syn-rift sandstones from Gulf of Suez outcrops are used to further constrain the uplift and unroofing history of this Neogene continental rift. Although earliest rifting began by approximately 24 Ma, as evidenced by minor basaltic volcanism, the main phase of crustal extension, tectonic subsidence of the axial trough, and rift-margin uplift began approximately 19 Ma. Oligocene and basal Miocene (Nukhul Formation) sandstones are dominated by monocrystalline quartz and clasts derived from only the youngest prerift strata (Eocene), indicating that relief was probably less than 200 m until 20 Ma. The lower Miocene Rudeis Formation records both major subsidence in the axial trough and peak unroofing of the prerift sedimentary sequence from 19-16 Ma. Middle Miocene sandstones derived from the Kareem and Belayim formations are increasingly dominated by crystalline basement-derived detritus, recording rapid increase in rift-margin relief after approximately 14 Ma. Diachronism in the first appearance of unroofed basement detritus across the rift indicates uplift of the western margin may have preceded that of the eastern margin by as much as 2 m.y. Once rapid uplift began, between about 20-17 Ma, unroofing of a maximum of 1000 m of the prerift strata occurred in less than 2 m.y. 9 figs., 2 tabs.

  2. 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.

  3. 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

  4. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  6. 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

  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.

  8. 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.

  9. 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

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

    SciTech Connect

    Hurst, J.M.

    1987-05-01

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

  11. 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.

  12. Association of BMPR-1B and GDF9 genes polymorphisms and secondary protein structure changes with reproduction traits in Mehraban ewes.

    PubMed

    Abdoli, R; Zamani, P; Deljou, A; Rezvan, H

    2013-07-25

    BMPR-1B and GDF9 genes are well known due to their important effects on litter size and mechanisms controlling ovulation rate in sheep. In the present study, polymorphisms of BMPR-1B gene exon 8 and GDF9 gene exon 1 were detected by single strand conformational polymorphism (SSCP) analysis and DNA sequencing methods in 100 Mehraban ewes. The PCR reaction forced to amplify 140 and 380-bp fragments of BMPR-1B and GDF9 genes, respectively. Two single nucleotide polymorphisms (SNPS) were identified in two different SSCP patterns of BMPR-1B gene (CC and CA genotypes) that deduced one amino acid exchange. Also, two SNPS were identified in three different SSCP patterns of GDF9 gene (AA, AG and GG genotypes) that deduced one amino acid exchanges. Two different secondary structures of protein were predicted for BMPR-1B exon 8, but the secondary protein structures predicted for GDF9 exon 1 were similar together. The evaluation of the associations between the SSCP patterns and the protein structure changes with reproduction traits showed that BMPR-1B exon 8 genotypes have significant effects on some of reproduction traits but the GDF9 genotypes did not have any significant effect. The CA genotype of BMPR-1B exon 8 had a significant positive effect on reproduction performance and could be considered as an important and new mutation, affecting the ewes reproduction performance. Marker assisted selection using BMPR-IB gene could be noticed to improve the reproduction traits in Mehraban sheep.

  13. A reporter promoter assay confirmed the role of a distal promoter NOBOX binding element in enhancing expression of GDF9 gene in buffalo oocytes.

    PubMed

    Roy, Bhaskar; Rajput, Sandeep; Raghav, Sarvesh; Kumar, Parveen; Verma, Arpana; Kumar, Sandeep; De, Sachinandan; Goswami, Surender Lal; Datta, Tirtha Kumar

    2012-11-01

    Growth differentiation factor 9 is primarily expressed in oocytes and plays a vital role in oocyte cumulus crosstalk. Earlier studies with buffalo oocytes revealed differential expression of this gene under different media stimulation conditions which, in turn, are correlated with the blastocyst yield. In this study, different germ cell specific cis elements including a NOBOX binding elements (NBE) and several E-boxes were identified at the 5' upstream region of buffalo GDF9 gene and their potential role in GDF9 expression was investigated. Transfecting oocytes with GDF9 promoter deletion constructs harbouring the NBE reporter gene revealed a 33% increase in GFP as well as the luciferase signal signifying its role in stimulating the minimal promoter activity of GDF9 in buffalo oocytes. Site directed mutation of core binding nucleotides at NBE at 1.8 kb upstream to TSS further confirmed its role for enhancing the basal transcriptional activity of GDF9 promoter in buffalo oocytes. Current work will provide important leads for understanding the role of GDF9 in oocytes competence and designing a more physiological IVF protocol in case of buffalo.

  14. Exogenous GDF9 but not Activin A, BMP15 or TGFβ alters tight junction protein transcript abundance in zebrafish ovarian follicles.

    PubMed

    Clelland, Eric S; Kelly, Scott P

    2011-04-01

    The tight junction (TJ) complex plays an important role in regulating paracellular permeability and provides mechanical stability in vertebrate epithelia and endothelia. In zebrafish ovarian follicles, TJ complexes in the follicular envelope degenerate as the follicles develop towards maturation. In the current study, transcript abundance of claudins (cldn d, g, h, 1, and 12) and occludins (ocln, and ocln b) were assessed in mid-vitellogenic follicles in response to treatment with exogenous growth factors that are reported to be involved in zebrafish follicle development (i.e. Activin A, BMP15, GDF9 and TGFβ). Exogenous GDF9 reduced the transcript abundance of cldn g, ocln and ocln b in mid-vitellogenic follicles, whereas Activin A, BMP15, and TGFβ had no effect. Subsequent studies with GDF9 revealed that this factor did not alter TJ protein transcript abundance in pre-vitellogenic follicles but did increase the abundance of ocln b in fully grown (maturing) follicles. GDF9 was also seen to increase the abundance of StAR mRNA in all but primary stage follicles. These data suggest a role for GDF9 in the regulation of TJ integrity in zebrafish ovarian follicles, perhaps in the facilitation of ovulation, and support a previously postulated role for GDF9 in zebrafish ovarian follicle development. In addition, data also support the idea that endocrine factors play an important role in the regulation of TJ proteins during ovarian follicle development.

  15. 6-Hydroxydopamine induces distinct alterations in GDF5 and GDNF mRNA expression in the rat nigrostriatal system in vivo.

    PubMed

    Gavin, Aisling M; Walsh, Sinéad; Wyatt, Sean; O'Keeffe, Gerard W; Sullivan, Aideen M

    2014-02-21

    Growth/differentiation factor (GDF)5 and glial cell line-derived neurotrophic factor (GDNF) are neurotrophic factors that promote the survival of midbrain dopaminergic neurons in vitro and in vivo. Both factors have potent neurotrophic and neuroprotective effects in rat models of Parkinson's disease (PD) and represent promising new therapies for PD. The aim of this study was to investigate the expression of GDF5, GDNF and their receptors in the nigrostriatal dopaminergic system in rat models of PD. It found that endogenous GDF5, GDNF and their receptors are differentially expressed in two 6-hydroxydopamine lesion models of PD. In both striatal and medial forebrain bundle (MFB) lesion models, striatal levels of GDF5 mRNA increased at 10 days post-lesion, while GDNF mRNA levels in the nigrostriatal system decreased after 10 and 28 days. Midbrain mRNA levels for both GDF5 receptors transiently increased after striatal lesion, whereas those of two GDNF receptors decreased at later time-points in both models. Despite the fact that exogenous GDF5 and GDNF have comparable effects on dopaminergic neurons in vitro and in vivo, their endogenous responses to neurotoxic injury are different. This highlights the importance of studying neurotrophic factor expression at distinct disease stages and in various animal models of PD.

  16. 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

  17. 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.

  18. The role of oocyte-secreted factors GDF9 and BMP15 in follicular development and oogenesis.

    PubMed

    Paulini, Fernanda; Melo, Eduardo O

    2011-04-01

    Ovarian physiology is controlled by endocrine and paracrine signals, and the transforming growth factor β (TGFβ) superfamily has a pivotal role in this control. The Bone morphogenetic protein 15 (BMP15) and Growth differentiation factor 9 (GDF9) genes are relevant members of the TGFβ superfamily that encode proteins secreted by the oocytes into the ovarian follicles. Through a paracrine signalling pathway, these factors induce the follicular somatic cells to undergo mitosis and differentiation during follicular development. These events are controlled by a mutually dependent and coordinated fashion during the formation of the granulosa cell layers. Many studies have contributed to our knowledge concerning the paracrine factors acting within the follicular environment, especially regarding GDF9 and BMP15. We aimed to review the relevant contributions of these two genes to animal reproductive physiology.

  19. 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

  20. Differential ovarian morphometry and follicular expression of BMP15, GDF9 and BMPR1B influence the prolificacy in goat.

    PubMed

    Pramod, R K; Sharma, S K; Singhi, A; Pan, S; Mitra, A

    2013-10-01

    The variation in the kidding size of Black Bengal and Sirohi breed of goats makes them an interesting genetic material to study the underlying genetic mechanism of prolificacy. Accordingly, we studied the comparative ovarian morphometry including disparity in numbers of antral follicles of different sizes between these two breeds. Further, we evaluated the differential expression of the important candidate genes (viz., BMP15, GDF9 and BMPR1B) known to influence the ovulation rates and the prolificacy. The ovaries of Black Bengal (n = 20) goat were lighter (p < 0.01) in weight and smaller (p < 0.01) in diameter than those of Sirohi (n = 19) goats but possessed more numbers (p < 0.05) of corpus luteum (CL), large and small antral follicles. Quantitative real-time PCR (RT-qPCR) analysis revealed differential expression of mRNAs encoding for the BMP15 and GDF9. Small antral follicles of Black Bengal goats expressed 2.78-fold more (p < 0.05) of BMP 15 than those of Sirohi goat. Expression of BMP15 (p < 0.01) and GDF9 (p < 0.05) mRNAs was more abundant in the small than the large antral follicles of Black Bengal goat. The more numbers of antral follicles per unit of ovarian mass and differential expression of BMP15 and GDF9 may serve as an important clue for higher prolificacy.

  1. Estrogen promotes the development of mouse cumulus cells in coordination with oocyte-derived GDF9 and BMP15.

    PubMed

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

    2010-12-01

    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.

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

    PubMed

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

    2014-11-01

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

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

    NASA Astrophysics Data System (ADS)

    Hagag, Wael; Obermeyer, Hennes

    2016-09-01

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

  5. 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.

  6. GDF11 forms a bone morphogenetic protein 1-activated latent complex that can modulate nerve growth factor-induced differentiation of PC12 cells.

    PubMed

    Ge, Gaoxiang; Hopkins, Delana R; Ho, Wen-Bin; Greenspan, Daniel S

    2005-07-01

    All transforming growth factor beta (TGF-beta) superfamily members are synthesized as precursors with prodomain sequences that are proteolytically removed by subtilisin-like proprotein convertases (SPCs). For most superfamily members, this is believed sufficient for activation. Exceptions are TGF-betas 1 to 3 and growth differentiation factor 8 (GDF8), also known as myostatin, which form noncovalent, latent complexes with their SPC-cleaved prodomains. Sequence similarities between TGF-betas 1 to 3, myostatin, and superfamily member GDF11, also known as bone morphogenetic protein 11 (BMP11), prompted us to examine whether GDF11 might be capable of forming a latent complex with its cleaved prodomain. Here we demonstrate that GDF11 forms a noncovalent latent complex with its SPC-cleaved prodomain and that this latent complex is activated via cleavage at a single specific site by members of the developmentally important BMP1/Tolloid family of metalloproteinases. Evidence is provided for a molecular model whereby formation and activation of this complex may play a general role in modulating neural differentiation. In particular, mutant GDF11 prodomains impervious to cleavage by BMP1/Tolloid proteinases are shown to be potent stimulators of neurodifferentiation, with potential for therapeutic applications.

  7. GDF11 Forms a Bone Morphogenetic Protein 1-Activated Latent Complex That Can Modulate Nerve Growth Factor-Induced Differentiation of PC12 Cells

    PubMed Central

    Ge, Gaoxiang; Hopkins, Delana R.; Ho, Wen-Bin; Greenspan, Daniel S.

    2005-01-01

    All transforming growth factor β (TGF-β) superfamily members are synthesized as precursors with prodomain sequences that are proteolytically removed by subtilisin-like proprotein convertases (SPCs). For most superfamily members, this is believed sufficient for activation. Exceptions are TGF-βs 1 to 3 and growth differentiation factor 8 (GDF8), also known as myostatin, which form noncovalent, latent complexes with their SPC-cleaved prodomains. Sequence similarities between TGF-βs 1 to 3, myostatin, and superfamily member GDF11, also known as bone morphogenetic protein 11 (BMP11), prompted us to examine whether GDF11 might be capable of forming a latent complex with its cleaved prodomain. Here we demonstrate that GDF11 forms a noncovalent latent complex with its SPC-cleaved prodomain and that this latent complex is activated via cleavage at a single specific site by members of the developmentally important BMP1/Tolloid family of metalloproteinases. Evidence is provided for a molecular model whereby formation and activation of this complex may play a general role in modulating neural differentiation. In particular, mutant GDF11 prodomains impervious to cleavage by BMP1/Tolloid proteinases are shown to be potent stimulators of neurodifferentiation, with potential for therapeutic applications. PMID:15988002

  8. 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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2015-10-15

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

  12. GDF-15 Secreted from Human Umbilical Cord Blood Mesenchymal Stem Cells Delivered Through the Cerebrospinal Fluid Promotes Hippocampal Neurogenesis and Synaptic Activity in an Alzheimer's Disease Model

    PubMed Central

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

    2015-01-01

    Our previous studies demonstrated that transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the hippocampus of a transgenic mouse model of Alzheimer's disease (AD) reduced amyloid-β (Aβ) plaques and enhanced cognitive function through paracrine action. Due to the limited life span of hUCB-MSCs after their transplantation, the extension of hUCB-MSC efficacy was essential for AD treatment. In this study, we show that repeated cisterna magna injections of hUCB-MSCs activated endogenous hippocampal neurogenesis and significantly reduced Aβ42 levels. To identify the paracrine factors released from the hUCB-MSCs that stimulated endogenous hippocampal neurogenesis in the dentate gyrus, we cocultured adult mouse neural stem cells (NSCs) with hUCB-MSCs and analyzed the cocultured media with cytokine arrays. Growth differentiation factor-15 (GDF-15) levels were significantly increased in the media. GDF-15 suppression in hUCB-MSCs with GDF-15 small interfering RNA reduced the proliferation of NSCs in cocultures. Conversely, recombinant GDF-15 treatment in both in vitro and in vivo enhanced hippocampal NSC proliferation and neuronal differentiation. Repeated administration of hUBC-MSCs markedly promoted the expression of synaptic vesicle markers, including synaptophysin, which are downregulated in patients with AD. In addition, in vitro synaptic activity through GDF-15 was promoted. Taken together, these results indicated that repeated cisterna magna administration of hUCB-MSCs enhanced endogenous adult hippocampal neurogenesis and synaptic activity through a paracrine factor of GDF-15, suggesting a possible role of hUCB-MSCs in future treatment strategies for AD. PMID:26154268

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

    PubMed Central

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

    2011-01-01

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

  14. The effects of immunizing sheep with different BMP15 or GDF9 peptide sequences on ovarian follicular activity and ovulation rate.

    PubMed

    McNatty, Kenneth P; Hudson, Norma L; Whiting, Lynda; Reader, Karen L; Lun, Stan; Western, Andrea; Heath, Derek A; Smith, Peter; Moore, Lloyd G; Juengel, Jennifer L

    2007-04-01

    The aims of these studies were to determine the abilities of antisera against different regions of ovine bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) to inhibit ovarian follicular activity, estrus (mating), and ovulation in sheep. The 9-15-mer peptides were conjugated to keyhole limpet hemocyanin (KLH) and used to generate antibodies against the flexible N-terminal regions of the mature protein as well as against regions in which dimerization of the protein or interaction with a type 1 BMP or a type 2 TGFB or BMP receptor was predicted to occur. Ewes (n = 10 per treatment group) were vaccinated with KLH or the KLH-BMP15 (n = 9 different peptides) or KLH-GDF9 (n = 10) peptides in Freund adjuvant at five consecutive monthly intervals. Overall, antisera generated against peptides that corresponded to amino acid residues 1-15 of the N-terminus of the BMP15 or GDF9 mature protein or GDF9 amino acid residues 21-34 were the most potent at inhibiting ovulation following primary and single booster vaccination. Several other BMP15 (8/9) or GDF9 (6/10) treatment groups, but not KLH alone, also produced significant reductions in the numbers of animals that ovulated, although 2, 3 or 4 booster vaccinations were required. Anovulation was commonly associated with the inhibition of normal ovarian follicular development and anestrus. The in vitro neutralization studies with IgG from the BMP15 or GDF9 immunized ewes showed that the mean inhibition of BMP15 plus GDF9 stimulation of (3)H-thymidine uptake by rat granulosa cells was approximately 70% for animals without corpora lutea (CL), whereas for animals with one to three CL or more than three CL, the inhibition was 24%-33% or 27%-42%, respectively. In summary, these data suggest that reagents that block the biological actions of BMP15 or GDF9 at their N-termini have potential as contraceptives or sterilizing agents.

  15. Identification of a GDF5 mutation in a Korean patient with brachydactyly type C without foot involvement.

    PubMed

    Seo, Soo Hyun; Park, Mi Jung; Kim, Shin-Hye; Kim, Ok-Hwa; Park, Seungman; Cho, Sung Im; Park, Sung Sup; Seong, Moon-Woo

    2013-03-01

    Brachydactyly type C (BDC) is characterized by shortening of the middle phalanges of the index, middle, and little fingers. Hyperphalangy of the index and middle finger and shortening of the first metacarpal can also be observed. BDC is a rare genetic condition associated with the GDF5 gene, and this condition has not been confirmed by genetic analysis so far in the Korean population. Herein, we present a case of a 6-yr-old girl diagnosed with BDC confirmed by molecular genetic analysis. The patient presented with shortening of the second and third digits of both hands. Sequence analysis of the GDF5 gene was performed and the pathogenic mutation, c.1312C>T (p.Arg438Cys), was identified. Interestingly, this mutation was previously described in a patient who presented with the absence of the middle phalanges in the second through fifth toes. However, our patient showed no involvement of the feet. Considering intrafamilial and interfamilial variability, molecular analysis of isolated brachydactyly is warranted to elucidate the genetic origin and establish a diagnosis.

  16. Polymorphisms in GDF9 and BMP15 associated with fertility and ovulation rate in Moghani and Ghezel sheep in Iran.

    PubMed

    Barzegari, A; Atashpaz, S; Ghabili, K; Nemati, Z; Rustaei, M; Azarbaijani, R

    2010-08-01

    The genetic base of fertility and ovulation rate in Moghani and Ghezel sheep in northwestern Iran and northeastern Turkey is important because of their fat-tailed meat and carpet quality wool. The genes encoding bone morphogenetic (BM) protein 15 and growth differentiation (GD) factor 9, respectively BMP15 and GDF9 have been shown to affect female productivity in domesticated sheep. Recently, numerous investigations have been performed on a variety of breeds to determine the association between mutations in these genes and fertility. Thus, in this study, we assessed such mutations in the Moghani and Ghezel breeds using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) with appropriate enzymes. Our data were similar to those of the previous studies showing that the genotypes were heterozygous for GD (G -->A) and BM (C -->T) mutations. These heterozygous genotypes resulted in higher ovulation rates, illustrating that one copy of each of the BMP15 and GDF9 mutations had equivalent effects on the ovulation rate. We demonstrate for the first time that the BM variant may not be sufficient on its own for infertility. In addition, although the previous studies have shown no notable relationship between the GD variant, known as the non-effecting mutation and sterility, we report that this mutation has an important role in the Moghani and Ghezel breeds.

  17. 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.

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

    SciTech Connect

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

    1990-07-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2001-02-01

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

  20. Kinematics of the oblique faults in the east central Gulf of Suez Rift, Wadi Araba, Sinai Peninsula, Egypt

    NASA Astrophysics Data System (ADS)

    Abdeen, Mamdouh; Abdelmaksoud, Ashraf

    2014-05-01

    The Oligo-Miocene Gulf of Suez rift is characterized by four fault trends; a rift-parallel trend, two trends oblique to the rift trend and a cross trend. The rift-parallel trend strikes 310o to 340o and is referred to as the Clysmic trend. The two trends, which are oblique to the Clysmic trend, strike 350o to 030o and 280o to 310o; the first has been referred to as the north-oblique (N-oblique), and the second as the northwest-oblique (NW-oblique). The cross trend includes faults nearly orthogonal to the Clysmic trend i.e. they strike between 050o and 075o. Image interpretation and detailed field mapping and structural studies at a scale of 1: 20,000 of the Wadi Araba area in southwest Sinai Peninsula indicate e Clysmic faults are mostly normal showing major dip-slip movements. The oblique faults were found to be younger than the Clysmic faults and that the N-oblique faults are characterized by major sinistral strike-slip movement, while the NW-oblique faults are characterized by major dextral strike-slip movement. Cross cutting relationship, geometry and palaeostress analysis indicate that the oblique faults are conjugate Riedel shears originated due to NE to NNE extension related to the Aqaba-Levant transform that has been active since the Middle Miocene.

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  2. 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

  3. 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

  4. GDF9 is transiently expressed in oocytes before follicle formation in the human fetal ovary and is regulated by a novel NOBOX transcript.

    PubMed

    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.

  5. Quantitative expression patterns of GDF9 and BMP15 genes in sheep ovarian follicles grown in vivo or cultured in vitro.

    PubMed

    Kona, S S R; Praveen Chakravarthi, V; Siva Kumar, A V N; Srividya, D; Padmaja, K; Rao, V H

    2016-01-15

    Quantitative patterns of expression of the growth differentiation factor 9 (GDF9) and bone morphogenic protein 15 (BMP15) genes in different development stages of in vivo and in vitro grown ovarian follicles in sheep were studied for the first time. Both GDF9 and BMP15 were expressed in the cumulus cells and oocytes at all the development stages of in vivo and in vitro grown ovarian follicles. Growth differentiation factor 9 and bone morphogenic protein 15 exhibited stage-specific undulations in the expression in the cumulus cells and oocytes isolated from in vivo grown ovarian follicles. These undulations could be related to discrete development events during the ovarian follicle development. The expression of GDF9 and BMP15 was highest (3.38 ± 0.02 and 2.69 ± 0.06, respectively; P ≤ 0.05) in the primordial follicles compared with preantral, early antral, antral, and large antral stages. Similarly, GDF9 and BMP15 expression in the cumulus cells (0 ± 0.16 and 0 ± 0.07) and oocytes (1.47 ± 0.07 and 1.32 ± 0.03) was lowest (P ≤ 0.05) in the in vivo grown antral follicles. In the cultured follicles, the stage-specific undulations observed in the expression of GDF9 and BMP15 in the in vivo grown follicles were either different or abolished. For example, in the oocytes from in vitro grown follicles, the expression of BMP15 did not change as the development progressed all the way from preantral to large antral follicle stage although in the oocytes from in vivo grown follicles BMP15 expression exhibited stage-specific variations. It is concluded that GDF9 and BMP15 follow a stage-specific pattern of expression during the in vivo development of ovarian follicles in sheep, and in vitro culture altered the stage-specific changes in the expression of these two genes.

  6. 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

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

    PubMed

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

    2008-09-10

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  9. Provenance, diagenesis, tectonic setting and 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.

  10. 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

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

    NASA Astrophysics Data System (ADS)

    Dicks, Brian

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

  12. 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

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

    PubMed

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

    2016-04-06

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

  14. 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

    2016-01-01

    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.

  15. A new polymorphism in the Growth and Differentiation Factor 9 (GDF9) gene is associated with increased ovulation rate and prolificacy in homozygous sheep.

    PubMed

    Silva, B D M; Castro, E A; Souza, C J H; Paiva, S R; Sartori, R; Franco, M M; Azevedo, H C; Silva, T A S N; Vieira, A M C; Neves, J P; Melo, E O

    2011-02-01

    Brazilian Santa Inês (SI) sheep are very well-adapted to the tropical conditions of Brazil and are an important source of animal protein. A high rate of twin births was reported in some SI flocks. Growth and Differentiation Factor 9 (GDF9) and Bone Morphogenetic Protein 15 (BMP15) are the first two genes expressed by the oocyte to be associated with an increased ovulation rate in sheep. All GDF9 and BMP15 variants characterized, until now, present the same phenotype: the heterozygote ewes have an increased ovulation rate and the mutated homozygotes are sterile. In this study, we have found a new allele of GDF9, named FecG(E) (Embrapa), which leads to a substitution of a phenylalanine with a cysteine in a conservative position of the mature peptide. Homozygote ewes presenting the FecG(E) allele have shown an increase in their ovulation rate (82%) and prolificacy (58%). This new phenotype can be very useful in better understanding the genetic control of follicular development; the mechanisms involved in the control of ovulation rate in mammals; and for the improvement of sheep production.

  16. 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

  17. Direct Evidence on the Contribution of a Missense Mutation in GDF9 to Variation in Ovulation Rate of Finnsheep

    PubMed Central

    Mullen, Michael P.; Hanrahan, James P.

    2014-01-01

    The Finnish Landrace (Finnsheep) is a well known high-prolificacy sheep breed and has been used in many countries as a source of genetic material to increase fecundity of local breeds. Analyses to date have indicated that mutations with a large effect on ovulation rate are not responsible for the exceptional prolificacy of Finnsheep. The objectives of this study were to ascertain if: 1) any of 12 known mutations with large effects on ovulation rate in sheep, or 2) any other DNA sequence variants within the candidate genes GDF9 and BMP15 are implicated in the high prolificacy of the Finnish Landrace breed; using material from lines developed by divergent selection on ovulation rate. Genotyping results showed that none of 12 known mutations (FecBB, FecXB, FecXG, FecXGR, FecXH, FecXI, FecXL, FecXO, FecXR, FecGE, FecGH, or FecGT) were present in a sample of 108 Finnsheep and, thus, do not contribute to the exceptional prolificacy of the breed. However, DNA sequence analysis of GDF9 identified a previously known mutation, V371M, whose frequency differed significantly (P<0.001) between High and Low ovulation rate lines. While analysis of ovulation rate data for Finnsheep failed to establish a significant association between this trait and V371M, analysis of data on Belclare sheep revealed a significant association between V371M and ovulation rate (P<0.01). Ewes that were heterozygous for V371M exhibited increased ovulation rate (+0.17, s.e. 0.080; P<0.05) compared to wild type and the effect was non-additive (ovulation rate of heterozygotes was significantly lower (P<0.01) than the mean of the homozygotes). This finding brings to 13 the number of mutations that have large effects on ovulation rate in sheep and to 5, including FecBB, FecGE, FecXO and FecXGR, the number of mutations within the TGFβ superfamily with a positive effect on prolificacy in the homozygous state. PMID:24751660

  18. Direct evidence on the contribution of a missense mutation in GDF9 to variation in ovulation rate of Finnsheep.

    PubMed

    Mullen, Michael P; Hanrahan, James P

    2014-01-01

    The Finnish Landrace (Finnsheep) is a well known high-prolificacy sheep breed and has been used in many countries as a source of genetic material to increase fecundity of local breeds. Analyses to date have indicated that mutations with a large effect on ovulation rate are not responsible for the exceptional prolificacy of Finnsheep. The objectives of this study were to ascertain if: 1) any of 12 known mutations with large effects on ovulation rate in sheep, or 2) any other DNA sequence variants within the candidate genes GDF9 and BMP15 are implicated in the high prolificacy of the Finnish Landrace breed; using material from lines developed by divergent selection on ovulation rate. Genotyping results showed that none of 12 known mutations (FecBB, FecXB, FecXG, FecXGR, FecXH, FecXI, FecXL, FecXO, FecXR, FecGE, FecGH, or FecGT) were present in a sample of 108 Finnsheep and, thus, do not contribute to the exceptional prolificacy of the breed. However, DNA sequence analysis of GDF9 identified a previously known mutation, V371M, whose frequency differed significantly (P<0.001) between High and Low ovulation rate lines. While analysis of ovulation rate data for Finnsheep failed to establish a significant association between this trait and V371M, analysis of data on Belclare sheep revealed a significant association between V371M and ovulation rate (P<0.01). Ewes that were heterozygous for V371M exhibited increased ovulation rate (+0.17, s.e. 0.080; P<0.05) compared to wild type and the effect was non-additive (ovulation rate of heterozygotes was significantly lower (P<0.01) than the mean of the homozygotes). This finding brings to 13 the number of mutations that have large effects on ovulation rate in sheep and to 5, including FecBB, FecGE, FecXO and FecXGR, the number of mutations within the TGFβ superfamily with a positive effect on prolificacy in the homozygous state.

  19. Differential expression dynamics of Growth differentiation factor9 (GDF9) and Bone morphogenetic factor15 (BMP15) mRNA transcripts during in vitro maturation of buffalo (Bubalus bubalis) cumulus-oocyte complexes.

    PubMed

    Kathirvel, Muralidharan; Soundian, Eswari; Kumanan, Vijayarani

    2013-12-01

    The present study has evaluated the association of growth differentiation factor9 (GDF9) and bone morphogenetic protein15 (BMP15) mRNA expression in cumulus-oocyte complexes (COCs) of buffalo ovary during in vitro maturation (IVM). GDF9 and BMP15 are expressed specifically in mammalian oocytes and also participate in cumulus-oocyte crosstalk. Quantitative real-time polymerase chain reaction (qRT-PCR) technique was applied to investigate the relative abundance (RA) of GDF9 and BMP15 mRNA transcripts throughout the IVM process. Relative mRNA expression pattern of these specific genes were assessed in oocytes and cumulus cells at 0, 6, 12 and 24 h of in vitro culture. Our results revealed that RA of GDF9 during different hours of IVM showed significant reduction between 0 h and 24 h of maturation in oocytes and BMP15 transcript increased significantly (P<0.05) between 6 h and 12 h and decreased again between 12 h and 24. In cumulus cells, GDF9 remained stable during IVM upto 12 h of maturation and decreased significantly between 12 h and 24 h of maturation. Conversely, significant reduction of BMP15 was observed between 0 h and 6 h, stayed stable upto 12 h and became undetectable at 24 h of maturation. In conclusion, these two genes were differentially expressed during the period of oocyte maturation process and notably, BMP15 expression pattern is associated specifically with the period of cumulus cell expansion.

  20. Biostratigraphy and paleoecology of the Burdigalian-Serravallian sediments in Wadi Sudr (Gulf of Suez, Egypt): comparison with the Central Paratethys evolution

    NASA Astrophysics Data System (ADS)

    Ied, Ibrahim M.; Holcová, Katarína; Abd-Elshafy, Ezzat

    2011-06-01

    Two main Miocene facies were recorded in the Gulf of Suez area: a deep marine and a coastal facies. The analysed sections in the Wadi Sudr area belong to the marine facies. The Lower Miocene (Burdigalian) is represented by coastal, shallow marine sediments, rich in coral, algae, gastropods and large pectinids followed by Langhian open marine sediments and Serravallian lagoonal carbonates. The open marine sediments contain well preserved planktonic and benthic foraminifers and abundant ostracods. The parts of the sections containing foraminifers have been correlated with three planktonic foraminiferal zones (Praeorbulina glomerosa Zone, Orbulina Zone and Globorotalia praemenardii-Globorotalia peripheroronda Zone). Two benthic ecozones were defined (Heterolepa dutemplei-Laevidentalina elegans Zone and Bolivina compressa-Elphidium spp. Zone). Two cycles of sea-level changes can be distinguished and correlated with global sea-level cycles Bur5/Lan1 and Ser1. The first (Langhian) cycle culminated in open marine sublittoral to upper bathyal well aerated sediments. The second (Serravallian) cycle was shallower, littoral suboxic sediments were overlaid by euryhaline carbonates. The studied foraminifera-bearing sediments can be correlated with the lower and Middle Badenian of the Central Paratethys. Though the area of the Gulf of Suez and the Central Paratethys were situated in different climatic zones, and influenced by different tectonic events, the main paleoenvironmental events (sea-level changes, oxygen decrease, salinity changes) are comparable. This correspondence shows that the decisive factors triggering these events were global climatic events.

  1. 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.

  2. Mutation in the protease cleavage site of GDF9 increases ovulation rate and litter size in heterozygous ewes and causes infertility in homozygous ewes.

    PubMed

    Souza, C J H; McNeilly, A S; Benavides, M V; Melo, E O; Moraes, J C F

    2014-10-01

    Litter size (LS) in sheep is determined mainly by ovulation rate (OR). Several polymorphisms have been identified in the growth differentiation factor 9 (GDF9) gene that result in an increase in OR and prolificacy of sheep. Screening the databank of the Brazilian Sheep Breeders Association for triplet delivery, we identified flocks of prolific Ile de France ewes. After resequencing of GDF9, a point mutation (c.943C>T) was identified, resulting in a non-conservative amino acid change (p.Arg315Cys) in the cleavage site of the propeptide. This new allele was called Vacaria (FecG(v) ). A flock of half-sib ewes was evaluated for OR in the first three breeding seasons, and Vacaria heterozygotes had higher OR (P < 0.001), averaging 2.1 ± 0.1 when compared to 1.2 ± 0.1 in wild-type ewes. The OR was also influenced by age, increasing in the second and third breeding seasons (P < 0.001). In flocks segregating this allele, the LS was higher in mutant sheep (P < 0.001), averaging 1.61 ± 0.07 in heterozygotes and 1.29 ± 0.03 in wild-type ewes. Analysis of homozygote reproductive tract morphology revealed uterine and ovarian hypoplasia. Ovarian follicles continue to develop up to small antral stages, although with abnormal oocyte morphology and altered arrangement of granulosa cells. After the collapse of the oocyte in most follicles, the remaining cells formed clusters that persisted in the ovary. This SNP is useful to improve selection for dam prolificacy and also as a model to investigate GDF9 post-translation processing and the fate of the follicular cells that remain after the oocyte demise.

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

    PubMed

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

    2016-09-01

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

  4. Synergistic roles of BMP15 and GDF9 in the development and function of the oocyte-cumulus cell complex in mice: genetic evidence for an oocyte-granulosa cell regulatory loop.

    PubMed

    Su, You-Qiang; Wu, Xuemei; O'Brien, Marilyn J; Pendola, Frank L; Denegre, James N; Matzuk, Martin M; Eppig, John J

    2004-12-01

    Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are oocyte-specific growth factors that appear to play key roles in granulosa cell development and fertility in most mammalian species. We have evaluated the role(s) of these paracrine factors in the development and function of both the cumulus cells and oocytes by assessing cumulus expansion, oocyte maturation, fertilization, and preimplantation embryogenesis in Gdf9+/-Bmp15-/- [hereafter, double mutant (DM)] mice. We found that cumulus expansion, as well as the expression of hyaluronon synthase 2 (Has2) mRNA was impaired in DM oocyte-cumulus cell complexes. This aberrant cumulus expansion was not remedied by coculture with normal wild-type (WT) oocytes, indicating that the development and/or differentiation of cumulus cells in the DM, up to the stage of the preovulatory luteinizing hormone (LH) surge, is impaired. In addition, DM oocytes failed to enable FSH to induce cumulus expansion in WT oocytectomized (OOX) cumulus. Moreover, LH-induced oocyte meiotic resumption was significantly delayed in vivo, and this delayed resumption of meiosis was correlated with the reduced activation of mitogen-activated protein kinase (MAPK) in the cumulus cells, thus suggesting that GDF9 and BMP15 also regulate the function of cumulus cells after the preovulatory LH surge. Although spontaneous in vitro oocyte maturation occurred normally, oocyte fertilization and preimplantation embryogenesis were significantly altered in the DM, suggesting that the full complement of both GDF9 and BMP15 are essential for the development and function of oocytes. Because receptors for GDF9 and BMP15 have not yet been identified in mouse oocytes, the effects of the mutations in the Bmp15 and Gdf9 genes on oocyte development and functions must be produced indirectly by first affecting the granulosa cells and then the oocyte. Therefore, this study provides further evidence for the existence and functioning of an oocyte

  5. DAN (NBL1) specifically antagonizes BMP2 and BMP4 and modulates the actions of GDF9, BMP2, and BMP4 in the rat ovary.

    PubMed

    Hung, Wei-Ting; Wu, Fang-Ju; Wang, Chun-Jen; Luo, Ching-Wei

    2012-05-01

    Although differential screening-selected gene aberrative in neuroblastoma (DAN, official symbol NBL1) is the founding member of the DAN subfamily of bone morphogenetic protein (BMP) antagonists, its antagonizing targets, gene regulation, and physiological functions remain unclear. Using diverse cell expression systems, we found that the generation of bioactive DAN is likely to be cell type specific. Unlike other phylogenetically close members, which are covalently linked homodimers, DAN forms a noncovalently linked homodimer during folding. Purified recombinant DAN specifically blocked signaling of BMP2 and BMP4 but not that of other ovarian-expressed transforming growth factor-beta members. Although widely distributed in many organs, DAN transcript level was periodically regulated by gonadotropins. Ovarian microdissection indicated that NBL1 (DAN) mRNA is mainly expressed in granulosa cells, where its transcript level is up-regulated by the gonadotropin-driven cAMP cascade. We further investigated the local regulation and ovarian functions of DAN. NBL1 (DAN) mRNA expression in granulosa cells was up-regulated by oocyte-derived growth differentiation factor 9 (GDF9), whereas treatment with DAN significantly reversed the inhibitory effect of BMP4 on follicle-stimulating hormone-induced progesterone production in cultured granulosa cells. Our findings suggest the DAN gradient in granulosa cells, established by oocyte-derived GDF9, may serve as an antagonist barrier that modulates the actions of theca-derived BMP4 and granulosa/theca-derived BMP2 during folliculogenesis both spatially and temporally.

  6. 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

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

    NASA Astrophysics Data System (ADS)

    Abdeen, Mamdouh M.; Abdelmaksoud, Ashraf S.

    2014-09-01

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

  8. Impact of gonadotropin supplementation on the expression of germ cell marker genes (MATER, ZAR1, GDF9, and BMP15) during in vitro maturation of buffalo (Bubalus bubalis) oocyte.

    PubMed

    Nath, Amar; Sharma, Veena; Dubey, Pawan K; Pratheesh, M D; Gade, Nitin E; Saikumar, G; Sharma, G Taru

    2013-01-01

    The present study was designed to investigate whether gonadotropins [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] and buffalo follicular fluid (bFF) supplementation in maturation medium influences the transcript abundance of germ cell marker genes [maternal antigen that embryos require (MATER), Zygote arrest 1 (ZAR1), growth differentiation factor 9 (GDF9), and bone morphogenetic protein 15 (BMP15)] mRNA in buffalo (Bubalus bubalis) oocytes. Buffalo ovaries were collected from local abattoir, oocytes were aspirated from antral follicles (5-8 mm) and matured in vitro using two different maturation regimens, viz, group A: gonadotropin (FSH and LH) and group B: non-gonadotropin-supplemented maturation medium containing 20% buffalo follicular fluid (bFF). mRNA was isolated from immature (330) and in vitro matured oocytes from both the groups (A, 320; B, 340), and reverse transcribed using Moloney murine leukemia virus reverse transcriptase. Expression levels of MATER, ZAR1, GDF9, and BMP15 mRNA transcripts were analyzed in oocytes of both maturation groups as well as immature oocytes using real-time PCR. QPCR results showed that GDF9 and BMP15 transcripts were significantly (p<0.05) influenced with gonadotropins and bFF supplementation during in vitro maturation of buffalo oocyte; however, MATER and ZAR1 transcripts were not influenced with gonadotropins and bFF supplementation in vitro. These results indicated that the expression levels of MATER, ZAR1, GDF9, and BMP15 mRNA were varied differentially during in vitro maturation of buffalo oocyte and were found to be gonadotropins (FSH and LH) or bFF dependent for GDF9 and BMP15.

  9. 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.

  10. 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

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

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

  12. 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

  13. 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.

  14. Oocyte-derived BMP15 but not GDF9 down-regulates connexin43 expression and decreases gap junction intercellular communication activity in immortalized human granulosa cells.

    PubMed

    Chang, Hsun-Ming; Cheng, Jung-Chien; Taylor, Elizabeth; Leung, Peter C K

    2014-05-01

    In the ovary, connexin-coupled gap junctions in granulosa cells play crucial roles in follicular and oocyte development as well as in corpus luteum formation. Our previous work has shown that theca cell-derived bone morphogenetic protein (BMP)4 and BMP7 decrease gap junction intercellular communication (GJIC) activity via the down-regulation of connexin43 (Cx43) expression in immortalized human granulosa cells. However, the effects of oocyte-derived growth factors on Cx43 expression remain to be elucidated. The present study was designed to investigate the effects of oocyte-derived growth differentiation factor (GDF)9 and BMP15 on the expression of Cx43 in a human granulosa cell line, SVOG. We also examined the effect relative to GJIC activity and investigated the potential mechanisms of action. In SVOG cells, treatment with BMP15 but not GDF9 significantly decreased Cx43 mRNA and protein levels and GJIC activity. These suppressive effects, along with the induction of Smad1/5/8 phosphorylation, were attenuated by co-treatment with a BMP type I receptor inhibitor, dorsomorphin. Furthermore, knockdown of the central component of the transforming growth factor-β superfamily signaling pathway, Smad4, using small interfering RNA reversed the suppressive effects of BMP15 on Cx43 expression and GJIC activity. The suppressive effects of BMP15 on Cx43 expression were further confirmed in primary human granulosa-lutein cells obtained from infertile patients undergoing an in vitro fertilization procedure. These findings suggest that oocyte-derived BMP15 decreases GJIC activity between human granulosa cells by down-regulating Cx43 expression, most likely via a Smad-dependent signaling pathway.

  15. Patterns of expression of messenger RNAs encoding GDF9, BMP15, TGFBR1, BMPR1B, and BMPR2 during follicular development and characterization of ovarian follicular populations in ewes carrying the Woodlands FecX2W mutation.

    PubMed

    Feary, Elisabeth S; Juengel, Jennifer L; Smith, Peter; French, Michelle C; O'Connell, Anne R; Lawrence, Stephen B; Galloway, Susan M; Davis, George H; McNatty, Kenneth P

    2007-12-01

    Woodlands sheep have a putative genetic mutation (FecX2(W)) that increases ovulation rate. At present, the identity of FecX2(W) is unknown. The trait does not appear to be due to the previously described mutations in bone morphogenetic protein 15 (BMP15), growth differentiation factor 9 (GDF9), or bone morphogenetic protein receptor type 1B (BMPR1B) that affect ovulation rate in sheep. Potentially, FecX2(W) could be an unidentified genetic mutation in BMP15 or in the closely related GDF9, which interacts with BMP15 to control ovarian function. Alternatively, FecX2(W) may affect ovulation rate by changing the expression patterns in the molecular pathways activated by genes known to regulate ovulation rate. The objectives of these experiments were to sequence the complete coding region of the BMP15 and GDF9 genes, determine the patterns of expression of mRNAs encoding GDF9, BMP15, TGFBR1, BMPR1B, and BMPR2 during follicular development, and characterize the follicular populations in ewes heterozygous for the Woodlands mutation and their wild-type contemporaries. No differences in the coding sequences of BMP15 or GDF9 genes were identified that were associated with enhanced ovulation rate. The expression patterns of GDF9 and BMPR2 mRNAs were not different between genotypes. However, expression of BMP15 mRNA was less in oocytes of FecX2(W) ewes in large preantral and antral follicles. Expression of ALK5 mRNA was significantly higher in the oocytes of FecX2(W) ewes, whereas expression of BMPR1B was decreased in both oocytes and granulosa cells of FecX2(W) ewes. FecX2(W) ewes also had increased numbers of antral follicles <1 mm in diameter. These follicles were smaller in average diameter, with the oocytes also being of a smaller mean diameter. Given that a mutation in BMP15 or BMPR1B results in increased ovulation rates in sheep, the differences in expression levels of BMP15 and BMPR1B may play a role in the increase in ovulation rate observed in Woodlands ewes with the

  16. 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

  17. 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.

  18. Heavy metals and hydrocarbon concentrations in water, sediments and tissue of Cyclope neritea from two sites in Suez Canal, Egypt and histopathological effects.

    PubMed

    Sharaf, Hesham M; Shehata, Abdalla M

    2015-01-01

    Heavy metals and hydrocarbons are of the most common marine pollutants around the world. The present study aimed to assess the concentration of petroleum hydrocarbons and heavy metals in tissues of the snail cyclope neritea, water and sediments from two sites of the study area (Temsah lake and Suez canal) represent polluted and unpolluted sites respectively. The results showed that, the levels of the heavy metals (Pb, Cd, Co, Mg and Zn) in the polluted area have reached harmful limits recorded globally. Lead in water, sediment and tissue of the snail reached to 0.95 ppm, 4.54 ppm and 7.93 ppm respectively. Cadmium reached 0.31 ppm, 1.15 ppm and 3.08 ppm in the corresponding samples. Cobalt was not detected in water, but it reached 1.42 ppm and 10.36 ppm in the sediment and snails tissue respectively. Magnesium in water, sediment and tissue of the snail reached 3.73 ppm, 9.44 ppm and12.6 ppm respectively. Zinc reached 0.11 ppm, 3.89 ppm and 12.60ppm in the corresponding samples. Meanwhile, hydrocarbons in the polluted area (site1) reached 110.10 μg/L, 980.15 μg/g and 228.00 μg/g in water sediment and digestive gland tissues of the snails respectively. Whereas, hydrocarbons in the unpolluted area (site2) were estimated as 14.20 μg/L, 55.60 μg/g and 22.66 μg/g in water, sediment and tissue of the snails respectively. The combination of histopathological image with monitoring of the metal level in the digestive gland of the present snail provides an important tool for early detection of impending environmental problems and potential public health issues. Petroleum hydrocarbons are toxic to the marine fauna when present above certain limit in the marine water. The major detoxification organ in molluscs is the digestive gland, which has been used as a bioindicator organ for toxicity assessment. The effect of high crude oil on the digestive gland tubules of exposed snails when examined microscopically reveals a series of histological changes which indicates that the

  19. Anti-Müllerian hormone (AMH), inhibin-α, growth differentiation factor 9 (GDF9), and bone morphogenic protein-15 (BMP15) mRNA and protein are influenced by photoperiod-induced ovarian regression and recrudescence in Siberian hamster ovaries.

    PubMed

    Shahed, Asha; Young, Kelly A

    2013-11-01

    Exposure of Siberian hamsters to short photoperiod (SD) inhibits ovarian function, including folliculogenesis, whereas function is restored with their transfer to long photoperiods (LD). To investigate the mechanism of photo-stimulated recrudescence, we assessed key folliculogenic factors-anti-Müllerian hormone (AMH), inhibin-α, growth differentiation factor-9 (GDF9), and bone morphogenic protein-15 (BMP15)-across the estrus cycle and in photo-regressed and recrudescing ovaries. Adult hamsters were exposed to either LD or SD for 14 weeks, which respectively represent functional and regressed ovaries. Select regressed hamsters were transferred back to LD for 2 (post-transfer week 2; PTw2) or 8 weeks (PTw8). Ovaries were collected and fixed in formalin for immunohistochemistry or frozen in liquid nitrogen for real-time PCR. AMH, inhibin-α, GDF9, and BMP15 mRNA and protein were detected in all stages of the estrus cycle. Fourteen weeks of SD exposure increased (P < 0.05) ovarian AMH, GDF9, and BMP15, but not inhibin-α mRNA levels as compared to LD. Transfer of regressed hamsters to stimulatory long photoperiod for 8 weeks returned AMH and GDF9 mRNA levels to LD-treated levels, and further increased mRNA levels for inhibin-α and BMP15. Immunostaining for AMH, inhibin-α, GDF9, and BMP15 proteins was most intense in preantral/antral follicles and oocytes. The overall immunostaining extent for AMH and inhibin-α generally mirrored the mRNA data, though no changes were observed for GDF9 or BMP15 immunostaining. Shifts in mRNA and protein levels across photoperiod conditions suggest possible syncretic roles for these folliculogenic factors in photo-stimulated recrudescence via potential regulation of follicle recruitment, preservation, and development.

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

    PubMed Central

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

    2015-01-01

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

  1. 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.

  2. 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

  3. 76 FR 77222 - Combined Notice of Filings #2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-12

    ... Corporation, FirstLight Power Resources Management, L,GDF SUEZ Energy Marketing NA, Inc., Green Mountain Power... Agreement Nos. 3156 and 3157-PJM Queue X2-082 to be effective 11/4/2011. Filed Date: 12/5/11. Accession.... Applicants: PJM Interconnection, L.L.C. Description: Original Service Agreement No. 3153; Queue No. W1-029...

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

    PubMed

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

    2013-01-01

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

  5. 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.

  6. 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.

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

    NASA Astrophysics Data System (ADS)

    Giordanengo, Maude

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

  8. 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.

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

    ERIC Educational Resources Information Center

    Ontario Ministry of Skills Development, Toronto.

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

  10. 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

  11. 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

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

    NASA Astrophysics Data System (ADS)

    Abdel-Wahab, Antar A.

    1992-01-01

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

  13. Diagenetic history of Cambrian quartzarenites, Ras Dib Zeit Bay area, Gulf of Suez, eastern desert, Egypt

    NASA Astrophysics Data System (ADS)

    Abdel Wahab, Antar

    1998-10-01

    In the northern corner of the 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 compositions of both sandstones are almost entirely quartz, with trace amounts of muscovite, K-feldspar and heavy minerals. Up to 21% oversize pores, some filled with younger cements, attest to extensive dissolution loss of detrital grains. Because the final mineralogical maturation of these quartzarenites reflects diagenesis, they are diagenetic quartzarenites. During burial diagenesis, the introduction of up to 8% quartz cement (inhomogeneously distributed, mean = 3%) was followed by local, pore-occluding calcite cement, which halted compaction. Sandstones without calcite cement underwent additional mechanical and chemical compaction sufficient to develop sutured quartz grain contacts and reduce porosity (˜27%). These events were followed by: (1) extensive dissolution loss of carbonate cement, detrital feldspars, micas, and heavy minerals; (2) formation of local patches of kaolinite (mean = 3%); and (3) formation of extensive iron-oxide cements, including specular hematite. These features suggest extensive invasion by oxidizing meteoric water. The timing 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. Sr 87/Sr 86 ratios of four samples of gypsum cement have values (0.7079 and 0.7085) that indicate Miocene and slightly younger seawater. Evaporites were evidently leached by modern meteoric water from nearby outcrops of Miocene and younger marine evaporite-bearing strata, transported in surface and ground water to the topographically low terrain where the Cambrian sandstones crop out, and reprecipitated by evaporation. Initial primary porosity (45%) was reduced to ˜27% by compaction in sands with minor quartz cement; compaction ceased where calcite was precipitated. Subsequent dissolution of some calcite cement and unstable detrital grains generated considerable secondary porosity.

  14. 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.

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

    NASA Astrophysics Data System (ADS)

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

    1999-04-01

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

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

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

    NASA Astrophysics Data System (ADS)

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

    1992-01-01

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

  2. 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.

  3. Electrostatic precipitator efficiency improvement using state-of-the-art electrical controls at Suez Cement Plant in Egypt

    SciTech Connect

    Taylor, B.

    1996-12-31

    A very common problem for many cement factories with regard to air pollution control can be described as follows: (1) the company plans to increase kiln capacity, (2) the company is at the same time faced by new Clean Air regulations from their authorities, requiring lower clean gas dust contents, (3) the company wants to achieve these goals with a minimum of investment costs and a minimum of additional running costs. An increased kiln capacity means for the electrostatic precipitator an increased gas flow rate and reduced specific collecting area, resulting in a reduced efficiency of the precipitator.

  4. An obligatory caravanserai stop on the silk road to neural induction: inhibition of BMP/GDF signaling.

    PubMed

    Vonica, Alin; Brivanlou, Ali H

    2006-02-01

    Work in Xenopus laevis produced the first molecular explanation for neural specification, the default model, where inactivation of the BMP pathway in ectodermal cells changes fates from epidermal to neural. This review covers the present status of our understanding of neural specification, with emphasis on Xenopus, but including relevant facts in other model systems. While recent experiments have increased the complexity of the molecular picture, they have also provided additional support for the default model and the central position of the BMP pathway. We conclude that synergy between accumulated knowledge and technical progress will maintain Xenopus at the forefront of research in neural development.

  5. 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.

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

    SciTech Connect

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

    2012-07-01

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

  7. 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

  8. 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.

  9. 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…

  10. 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

  11. Impact of Thermal Stresses on Wellbore Integrity during CO2 Injection

    NASA Astrophysics Data System (ADS)

    Roy, P.; Walsh, S.; Morris, J.; Carroll, S.; Hao, Y.; Iyer, J.; Torsater, M.; Gawel, K.; Todorovic, J.

    2015-12-01

    Thermal stresses caused by injection of cold CO2 into warmer storage reservoirs could create leakage pathways out of the storage reservoir. Although few studies have been conducted to investigate the well bore integrity subjected to thermal cycling during CO2injection, a systematic investigation on thermally induced expansion and contraction affecting the debonding and cracking of the well barrier materials has not yet been performed. In this work, we have analyzed the thermo-mechanical characteristics of the well barrier materials undergoing repeated thermal cycling using a multiscale, multiphysics platform named GEOS. More specifically, we model the modes of failure during thermal cycling to assess the temperature range for minimal impact on well integrity. A finite element solver was used for the geomechanics and a finite volume solver was used for the thermal diffusion. Results of the initiation and propagation of fractures due to temperature variations in the cement sheath are presented. Preliminary results suggest that radial fracture develops as the cement is heated while debonding occurs in the casing-cement and cement-rock interfaces during the cooling period. The effects of different confinement conditions based on in-situ stresses were also analyzed. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under the Contract DE-AC52-07NA27344. This work has been produced with support from the BIGCCS Centre, performed under the Norwegian research program Centres for Environment-friendly Energy Research (FME) and the KPN project "Ensuring well integrity during CO2 injection". The authors acknowledge the following partners for their contributions: Gassco, Shell, Statoil, TOTAL, GDF SUEZ and the Research Council of Norway (193816/S60 and 23389).

  12. Biogeochemical and microbial analyses around gas wells and in the reservoir in a long-term used gas field

    NASA Astrophysics Data System (ADS)

    Kock, Dagmar; Krüger, Martin

    2010-05-01

    As part of a joint research project microbial communities in the area of the second largest natural gas field in Europe in the Altmark, Germany are analyzed. The Altmark gas field operated by GDF SUEZ E&P Germany GmbH is located at the southern edge of the Northeast German Basin. The reservoir horizons belong to the Permian Rotliegend formation (Saxon) and have an average depth of about 3300 m. CO2 will be injected to enhance the recovery of gas in this with conventional extraction methods nearly depleted gas field (Enhanced Gas Recovery - EGR, BMBF project CLEAN). Microbiological analyses are used to supplement a continuous gas monitoring program at the soil surface above the EGR-site. Microbial production and consumption of CH4 and CO2 are determined together with the carbon isotopic compositions to separate these indigenous biological activities from possibly upward migrating reservoir gases including CO2. The δ13C of CO2 collected in situ was similar to those in incubations, confirming a biological origin. Archaeal cell numbers were approximately one magnitude lower than bacterial cell numbers. In all samples the total number of detectable microorganisms was high in contrast to a generally low activity for CO2 and CH4 production and oxidation. For monitoring of the deep reservoir microbiological and isotopic analyses are used to investigate the microbial community before and after injection of CO2. The δ13C of CO2 and CH4 collected in situ in production waters indicate a thermogenic origin. High cell numbers for bacteria and archaea were detected in production waters from different wells. In contrast microbial activities for CO2 and CH4 production and oxidation were relatively low. So far microbial activities in reservoir fluids collected with in situ samplers at 3512m depth could not be determined in this hypersaline (salinity of 400 per mille) and hot (around 130° C) environment.

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

    PubMed Central

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

    2015-01-01

    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 overexpression 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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. Molecular characterization of growth differentiation factor 9 and its spatio-temporal expression pattern in gibel carp (Carassius auratus gibelio).

    PubMed

    Liu, Zhiwei; Chen, Aqin; Yang, Zhigang; Wei, Hua; Leng, Xiangjun

    2012-04-01

    Growth differentiation factor 9 (GDF9) is a member of the transforming growth factor β (TGF-β) superfamily with a key role in regulating follicle development. In this study, the GDF9 full-length genomic DNA and cDNA were isolated and characterized from the gibel carp ovary using rapid-amplification of cDNA ends (RACE) and LD-PCR. The full-length genomic DNA and cDNA sequences of GDF9 are 3979 and 2044 bp which code 428 amino acid residues with a specific RKKR protease cleavage site of TGF-β superfamily. Sequence analysis showed that gibel carp was similar to zebrafish and other fish species. Spatio-temporal expression analysis using real-time quantitative PCR revealed that GDF9 mRNA was largely expressed in ovary and testis. GDF9 is mainly present at stage I follicles indicating its important role in early follicles development. The same result was obtained in immunohistochemistry localization of GDF9 protein. Within the follicle, the follicle layer cells were barely expressed whereas GDF9 mRNA was mostly expressed in the oocytes. Supplemented with human chorionic gonadotropin (hCG) in isolated follicles, the expression of GDF9 mRNA was increased firstly and then decreased. The results of this study indicated that GDF9 gene played a role in fish during development of follicles, especially in the early stage follicles.

  1. Transcutaneous auricular vagus nerve stimulation regulates expression of growth differentiation factor 11 and activin-like kinase 5 in cerebral ischemia/reperfusion rats.

    PubMed

    Ma, Jingxi; Zhang, Lina; He, Guoqian; Tan, Xiaodan; Jin, Xinhao; Li, Changqing

    2016-10-15

    Growth differentiation factor 11 (GDF11), as a rejuvenation factor in heterochronic parabiosis, can increase proliferation of primary brain capillary endothelial cells (ECs). However, the angiogenic role of GDF11 in ischemia-induced brain injury is still unclear. There are no previous reports on the spatiotemporal expression of GDF11 in cerebral ischemia/reperfusion (I/R) rats. Our recent work has strongly suggested that transcutaneous auricular vagus nerve stimulation (ta-VNS) reduces infarct size and induces angiogenesis in focal cerebral I/R rats. This study focused on expression of GDF11 and activin-like kinase 5 (ALK5) and the effects of ta-VNS in a rat cerebral I/R model. For ta-VNS, electrical stimulation of the left cavum concha (1h duration) using percutaneous needles was initiated 30min after induction of ischemia. Expression of GDF11 was analyzed by enzyme-linked immunosorbent assay, immunohistochemistry, real-time polymerase chain reaction, and western blot 24h, 3d, and 7d after reperfusion. In addition, neurobehavioral function, EC proliferation, and expression of ALK5 in ECs in the peri-infarct cortex were measured. Results showed that levels of GDF11 were significantly elevated after cerebral I/R, both in plasma and the peri-infarct cerebral cortex. Interestingly, splenic GDF11 levels decreased after ischemia. ALK5 was expressed in ECs in the peri-infarct cerebral cortex where active vessel remodeling was noted. ta-VNS improved neurobehavioral recovery, upregulated cerebral GDF11 and downregulated splenic GDF11, indicating a brain-spleen communication during stroke. ta-VNS also increased expression of ALK5 in ECs and stimulated proliferation of ECs. These results suggest that, after cerebral ischemia, GDF11 redistributes and participates in angiogenesis as an angiogenic factor that acts at least in part through ALK5. GDF11/ALK5 may represent a new potential therapy target for stroke. PMID:27653860

  2. 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.

  3. 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

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

    PubMed

    Feng, Gang; Wan, Yuqing; Balian, Gary; Laurencin, Cato T; Li, Xudong

    2008-06-01

    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-beta (TGF-beta1; 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-beta1. 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

  5. Growth differentiation factor 9:bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions.

    PubMed

    Peng, Jia; Li, Qinglei; Wigglesworth, Karen; Rangarajan, Adithya; Kattamuri, Chandramohan; Peterson, Randall T; Eppig, John J; Thompson, Thomas B; Matzuk, Martin M

    2013-02-19

    The TGF-β superfamily is the largest family of secreted proteins in mammals, and members of the TGF-β family are involved in most developmental and physiological processes. Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), oocyte-secreted paralogs of the TGF-β superfamily, have been shown genetically to control ovarian physiology. Although previous studies found that GDF9 and BMP15 homodimers can modulate ovarian pathways in vitro, the functional species-specific significance of GDF9:BMP15 heterodimers remained unresolved. Therefore, we engineered and produced purified recombinant mouse and human GDF9 and BMP15 homodimers and GDF9:BMP15 heterodimers to compare their molecular characteristics and physiological functions. In mouse granulosa cell and cumulus cell expansion assays, mouse GDF9 and human BMP15 homodimers can up-regulate cumulus expansion-related genes (Ptx3, Has2, and Ptgs2) and promote cumulus expansion in vitro, whereas mouse BMP15 and human GDF9 homodimers are essentially inactive. However, we discovered that mouse GDF9:BMP15 heterodimer is ∼10- to 30-fold more biopotent than mouse GDF9 homodimer, and human GDF9:BMP15 heterodimer is ∼1,000- to 3,000-fold more bioactive than human BMP15 homodimer. We also demonstrate that the heterodimers require the kinase activities of ALK4/5/7 and BMPR2 to activate SMAD2/3 but unexpectedly need ALK6 as a coreceptor in the signaling complex in granulosa cells. Our findings that GDF9:BMP15 heterodimers are the most bioactive ligands in mice and humans compared with homodimers explain many puzzling genetic and physiological data generated during the last two decades and have important implications for improving female fertility in mammals.

  6. 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

  7. Concise review: growth differentiation factor 15 in pathology: a clinical role?

    PubMed

    Corre, Jill; Hébraud, Benjamin; Bourin, Philippe

    2013-12-01

    Growth differentiation factor 15 (GDF15) is a divergent member of the transforming growth factor β family discovered in a broad range of cells, as indicated by the diversity of its nomenclature. However, the only tissue that expresses a high amount of GDF15 in the physiologic state is placenta. GDF15 is easily detected in blood, and its concentration varies with age. In fact, increased blood concentration of GDF15 is associated with numerous pathological conditions. However, the biological significance underlying these observations is far from clear. GDF15 could have a positive or negative role depending on the state of cells or their environment. Furthermore, study of its biology is hampered by lack of knowledge of its receptor and thus the signaling pathways that drive its action. GDF15 seems to be an integrative signal in pathologic conditions, giving information on severity of disease. Its effectiveness in classifying patients to modulate treatment remains to be shown. Development of therapeutic interventions with GDF15 or anti-GDF15 agents remains difficult until we uncover the mechanism that drives its activity.

  8. Concise Review: Growth Differentiation Factor 15 in Pathology: A Clinical Role?

    PubMed Central

    Corre, Jill; Hébraud, Benjamin

    2013-01-01

    Growth differentiation factor 15 (GDF15) is a divergent member of the transforming growth factor β family discovered in a broad range of cells, as indicated by the diversity of its nomenclature. However, the only tissue that expresses a high amount of GDF15 in the physiologic state is placenta. GDF15 is easily detected in blood, and its concentration varies with age. In fact, increased blood concentration of GDF15 is associated with numerous pathological conditions. However, the biological significance underlying these observations is far from clear. GDF15 could have a positive or negative role depending on the state of cells or their environment. Furthermore, study of its biology is hampered by lack of knowledge of its receptor and thus the signaling pathways that drive its action. GDF15 seems to be an integrative signal in pathologic conditions, giving information on severity of disease. Its effectiveness in classifying patients to modulate treatment remains to be shown. Development of therapeutic interventions with GDF15 or anti-GDF15 agents remains difficult until we uncover the mechanism that drives its activity. PMID:24191265

  9. The trajectory prediction of spacecraft by grey method

    NASA Astrophysics Data System (ADS)

    Wang, Qiyue; Zhang, Zili; Wang, Zhongyu; Wang, Yanqing; Zhou, Weihu

    2016-08-01

    The real-time and high-precision trajectory prediction of a moving object is a core technology in the field of aerospace engineering. The real-time monitoring and tracking technology are also significant guarantees of aerospace equipment. A dynamic trajectory prediction method called grey dynamic filter (GDF) which combines the dynamic measurement theory and grey system theory is proposed. GDF can use coordinates of the current period to extrapolate coordinates of the following period. At meantime, GDF can also keep the instantaneity of measured coordinates by the metabolism model. In this paper the optimal model length of GDF is firstly selected to improve the prediction accuracy. Then the simulation for uniformly accelerated motion and variably accelerated motion is conducted. The simulation results indicate that the mean composite position error of GDF prediction is one-fifth to that of Kalman filter (KF). By using a spacecraft landing experiment, the prediction accuracy of GDF is compared with the KF method and the primitive grey method (GM). The results show that the motion trajectory of spacecraft predicted by GDF is much closer to actual trajectory than the other two methods. The mean composite position error calculated by GDF is one-eighth to KF and one-fifth to GM respectively.

  10. 78 FR 10172 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-13

    ... ports in North Asia, 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...

  11. 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.

  12. Egypt western desert activity hits high gear

    SciTech Connect

    Petzet, G.A.

    1996-11-04

    Exploration in Egypt`s western desert is turning up large oil and gas reserves in several sub-basins. Though not a threat to the Gulf of Suez`s oil production dominance, the western desert`s output is climbing. And gas production is also set to rise as more pipelines are built. The paper describes the geology, Qarun field production, further exploration at Qarun and the Khalda/Obaiyed gas.

  13. 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

  14. 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

    2016-03-17

    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.

  15. 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

  16. Identification of Follistatin-Like 1 by Expression Cloning as an Activator of the Growth Differentiation Factor 15 Gene and a Prognostic Biomarker in Acute Coronary Syndrome

    PubMed Central

    Widera, Christian; Giannitsis, Evangelos; Kempf, Tibor; Korf-Klingebiel, Mortimer; Fiedler, Beate; Sharma, Sarita; Katus, Hugo A.; Asaumi, Yasuhide; Shimano, Masayuki; Walsh, Kenneth; Wollert, Kai C.

    2012-01-01

    BACKGROUND Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine and biomarker that is produced after myocardial infarction and that is related to prognosis in acute coronary syndrome (ACS). We hypothesized that secreted proteins that activate GDF15 production may represent new ACS biomarkers. METHODS We expressed clones from an infarcted mouse heart cDNA library in COS1 cells and assayed for activation of a luciferase reporter gene controlled by a 642-bp fragment of the mouse growth differentiation factor 15 (GDF15) gene promoter. We measured the circulating concentrations of follistatin-like 1 (FSTL1) and GDF15 in 1369 patients with ACS. RESULTS One cDNA clone that activated the GDF15 promoter–luciferase reporter encoded the secreted protein FSTL1. Treatment with FSTL1 activated GDF15 production in cultured cardiomyocytes. Transgenic production of FSTL1 stimulated GDF15 production in the murine heart, whereas cardiomyocyte-selective deletion of FSTL1 decreased production of GDF15 in cardiomyocytes, indicating that FSTL1 is sufficient and required for GDF15 production. In ACS, FSTL1 emerged as the strongest independent correlate of GDF15 (partial R2 = 0.26). A total of 106 patients died of a cardiovascular cause during a median follow-up of 252 days. Patients with an FSTL1 concentration in the top quartile had a 3.7-fold higher risk of cardiovascular death compared with patients in the first 3 quartiles (P < 0.001). FSTL1 remained associated with cardiovascular death after adjustment for clinical, angiographic, and biochemical variables. CONCLUSIONS Our study is the first to use expression cloning for biomarker discovery upstream of a gene of interest and to identify FSTL1 as an independent prognostic biomarker in ACS. PMID:22675198

  17. 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.

  18. Nuclear factor-κB is a common upstream signal for growth differentiation factor-5 expression in brown adipocytes exposed to pro-inflammatory cytokines and palmitate

    SciTech Connect

    Hinoi, Eiichi; Iezaki, Takashi; Ozaki, Kakeru; Yoneda, Yukio

    2014-10-03

    Highlights: • GDF5 expression is up-regulated by IL-1β, TNF-α and palmitate in brown pre-adipocytes. • NF-κB stimulates promoter activity and expression of GDF5 in brown pre-adipocytes. • Recruitment of NF-κB to the GDF5 promoter is facilitated in BAT from ob/ob mice. • An NF-κB inhibitor prevents upregulation of GDF5 expression in brown pre-adipocytes. - Abstract: We have previously demonstrated that genetic and acquired obesity similarly led to drastic upregulation in brown adipose tissue (BAT), rather than white adipose tissue, of expression of both mRNA and corresponding protein for the bone morphogenic protein/growth differentiation factor (GDF) member GDF5 capable of promoting brown adipogenesis. In this study, we evaluated expression profiles of GDF5 in cultured murine brown pre-adipocytes exposed to pro-inflammatory cytokines and free fatty acids (FFAs), which are all shown to play a role in the pathogenesis of obesity. Both interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were effective in up-regulating GDF5 expression in a concentration-dependent manner, while similar upregulation was seen in cells exposed to the saturated FFA palmitate, but not to the unsaturated FFA oleate. In silico analysis revealed existence of the putative nuclear factor-κB (NF-κB) binding site in the 5′-flanking region of mouse GDF5, whereas introduction of NF-κB subunits drastically facilitated both promoter activity and expression of GDF5 in brown pre-adipocytes. Chromatin immunoprecipitation analysis confirmed significant facilitation of the recruitment of NF-κB to the GDF5 promoter in lysed extracts of BAT from leptin-deficient ob/ob obese mice. Upregulation o GDF5 expression was invariably inhibited by an NF-κB inhibitor in cultured brown pre-adipocytes exposed to IL-1β, TNF-α and palmitate. These results suggest that obesity leads to upregulation of GDF5 expression responsible for the promotion of brown adipogenesis through a mechanism

  19. 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

  20. 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.

  1. One year continuous soil gas monitoring above an EGR test site

    NASA Astrophysics Data System (ADS)

    Furche, Markus; Schlömer, Stefan; Faber, Eckhard; Dumke, Ingolf

    2010-05-01

    information about hardware configurations at the stations, maintenance carried out and special events which might have influenced the results. An interactive database application has been developed to allow versatile graphical output and statistical processing of the collected time series. On a large scale CO2 concentrations show natural seasonal variations with higher values during summer (July to September) and lower values during winter. This behaviour is expected and mainly caused by temperature dependent activities of bacterial CO2 production. Absolute concentrations however vary extremely between different locations. While several stations show more than 10% CO2 during summer, others stay below 0.1% at the same time. The conclusion is that individual baselines at all sites for a sufficient time without CO2 sequestration are necessary. The CLEAN project is financed by the German Federal Ministry of Education and Research (BMBF) within the special program Geotechnologien. We would like to thank GDF SUEZ E&P Deutschland GmbH for supporting our field work at the well sites.

  2. 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

  3. 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

  4. 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.

  5. Redundancy of myostatin and growth/differentiation factor 11 function

    PubMed Central

    McPherron, Alexandra C; Huynh, Thanh V; Lee, Se-Jin

    2009-01-01

    Background Myostatin (Mstn) and growth/differentiation factor 11 (Gdf11) are highly related transforming growth factor β (TGFβ) family members that play important roles in regulating embryonic development and adult tissue homeostasis. Despite their high degree of sequence identity, targeted mutations in these genes result in non-overlapping phenotypes affecting distinct biological processes. Loss of Mstn in mice causes a doubling of skeletal muscle mass while loss of Gdf11 in mice causes dramatic anterior homeotic transformations of the axial skeleton, kidney agenesis, and an increase in progenitor cell number in several tissues. In order to investigate the possible functional redundancy of myostatin and Gdf11, we analyzed the effect of eliminating the functions of both of these signaling molecules. Results We show that Mstn-/- Gdf11-/- mice have more extensive homeotic transformations of the axial skeleton than Gdf11-/- mice in addition to skeletal defects not seen in single mutants such as extra forelimbs. We also show that deletion of Gdf11 specifically in skeletal muscle in either Mstn+/+ or Mstn-/- mice does not affect muscle size, fiber number, or fiber type. Conclusion These results provide evidence that myostatin and Gdf11 have redundant functions in regulating skeletal patterning in mice but most likely not in regulating muscle size. PMID:19298661

  6. 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

  7. CYP51A1 induced by growth differentiation factor 9 and follicle-stimulating hormone in granulosa cells is a possible predictor for unfertilization.

    PubMed

    Nakamura, Tomoko; Iwase, Akira; Bayasula, B; Nagatomo, Yoshinari; Kondo, Mika; Nakahara, Tatsuo; Takikawa, Sachiko; Goto, Maki; Kotani, Tomomi; Kiyono, Tohru; Kikkawa, Fumitaka

    2015-03-01

    Growth differentiation factor 9 (GDF9), an oocyte-secreted factor, whose receptors exist in granulosa cells, is involved in follicle progression. Therefore, GDF9 is considered to potentially mediate signals necessary for follicular growth. However, the effect of GDF9 on human granulosa cells is not fully understood. Human immortalized nonluteinized granulosa cell line (HGrC1) which we have previously reported was stimulated with GDF9 and/or follicle-stimulating hormone (FSH). Granulosa cells obtained from in vitro fertilization (IVF) patients were also evaluated with quantitative reverse transcription polymerase chain reaction (RT-PCR). Real-time RT-PCR showed that GDF9 increased messenger RNA (mRNA) levels of enzymes required for cholesterol biosynthesis, such as 3-hydroxy-3-methylglutanyl-CoA synthase 1 (HMGCS1), farnesyl-diphosphate farnesyltransferase 1, squalene epoxidase, lanosterol synthase, and cytochrome P450, family 51, subfamily A, polypeptide 1 (CYP51A1). A greater increase in mRNA levels of HMGCS1 and CYP51A1 was observed by combined treatment with GDF9 and FSH. Clinical samples showed a significant increase in CYP51A1 mRNA in the group of granulosa cells connected with unfertilized oocytes. Our results suggest that GDF9, possibly with FSH, may play significant roles in the regulation of cholesterol biosynthesis and the expression of CYP51A1 which might be a predictor for unfertilization.

  8. Growth differentiation factor 9 of Megalobrama amblycephala: molecular characterization and expression analysis during the development of early embryos and growing ovaries.

    PubMed

    Huang, Chun Xiao; Wei, Xin Lan; Chen, Nan; Zhang, Jie; Chen, Li Ping; Wang, Wei Min; Li, Jun Yan; Wang, Huan Ling

    2014-02-01

    Growth differentiation factor 9 (GDF9) is a member of the transforming growth factorβ superfamily and plays an essential role during follicle maturation in mammals. In the present study, the full-length complementary DNA (cDNA) of gdf9 was obtained from Megalobrama amblycephala. The cDNA sequence is 2,061 bp in length with an open reading frame of 1,287 bp encoding 428 amino acid residues. The deduced amino acid sequence shared identities of about 42-86 % with the homologues of other vertebrates. During the early development of embryos, the gdf9 mRNA was detected in zygote with significantly high level and declined sharply by 47 and 87 % at 4 hours post-fertilization (hpf) and 6 hpf and even to an undetectable level through advancing stages. Expression analysis based on quantitative real-time PCR revealed that gdf9 mRNA was mainly expressed in ovary, but much lower levels were also found in some nonovarian tissues. Within the follicle, gdf9 mRNA was localized both in the oocytes and the follicle layer cells by in situ hybridization. During the ovarian cycle, gdf9 mRNA significantly decreased after the previtellogenic stage and became to increase again after the fully grown stage. The results imply that Gdf9 may play critical physiological functions in M. amblycephala early embryonic development and reproduction.

  9. 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

  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. Association between growth differentiation factor-15 and chronic heart failure in coronary atherosclerosis patients.

    PubMed

    Zhu, Z D; Sun, T

    2015-03-27

    We explored the association between plasma growth differentiation factor 15 (GDF-15) levels and chronic heart failure (CHF) in coronary heart disease patients. We measured plasma GDF-15 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in 269 untreated coronary heart disease patients (98 with CHF, 84 without CHF, and 87 control patients) using an enzyme-linked immunosorbent assay. All subjects were examined by echocardiography and left ventricular ejection fraction. We found that plasma GDF-15 levels in coronary atherosclerosis patients with CHF [median 1622.48 (25-75th percentile: 887.53-1994.93) ng/L] were higher than those in coronary atherosclerosis patients without CHF [944.99 (856.12-999.78) ng/L] and control patients (P < 0.05). NT-proBNP showed the same trend as GDF-15. We also used the New York Heart Association functional classification to subgroup CHF patients and found that the GDF-15 level was higher in all subgroup patients with CHF. After adjusting for covariates, plasma GDF-15 levels were found to be positively related to NT-proBNP (r = 0.861, P < 0.001) and negatively related to left ventricular ejection fraction (r = -0.936, P < 0.001). Furthermore, receiver operating characteristic curves of GDF-15 and NT-proBNP were constructed and the area under the curve for the untransformed GDF-15 and NT-proBNP was 0.804 and 0.795, respectively. Plasma GDF-15 levels and NT-proBNP are associated with CHF in coronary atherosclerosis patients and can be used as biomarkers.

  12. Growth differentiation factor 8 induces SKOV3 ovarian cancer cell migration and E-cadherin down-regulation.

    PubMed

    Zhao, Jianfang; Klausen, Christian; Xiong, Siyuan; Cheng, Jung-Chien; Chang, Hsun-Ming; Leung, Peter C K

    2016-11-01

    Epithelial ovarian cancer is the most lethal gynecological malignancy because most women present with late stage disseminated disease. Epithelial-mesenchymal transition (EMT) is characterized by the down-regulation of E-cadherin and up-regulation of N-cadherin, and is a crucial event in the pathogenesis of ovarian cancer. Transforming growth factor-β (TGF-β) is a major regulator of EMT in many normal and neoplastic cell types. Growth differentiation factor 8 (GDF8), which also activates TGF-β-like SMAD2/3 signaling, is best known for negatively regulating muscle growth. Though recent studies suggest that GDF8 enhances placental trophoblast cell migration, little is known about the role of GDF8 in EMT and cancer metastasis. We hypothesized that GDF8 could enhance ovarian cancer cell migration by inducing EMT. Here we demonstrate for the first time that GDF8 down-regulates E-cadherin but does not alter N-cadherin in SKOV3 ovarian cancer cells. This effect is abolished by the activin receptor-like kinase (ALK)4/5/7 inhibitor SB431542 or siRNA-mediated knockdown of ALK5, whereas knockdown of ALK4 is only partially inhibitory. GDF8 treatment increases the phosphorylation of SMAD2/3 and up-regulates the E-cadherin transcriptional repressors Snail and Slug; and these effects are abolished by pre-treatment with SB431542. Knockdown of common SMAD4 fully reverses the effects of GDF8 on E-cadherin and partially attenuates its effects on Snail and Slug. Importantly, GDF8 treatment increases SKOV3 cell migration and this effect is blocked by SB431542. Our study suggests that GDF8 promotes ovarian cancer cell migration via ALK4/5-SMAD2/3-E-cadherin signaling. PMID:27481097

  13. Plasma growth differentiation factor 15 predicts first-ever stroke in hypertensive patients.

    PubMed

    Wang, Xiaojian; Zhu, Ling; Wu, Yan; Sun, Kai; Su, Ming; Yu, Liping; Chen, Jingzhou; Li, Weiju; Yang, Jing; Yuan, Zuyi; Hui, Rutai

    2016-07-01

    Growth differentiation factor 15 (GDF-15) is a relatively new biomarker that predicts adverse stroke outcomes. However, the association of GDF-15 with first-ever stroke in hypertensive patients has not yet been evaluated. The objective of this study was to evaluate the clinical implications of plasma GDF-15 on the development of first-ever stroke in patients with hypertension.In total, 254 patients with hypertension without a history of stroke were included from March 2010 to August 2010 and followed up until June 2013. The baseline circulating GDF-15 was determined by enzyme-linked immunosorbent assays.During a follow-up of 3.0 ± 0.6 years, 22 (8.7%) first-ever strokes were identified, including 12 ischemic strokes and 10 intracerebral hemorrhages (ICH). According to tertiles of GDF-15, survival free of first-ever stroke was lower in the highest tertile of GDF-15 (log-rank P = 0.001). By backward stepwise Cox-regression analysis, adjusted for age, gender, diabetes mellitus, hyperlipidemia, hypertension stage, body mass index, cigarette smoking, anti-hypertensive drugs, and uric acid, every 100 pg/mL-increase in plasma of GDF-15 predicted an 11% greater risk of first-ever stroke (hazard ratios [HR]: 1.11, 95% confidence interval [CI]: 1.03-1.20, P = 0.010) and an 18% increase in ischemic stroke risk (HR: 1.18, 95% CI: 1.07-1.30, P = 0.001). Receiver operating characteristic analysis indicated that GDF-15 had reasonable accuracy to predict first-ever stroke (area under curve = 0.73, 95% CI: 0.62-0.83, P < 0.001).This study identifies that GDF-15 is an independent predictor of first-ever stroke, especially for ischemic stroke in the patients with hypertension. PMID:27472718

  14. 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.

  15. Signalling pathways involved in the synergistic effects of human growth differentiation factor 9 and bone morphogenetic protein 15.

    PubMed

    Reader, Karen L; Mottershead, David G; Martin, Georgia A; Gilchrist, Robert B; Heath, Derek A; McNatty, Kenneth P; Juengel, Jennifer L

    2016-03-01

    Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) act synergistically to regulate granulosa cell proliferation and steroid production in several species. Several non-Sma and mothers against decapentaplegic (SMAD) signalling pathways are involved in the action of murine and ovine GDF9 and BMP15 in combination, with the pathways utilised differing between the two species. The aims of this research were to determine if human GDF9 and BMP15 also act in a synergistic manner to stimulate granulosa cell proliferation and to identify which non-SMAD signalling pathways are activated. Human GDF9 with BMP15 (GDF9+BMP15) stimulated an increase in (3)H-thymidine incorporation (P<0.001), which was greater than the increase with BMP15 alone, while GDF9 alone had no effect. The stimulation of (3)H-thymidine incorporation by GDF9+BMP15 was reduced by the addition of inhibitors to the SMAD2/3, nuclear factor-KB (NF-KB) and c-Jun N-terminal kinase (JNK) signalling pathways. Inhibitors to the SMAD1/5/8, extracellular signal-regulated kinase mitogen-activated protein kinase (ERK-MAPK) or p38-MAPK pathways had no effect. The addition of the BMP receptor 2 (BMPR2) extracellular domain also inhibited stimulation of (3)H-thymidine incorporation by GDF9+BMP15. In conclusion, human GDF9 and BMP15 act synergistically to stimulate granulosa cell proliferation, a response that also involves species-specific non-SMAD signalling pathways.

  16. Evolutionary origin of bone morphogenetic protein 15 and growth and differentiation factor 9 and differential selective pressure between mono- and polyovulating species.

    PubMed

    Monestier, Olivier; Servin, Bertrand; Auclair, Sylvain; Bourquard, Thomas; Poupon, Anne; Pascal, Géraldine; Fabre, Stéphane

    2014-10-01

    Bone morphogenetic protein 15 (BMP15) and growth and differentiation factor 9 (GDF9) are TGFbeta-like oocyte-derived growth factors involved in ovarian folliculogenesis as critical regulators of many granulosa cell processes and ovulation rate. Ovarian phenotypic effect caused by alterations in BMP15 and GDF9 genes appears to differ between species and may be relevant to their mono- or polyovulating status. Through phylogenetic analysis we recently showed that these two paralogous genes are strongly divergent and in rapid evolution as compared to other members of the TGFbeta superfamily. Here, we evaluate the amino acid substitution rates of a set of proteins implicated in the ovarian function, including BMP15 and GDF9, with special attention to the mono- or polyovulating status of the species. Among a panel of mono- and polyovulating mammals, we demonstrate a better conservation of some areas in BMP15 and GDF9 within mono-ovulating species. Homology modeling of BMP15 and GDF9 homodimer and heterodimer 3-D structures was suggestive that these areas may be involved in dimer formation and stability. A phylogenetic study of BMP15/GDF9-related proteins reveals that these two genes diverged from the same ancestral gene along with BMP3 and GDF10, two other paralogous genes. A substitution rate analysis based on this phylogenetic tree leads to the hypothesis of an acquisition of BMP15/GDF9-specific functions in ovarian folliculogenesis in mammals. We propose that high variations observed in specific areas of BMP15 and GDF9 in polyovulating species change the equilibrium between homodimers and heterodimers, modifying the biological activity and thus allowing polyovulation to occur.

  17. Association study between growth differentiation factor 5 polymorphism and non-contact anterior cruciate ligament rupture in Chinese Han population

    PubMed Central

    Chen, Biao; Li, Bin; Qi, Yong-Jian; Tie, Kai; Chen, Liao-Bin

    2015-01-01

    Background: Anterior cruciate ligament (ACL) rupture is the most common ligamentous injury for active adolescents and young adults each year. However, the precise etiologies of ACL injury are not fully understood. The present study was to investigate +104T/C polymorphism of growth differentiation factor 5 (GDF5) gene in patients with ACL rupture, and evaluate the effects of polymorphism on GDF5 mRNA levels in ligament of patients with ACL rupture in central China. Methods: A total of 286 Chinese patients with ACL rupture and 500healthy controls were enrolled in this study. The +104T/C polymorphism in GDF5 gene were genotyped by DNA sequencing. GDF5 mRNA expressions levels in ligament were determined by quantitative PCR. Results: The frequency of the TT genotype tended to be higher in ACL rupture group than in control group (62.6% vs. 48.0%, P< 0.001, OR = 1.81, 95% CI: 1.35-2.44). T allele of the GDF5 +104T/C polymorphism was more common in ACL rupture group than in control group (P< 0.001). Patients carrying TT genotype expressed lower levels of GDF5 mRNA than C carriers (P = 0.005) among ACL rupture. Conclusion: Our study indicated that GDF5 +104T/C polymorphism was associated with ACL rupture patients in central China. This is likely from decreased expressions of GDF5 mRNA. Further studies are necessary to explore the functional implication of the GDF5 +104T/C polymorphism in Chinese ACL rupture patients. PMID:26885231

  18. Temporal variation of the IBEX Ribbon

    NASA Astrophysics Data System (ADS)

    Janzen, P. H.

    2015-12-01

    We present a study of the time variation over half a solar cycle of the ENA flux composing the IBEX Ribbon, with the goal of determining how closely the Ribbon's temporal variation matches that of the adjacent globally distributed ENA flux (GDF). A high degree of similarity implies that the Ribbon flux originates in the same heliospheric regions as the GDF, presumably the inner heliosheath. If the Ribbon flux shows a separate time history, then it likely originates elsewhere, possibly in the outer heliosheath or beyond. Determining the source region places strong constraints on Ribbon formation theories. Prior Ribbon studies have either treated the Ribbon and the GDF as static over the mission, or have not attempted to separate the GDF from the Ribbon when looking at time variation.

  19. 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

  20. 40 CFR Table 1 to Subpart Cccccc... - Applicability Criteria and Management Practices for Gasoline Dispensing Facilities With Monthly...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Gallons of Gasoline or More If you own or operate Then you must 1. A new, reconstructed, or existing GDF... fill tube is used, it shall be provided with a submerged drop tube that extends the same distance...

  1. 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.

  2. Switching axial progenitors from producing trunk to tail tissues in vertebrate embryos.

    PubMed

    Jurberg, Arnon Dias; Aires, Rita; Varela-Lasheras, Irma; Nóvoa, Ana; Mallo, Moisés

    2013-06-10

    The vertebrate body is made by progressive addition of new tissue from progenitors at the posterior embryonic end. Axial extension involves different mechanisms that produce internal organs in the trunk but not in the tail. We show that Gdf11 signaling is a major coordinator of the trunk-to-tail transition. Without Gdf11 signaling, the switch from trunk to tail is significantly delayed, and its premature activation brings the hindlimbs and cloaca next to the forelimbs, leaving extremely short trunks. Gdf11 activity includes activation of Isl1 to promote formation of the hindlimbs and cloaca-associated mesoderm as the most posterior derivatives of lateral mesoderm progenitors. Gdf11 also coordinates reallocation of bipotent neuromesodermal progenitors from the anterior primitive streak to the tail bud, in part by reducing the retinoic acid available to the progenitors. Our findings provide a perspective to understand the evolution of the vertebrate body plan.

  3. Meat and Livestock Association Plenary Lecture 2005. Oocyte signalling molecules and their effects on reproduction in ruminants.

    PubMed

    McNatty, Kenneth P; Lawrence, Stephen; Groome, Nigel P; Meerasahib, Mohammed F; Hudson, Norma L; Whiting, Lynda; Heath, Derek A; Juengel, Jennifer L

    2006-01-01

    Sheep (Ovis aries) are a highly diverse species, with more than 900 different breeds that vary significantly in their physiological characteristics, including ovulation rate and fecundity. From examination of inherited patterns of ovulation rate, several breeds have been identified with point mutations in two growth factor genes that are expressed in oocytes. Currently, five different point mutations have been identified in the BMP15 (GDF9b) gene and one in GDF9. Animals heterozygous for the GDF9 and/or the BMP15 mutations have higher ovulation rates than their wild-type counterparts. In contrast, those homozygous for any of the aforementioned BMP15 or GDF9 mutations are sterile owing to arrested follicular development. In bovine and ovine ovaries, GDF9 was expressed exclusively in oocytes throughout follicular growth from the primordial stage of development, whereas in sheep BMP15 was expressed exclusively in oocytes from the primary stage: no data for the ontogeny of BMP15 expression are currently available for cattle. In vitro, ovine growth differentiation factor 9 (oGDF9) has no effect on (3)H-thymidine incorporation by either bovine or ovine granulosa cells, whereas ovine bone morphogenetic protein 15 (oBMP15) has modest (1.2- to 1.6-fold; P < 0.05) stimulatory effects. Ovine GDF9 or oBMP15 alone inhibited progesterone production by bovine granulosa cells, whereas in ovine cells only oGDF9 was inhibitory. The effects of oGDF9 and oBMP15 together were often cooperative and not always the same as those observed for each factor alone. Active immunisation of ewes with BMP15 and/or GDF9 peptides affected ovarian follicular development and ovulation rate. Depending on the GDF9 and/or BMP15 vaccine formulation, ovulation rate was either increased or suppressed. A primary and single booster immunisation of ewes with a BMP15 peptide in a water-based adjuvant has led to 19-40% increases in lambs born per ewe lambing. Collectively, the evidence suggests that oocyte

  4. 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

  5. Bone morphogenetic protein 15 and growth differentiation factor 9 expression in the ovary of European sea bass (Dicentrarchus labrax): cellular localization, developmental profiles, and response to unilateral ovariectomy.

    PubMed

    García-López, Ángel; Sánchez-Amaya, María Isabel; Halm, Silke; Astola, Antonio; Prat, Francisco

    2011-12-01

    Vertebrate oocytes actively contribute to follicle development by secreting a variety of growth factors, among which bone morphogenetic protein 15 (BMP15/Bmp15) and growth differentiation factor 9 (GDF9/Gdf9) have been paid particular attention. In the present study, we describe the cellular localization, the developmental profiles, and the response to unilateral ovariectomy (a procedure implying the surgical removal of one of the ovaries) of protein and mRNA steady-state levels of Bmp15 and Gdf9 in the ovary of European sea bass, an important fish species for marine aquaculture industry. In situ hybridization and immunohistochemistry demonstrated that the oocyte is the main production site of Bmp15 and Gdf9 in European sea bass ovary. During oocyte development, Bmp15 protein expression started to be detected only from the lipid vesicle stage onwards but not in primary pre-vitellogenic (i.e. perinucleolar) oocytes as the bmp15 mRNA already did. Gdf9 protein and gdf9 mRNA expression were both detected in primary perinucleolar oocytes and followed similar decreasing patterns thereafter. Unilateral ovariectomy induced a full compensatory growth of the remaining ovary in the 2-month period following surgery (Á. García-López, M.I. Sánchez-Amaya, C.R. Tyler, F. Prat 2011). The compensatory growth elicited different changes in the expression levels of mRNA and protein of both factors, although the involvement of Bmp15 and Gdf9 in the regulatory network orchestrating such process remains unclear at present. Altogether, our results establish a solid base for further studies focused on elucidating the specific functions of Bmp15 and Gdf9 during primary and secondary oocyte growth in European sea bass.

  6. 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

  7. 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.

  8. Effects of growth differentiation factor 9 and bone morphogenetic protein 15 on the in vitro maturation of porcine oocytes.

    PubMed

    Lin, Z-L; Li, Y-H; Xu, Y-N; Wang, Q-L; Namgoong, S; Cui, X-S; Kim, N-H

    2014-04-01

    Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are members of the transforming growth factor-β (TGF-β) family, and their roles in oocyte maturation and cumulus expansion are well known in the mouse and human, but not in the pig. We investigated GDF9 and BMP15 expressions in porcine oocytes during in vitro maturation. A significant increase in the mRNA levels of GDF9 and BMP15 was observed at germinal vesicle breakdown, with expression levels peaking at metaphase I (MI), but decreasing at metaphase II (MII). GDF9 and BMP15 protein localized to the oocyte cytoplasm. While treatment with GDF9 and BMP15 increased the expression of genes involved in both oocyte maturation (c-mos, cyclinb1 and cdc2) and cumulus expansion (has2, ptgs2, ptx3 and tnfaip6), SB431542 (a TGFβ-GDF9 inhibitor) decreased meiotic maturation at MII. Following parthenogenetic activation, the percentage of blastocysts in SB431542 treatment was lower than in the control (41.3% and 74.4%, respectively). Treatment with GDF9 and BMP15 also increased the mRNA levels of maternal genes such as c-mos [a regulatory subunit of mitogen-activated protein kinase (MAPK)], and cyclinb1 and cdc2 [regulatory subunits of maturation/M-phase-promoting factor (MPF)]; however, SB431542 significantly decreased their mRNA levels. These data were supported by poly (A)-test PCR and protein activity analyses. Our results show that GDF9 and BMP15 participate in cumulus expansion and that they stimulate MPF and MAPK activities in porcine oocytes during in vitro maturation.

  9. Recombinant human growth differentiation factor-9 improves oocyte reprogramming competence and subsequent development of bovine cloned embryos.

    PubMed

    Su, Jianmin; Hu, Guangdong; Wang, Yongsheng; Liang, Dong; Gao, Mingqing; Sun, Hongzheng; Zhang, Yong

    2014-08-01

    Previously, we found that oocyte-secreted factors (OSFs) secreted by denuded oocytes during in vitro maturation (IVM) enhance subsequent development of bovine somatic cell nuclear transfer (SCNT) embryos. This treatment requires many oocytes during IVM. Hence, the aim of this study was to investigate whether supplementing with recombinant growth differentiation factor-9 (GDF9), one of crucial OFSs, in oocyte maturation medium could improve developmental competence of bovine oocytes and subsequent development of cloned embryos. Cumulus-oocyte complexes (COCs) from antral follicles of bovine ovaries collected from an abattoir were cultured with (SCNT+GDF9 group) or without (SCNT group) 200 ng/mL recombinant human GDF9 in oocyte maturation medium. After 22 h, metaphase II (MII) oocytes were used for SCNT. The presence of 200 ng/mL GDF9 significantly increased oocyte maturation rates, the cleavage rate, and blastocyst formation rates of bovine cloned embryos. The blastocyst total, inner cell mass (ICM) cell numbers, and ratio of ICM:TE were higher, whereas the rate of apoptosis in bovine cloned blastocysts was lower in the SCNT+GDF9 group than in the SCNT group. The histone modifications at various sites were also different between each group. These results suggest that COCs cultured with recombinant GDF9 in oocyte maturation medium improve oocyte developmental competence and subsequent developmental competence of cloned embryo in cattle.

  10. The ratio of growth differentiation factor 9: bone morphogenetic protein 15 mRNA expression is tightly co-regulated and differs between species over a wide range of ovulation rates.

    PubMed

    Crawford, Janet L; McNatty, Kenneth P

    2012-01-01

    Recent evidence suggests that the species-specific ovulation-rate phenotypes may be influenced by differences in the expression levels of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) mRNA and protein. The aim of this study was to compare GDF9 and BMP15 mRNA levels in individual denuded oocytes (DO) from a range of single (i.e. cow, red deer), single-to-triple (i.e. sheep) and high (i.e. pig, mouse, rat) ovulation-rate species. Compared to all other species studied, GDF9 mRNA levels were lower in DO of cows and deer, whilst BMP15 levels were highest in DO of pigs. There was no detectable expression of either GDF9 or BMP15 mRNA in CC from any species. The ratio of GDF9:BMP15 mRNA expression was highly correlated (R(2)>0.80) within each species but differed markedly between species (P<0.01). Thus, we conclude that the ratio of GDF9:BMP15 mRNA is species-specific across a wide range of ovulation-rate phenotypes.

  11. Folic acid protects against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1.

    PubMed

    Ma, Yan; Zhang, Chen; Gao, Xiao-Bo; Luo, Hai-Yan; Chen, Yang; Li, Hui-hua; Ma, Xu; Lu, Cai-Ling

    2015-11-05

    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.

  12. Insulin-like 3-induced rat preantral follicular growth is mediated by growth differentiation factor 9.

    PubMed

    Xue, Kai; Kim, Ji Young; Liu, Jia-yin; Tsang, Benjamin K

    2014-01-01

    The communication of somatic cells and oocytes by intrafollicular paracrine factors is essential for follicular growth in the ovary. Insulin-like 3 (INSL3) is a theca cell-secreted paracrine factor. Androgens and growth differentiation factor 9 (GDF9), an oocyte-derived growth factor, are essential for follicular development. Using a rat preantral follicle culture model, we examined in the present study the influence of INSL3 on preantral follicular growth and the molecular mechanisms involved. We have observed that the receptor for INSL3, relaxin/insulin-like family peptide receptor 2 (RXFP2), was exclusively expressed in oocytes. Recombinant INSL3 stimulated Gdf9 expression, preantral follicular growth, and testosterone synthesis in vitro. Inhibition of the cAMP/protein kinase A signaling pathway (with cAMP antagonist, 8-bromoadenosine 3',5'-cyclic monophosphorothioate, Rp-isomer) attenuated INSL3-induced Gdf9 expression and preantral follicular growth. Moreover, knocking down Gdf9 expression (with small interfering RNA) or inhibiting GDF9 signaling (with SB431542, an activin receptor-like kinase receptor 5 inhibitor, or specific inhibitor of mothers against decapentaplegic homolog 3) or androgen action (with flutamide, an androgen receptor antagonist) suppressed INSL3-induced preantral follicular growth. In addition, LH and DHT regulated the expression of Insl3 mRNA in preantral follicles. These observations suggest that INSL3 is a key theca cell-derived growth factor for preantral follicle and that its action is mediated by GDF9.

  13. 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

  14. 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

  15. 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

  16. Tribulus terrestris Alters the Expression of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Rabbit Ovaries of Mothers and F1 Female Offspring.

    PubMed

    Abadjieva, Desislava; Kistanova, Elena

    2016-01-01

    Although previous research has demonstrated the key role of the oocyte-derived factors, bone morphogenetic protein (BMP) 15 and growth differentiation factor (GDF) 9, in follicular development and ovulation, there is a lack of knowledge on the impact of external factors, which females are exposed to during folliculogenesis, on their expression. The present study investigated the effect of the aphrodisiac Tribulus terrestris on the GDF9 and BMP15 expression in the oocytes and cumulus cells at mRNA and protein levels during folliculogenesis in two generations of female rabbits. The experiment was conducted with 28 New Zealand rabbits. Only the diet of the experimental mothers group was supplemented with a dry extract of T. terrestris for the 45 days prior to insemination. The expression of BMP15 and GDF9 genes in the oocytes and cumulus cells of mothers and F1 female offspring was analyzed using real-time polymerase chain reaction (RT-PCR). The localization of the GDF9 and BMP15 proteins in the ovary tissues was determined by immunohistochemical analysis. The BMP15 and GDF9 transcripts were detected in the oocytes and cumulus cells of rabbits from all groups. T. terrestris caused a decrease in the BMP15 mRNA level in the oocytes and an increase in the cumulus cells. The GDF9 mRNA level increased significantly in both oocytes and cumulus cells. The downregulated expression of BMP15 in the treated mothers' oocytes was inherited in the F1 female offspring born to treated mothers. BMP15 and GDF9 show a clearly expressed sensitivity to the bioactive compounds of T. terrestris.

  17. Usefulness of growth differentiation factor-15 levels to predict diabetic cardiomyopathy in asymptomatic patients with type 2 diabetes mellitus.

    PubMed

    Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; Avanzas, Pablo

    2014-09-15

    Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that increased in patients with established type 2 diabetes mellitus (DM). Diabetic cardiomyopathy (DC), defined as left ventricular diastolic dysfunction (LVDD) in patients with type 2 DM in the absence of arterial hypertension, heart disease, or other heart disease, was assessed by GDF-15 levels in type 2 DM patients with and without DC. A total of 213 DM outpatients had blood samples drawn and on the same day (basal) underwent echocardiography and treadmill exercise testing. Plasma GDF-15 concentrations were measured by an enzyme-linked immunosorbent assay (ELISA) at baseline. DC was diagnosed in the presence of LVDD, defined when early mitral valve flow velocity (E) and early diastolic lengthening velocity (E') ratio was E/E' ≥ 15. The prevalence of DC was 21.13%. GDF-15 levels were higher in patients with DC compared with those without DC (5,273 [8,708.4] vs 2,812.66 [7,662.1] pg/ml, respectively, p <0.001). We assessed predictors of DC using multivariate regression analysis. GDF-15 (odds ratio 9.9; 95% confidence interval [3.9 to 24.5], p <0.001) was the unique independent predictor of DC. The results of receiver operating characteristic curve show that the cut-off point of 3,812 pg/ml of GDF-15 was indicative for DC (AUC = 0.83, sensitivity = 82.2% and specificity = 70.2%, p <0.0001). In conclusion, GDF-15 represents a useful and novel tool to screen DC in patients with type 2 DM. PMID:25073564

  18. 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

  19. Effects of species differences on oocyte regulation of granulosa cell function.

    PubMed

    Lin, Jia Yi; Pitman-Crawford, Janet L; Bibby, Adrian H; Hudson, Norma L; McIntosh, C Joy; Juengel, Jennifer L; McNatty, Kenneth P

    2012-11-01

    The aims were to investigate whether oocyte-secreted growth factors from a high (i.e. rat) and low (i.e. sheep) ovulation rate species could stimulate (3)H-thymidine incorporation in granulosa cells (GC) from antral follicles from the same or across species. Denuded oocytes (DO) were co-incubated with GC with or without specific antibodies to growth differentiating factor 9 (GDF9) or bone morphogenetic protein 15 (BMP15). Co-incubations of DO-GC from the same or across species significantly increased thymidine incorporation in GC with increasing numbers of DO. GDF9 immuno-neutralisation reduced thymidine incorporation in rat GC co-incubated with either rat or ovine DO and in ovine GC co-incubated with ovine or rat DO. BMP15 immuno-neutralisation only reduced thymidine incorporation when ovine DO were co-incubated with either ovine or rat GC. Western blotting of oocytes co-incubated with GC identified GDF9 and BMP15 proteins for sheep and GDF9 protein for rats in oocyte lysates and incubation media. With respect to rat BMP15, a promature protein was identified in the oocyte lysate but not in media. Expression levels of GDF9 relative to BMP15 mRNA in DO co-incubated with GC were highly correlated (R (2)=0.99) within both species. However, the expression ratios were markedly different for the rat and sheep (4.3 vs 1.0 respectively). We conclude that during follicular development, rat oocytes secrete little, if any, BMP15 and that GDF9 without BMP15 can stimulate proliferation of rat and ovine GC. In contrast, ovine oocytes secrete both BMP15 and GDF9, and both were found to stimulate proliferation in ovine and rat GC.

  20. 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.

  1. Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-β Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality*

    PubMed Central

    Mottershead, David G.; Sugimura, Satoshi; Al-Musawi, Sara L.; Li, Jing-Jie; Richani, Dulama; White, Melissa A.; Martin, Georgia A.; Trotta, Andrew P.; Ritter, Lesley J.; Shi, Junyan; Mueller, Thomas D.; Harrison, Craig A.; Gilchrist, Robert B.

    2015-01-01

    Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-specific growth factors with central roles in mammalian reproduction, regulating species-specific fecundity, ovarian follicular somatic cell differentiation, and oocyte quality. In the human, GDF9 is produced in a latent form, the mechanism of activation being an open question. Here, we produced a range of recombinant GDF9 and BMP15 variants, examined their in silico and physical interactions and their effects on ovarian granulosa cells (GC) and oocytes. We found that the potent synergistic actions of GDF9 and BMP15 on GC can be attributed to the formation of a heterodimer, which we have termed cumulin. Structural modeling of cumulin revealed a dimerization interface identical to homodimeric GDF9 and BMP15, indicating likely formation of a stable complex. This was confirmed by generation of recombinant heterodimeric complexes of pro/mature domains (pro-cumulin) and covalent mature domains (cumulin). Both pro-cumulin and cumulin exhibited highly potent bioactivity on GC, activating both SMAD2/3 and SMAD1/5/8 signaling pathways and promoting proliferation and expression of a set of genes associated with oocyte-regulated GC differentiation. Cumulin was more potent than pro-cumulin, pro-GDF9, pro-BMP15, or the two combined on GC. However, on cumulus-oocyte complexes, pro-cumulin was more effective than all other growth factors at notably improving oocyte quality as assessed by subsequent day 7 embryo development. Our results support a model of activation for human GDF9 dependent on cumulin formation through heterodimerization with BMP15. Oocyte-secreted cumulin is likely to be a central regulator of fertility in mono-ovular mammals. PMID:26254468

  2. A bitter aftertaste: unintended effects of artificial sweeteners on the gut microbiome.

    PubMed

    Bokulich, Nicholas A; Blaser, Martin J

    2014-11-01

    Intestinal microbial communities regulate a range of host physiological functions, from energy harvest and glucose homeostasis to immune development and regulation. Suez et al. (2014) recently demonstrated that artificial sweeteners alter gut microbial communities, leading to glucose intolerance in both mice and humans. PMID:25440050

  3. 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.

  4. The Arabian scad Trachurus indicus, a new Indo-Pacific species in the Mediterranean Sea.

    PubMed

    Dalyan, C; Eryilmaz, L

    2009-05-01

    The Arabian scad Trachurus indicus is recorded for the first time from the Mediterranean Sea (Iskenderun Bay, Turkey). The presence of this Indo-Pacific fish in the Mediterranean Sea is probably because of migration from the Red Sea via the Suez Canal.

  5. 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,…

  6. Mussolini's Marriage and a Game in the Playground: Using Analogy to Help Pupils Understand the Past

    ERIC Educational Resources Information Center

    Laffin, Diana; Wilson, Maggie

    2005-01-01

    Diana Laffin and Maggie Wilson want their pupils to connect with people in the past and to experience some of their emotions. The emotional factor is a difficult one in history, both for pupils and professional historians. When studying Eden's actions at Suez, for example, what we lack is a proper insight into the immediate pressures he faced and…

  7. 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…

  8. Cultural Considerations for Evaluation Consulting in the Egyptian Context.

    ERIC Educational Resources Information Center

    Seefeldt, Michael F.

    1985-01-01

    Reflecting on his experiences as an evaluation consultant at the Suez Canal University Faculty of Medicine in Egypt the author discusses: (1) implications of the Egyptian political context; (2) adapting to the host culture; and (3) maintaining distance from one's own culture. Personal qualities to complement the recommended naturalistic methods…

  9. Paleozoic vertical movements in Um Bogma area, southwestern Sinai

    SciTech Connect

    Beyth, M.

    1981-01-01

    The Wadi Khaboba-Gebel Nukhul high, in the Um Bogma area of southwestern Sinai, underwent a small-scale uplift-subsidence cycle during the Paleozoic. The trend of this structure is close to and almost parallel with the Suez rift, indicating that the young rift is related to older structures.

  10. The Flipped Classroom Model to Develop Egyptian EFL Students' Listening Comprehension

    ERIC Educational Resources Information Center

    Ahmad, Samah Zakareya

    2016-01-01

    The present study aimed at investigating the effect of the flipped classroom model on Egyptian EFL students' listening comprehension. A one-group pre-posttest design was adopted. Thirty-four 3rd-year EFL students at the Faculty of Education, Suez University, were pretested on listening comprehension before the experiment and then posttested after…

  11. Mutations in bone morphogenetic protein 15 and growth differentiation factor 9 genes are associated with increased litter size in fat-tailed sheep breeds.

    PubMed

    Javanmard, Arash; Azadzadeh, N; Esmailizadeh, Ali K

    2011-03-01

    The objective of this study was to investigate association between GDF9 and BMP15 gene polymorphism and litter size in fat-tailed sheep, a total of 97 mature ewes from four breeds (Afshari=19; Baluchi=18; Makui=30 and Mehraban=30) were genotyped for the BMP15 HinfI and GDF9 HhaI polymorphisms by PCR-RFLP technique. The highest and lowest mutant allele frequencies were found in Makui (0.27) and Afshari (0.10) sheep for the BMP15 gene and in Afshari (0.24) and Mehraban (0.18) sheep for the GDF9 gene, respectively. Litter size was significantly influenced by genotype of the ewe for two genes (P < 0.01). Heterozygous genotypes for both loci showed higher litter size than homozygous genotypes (P < 0.01). None of the individuals carried homozygous genotype for both of the GDF9 and BMP15 variants in these breeds. The individuals carrying the mutant allele for one of the investigated candidate gene still showed fertile phenotype. Thus, existence of homozygosity at one of the BMP15 and GDF9 variant is not probably able to block normal hormonal pathway of reproduction in fat-tailed sheep.

  12. 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

  13. 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

  14. A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.

    PubMed

    Choe, Youngshik; Siegenthaler, Julie A; Pleasure, Samuel J

    2012-02-23

    The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. By using mice either with meningeal overgrowth or selective loss of meninges, we have identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development.

  15. 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

  16. 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.

  17. 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.

  18. 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...

  19. Single nucleotide polymorphisms in the bovine genome are associated with the number of oocytes collected during ovum pick up.

    PubMed

    Santos-Biase, W K F; Biase, F H; Buratini, J; Balieiro, J; Watanabe, Y F; Accorsi, M F; Ferreira, C R; Stranieri, P; Caetano, A R; Meirelles, F V

    2012-10-01

    The number of follicles recruited in each estrous cycle has gained practical importance in artificial reproductive technology, as it determines the oocyte yield from ultrasound-guided ovum pickup for in vitro embryo production. We aimed to identify single nucleotide polymorphisms (SNPs) in bovine genes related to reproductive physiology and evaluate the association between the candidate SNPs and the number of oocytes collected from ultrasound-guided ovum pickup. We sequenced genomic segments of GDF9, FGF8, FGF10 and BMPR2 and identified seventeen SNPs in the Bos taurus and Bos indicus breeds. Two SNPs cause amino acid changes in the proteins GDF9 and FGF8. Three SNPs in GDF9, FGF8 and BMPR2 were genotyped in 217 Nelore cows (B. indicus), while two previously identified mutations in LHCGR and mitochondrial DNA (mtDNA) were genotyped in the same group. The polymorphisms in GDF9, FGF8, BMRP2 and LHCGR were significantly associated (P<0.01) with the number of oocytes collected by ovum pickup, whereas the SNP in the mtDNA was not. In addition, we estimated an allelic substitution effect of 1.13±0.01 (P<0.01) oocytes for the SNP in the FGF8 gene. The results we report herein provide further evidence to support the hypothesis that genetic variability is an important component of the number of antral follicles in the bovine ovary.

  20. Oocyte expression, secretion and somatic cell interaction of mouse bone morphogenetic protein 15 during the peri-ovulatory period.

    PubMed

    Mester, Brigitta; Ritter, Lesley J; Pitman, Janet L; Bibby, Adrian H; Gilchrist, Robert B; McNatty, Kenneth P; Juengel, Jennifer L; McIntosh, C Joy

    2015-06-01

    Bone morphogenetic protein 15 (BMP15) is a key intraovarian growth factor regulating mammalian fertility, yet expression and localisation of different BMP15 protein forms within ovarian follicles around the time of the preovulatory LH surge remains unclear. Using immunoblotting and immunocytochemistry, the present study identified that post-translationally processed BMP15 proregion and mature proteins are increasingly expressed and localised with cumulus and granulosa cells from mice treated with pregnant mare's serum gonadotropin (PMSG) + human chorionic gonadotrophin (hCG). However, this increased expression was absent in cumulus-oocyte complexes matured in vitro. Pull-down assays further revealed that the recombinant BMP15 proregion is capable of specific interaction with isolated granulosa cells. To verify an oocyte, and not somatic cell, origin of Bmp15 mRNA and coregulated growth differentiation factor 9 (Gdf9), in situ hybridisation and quantitative polymerase chain reaction results confirmed the exclusive oocyte localisation of Bmp15 and Gdf9, regardless of treatment or assay method. Relative oocyte expression levels of Bmp15 and Gdf9 decreased significantly after PMSG + hCG treatment; nevertheless, throughout all treatments, the Bmp15:Gdf9 mRNA expression ratio remained unchanged. Together, these data provide evidence that the preovulatory LH surge leads to upregulation of several forms of BMP15 protein secreted by the oocyte for putative sequestration and/or interaction with ovarian follicular somatic cells.

  1. 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

  2. Granulosa cells and retinoic acid co-treatment enrich potential germ cells from manually selected Oct4-EGFP expressing human embryonic stem cells.

    PubMed

    Chen, Hsin-Fu; Jan, Pey-Shynan; Kuo, Hung-Chih; Wu, Fang-Chun; Lan, Chen-Wei; Huang, Mei-Chi; Chien, Chung-Liang; Ho, Hong-Nerng

    2014-09-01

    Differentiation of human embryonic stem (HES) cells to germ cells may become clinically useful in overcoming diseases related to germ-cell development. Niches were used to differentiate HES cell lines, NTU1 and H9 Oct4-enhanced green fluorescence protein (EGFP), including laminin, granulosa cell co-culture or conditioned medium, ovarian stromal cell co-culture or conditioned medium, retinoic acid, stem cell factor (SCF) and BMP4-BMP7-BMP8b treatment. Flow cytometry showed that granulosa cell co-culture (P < 0.001) or conditioned medium (P = 0.007) treatment for 14 days significantly increased the percentages of differentiated H9 Oct4-EGFP cells expressing early germ cell marker stage-specific embryonic antigen 1(SSEA1); sorted SSEA1[+] cells did not express higher levels of germ cell gene VASA and GDF9. Manually collected H9 Oct4-EGFP[+] cells expressed significantly higher levels of VASA (P = 0.005) and GDF9 (P = 0.001). H9 Oct4-EGFP[+] cells developed to ovarian follicle-like structures after culture for 28 days but with low efficiency. Unlike SCF and BMP4, retinoic acid co-treatment enhanced VASA, GDF9 and SCP3 expression. A protocol is recommended to enrich differentiated HES cells with germ-cell potential by culture with granulosa cells, conditioned medium or retinoic acid, manual selection of Oct4-EGFP[+] cells, and analysis of VASA, GDF9 expression, or both.

  3. The procurement landscape of pediatric tuberculosis treatment: a Global Drug Facility perspective.

    PubMed

    Scott, C; Gardiner, E; de Lucia, A

    2015-12-01

    Simple, quality-assured, child-friendly formulations of existing first-line anti-tuberculosis (TB) drugs in the correct dosages are now becoming available. Efforts are currently underway by the TB Alliance, the World Health Organization (WHO), and its partners to make appropriate medicines available to treat children diagnosed with TB. The functioning of the current market and the distribution pathways in pediatric TB drugs now require characterization and understanding in order to develop appropriate strategies for delivery of these and other future pediatric TB medicines. The Stop TB Partnership's Global Drug Facility (GDF) plays a major role in supplying pediatric TB medications worldwide. GDF is considered to be the largest procurer of pediatric TB treatment and the largest supplier to national TB programs of quality pediatric drugs. Between 2007 and 2013, the GDF delivered more than 580, 000 treatments to children in over 50 countries, 14 of which are among the 22 high TB burden countries. We analyzed this data set in the context of WHO estimates of pediatric TB as well as other available information to assess the functioning of the current market, lessons learnt from the GDF experience in the market, and opportunities for future products.

  4. 40 CFR Table 1 to Subpart Cccccc... - Applicability Criteria and Management Practices for Gasoline Dispensing Facilities With Monthly...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Gallons of Gasoline or More1 If you own or operate Then you must 1. A new, reconstructed, or existing GDF... fill tube is used, it shall be provided with a submerged drop tube that extends the same distance from... specified in this Table are not applicable if you are complying with the requirements in §...

  5. 40 CFR Table 1 to Subpart Cccccc... - Applicability Criteria and Management Practices for Gasoline Dispensing Facilities With Monthly...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Gallons of Gasoline or More1 If you own or operate Then you must 1. A new, reconstructed, or existing GDF... fill tube is used, it shall be provided with a submerged drop tube that extends the same distance from... specified in this Table are not applicable if you are complying with the requirements in §...

  6. 40 CFR Table 1 to Subpart Cccccc... - Applicability Criteria and Management Practices for Gasoline Dispensing Facilities With Monthly...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Gallons of Gasoline or More1 If you own or operate Then you must 1. A new, reconstructed, or existing GDF... fill tube is used, it shall be provided with a submerged drop tube that extends the same distance from... specified in this Table are not applicable if you are complying with the requirements in §...

  7. Microbial degradation of isosaccharinic acid at high pH.

    PubMed

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

    2015-02-01

    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

  8. 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

  9. The procurement landscape of pediatric tuberculosis treatment: a Global Drug Facility perspective.

    PubMed

    Scott, C; Gardiner, E; de Lucia, A

    2015-12-01

    Simple, quality-assured, child-friendly formulations of existing first-line anti-tuberculosis (TB) drugs in the correct dosages are now becoming available. Efforts are currently underway by the TB Alliance, the World Health Organization (WHO), and its partners to make appropriate medicines available to treat children diagnosed with TB. The functioning of the current market and the distribution pathways in pediatric TB drugs now require characterization and understanding in order to develop appropriate strategies for delivery of these and other future pediatric TB medicines. The Stop TB Partnership's Global Drug Facility (GDF) plays a major role in supplying pediatric TB medications worldwide. GDF is considered to be the largest procurer of pediatric TB treatment and the largest supplier to national TB programs of quality pediatric drugs. Between 2007 and 2013, the GDF delivered more than 580, 000 treatments to children in over 50 countries, 14 of which are among the 22 high TB burden countries. We analyzed this data set in the context of WHO estimates of pediatric TB as well as other available information to assess the functioning of the current market, lessons learnt from the GDF experience in the market, and opportunities for future products. PMID:26564536

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. Correlation between growth differentiation factor-15 and collagen metabolism indicators in patients with myocardial infarction and heart failure

    PubMed Central

    Wang, Fang-Fang; Chen, Bao-Xia; Yu, Hai-Yi; Mi, Lin; Li, Zi-Jian; Gao, Wei

    2016-01-01

    Background Growth differentiation factor (GDF)-15, a divergent member of the transforming growth factor beta super-family does appear to be up-regulated in response to experimental pressure overload and progression of heart failure (HF). HF frequently develops after myocardial infarction (MI), contributing to worse outcome. The aim of this study is to assess the correlation between GDF-15 levels and markers related to collagen turnover in different stages of HF. Methods The study consists of a cohort of 179 patients, including stable angina pectoris patients (AP group, n = 50), old MI patients without HF (OMI group, n = 56), old MI patients with HF (OMI-HF group, n = 38) and normal Control group (n = 35). Both indicators reflecting the synthesis and degradation rates of collagen including precollagen I N-terminal peptide (PINP), type I collagen carboxy-terminal peptide (ICTP), precollagen III N-terminal peptide (PIIINP) and GDF-15 were measured using an enzyme-linked inmunosorbent assay. Results The plasma GDF-15 level was higher in OMI-HF group (1373.4 ± 275.4 ng/L) than OMI group (1036.1 ± 248.6 ng/L), AP group (784.6 ± 222.4 ng/L) and Control group (483.8 ± 186.4 ng/L) (P < 0.001). The indicators of collagen turnover (ICTP, PINP, PIIINP) all increased in the OMI-HF group compared with Control group (3.03 ± 1.02 µg/L vs. 2.08 ± 0.95 µg/L, 22.2 ± 6.6 µg/L vs. 16.7 ± 5.1 µg/L and 13.2 ± 7.9 µg/L vs. 6.4 ± 2.1 µg/L, respectively; P < 0.01). GDF-15 positively correlated with ICTP and PIIINP (r = 0.302, P < 0.001 and r = 0.206, P = 0.006, respectively). GDF-15 positively correlated to the echocardiographic diastolic indicators E/Em and left atrial pressure (r = 0.349 and r = 0.358, respectively; P < 0.01), and inversely correlated to the systolic indicators left ventricular ejection fraction and the average of peak systolic myocardial velocities (Sm) (r = −0.623 and r = −0.365, respectively; P < 0.01). Conclusion Plasma GDF-15 is associated with

  15. 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

  16. Comparison of Gadofluorine-M and Gd-DTPA for Non-Invasive Staging of Atherosclerotic Plaque Stability Using MRI

    PubMed Central

    Ronald, John A.; Chen, Yuanxin; Belisle, Andre J.-L.; Hamilton, Amanda M.; Rogers, Kem A.; Hegele, Robert A.; Misselwitz, Bernd; Rutt, Brian K.

    2009-01-01

    Background Inflammation and neovascularization play critical roles in the stability of atherosclerotic plaques. Whole-body quantitative assessment of these plaque features may improve patient risk-stratification for life-threatening thromboembolic events and direct appropriate intervention. Here we determined the utility of the MR contrast agent Gadofluorine-M (GdF) for staging plaque stability and compared this to the conventional agent Gd-DTPA. Methods and Results 5 control and 7 atherosclerotic rabbits were sequentially imaged following administration of Gd-DTPA (0.2 mmol/kg) and GdF (0.1 mmol/kg) using a T1-weighted pulse sequence on a 3T MRI scanner. Diseased aortic wall could be distinguished from normal wall based on wall-to-muscle contrast-to-noise values following GdF administration. RAM-11 (macrophages) and CD-31 (endothelial cells) immunostaining of MR-matched histological sections revealed that GdF accumulation was related to the degree of inflammation at the surface of plaques and the extent of core neovascularization. Importantly, an MR measure of GdF accumulation at both 1 and 24 hours post-injection, but not Gd-DTPA at peak enhancement, was shown to correlate with a quantitative histological morphology index related to these two plaque features. Conclusions GdF-enhanced MRI of atherosclerotic plaques allows non-invasive quantitative information about plaque composition to be acquired at multiple time points post-injection (within 1 and up to 24 hours post-injection). This dramatically widens the imaging window for assessing plaque stability that is currently attainable with clinically approved MR agents, therefore opening the possibility of whole-body (including coronary) detection of unstable plaques in the future and potentially improved mitigation of cataclysmic cardiovascular events. PMID:19808597

  17. Oocytes in sheep homozygous for a mutation in bone morphogenetic protein receptor 1B express lower mRNA levels of bone morphogenetic protein 15 but not growth differentiation factor 9.

    PubMed

    Crawford, Janet L; Heath, Derek A; Reader, Karen L; Quirke, Laurel D; Hudson, Norma L; Juengel, Jennifer L; McNatty, Kenneth P

    2011-07-01

    The aim of this study was to test the hypothesis that the high ovulation rate in ewes (BB) homozygous for a mutation in the bone morphogenetic protein receptor type 1B (BMPR1B) gene is linked to lower BMP15 and/or GDF9 mRNA in oocytes compared with those in wild-type (++) ewes. Cumulus cell-oocyte complexes (COC) and granulosa cells (GC) were recovered from ≥1 mm diameter follicles of BB and ++ ewes during a prostaglandin-induced follicular phase. Expression levels of GDF9 and BMP15 were measured by multiplex qPCR from individual COC. The gonadotropin-induced cAMP responses of the GC from each non-atretic follicle were measured following treatment with FSH or human chorionic gonadotropin. In a separate validation experiment, GDF9 and BMP15 expression was present only in oocytes and not in cumulus cells. There was no effect of follicular diameter on oocyte-derived GDF9 or BMP15 mRNA levels. The mean expression levels of BMP15, but not GDF9, were significantly lower in all non-atretic follicles, including the subsets containing either FSH- or LH-responsive GC in BB, compared with ++, ewes. No genotype effects were noted for FSH-induced cAMP production by GC either with respect to dose of, or number of follicles responding to, FSH. However, ovaries from BB ewes contained significantly more follicles responsive to LH, with respect to cAMP production in GC. We propose that these findings are consistent with the hypothesis that the higher ovulation rate in BB sheep is due, at least in part, to lower oocyte-derived BMP15 mRNA levels together with the earlier onset of LH-responsiveness in GC.

  18. Oocyte-secreted growth differentiation factor 9 inhibits BCL-2-interacting mediator of cell death-extra long expression in porcine cumulus cell.

    PubMed

    Wang, Xian-Long; Wang, Kun; Zhao, Shuan; Wu, Yi; Gao, Hui; Zeng, Shen-Ming

    2013-09-01

    Oocyte-secreted factors (OSFs) maintain the low incidence of cumulus cell apoptosis. In this report, we described that the presence of oocytes suppressed the expression of proapoptotic protein BCL-2-interacting mediator of cell death-extra long (BIMEL) in porcine cumulus cells. Atretic (terminal deoxynucleotidyl transferase dUTP nick end labeling-positive) cumulus cells strongly expressed BIMEL protein. The healthy cumulus- oocyte complex exhibited a low BIMEL expression in cumulus cell while the removal of oocyte led to an about 2.5-fold (P < 0.5) increased expression in oocytectomized complex (OOX). Coculturing OOXs with denuded oocytes decreased BIMEL expression to the normal level. The similar expression pattern could also be achieved in OOXs treated with exogenous recombinant mouse growth differentiation factor 9 (GDF9), a well-characterized OSF. This inhibitory action of GDF9 was prevented by the addition of a phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Luciferase assay further demonstrated that BIM gene expression was forkhead box O3a (FOXO3a)-dependent because mutation of FOXO3a-binding site on the BIM promoter inhibited luciferase activities. Moreover, the activity of BIM promoter encompassing the FOXO3a-binding site could be regulated by GDF9. Additionally, we found that GDF9 elevated the levels of phosphorylated AKT and FOXO3a, and this process was independent of the SMAD signal pathway. Taken together, we concluded that OSFs, particularly GDF9, maintained the low level of BIMEL expression in cumulus cell through activation of the PI3K/FOXO3a pathway.

  19. 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.

  20. Growth differentiation factor-9 mediates follicle-stimulating hormone-thyroid hormone interaction in the regulation of rat preantral follicular development.

    PubMed

    Kobayashi, Noriko; Orisaka, Makoto; Cao, Mingju; Kotsuji, Fumikazu; Leader, Arthur; Sakuragi, Noriaki; Tsang, Benjamin K

    2009-12-01

    FSH regulates follicular growth in a stage-development fashion. Although preantral follicle stage is gonadotropin responsive, FSH is not required for preantral follicular growth. With the antrum, the follicles continue growing under the influence of FSH and become gonadotropin dependent. Although thyroid hormone is important for normal female reproductive function, its role and interaction with FSH in the regulation of preantral ovarian follicular growth is yet to be defined. In the present study, we have examined the action and interaction of FSH and T(3) in the regulation of the growth of preantral follicles, especially in their transition from preantral to early antral stage, using an established follicle culture system and evaluated the involvement of growth differentiation factor-9 (GDF-9) in this process in vitro. We have demonstrated that although T(3) alone had no effect on follicular development, it markedly enhanced FSH-induced preantral follicular growth. Although FSH alone significantly down-regulated FSH receptor (FSHR) mRNA abundance in the preantral follicles and T(3) alone was ineffective, expression of the message was significantly increased in the presence of both hormones. In addition, intra-oocyte injection of GDF-9 antisense oligonucleotides (GDF-9 morpholino) induced follicular cell apoptosis and suppressed follicular growth induced by FSH and T(3). These responses were attenuated by exogenous GDF-9. Our findings support the concept that thyroid hormone regulates ovarian follicular development through its direct action on the ovary and that promotes FSH-induced preantral follicular growth through up-regulation of FSHR, a mechanism dependent on the expression and action of oocyte-derived GDF-9.

  1. Mites infesting two migratory birds, Coturnix c. coturnix (quail or Simmaan) and Sturnus v. vulgaris (starling or zarzuur) with reference to avian zoonosis.

    PubMed

    Mazyad, S A; Morsy, T A; Fekry, A A; Farrag, A M

    1999-01-01

    Birds are a marvelous group of creatures. Their beautiful coloration, singing, dancing and their attractive ways of life offer great pleasure to birdwatcher. Egypt is one of the most important countries of migratory birds. Not less than 300 species of birds visit Egypt annually from allover the world. The mite fauna of two migratory birds was studied in North Sinai Governorate and Suez Canal Zone. Thirty-one species of mites were recovered from quail and 39 from starling. Both types of birds serve hosts for 26 species of mites. Besides, five species were only recovered from quail and 13 species from starling. These totaled 44 species belonging to 30 families of three suborders (Mesostigmata, Trombidiformes and Sarcoptidiformes). The mite index on quail ranged between 1.0 to 5.0 in North Sinai G. and 1.0 to 17.0 in Suez Canal Z. The mite index on starling ranged between 1.0 to 4.75 in North Sinai G. and 1.0 to 4.5 in Suez Canal Z. Sixteen of the recovered species of mites were not recorded before on the Egyptian resident birds (house sparrow and laughing dove). The medical and veterinary importance of avian zoonosis was discussed. It is hoped to stimulate the awareness to migratory birds as reservoir hosts for microorganisms and parasites from allover the world. Besides, there is an urgent need to protect the resident and the visiting birds.

  2. 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.

  3. Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation.

    PubMed

    Gilchrist, Robert B; Ritter, Lesley J; Myllymaa, Samu; Kaivo-Oja, Noora; Dragovic, Rebecca A; Hickey, Theresa E; Ritvos, Olli; Mottershead, David G

    2006-09-15

    Oocytes regulate follicle growth by secreting paracrine growth factors that act on neighbouring granulosa cells (GCs). Those factors identified to date are mainly members of the transforming growth factor-beta (TGFbeta) superfamily, but little is known about which specific receptor/signalling system(s) they employ. This study was conducted to determine the requisite pathways utilised by oocytes to promote GC proliferation. We used an established oocyte-secreted mitogen bioassay, where denuded mouse oocytes are co-cultured with mural GCs. Oocytes, growth differentiation factor-9 (GDF9), TGFbeta1 and activin-A all promoted GC DNA synthesis, but bone-morphogenetic protein 6 (BMP6) did not. Subsequently, we tested the capacity of various TGFbeta superfamily receptor ectodomains (ECD) to neutralise oocyte- or specific growth factor-stimulated GC proliferation. The BMP type-II receptor (BMPR-II) ECD antagonised oocyte and GDF9 bioactivity dose-dependently, but had no or minimal effect on TGFbeta1 and activin-A bioactivity, demonstrating its specificity. The TGFbetaR-II, activinR-IIA and activinR-IIB ECDs all failed to neutralise oocyte- or GDF9-stimulated GC DNA synthesis, whereas they did antagonise the activity of their respective native ligands. An activin receptor-like kinase (ALK) 4/5/7 inhibitor, SB431542, also antagonised both oocyte and GDF9 bioactivity in a dose-dependent manner. Consistent with these findings, oocytes, GDF9 and TGFbeta1 all activated SMAD2/3 reporter constructs in transfected GC, and led to phosphorylation of SMAD2 proteins in treated cells. Surprisingly, oocytes did not activate the SMAD1/5/8 pathway in transfected GCs although exogenous BMP6 did. This study indicates that oocyte paracrine factors primarily utilise a similar signalling pathway first identified for GDF9 that employs an unusual combination of TGFbeta superfamily receptors, the BMPR-II and a SMAD2/3 stimulatory ALK (4, 5 or 7), for transmitting their mitogenic actions in GC. This

  4. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep.

    PubMed

    Clop, Alex; Marcq, Fabienne; Takeda, Haruko; Pirottin, Dimitri; Tordoir, Xavier; Bibé, Bernard; Bouix, Jacques; Caiment, Florian; Elsen, Jean-Michel; Eychenne, Francis; Larzul, Catherine; Laville, Elisabeth; Meish, Françoise; Milenkovic, Dragan; Tobin, James; Charlier, Carole; Georges, Michel

    2006-07-01

    Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin (GDF8) gene. We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of SNP databases for humans and mice demonstrates that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation.

  5. Illustrative assessment of human health issues arising from the potential release of chemotoxic substances from a generic geological disposal facility for radioactive waste.

    PubMed

    Wilson, James C; Thorne, Michael C; Towler, George; Norris, Simon

    2011-12-01

    Many countries have a programme for developing an underground geological disposal facility for radioactive waste. A case study is provided herein on the illustrative assessment of human health issues arising from the potential release of chemotoxic and radioactive substances from a generic geological disposal facility (GDF) for radioactive waste. The illustrative assessment uses a source-pathway-receptor methodology and considers a number of human exposure pathways. Estimated exposures are compared with authoritative toxicological assessment criteria. The possibility of additive and synergistic effects resulting from exposures to mixtures of chemical contaminants or a combination of radiotoxic and chemotoxic substances is considered. The case study provides an illustration of how to assess human health issues arising from chemotoxic species released from a GDF for radioactive waste and highlights potential difficulties associated with a lack of data being available with which to assess synergistic effects. It also highlights how such difficulties can be addressed.

  6. NOBOX is a strong autosomal candidate gene in Tunisian patients with primary ovarian insufficiency.

    PubMed

    Bouali, N; Francou, B; Bouligand, J; Lakhal, B; Malek, I; Kammoun, M; Warszawski, J; Mougou, S; Saad, A; Guiochon-Mantel, A

    2016-05-01

    Premature ovarian insufficiency (POI) affects approximately 1% of women before the age of 40. Genetic contribution is a significant component of POI. In this context, heterozygous mutations in NOBOX, BMP15 and GDF9 have been reported. The objective of our study was to evaluate the prevalence of these genes mutations in 125 unrelated Tunisian patients diagnosed with POI. The screening of NOBOX gene revealed three missense mutations (p.Arg117Trp; p.Gly91Trp and p.Pro619Leu) in eight patients. These mutations were not found in a 200 ethnically matched women without fertility problem. The sequencing of BMP15 and GDF9 gene revealed only previously reported variants. In contrast to previous studies, the prevalence of BMP15 variations is not higher than in the control population. Conversely, 6.4% of the cases present a NOBOX mutations; this high prevalence strengthens the consideration of NOBOX gene as strong autosomal candidate for POI.

  7. Mixed Organic Solvents Induce Renal Injury in Rats

    PubMed Central

    Qin, Weisong; Xu, Zhongxiu; Lu, Yizhou; Zeng, Caihong; Zheng, Chunxia; Wang, Shengyu; Liu, Zhihong

    2012-01-01

    To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD) rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF) in the ratio of 2∶2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5–6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16) and 25% (4/16), respectively. Urinary N-Acetyl-β-(D)-Glucosaminidase (NAG) activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM). Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli. PMID:23029287

  8. Prodomains of transforming growth factor beta (TGFbeta) superfamily members specify different functions: extracellular matrix interactions and growth factor bioavailability.

    PubMed

    Sengle, Gerhard; Ono, Robert N; Sasaki, Takako; Sakai, Lynn Y

    2011-02-18

    The specific functions of the prodomains of TGFβ superfamily members are largely unknown. Interactions are known between prodomains of TGFβ-1-3 and latent TGFβ-binding proteins and between prodomains of BMP-2, -4, -7, and -10 and GDF-5 and fibrillins, raising the possibility that latent TGFβ-binding proteins and fibrillins may mediate interactions with all other prodomains of this superfamily. This possibility is tested in this study. Results show that the prodomain of BMP-5 interacts with the N-terminal regions of fibrillin-1 and -2 in a site similar to the binding sites for other bone morphogenetic proteins. However, in contrast, the prodomain of GDF-8 (myostatin) interacts with the glycosaminoglycan side chains of perlecan. The binding site for the GDF-8 prodomain is likely the heparan sulfate chain present on perlecan domain V. These results support and extend the emerging concept that TGFβ superfamily prodomains target their growth factor dimers to extracellular matrix macromolecules. In addition, biochemical studies of prodomain·growth factor complexes were performed to identify inactive complexes. For some members of the superfamily, the prodomain is noncovalently associated with its growth factor dimer in an inactive complex; for others, the prodomain·growth factor complex is active, even though the prodomain is noncovalently associated with its growth factor dimer. Results show that the BMP-10 prodomain, in contrast to BMP-4, -5, and -7 prodomains, can inhibit the bioactivity of the BMP-10 growth factor and suggest that the BMP-10 complex is like TGFβ and GDF-8 complexes, which can be activated by cleavage of the associated prodomain.

  9. Effect of anti-Mullerian hormone in culture medium on quality of mouse oocytes matured in vitro.

    PubMed

    Zhang, Yihui; Shao, Li; Xu, Yixin; Cui, Yigui; Liu, Jiayin; Chian, Ri-Cheng

    2014-01-01

    Anti-mullerian hormone (AMH) is thought to reflect the growth of follicles and the ovarian function. However, the role of AMH in culture medium during in vitro maturation (IVM) on oocyte quality and subsequent development potential is unclear. The objective of this study is to investigate the effect of recombinant human AMH (rh-AMH) supplemented into IVM medium on oocyte quality. Cumulus-oocyte complexes (COCs) were obtained from ICR mice and cultured in vitro with the different concentrations (0-1,000 ng/ml) of rh-AMH. Following 16-18 h of culture, quantitative PCR and ELISA were performed to analyze GDF9 and BMP15 mRNA expression and protein production from the oocytes. Subsequently, in vitro fertilization (IVF) and early embryonic development were employed to further evaluate the quality of in vitro matured oocytes. The results showed that AMH was only expressed in cumulus cells but not in the oocytes. However, AMH most specific receptor, AMHR-II, was expressed in both oocytes and cumulus cells. The levels of GDF9 and BMP15 expression and blastocyst formation rate were significantly increased (p<0.05) when the IVM medium was supplemented with 100 ng/ml of rh-AMH. With AdH1-SiRNA/AMH for knocking down of AMH expression during IVM significantly reduced (p<0.05) the levels of GDF9 and BMP15 expression and blastocysts formation rate. These results suggest that AHM improves oocytes quality by up-regulating GDF9 and BMP15 expressions during IVM.

  10. Bone morphogenetic protein 15 in the pro-mature complex form enhances bovine oocyte developmental competence.

    PubMed

    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.

  11. Effect of Anti-Mullerian Hormone in Culture Medium on Quality of Mouse Oocytes Matured In Vitro

    PubMed Central

    Zhang, Yihui; Shao, Li; Xu, Yixin; Cui, Yigui; Liu, Jiayin; Chian, Ri-Cheng

    2014-01-01

    Anti-mullerian hormone (AMH) is thought to reflect the growth of follicles and the ovarian function. However, the role of AMH in culture medium during in vitro maturation (IVM) on oocyte quality and subsequent development potential is unclear. The objective of this study is to investigate the effect of recombinant human AMH (rh-AMH) supplemented into IVM medium on oocyte quality. Cumulus-oocyte complexes (COCs) were obtained from ICR mice and cultured in vitro with the different concentrations (0–1,000 ng/ml) of rh-AMH. Following 16–18 h of culture, quantitative PCR and ELISA were performed to analyze GDF9 and BMP15 mRNA expression and protein production from the oocytes. Subsequently, in vitro fertilization (IVF) and early embryonic development were employed to further evaluate the quality of in vitro matured oocytes. The results showed that AMH was only expressed in cumulus cells but not in the oocytes. However, AMH most specific receptor, AMHR-II, was expressed in both oocytes and cumulus cells. The levels of GDF9 and BMP15 expression and blastocyst formation rate were significantly increased (p<0.05) when the IVM medium was supplemented with 100 ng/ml of rh-AMH. With AdH1-SiRNA/AMH for knocking down of AMH expression during IVM significantly reduced (p<0.05) the levels of GDF9 and BMP15 expression and blastocysts formation rate. These results suggest that AHM improves oocytes quality by up-regulating GDF9 and BMP15 expressions during IVM. PMID:24932501

  12. 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

  13. 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

  14. BMP15 suppresses progesterone production by down-regulating StAR via ALK3 in human granulosa cells.

    PubMed

    Chang, Hsun-Ming; Cheng, Jung-Chien; Klausen, Christian; Leung, Peter C K

    2013-12-01

    In addition to somatic cell-derived growth factors, oocyte-derived growth differentiation factor (GDF)9 and bone morphogenetic protein (BMP)15 play essential roles in female fertility. However, few studies have investigated their effects on human ovarian steroidogenesis, and fewer still have examined their differential effects or underlying molecular determinants. In the present study, we used immortalized human granulosa cells (SVOG) and human granulosa cell tumor cells (KGN) to compare the effects of GDF9 and BMP15 on steroidogenic enzyme expression and investigate potential mechanisms of action. In SVOG cells, neither GDF9 nor BMP15 affects the mRNA levels of P450 side-chain cleavage enzyme or 3β-hydroxysteroid dehydrogenase. However, treatment with BMP15, but not GDF9, significantly decreases steroidogenic acute regulatory protein (StAR) mRNA and protein levels as well as progesterone production. These suppressive effects, along with the induction of Sma and Mad-related protein (SMAD)1/5/8 phosphorylation, are attenuated by cotreatment with 2 different BMP type I receptor inhibitors (dorsomorphin and DMH-1). Furthermore, depletion of activin receptor-like kinase (ALK)3 using small interfering RNA reverses the effects of BMP15 on SMAD1/5/8 phosphorylation and StAR expression. Similarly, knockdown of ALK3 abolishes BMP15-induced SMAD1/5/8 phosphorylation in KGN cells. These results provide evidence that oocyte-derived BMP15 down-regulates StAR expression and decreases progesterone production in human granulosa cells, likely via ALK3-mediated SMAD1/5/8 signaling. Our findings suggest that oocyte may play a critical role in the regulation of progesterone to prevent premature luteinization during the late stage of follicle development.

  15. 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

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

    PubMed Central

    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

  17. 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.

  18. 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

  19. The effects of unilateral varicose ovarian vein on antioxidant capacity and oocyte quality in rat ovary

    PubMed Central

    Kehinde, Babatunde Adebayo; Abolhassani, Farid; Yazdekhasti, Hossein; Abbasi, Niloufar; Heydari, Leyla; Daneshi, Erfan; Rajabi, Zahra; Hamada, Alaa; Agarwal, Ashok; Abbasi, Mehdi

    2016-01-01

    Objective(s): Several researchers have reported the relationship between infertility in male and varicocele for so many years but the implication of varicocele in female patients is remains elusive. Here, we aim to examine the effects of unilateral varicose ovarian vein on antioxidant capacity and oocyte quality of rat ovary after the experimental creation of varicocele in female rats. Materials and Methods: In this study, thirty adult female albino rats were divided into three equal groups: Group 1 as the control group has 10 rats, Group 2 as the sham group has 10 rats and they underwent a sham operation and finally Group 3 has the varicocele group has 10 rats. Antioxidant assays for superoxide dismutase, glutathione peroxidase and catalase were performed using specific assay kits and gene expression for Bax, Bmp-15, Hsp-27 and Gdf-9 was done via real time PCR. Results: The adverse effects of the experimentally induced varicocele were reported and recorded on the left ovary compared to the right sided ovary (no varicocele induction) in the varicocele group. Real time PCR data shows that the expression of Gdf-9, Hsp-27 and Bmp-15 genes were all significantly reduced at p≤ 0.05. Conclusion: The results of this study show that reduced gene expression of Bmp-15, Gdf-9 and Hsp-27, increased gene expression of bax and an imbalance between pro-oxidant/antioxidant ratio are few of the several mechanisms by which varicocele may lead to infertility in female. PMID:27746868

  20. 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

  1. 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

  2. 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

  3. 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.

  4. The Global Drug Facility: a unique, holistic and pioneering approach to drug procurement and management

    PubMed Central

    Ryan, Timothy

    2007-01-01

    Abstract In January 2006, the Stop TB Partnership launched the Global Plan to Stop TB 2006–2015, which describes the actions and resources needed to reduce tuberculosis (TB) incidence, prevalence and deaths. A fundamental aim of the Global Plan is to expand equitable access to affordable high-quality anti-tuberculous drugs and diagnostics. A principal tool developed by the Stop TB Partnership to achieve this is the Global Drug Facility (GDF). This paper demonstrates the GDF’s unique, holistic and pioneering approach to drug procurement and management by analysing its key achievements. One of these has been to provide 9 million patient-treatments to 78 countries in its first 6 years of operation. The GDF recognized that the incentives provided by free or affordable anti-tuberculosis drugs are not sufficient to induce governments to improve their programmes’ standards and coverage, nor does the provision of free or affordable drugs guarantee that there is broad access to, and use of, drug treatment in cases where procurement systems are weak, regulatory hurdles exist or there are unreliable distribution and storage systems. Thus, the paper also illustrates how the GDF has contributed towards making sustained improvements in the capacity of countries worldwide to properly manage their anti-TB drugs. This paper also assesses some of the limitations, shortcomings and risks associated with the model. The paper concludes by examining the GDF’s key plans and strategies for the future, and the challenges associated with implementation. PMID:17639218

  5. Expression of growth/differentiation factor 1 in the nervous system: Conservation of a bicistronic structure

    SciTech Connect

    Lee, Sejin )

    1991-05-15

    Growth/differentiation factor 1 (GDF-1) is a recently described member of the transforming growth factor {beta} superfamily isolated from a day-8.5 mouse embryo cDNA library. Northern (RNA) analysis of embryonic mRNA detected two GDF-1 transcripts (1.4 kilobases (kb) and 3.0 kb in length) displaying distinct temporal patterns of expression. Only the 3.0-kb transcript was detected in adult tissues, where its expression was restricted almost exclusively to the central nervous system. Comparison of murine and human brain cDNA sequences corresponding to the 3.0-kb transcript revealed high conservation of two nonoverlapping open reading frames with poor conservation of the intervening spacer region and the putative 5{prime} and 3{prime} untranslated sequences. By immunohistochemical analysis, the protein encoded by the downstream open reading frame (GDF-1) was detected exclusively in the brain, spinal cord, and peripheral nerves in day-14.5 mouse embryos. The upstream open reading frame encodes a protein of unknown function containing multiple putative membrane-spanning domains. These findings raise the possibility that this mRNA may give rise to two different proteins.

  6. 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

  7. GPS Evidence for Northward Motion of the Sinai Block: Implications for E. Mediterranean Tectonics

    NASA Astrophysics Data System (ADS)

    Mahmoud, S.; Reilinger, R. E.; McClusky, S.; Vernant, P.; Tealeb, A.

    2004-12-01

    We present GPS yearly survey-mode observations for the period 1997 to 2003 at 12 sites within and adjacent to the Sinai Peninsula to constrain motion of the Sinai Block. Sites in the Sinai Peninsula show northerly motion relative to Africa (Nubian plate) at an average rate of 1.5 +/- 1 mm/yr north and -0.8 +/- 1 mm/yr west (1 sigma). While there is some variability, 11 of 12 sites show northerly motion strongly suggesting that the Sinai as a whole is moving northward relative to Nubia. Continuous IGS GPS sites in Israel, west of the Dead Sea fault (greater than 45 km from the fault trace and outside the main zone of elastic strain accumulation) show a similar northerly sense of motion relative to Africa (~ 2.7 +/- 1mm/yr north and -0.9 +/- 1 mm/yr west), suggesting that the entire Sinai Block south of Lebanon is characterized by northward translation relative to Africa. Using an elastic block model we estimate slip rates for the Gulf of Aqaba - southern Dead Sea fault system of 5.1 +/- 0.7 mm/yr, left lateral, and along the Gulf of Suez of 3.0 +/- 0.5 mm/yr left lateral. Present-day opening of the Gulf of Suez is less than 1 mm/yr. This block model provides a quantitative, kinematic explanation for the first order, present-day tectonic character of the easternmost Mediterranean, including the Dead Sea fault system, the Gulf of Suez, and the Cyprus Arc.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Ciguatera-like poisoning in the Mediterranean.

    PubMed

    Raikhlin-Eisenkraft, B; Finkelstein, Y; Spanier, E

    1988-12-01

    A case of group poisoning from the consumption of the fish Sarpa salpa, caught in the Mediterranean coastal waters of Israel, is presented. Mullets and rabbitfish caught at the same site caused no harm. This is the third case of ciguatera poisoning in the region and the first to be transferred by a fish which is not a Red Sea immigrant. It implies that toxic algae dinoflagellates, originating from the Red Sea, crossed the Suez Canal and found their way to the Mediterranean coastal waters.

  13. 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.

  14. 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

  15. Cooperative Effects of FOXL2 with the Members of TGF-β Superfamily on FSH Receptor mRNA Expression and Granulosa Cell Proliferation from Hen Prehierarchical Follicles

    PubMed Central

    Qin, Ning; Fan, Xian-Cong; Xu, Xiao-Xing; Tyasi, Thobela Louis; Li, Shi-Jun; Zhang, Ying-Ying; Wei, Man-Li; Xu, Ri-Fu

    2015-01-01

    Forkhead box L2 (FOXL2) is a member of the forkhead nuclear factor 3 gene family and plays an essential role in ovarian growth and maturation in mammals. However, its potential effects and regulative mechanism in development of chicken ovarian prehierarchical follicles remain unexplored. In this study, the cooperative effects of FOXL2 with activin A, growth differentiation factor-9 (GDF9) and follistatin, three members of the transforming growth factor beta (TGF-β) superfamily that were previously suggested to exert a critical role in follicle development was investigated. We demonstrated herein, using in-situ hybridization, Northern blot and immunohistochemical analyses of oocytes and granulosa cells in various sizes of prehierarchical follicles that both FOXL2 transcripts and FOXL2 proteins are predominantly expressed in a highly similar expression pattern to that of GDF9 gene. In addition, the FOXL2 transcript was found at lower levels in theca cells in the absence of GDF9. Furthermore, culture of granulosa cells (GCs) from the prehierarchical follicles (6–8 mm) in conditioned medium revealed that in the pcDNA3.0-FOXL2 transfected GCs, there was a more dramatic increase in FSHR mRNA expression after treatment with activin A (10 ng/ml) or GDF9 (100 ng/ml) for 24 h which caused a stimulatory effect on the GC proliferation. In contrast, a significant decrease of FSHR mRNA was detected after treatment with follistatin (50 ng/ml) and resulted in an inhibitory effect on the cell proliferation. The results of this suggested that FOXL2 plays a bidirectional modulating role involved in the intracellular FSHR transcription and GC proliferation via an autocrine regulatory mechanism in a positive or negative manner through cooperation with activin A and/or GDF9, and follistatin in the hen follicle development. This cooperative action may be mediated by the examined Smad signals and simultaneously implicated in modulation of the StAR, CCND2, and CYP11A1 expression. PMID

  16. Cooperative Effects of FOXL2 with the Members of TGF-β Superfamily on FSH Receptor mRNA Expression and Granulosa Cell Proliferation from Hen Prehierarchical Follicles.

    PubMed

    Qin, Ning; Fan, Xian-Cong; Xu, Xiao-Xing; Tyasi, Thobela Louis; Li, Shi-Jun; Zhang, Ying-Ying; Wei, Man-Li; Xu, Ri-Fu

    2015-01-01

    Forkhead box L2 (FOXL2) is a member of the forkhead nuclear factor 3 gene family and plays an essential role in ovarian growth and maturation in mammals. However, its potential effects and regulative mechanism in development of chicken ovarian prehierarchical follicles remain unexplored. In this study, the cooperative effects of FOXL2 with activin A, growth differentiation factor-9 (GDF9) and follistatin, three members of the transforming growth factor beta (TGF-β) superfamily that were previously suggested to exert a critical role in follicle development was investigated. We demonstrated herein, using in-situ hybridization, Northern blot and immunohistochemical analyses of oocytes and granulosa cells in various sizes of prehierarchical follicles that both FOXL2 transcripts and FOXL2 proteins are predominantly expressed in a highly similar expression pattern to that of GDF9 gene. In addition, the FOXL2 transcript was found at lower levels in theca cells in the absence of GDF9. Furthermore, culture of granulosa cells (GCs) from the prehierarchical follicles (6-8 mm) in conditioned medium revealed that in the pcDNA3.0-FOXL2 transfected GCs, there was a more dramatic increase in FSHR mRNA expression after treatment with activin A (10 ng/ml) or GDF9 (100 ng/ml) for 24 h which caused a stimulatory effect on the GC proliferation. In contrast, a significant decrease of FSHR mRNA was detected after treatment with follistatin (50 ng/ml) and resulted in an inhibitory effect on the cell proliferation. The results of this suggested that FOXL2 plays a bidirectional modulating role involved in the intracellular FSHR transcription and GC proliferation via an autocrine regulatory mechanism in a positive or negative manner through cooperation with activin A and/or GDF9, and follistatin in the hen follicle development. This cooperative action may be mediated by the examined Smad signals and simultaneously implicated in modulation of the StAR, CCND2, and CYP11A1 expression.

  17. 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.

  18. "The Electric City": Sherbrooke et son paysage hydroelectrique (1880--1930)

    NASA Astrophysics Data System (ADS)

    Guillemette, Remi

    Ce memoire presente l'imbrication des elements hydroelectrique au sein du paysage de la ville de Sherbrooke entre 1880 et 1930. Nous cherchons a comprendre comment les nouveaux elements energetiques s'integrent a celui-ci et comment la population sherbrookoise se represente ces espaces transformes. Comment le paysage hydroelectrique, en tant qu'espace vu et vecu, interagit-il avec la societe sherbrookoise ? A l'interieur de cette problematique generale, nous chercherons a repondre a trois sous-questions. Quelles sont les transformations physiques et materielles engendrees par l'implantation de cette nouvelle technologie hydroelectrique sur le paysage urbain sherbrookois ? Qu'est-ce que les differents groupes valorisent au sein du paysage ? Quel sens prennent ces nouveaux paysages pour les Sherbrookois ? En effet, l'etude du developpement rapide du potentiel hydroelectrique de la riviere Magog nous amene a demontrer que l'exploitation des ressources energetiques a profondement transforme le paysage de Sherbrooke : vastes modifications du trace des cours d'eau, apparition de batiments specifiques a la production energetique, structures de distributions et infrastructures permettant l'illumination de la ville. Nous avancons aussi que differents groupes d'individus ne valorisent pas les memes elements paysagers. Finalement, nous proposons que le regard porte par les citoyens sur le paysage energetique est tributaire de l'usage qu'ils en font. Comme la fonction des elements energetiques paysagers evolue, le regard qu' ils portent vers ces structures se transforme lui aussi. Mots cles: histoire de Sherbrooke, paysage, hydroelectricite, electricite, transformation de l'espace, histoire environnementale

  19. 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.

  20. Evidence for deep-water evaporite deposition in the Miocene Kareem Formation, Gemsa basin, eastern Egypt

    SciTech Connect

    May, J.A.; Stonecipher, S.A.; Steinmetz, J.C. ); Dyess, J.N. )

    1991-03-01

    The correct interpretation of intercalated Miocene siliciclastics and evaporites of Gemsa basin is crucial for understanding early rift tectonics of the Gulf of Suez, pinpointing the timing of isolation of the Gulf from the Mediterranean, and developing exploration plays. Evaporites of the Kareem Formation comprise celestites and massive, 'chicken-wire,' and laminated anhydrites. Although previously interpreted as sabkha deposits; sedimentologic, petrographic, and paleontologic analyses indicate these evaporites more likely formed in a submarine setting. Marls that encase the evaporites contain a diverse and abundant assemblage of nannoplankton, planktonic foraminifera, diatoms, pteropods, and fish scales indicative of basinal deposition. Associated turbidites also denote deep-water sedimentation. The paucity of benthic diatoms and foraminifera, plus the presence of unburrowed shales, phosphate nodules, early ferroan carbonate cements, and authigenic pyrite, suggest periodic anoxic, or at least disaerobic, bottom waters. These sequences probably represent partial isolation of the Gulf of Suez by middle Miocene, producing periodic basin restriction and evaporative drawdown. Episodes of increasing salinity likely caused the progressive decreases in foram abundance and diversity in marls beneath the anhydrites, culminating in subaqueous evaporite formation. Diverse, indigenous nannoplankton assemblages from shale seams within the anhydrites suggest Gemsa basin was stratified; shallow open-marine conditions coexisted with anhydrite crystallization from deeper hypersaline waters.

  1. Estimating Curie Point Depth and Heat Flow Map for Northern Red Sea Rift of Egypt and Its Surroundings, from Aeromagnetic Data

    NASA Astrophysics Data System (ADS)

    Saleh, Salah; Salk, Müjgan; Pamukçu, Oya

    2013-05-01

    In this study, we aim to map the Curie point depth surface for the northern Red Sea rift region and its surroundings based on the spectral analysis of aeromagnetic data. Spectral analysis technique was used to estimate the boundaries (top and bottom) of the magnetized crust. The Curie point depth (CPD) estimates of the Red Sea rift from 112 overlapping blocks vary from 5 to 20 km. The depths obtained for the bottom of the magnetized crust are assumed to correspond to Curie point depths where the magnetic layer loses its magnetization. Intermediate to deep Curie point depth anomalies (10-16 km) were observed in southern and central Sinai and the Gulf of Suez (intermediate heat flow) due to the uplifted basement rocks. The shallowest CPD of 5 km (associated with very high heat flow, ~235 mW m-2) is located at/around the axial trough of the Red Sea rift region especially at Brothers Island and Conrad Deep due to its association with both the concentration of rifting to the axial depression and the magmatic activity, whereas, beneath the Gulf of Aqaba, three Curie point depth anomalies belonging to three major basins vary from 10 km in the north to about 14 km in the south (with a mean heat flow of about 85 mW m-2). Moreover, low CPD anomalies (high heat flow) were also observed beneath some localities in the northern part of the Gulf of Suez at Hammam Fraun, at Esna city along River Nile, at west Ras Gharib in the eastern desert and at Safaga along the western shore line of the Red Sea rift. These resulted from deviatoric tensional stresses developing in the lithosphere which contribute to its further extension and may be due to the opening of the Gulf of Suez and/or the Red Sea rift. Furthermore, low CPD (with high heat flow anomaly) was observed in the eastern border of the study area, beneath northern Arabia, due to the quasi-vertical low-velocity anomaly which extends into the lower mantle and may be related to volcanism in northern Arabia. Dense microearthquakes

  2. Bone morphogenetic protein 4 (BMP4) induces buffalo (Bubalus bubalis) embryonic stem cell differentiation into germ cells.

    PubMed

    Shah, Syed Mohmad; Saini, Neha; Ashraf, Syma; Singh, Manoj Kumar; Manik, Radhey Sham; Singla, Suresh Kumar; Palta, Prabhat; Chauhan, Manmohan Singh

    2015-12-01

    The aim of the present study was to investigate the effect of Bone morphogenetic protein 4 (BMP4) stimulation on differentiation of buffalo embryonic stem (ES) cells into germ lineage cells. ES cells were subjected to in vitro differentiation in floating and adherent cultures, under different BMP4 concentrations (20, 50 and 100 ngml(-1)) for different culture intervals (4, 8 and 14 days). qPCR analysis revealed that BMP4 at a concentration of 50-100 ngml(-1) for a culture period of 14 days led to maximum induction of germ lineage genes like DAZL, VASA, PLZF (PGC-specific); SYCP3, MLH1, TNP1/2 and PRM2 (Meiotic genes); BOULE and TEKT1 (Spermatocyte markers); GDF9, ZP2 and 3 (Oocyte markers). The expression levels of all the genes were significantly higher under BMP4 differentiation as compared to BMP4 + NOGGIN and spontaneously differentiated cultures. Immunocytochemical analysis of embryoid bodies (EBs) and monolayer adherent cultures revealed expression of PGC- (c-KIT, DAZL and VASA); Meiotic- (SYCP3, MLH1 and PROTAMINE1); Spermatocyte- (ACROSIN and HAPRIN); and Oocyte- markers (GDF9 and ZP4). Western blotting was positive for VASA, GDF9 and ZP4. Oocyte-like structures (OLS) obtained in monolayer differentiated cultures harbored a big nucleus and a ZP4 coat. They showed embryonic development and progressed through 2-cell, 4-cell, 8-cell and blastocyst-like structures. Global DNA methylation analysis showed significantly (p < 0.05) decreased levels of 5-methyl-2-deoxycytidine in EBs obtained in optimum differentiation medium. The expression of meiotic markers coupled with expression of spermatocyte and oocyte markers is an indication of post-meiotic progression into spermatogenesis and oogenesis, respectively.

  3. 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

  4. Anti-Müllerian hormone is a gonadal cytokine with two circulating forms and cryptic actions.

    PubMed

    McLennan, Ian S; Pankhurst, Michael W

    2015-09-01

    Anti-Müllerian hormone (AMH) is a multi-faceted gonadal cytokine. It is present in all vertebrates with its original function in phylogeny being as a regulator of germ cells in both sexes, and as a prime inducer of the male phenotype. Its ancient functions appear to be broadly conserved in mammals, but with this being obscured by its overt role in triggering the regression of the Müllerian ducts in male embryos. Sertoli and ovarian follicular cells primarily release AMH as a prohormone (proAMH), which forms a stable complex (AMHN,C) after cleavage by subtilisin/kexin-type proprotein convertases or serine proteinases. Circulating AMH is a mixture of proAMH and AMHN,C, suggesting that proAMH is activated within the gonads and putatively by its endocrine target-cells. The gonadal expression of the cleavage enzymes is subject to complex regulation, and the preliminary data suggest that this influences the relative proportions of proAMH and AMHN,C in the circulation. AMH shares an intracellular pathway with the bone morphogenetic protein (BMP) and growth differentiation factor (GDF) ligands. AMH is male specific during the initial stage of development, and theoretically should produce male biases throughout the body by adding a male-specific amplification of BMP/GDF signalling. Consistent with this, some of the male biases in neuron number and the non-sexual behaviours of mice are dependent on AMH. After puberty, circulating levels of AMH are similar in men and women. Putatively, the function of AMH in adulthood maybe to add a gonadal influence to BMP/GDF-regulated homeostasis.

  5. Real-time gamma imaging of technetium transport through natural and engineered porous materials for radioactive waste disposal.

    PubMed

    Corkhill, Claire L; Bridge, Jonathan W; Chen, Xiaohui C; Hillel, Phil; Thornton, Steve F; Romero-Gonzalez, Maria E; Banwart, Steven A; Hyatt, Neil C

    2013-12-01

    We present a novel methodology for determining the transport of technetium-99m, a γ-emitting metastable isomer of (99)Tc, 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 (99m)Tc activity were collected at millimeter-resolution using decay-corrected gamma camera images. Pulse-inputs of ~20 MBq (99m)Tc 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 (99m)Tc 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 (99)Tc 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.

  6. 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

  7. Gene Expression of Monocarboxylate Transporters and Oocyte-secreted Factors in Bovine Cumulus-oocyte Complexes Selected by Brilliant Cresyl Blue.

    PubMed

    Lopes, E F; Marques, L S; Duranti, R G; de Oliveira, A T D; Lopes, R F F; Rodrigues, J L

    2015-10-01

    Oocyte selection based on the brilliant cresyl blue (BCB) staining test has been successfully used to differentiate between competent and incompetent bovine oocytes. Here, the expression of genes involved in transport of monocarboxylates (Mct1-4) and oogenesis specific genes (Bmp15, Gdf9 and Has2) in BCB+ and BCB- selected immature and mature bovine cumulus-oocyte complexes (COC) was evaluated. In order to find specific molecular markers to characterize successful oocyte maturation, our study was also aimed at identifying the expression of Mcts and oogenesis specific genes in denuded oocytes and cumulus cells. Immature COCs morphological appropriate were (i) stained with 26 mm BCB for 90 min before IVM, (ii) exposed to same incubation conditions as stained COCs, but without BCB (holding group) or (iii) transferred into a maturation medium immediately after morphological selection (control group). mRNA expression was investigated by RT-PCR in COCs before and after IVM. No relationship was observed in the relative expression of Has2, Gdf9, Bmp15 or Mct1, 2 and 4 transcripts between BCB+ and BCB- COCs. Transcripts analysis showed that Gdf9 and Bmp15 in BCB+, BCB- and holding groups were up-regulated (p < 0.05) before IVM, while Has2 was up-regulated (p < 0.01) after IVM in the control group. Other genes remained stable during maturation (Mct1, 2 and 4). Our results showed, for the first time, Mct1, 2 and 4 expression in bovine COCs. Mct1 and Mct4 transcripts were present in denuded oocytes and cumulus cell, while Mct2 was detected only in cumulus cells. These differences between the three isoforms in localization suggest unique roles for each in monocarboxylate transport during maturation.

  8. 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

  9. Metabolomic profiles indicate distinct physiological pathways affected by two loci with major divergent effect on Bos taurus growth and lipid deposition.

    PubMed

    Weikard, Rosemarie; Altmaier, Elisabeth; Suhre, Karsten; Weinberger, Klaus M; Hammon, Harald M; Albrecht, Elke; Setoguchi, Kouji; Takasuga, Akiko; Kühn, Christa

    2010-10-01

    Identifying trait-associated genetic variation offers new prospects to reveal novel physiological pathways modulating complex traits. Taking advantage of a unique animal model, we identified the I442M mutation in the non-SMC condensin I complex, subunit G (NCAPG) gene and the Q204X mutation in the growth differentiation factor 8 (GDF8) gene as substantial modulators of pre- and/or postnatal growth in cattle. In a combined metabolomic and genotype association approach, which is the first respective study in livestock, we surveyed the specific physiological background of the effects of both loci on body-mass gain and lipid deposition. Our data provided confirming evidence from two historically and geographically distant cattle populations that the onset of puberty is the key interval of divergent growth. The locus-specific metabolic patterns obtained from monitoring 201 plasma metabolites at puberty mirror the particular NCAPG I442M and GDF8 Q204X effects and represent biosignatures of divergent physiological pathways potentially modulating effects on proportional and disproportional growth, respectively. While the NCAPG I442M mutation affected the arginine metabolism, the 204X allele in the GDF8 gene predominantly raised the carnitine level and had concordant effects on glycerophosphatidylcholines and sphingomyelins. Our study provides a conclusive link between the well-described growth-regulating functions of arginine metabolism and the previously unknown specific physiological role of the NCAPG protein in mammalian metabolism. Owing to the confirmed effect of the NCAPG/LCORL locus on human height in genome-wide association studies, the results obtained for bovine NCAPG might add valuable, comparative information on the physiological background of genetically determined divergent mammalian growth.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. Immunolocalization of Growth, Inhibitory, and Proliferative Factors Involved in Initial Ovarian Folliculogenesis From Adult Common Squirrel Monkey (Saimiri collinsi)

    PubMed Central

    Brito, A. B.; Domingues, S. F. S.; Santos, R. R.; Amorim, C. A.

    2015-01-01

    We performed an immunohistochemical (IHC) study to determine the follicular expression of growth differentiation factor 9 (GDF-9), anti-Müllerian hormone (AMH), Kit Ligand (KL), and c-Kit in squirrel monkey ovary. Ovarian tissue fragments from 4 squirrel monkeys were collected by laparotomy and processed for classical histology and IHC. Additionally, follicle development was assessed by Ki67 immunostaining to evaluate proliferative status of granulosa cells. A total of 4025 follicles were examined (1475 for classical histology and 2550 for immunohistochemistry). More than 80% of the evaluated follicles were morphologically normal. The GDF-9 protein was detectable in oocyte cytoplasm from primordial (100%), primary (99.1%), and secondary (100%) follicles. The AMH was not expressed in primordial follicles but just in few primary follicles (13.8%). On the other hand, it was highly expressed in granulosa cells from secondary follicles (67.9%). c-Kit, KL receptor, was found in the oolemma of primordial (100%), primary (100%), and secondary (100%) follicles. The KL expression was observed in oocytes and granulosa cells from primordial (94.9%), primary (91.6%) and secondary follicles (100%). Ki67 immunostaining was observed in granulosa cells from primary (5.7%) and secondary (54.8%) follicles but not in primordial follicles. In conclusion, we described the localization of GDF-9, KL, c-Kit, and Ki67 proteins and confirmed the presence of AMH protein in preantral follicles from squirrel monkey. Our results offer contribution for understanding of folliculogenesis in neotropical nonhuman primates. Moreover, these markers can be used to assess follicular viability and functionality after cryopreservation, transplantation, or in vitro culture of ovarian tissue. PMID:24784715

  15. Effects of jacalin and follicle-stimulating hormone on in vitro goat primordial follicle activation, survival and gene expression.

    PubMed

    Ribeiro, Regislane P; Portela, Antonia M L R; Silva, Anderson W B; Costa, José J N; Passos, José R S; Cunha, Ellen V; Souza, Glaucinete B; Saraiva, Márcia V A; Donato, Mariana A M; Peixoto, Christina A; van den Hurk, Robert; Silva, José R V

    2015-08-01

    This study aims to investigate the effects of jacalin and follicle-stimulating hormone (FSH) on activation and survival of goat primordial follicles, as well as on gene expression in cultured ovarian tissue. Ovarian fragments were cultured for 6 days in minimum essential medium (MEM) supplemented with jacalin (10, 25, 50 or 100 μg/ml - Experiment 1) or in MEM supplemented with jacalin (50 μg/ml), FSH (50 ng/ml) or both (Experiment 2). Non-cultured and cultured tissues were processed for histological and ultrastructural analysis. Cultured tissues from Experiment 2 were also stored to evaluate the expression of BMP-15, KL (Kit ligand), c-kit, GDF-9 and proliferating cell nuclear antigen (PCNA) by real-time polymerase chain reaction (PCR). The results of Experiment 1 showed that, compared with tissue that was cultured in control medium, the presence of 50 μg/ml of jacalin increased both the percentages of developing follicles and viability. In Experiment 2, after 6 days, higher percentages of normal follicles were observed in tissue cultured in presence of FSH, jacalin or both, but no synergistic interaction between FSH and jacalin was observed. These substances had no significant effect on the levels of mRNA for BMP-15 and KL, but FSH increased significantly the levels of mRNA for PCNA and c-kit. On the other hand, jacalin reduced the levels of mRNA for GDF-9. In conclusion, jacalin and FSH are able to improve primordial follicle activation and survival after 6 days of culture. Furthermore, presence of FSH increases the expression of mRNA for PCNA and c-kit, but jacalin resulted in lower GDF-9 mRNA expression. PMID:24869637

  16. Growth differentiation factor-15 encodes a novel microRNA 3189 that functions as a potent regulator of cell death

    PubMed Central

    Jones, M F; Ling Li, X; Subramanian, M; Shabalina, Svetlana A; Hara, T; Zhu, Y; Huang, J; Yang, Y; Wakefield, L M; Prasanth, K V; Lal, A

    2015-01-01

    According to the latest version of miRBase, approximately 30% of microRNAs (miRNAs) are unique to primates, but the physiological function of the vast majority remains unknown. In this study, we identified miR-3189 as a novel, p53-regulated, primate-specific miRNA embedded in the intron of the p53-target gene GDF15. Antagonizing miR-3189 increased proliferation and sensitized cells to DNA damage-induced apoptosis, suggesting a tumor suppressor function for endogenous miR-3189. Identification of genome-wide miR-3189 targets revealed that miR-3189 directly inhibits the expression of a large number of genes involved in cell cycle control and cell survival. In addition, miR-3189 downregulated the expression of multiple p53 inhibitors resulting in elevated p53 levels and upregulation of several p53 targets including p21 (CDKN1A), GADD45A and the miR-3189 host gene GDF15, suggesting miR-3189 auto-regulation. Surprisingly, miR-3189 overexpression in p53-/- cells upregulated a subset of p53-targets including GDF15, GADD45A, and NOXA, but not CDKN1A. Consistent with these results, overexpression of miR-3189 potently induced apoptosis and inhibited tumorigenicity in vivo in a p53-independent manner. Collectively, our study identified miR-3189 as a novel, primate-specific miRNA whose effects are mediated by both p53-dependent and p53-independent mechanisms. miR-3189 may, therefore, represent a novel tool that can be utilized therapeutically to induce a potent proapoptotic effect even in p53-deficient tumors. PMID:25698447

  17. 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

  18. 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

  19. 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

  20. Human Masseter Muscle Fiber Type Properties, Skeletal Malocclusions, and Muscle Growth Factor Expression

    PubMed Central

    Sciote, James Joseph; Horton, Michael J.; Rowlerson, Anthea M.; Ferri, Joel; Close, John M.; Raoul, Gwenael

    2013-01-01

    Purpose We identified masseter muscle fiber type property differences in subjects with dentofacial deformities. Patients and Methods Samples of masseter muscle were collected from 139 young adults during mandibular osteotomy procedures to assess mean fiber areas and percent tissue occupancies for the 4 fiber types that comprise the muscle. Subjects were classified into 1 of 6 malocclusion groups based on the presence of a skeletal Class II or III sagittal dimension malocclusion and either a skeletal open, deep, or normal bite vertical dimension malocclusion. In a subpopulation, relative quantities of the muscle growth factors IGF-I and GDF-8 gene expression were quantified by real-time polymerase chain reaction. Results Fiber properties were not different in the sagittal malocclusion groups, but were very different in the vertical malocclusion groups (P ≤ .0004). There were significant mean fiber area differences for type II (P ≤ .0004) and type neonatal—atrial (P = .001) fiber types and for fiber percent occupancy differences for both type I–II hybrid fibers and type II fibers (P ≤ .0004). Growth factor expression differed by gender for IGF-I (P = .02) and GDF-8 (P < .01). The ratio of IGF-I:GDF-8 expression associates with type I and II mean fiber areas. Conclusion Fiber type properties are very closely associated with variations in vertical growth of the face, with statistical significance for overall comparisons at P ≤ .0004. An increase in masseter muscle type II fiber mean fiber areas and percent tissue occupancies is inversely related to increases in vertical facial dimension. PMID:21821327

  1. Genetics of human isolated acromesomelic dysplasia.

    PubMed

    Khan, Saadullah; Basit, Sulman; Khan, Muzammil Ahmad; Muhammad, Noor; Ahmad, Wasim

    2016-04-01

    Acromesomelic dysplasia is a type of skeletal malformation affecting distal and middle segments of the extremities. It occurs in both isolated (non-syndromic) and syndromic forms. In later case, it shows association with cardiac, respiratory, neurological and genital abnormalities. Acromesomelic dysplasia segregates in autosomal recessive mode. Mutations in three genes (GDF5, NPR2, BMPR1B) have been reported to cause different forms of acromesomelic dysplasia. In the present review, we have discussed clinical spectrum, genetics and signalopathies of isolated acromesomelic dysplasias. PMID:26926249

  2. Genetics of human isolated acromesomelic dysplasia.

    PubMed

    Khan, Saadullah; Basit, Sulman; Khan, Muzammil Ahmad; Muhammad, Noor; Ahmad, Wasim

    2016-04-01

    Acromesomelic dysplasia is a type of skeletal malformation affecting distal and middle segments of the extremities. It occurs in both isolated (non-syndromic) and syndromic forms. In later case, it shows association with cardiac, respiratory, neurological and genital abnormalities. Acromesomelic dysplasia segregates in autosomal recessive mode. Mutations in three genes (GDF5, NPR2, BMPR1B) have been reported to cause different forms of acromesomelic dysplasia. In the present review, we have discussed clinical spectrum, genetics and signalopathies of isolated acromesomelic dysplasias.

  3. Are There Oceanographic Explanations for the Israelites'Crossing of the Red Sea?.

    NASA Astrophysics Data System (ADS)

    Nof, Doron; Paldor, Nathan

    1992-03-01

    Two relatively simple physical oceanographic processes are suggested as plausible explanations for the biblical description of the Israelites' Crossing of the Red Sea during their exodus from Egypt. The first involves strong wind that blows along the Gulf of Suez and pushes the water a considerable distance away from the regular shoreline. This process is examined with the aid of a simple conceptual model consisting of a shallow, narrow, and long channel (corresponding to the Gulf of Suez) connected to a large body of water (corresponding to the main body of the Red Sea). Uniform wind is allowed to blow over the entire gulf for a period of about a day and the resulting phenomena are examined by solving the appropriate governing equations.It is shown that, in a similar fashion to the familiar wind setup in a long and narrow lake, the water at the edge of the gulf slowly recedes away from its original prewind position. The receding distance of the shoreline and the associated sea level drop are computed by solving the nonlinear equation that governs the motion resulting from the wind. It is found that, even for moderate storms with wind speed of about 20 s1 receding distance of more than 1 km and a sea level drop of more than 2.5 m are obtained. These relatively high values are a result of the unique geometry of the gulf (i.e., its rather small width-to-length and depth-to-length ratios) and the nonlinearity of the governing equation. Upon an abrupt relaxation of the wind, the water returns to its prewind position as a fast (nonlinear) gravity wave that floods the entire receding zone within minutes. It is suggested that the crossing occurred while the water receded and that the drowning of the Egyptians was a result of the rapidly returning wave.The second possible mechanism that is considered is a tsunami (i.e., a flood resulting from an earthquake under the sea)m that arrived at the Gulf of Suez from the main body of the Red Sea. In a similar fashion to the wind

  4. 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

  5. Stress analysis and tectonic trends of southern Sinai Peninsula, using potential field data analysis and anisotropy technique

    NASA Astrophysics Data System (ADS)

    Saleh, Salah; Saleh, Ahmed

    2012-09-01

    The aim of the present work is to evaluate the stress direction and the tectonic trends of the study area using magnetic anisotropy and potential field data interpretations (Bouguer and aeromagnetic). The specific objective of the gravity and aeromagnetic interpretation is to establish the trend and depth of the structural configuration of the basement rocks. Horizontal gradient techniques could to delineate directions of deep sources and enabled tracing several faults, lineaments and tectonic boundaries of basement rocks. The trend analysis shows N40°-50°W, N10°-20°W and N10°-20°E which may be related to the Gulf of Suez, Red Sea and Gulf of Aqaba stresses. However, Euler Deconvolution technique was applied using the aeromagnetic data to provide reliable information about penetrated source depth (100 m and ˜10.0 km) and trends of the subsurface sources (principally in NW and NE directions). Moreover, representative 72 oriented rock samples have been collected from seven sites in the study area. The rock magnetic properties and magnetic anisotropy analysis have been determined for all the studied samples. The interpretation clearly defined magnetic lineation at all sites and anisotropy of magnetic susceptibility (AMS) parameters. The stress direction of the studied area has been evaluated using magnetic anisotropy and geophysical analysis. Generally the estimated geophysical data analysis (Bouguer and aeromagnetic) are well consistent with the AMS interpretations of this study. The results indicated that the directions of predominant faults and foliations are NW-SE (related to the Gulf of Suez and Red Sea rifting) which indicate that the main stress and tectonic trend is NE-SW, which is more predominant in southern Sinai region. Moreover, it is clear that, the studied area was affected also by less predominant sources trended in NE-SW direction, which related to the tectonic activity of Gulf of Aqaba. The least predominant is north 40°-50° east that is

  6. Stress analysis and tectonic trends of southern Sinai Peninsula, using potential field data analysis and anisotropy technique

    NASA Astrophysics Data System (ADS)

    Saleh, Salah; Saleh, Ahmed

    2012-09-01

    The aim of the present work is to evaluate the stress direction and the tectonic trends of the study area using magnetic anisotropy and potential field data interpretations (Bouguer and aeromagnetic). The specific objective of the gravity and aeromagnetic interpretation is to establish the trend and depth of the structural configuration of the basement rocks. Horizontal gradient techniques could to delineate directions of deep sources and enabled tracing several faults, lineaments and tectonic boundaries of basement rocks. The trend analysis shows N40°-50°W, N10°-20°W and N10°-20°E which may be related to the Gulf of Suez, Red Sea and Gulf of Aqaba stresses. However, Euler Deconvolution technique was applied using the aeromagnetic data to provide reliable information about penetrated source depth (100 m and ˜10.0 km) and trends of the subsurface sources (principally in NW and NE directions). Moreover, representative 72 oriented rock samples have been collected from seven sites in the study area. The rock magnetic properties and magnetic anisotropy analysis have been determined for all the studied samples. The interpretation clearly defined magnetic lineation at all sites and anisotropy of magnetic susceptibility ( AMS) parameters. The stress direction of the studied area has been evaluated using magnetic anisotropy and geophysical analysis. Generally the estimated geophysical data analysis (Bouguer and aeromagnetic) are well consistent with the AMS interpretations of this study. The results indicated that the directions of predominant faults and foliations are NW-SE (related to the Gulf of Suez and Red Sea rifting) which indicate that the main stress and tectonic trend is NE-SW, which is more predominant in southern Sinai region. Moreover, it is clear that, the studied area was affected also by less predominant sources trended in NE-SW direction, which related to the tectonic activity of Gulf of Aqaba. The least predominant is north 40°-50° east that is

  7. 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.

  8. 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.

  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. Rare Variants in the Notch Signaling Pathway Describe a Novel Type of Autosomal Recessive Klippel–Feil Syndrome

    PubMed Central

    Karaca, Ender; Yuregir, Ozge O.; Bozdogan, Sevcan T.; Aslan, Huseyin; Pehlivan, Davut; Jhangiani, Shalini N.; Akdemir, Zeynep C.; Gambin, Tomasz; Bayram, Yavuz; Atik, Mehmed M.; Erdin, Serkan; Muzny, Donna; Gibbs, Richard A.; Lupski, James R.

    2016-01-01

    Klippel–Feil syndrome is a rare disorder represented by a subgroup of segmentation defects of the vertebrae and characterized by fusion of the cervical vertebrae, low posterior hairline, and short neck with limited motion. Both autosomal dominant and recessive inheritance patterns were reported in families with Klippel–Feil. Mutated genes for both dominant (GDF6 and GDF3) and recessive (MEOX1) forms of Klippel–Feil syndrome have been shown to be involved in somite development via transcription regulation and signaling pathways. Heterotaxy arises from defects in proteins that function in the development of left–right asymmetry of the developing embryo. We describe a consanguineous family with a male proband who presents with classical Klippel–Feil syndrome together with heterotaxy (situs inversus totalis). The present patient also had Sprengel’s deformity, deformity of the sternum, and a solitary kidney. Using exome sequencing, we identified a homozygous frameshift mutation (c.299delT; p.L100fs) in RIPPLY2, a gene shown to play a crucial role in somitogenesis and participate in the Notch signaling pathway via negatively regulating Tbx6. Our data confirm RIPPLY2 as a novel gene for autosomal recessive Klippel–Feil syndrome, and in addition—from a mechanistic standpoint—suggest the possibility that mutations in RIPPLY2 could also lead to heterotaxy. PMID:26238661

  11. Major genes affecting ovulation rate in sheep

    PubMed Central

    2005-01-01

    Research conducted since 1980 in relation to inheritance patterns and DNA testing of major genes for prolificacy has shown that major genes have the potential to significantly increase the reproductive performance of sheep flocks throughout the world. Mutations that increase ovulation rate have been discovered in the BMPR-1B, BMP15 and GDF9 genes, and others are known to exist from the expressed inheritance patterns although the mutations have not yet been located. In the case of BMP15, four different mutations have been discovered but each produces the same phenotype. The modes of inheritance of the different prolificacy genes include autosomal dominant genes with additive effects on ovulation rate (BMPR-1B; Lacaune), autosomal over-dominant genes with infertility in homozygous females (GDF9), X-linked over-dominant genes with infertility in homozygous females (BMP15), and X-linked maternally imprinted genes (FecX2). The size of the effect of one copy of a mutation on ovulation rate ranges from an extra 0.4 ovulations per oestrus for the FecX2 mutation to an extra 1.5 ovulations per oestrus for the BMPR-1B mutation. A commercial DNA testing service enables some of these mutations to be used in genetic improvement programmes based on marker assisted selection. PMID:15601592

  12. Fast computation of a gated dipole field.

    PubMed

    Mengov, George; Georgiev, Kalin; Pulov, Stefan; Trifonov, Trifon; Atanassov, Krassimir

    2006-12-01

    We address the need to develop efficient algorithms for numerical simulation of models, based in part or entirely on adaptive resonance theory. We introduce modifications that speed up the computation of the gated dipole field (GDF) in the Exact ART neural network. The speed increase of our solution amounts to at least an order of magnitude for fields with more than 100 gated dipoles. We adopt a 'divide and rule' approach towards the original GDF differential equations by grouping them into three categories, and modify each category in a separate way. We decouple the slow-dynamics part - the neurotransmitters from the rest of system, solve their equations analytically, and adapt the solution to the remaining fast-dynamics processes. Part of the node activations are integrated by an unsophisticated numerical procedure switched on and off according to rules. The remaining activations are calculated at equilibrium. We implement this logic in a Generalized Net (GN) - a tool for parallel processes simulation which enables a fresh look at developing efficient models. Our software implementation of generalized nets appears to add little computational overhead.

  13. 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

  14. 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

  15. Molecular findings and clinical data in a cohort of 150 patients with anophthalmia/microphthalmia.

    PubMed

    Chassaing, N; Causse, A; Vigouroux, A; Delahaye, A; Alessandri, J-L; Boespflug-Tanguy, O; Boute-Benejean, O; Dollfus, H; Duban-Bedu, B; Gilbert-Dussardier, B; Giuliano, F; Gonzales, M; Holder-Espinasse, M; Isidor, B; Jacquemont, M-L; Lacombe, D; Martin-Coignard, D; Mathieu-Dramard, M; Odent, S; Picone, O; Pinson, L; Quelin, C; Sigaudy, S; Toutain, A; Thauvin-Robinet, C; Kaplan, Josseline; Calvas, Patrick

    2014-10-01

    Anophthalmia and microphthalmia (AM) are the most severe malformations of the eye, corresponding respectively to reduced size or absent ocular globe. Wide genetic heterogeneity has been reported and different genes have been demonstrated to be causative of syndromic and non-syndromic forms of AM. We screened seven AM genes [GDF6 (growth differentiation factor 6), FOXE3 (forkhead box E3), OTX2 (orthodenticle protein homolog 2), PAX6 (paired box 6), RAX (retina and anterior neural fold homeobox), SOX2 (SRY sex determining region Y-box 2), and VSX2 (visual system homeobox 2 gene)] in a cohort of 150 patients with isolated or syndromic AM. The causative genetic defect was identified in 21% of the patients (32/150). Point mutations were identified by direct sequencing of these genes in 25 patients (13 in SOX2, 4 in RAX, 3 in OTX2, 2 in FOXE3, 1 in VSX2, 1 in PAX6, and 1 in GDF6). In addition eight gene deletions (five SOX2, two OTX2 and one RAX) were identified using a semi-quantitative multiplex polymerase chain reaction (PCR) [quantitative multiplex PCR amplification of short fluorescent fragments (QMPSF)]. The causative genetic defect was identified in 21% of the patients. This result contributes to our knowledge of the molecular basis of AM, and will facilitate accurate genetic counselling.

  16. The genetic architecture of microphthalmia, anophthalmia and coloboma.

    PubMed

    Williamson, Kathleen A; FitzPatrick, David R

    2014-08-01

    Microphthalmia, anophthalmia and coloboma (MAC) are distinct phenotypes that represent a continuum of structural developmental eye defects. In severe bilateral cases (anophthalmia or severe microphthalmia) the genetic cause is now identifiable in approximately 80 percent of cases, with de novo heterozygous loss-of-function mutations in SOX2 or OTX2 being the most common. The genetic cause of other forms of MAC, in particular isolated coloboma, remains unknown in the majority of cases. This review will focus on MAC phenotypes that are associated with mutation of the genes SOX2, OTX2, PAX6, STRA6, ALDH1A3, RARB, VSX2, RAX, FOXE3, BMP4, BMP7, GDF3, GDF6, ABCB6, ATOH7, C12orf57, TENM3 (ODZ3), and VAX1. Recently reported mutation of the SALL2 and YAP1 genes are discussed in brief. Clinical and genetic features were reviewed in a total of 283 unrelated MAC cases or families that were mutation-positive from these 20 genes. Both the relative frequency of mutations in MAC cohort screens and the level of confidence in the assignment of disease-causing status were evaluated for each gene.

  17. 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

  18. Effects of increased muscle mass on mouse sagittal suture morphology and mechanics.

    PubMed

    Byron, Craig D; Borke, James; Yu, Jack; Pashley, David; Wingard, Christopher J; Hamrick, Mark

    2004-07-01

    The purpose of this study is to test predicted form-function relationships between cranial suture complexity and masticatory muscle mass and biomechanics in a mouse model. Specifically, to test the hypothesis that increased masticatory muscle mass increases sagittal suture complexity, we measured the fractal dimension (FD), temporalis mass, and temporalis bite force in myostatin-deficient (GDF8(-/-)) mice and wild-type CD-1 mice (all male, 6 months old). Myostatin is a negative regulator of muscle mass, and myostatin-deficient mice show a marked increase in muscle mass compared to normal mice. We predicted that increased sagittal suture complexity would decrease suture stiffness. The data presented here demonstrate that increased suture complexity (measured as FD) was observed in a hypermuscular mouse model (GDF8(-/-)) with significantly increased temporalis muscle mass and bite forces. Hypermuscular mice were also found to possess suture connective tissue that was less stiff (i.e., underwent more displacement before failure occurred) when loaded in tension. By decreasing stiffness, suture complexity apparently helps to dissipate mechanical loads within the cranium that are related to chewing. These results suggest that cranial suture connective tissue locally adapts to functional demands of the biomechanical suture environment. As such, cranial sutures provide a novel model for studies in connective tissue mechanotransduction.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. hNAG-1 increases lifespan by regulating energy metabolism and insulin/IGF-1/mTOR signaling.

    PubMed

    Wang, Xingya; Chrysovergis, Kali; Kosak, Justin; Kissling, Grace; Streicker, Mike; Moser, Glenda; Li, Ruifang; Eling, Thomas E

    2014-08-01

    Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) or GDF15 is a divergent member of the transforming growth factor beta (TGF-β) superfamily and mice expressing hNAG-1/hGDF15 have been shown to be resistant to HFD-induced obesity and inflammation. This study investigated if hNAG-1 increases lifespan in mice and its potential mechanisms. Here we report that female hNAG-1 mice had significantly increased both mean and median life spans in two transgenic lines, with a larger difference in life spans in mice on a HFD than on low fat diet. hNAG-1 mice displayed significantly reduced body and adipose tissue weight, lowered serum IGF-1, insulin and glucose levels, improved insulin sensitivity, and increased oxygen utilization, oxidative metabolism and energy expenditure. Gene expression analysis revealed significant differences in conserved gene pathways that are important regulators of longevity, including IGF-1, p70S6K, and PI3K/Akt signaling cascades. Phosphorylation of major components of IGF-1/mTOR signaling pathway was significantly lower in hNAG-1mice. Collectively, hNAG-1 is an important regulator of mammalian longevity and may act as a survival factor. Our study suggests that hNAG-1 has potential therapeutic uses in obesity-related diseases where life span is frequently shorter. PMID:25239873

  4. Rare variants in the notch signaling pathway describe a novel type of autosomal recessive Klippel-Feil syndrome.

    PubMed

    Karaca, Ender; Yuregir, Ozge O; Bozdogan, Sevcan T; Aslan, Huseyin; Pehlivan, Davut; Jhangiani, Shalini N; Akdemir, Zeynep C; Gambin, Tomasz; Bayram, Yavuz; Atik, Mehmed M; Erdin, Serkan; Muzny, Donna; Gibbs, Richard A; Lupski, James R

    2015-11-01

    Klippel-Feil syndrome is a rare disorder represented by a subgroup of segmentation defects of the vertebrae and characterized by fusion of the cervical vertebrae, low posterior hairline, and short neck with limited motion. Both autosomal dominant and recessive inheritance patterns were reported in families with Klippel-Feil. Mutated genes for both dominant (GDF6 and GDF3) and recessive (MEOX1) forms of Klippel-Feil syndrome have been shown to be involved in somite development via transcription regulation and signaling pathways. Heterotaxy arises from defects in proteins that function in the development of left-right asymmetry of the developing embryo. We describe a consanguineous family with a male proband who presents with classical Klippel-Feil syndrome together with heterotaxy (situs inversus totalis). The present patient also had Sprengel's deformity, deformity of the sternum, and a solitary kidney. Using exome sequencing, we identified a homozygous frameshift mutation (c.299delT; p.L100fs) in RIPPLY2, a gene shown to play a crucial role in somitogenesis and participate in the Notch signaling pathway via negatively regulating Tbx6. Our data confirm RIPPLY2 as a novel gene for autosomal recessive Klippel-Feil syndrome, and in addition-from a mechanistic standpoint-suggest the possibility that mutations in RIPPLY2 could also lead to heterotaxy. © 2015 Wiley Periodicals, Inc. PMID:26238661

  5. Skeletal muscle-derived progenitors capable of differentiating into cardiomyocytes proliferate through myostatin-independent TGF-{beta} family signaling

    SciTech Connect

    Nomura, Tetsuya; Ueyama, Tomomi; Ashihara, Eishi; Tateishi, Kento; Asada, Satoshi; Nakajima, Norio; Isodono, Koji; Takahashi, Tomosaburo; Matsubara, Hiroaki Oh, Hidemasa

    2008-01-25

    The existence of skeletal muscle-derived stem cells (MDSCs) has been suggested in mammals; however, the signaling pathways controlling MDSC proliferation remain largely unknown. Here we report the isolation of myosphere-derived progenitor cells (MDPCs) that can give rise to beating cardiomyocytes from adult skeletal muscle. We identified that follistatin, an antagonist of TGF-{beta} family members, was predominantly expressed in MDPCs, whereas myostatin was mainly expressed in myogenic cells and mature skeletal muscle. Although follistatin enhanced the replicative growth of MDPCs through Smad2/3 inactivation and cell cycle progression, disruption of myostatin did not increase the MDPC proliferation. By contrast, inhibition of activin A (ActA) or growth differentiation factor 11 (GDF11) signaling dramatically increased MDPC proliferation via down-regulation of p21 and increases in the levels of cdk2/4 and cyclin D1. Thus, follistatin may be an effective progenitor-enhancing agent neutralizing ActA and GDF11 signaling to regulate the growth of MDPCs in skeletal muscle.

  6. 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

  7. Climate penalty for shifting shipping to the Arctic.

    PubMed

    Fuglestvedt, Jan S; Dalsøren, Stig Bjørløw; Samset, Bjørn Hallvard; Berntsen, Terje; Myhre, Gunnar; Hodnebrog, Øivind; Eide, Magnus Strandmyr; Bergh, Trond Flisnes

    2014-11-18

    The changing climate in the Arctic opens new shipping routes. A shift to shorter Arctic transit will, however, incur a climate penalty over the first one and a half centuries. We investigate the net climate effect of diverting a segment of Europe-Asia container traffic from the Suez to an Arctic transit route. We find an initial net warming for the first one-and-a-half centuries, which gradually declines and transitions to net cooling as the effects of CO2 reductions become dominant, resulting in climate mitigation only in the long term. Thus, the possibilities for shifting shipping to the Arctic confront policymakers with the question of how to weigh a century-scale warming with large uncertainties versus a long-term climate benefit from CO2 reductions. PMID:25347302

  8. Ship canals and aquatic ecosystems

    USGS Publications Warehouse

    Aron, William I.; Smith, Stanford H.

    1971-01-01

    Through a combination of ecosystem homeostasis and the perversity of man and nature, oftentimes the significant biological changes effected by environmental modifications are not detected until long after the initial change has taken place. The immediate impact, which may range from the spectacular to the undetectable, is a deceptive measure of the long-term and often more important changes in the ecosystem. Two major engineering achievements illustrate this premise: (i) construction of the Erie Canal, which provided access from the Atlantic Ocean to the Great Lakes, and the Welland Canal, which bypasses the block between Lakes Ontario and Erie created by Niagara Falls (Fig. 1), and (ii) construction of the Suez Canal between the Red Sea and the Mediterranean Sea.

  9. 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.

  10. Monogenean infestations and mortality in wild and cultured Red Sea fishes

    NASA Astrophysics Data System (ADS)

    Paperna, I.; Diamant, A.; Overstreet, R. M.

    1984-03-01

    Hyperinfection by the gill-infesting monogenean Allobivagina sp. (Microcotylea) caused mass mortalities in juveniles of Siganus luridus cultured in seawater earthen ponds and holding tanks in Eilat (Gulf of Aqaba, Red Sea). Other species of Siganus and adults of S. luridus cultured in the same systems acquired a low intensity of infestation. Most hyperinfected fish were emaciated and anaemic with hematocrit values below 10 %. Skin and mouth infestations by the monogenean Benedenia monticelli (Capsaloidea) caused mass mortalities in grey mullets (Mugilidae). These mortalities occurred in large individuals in wild populations of Liza carinata from lagoonal habitats in the Gulf of Suez and in most species of grey mullets cultured in Eilat. The intensity of infestation correlated positively with severity of infestation, and the common sites of infestation corresponded with areas of severe pathological alterations. Spontaneous recovery followed the climax of an epizootic, both for infested S. luridus and infested grey mullets. Decline in infestation coincided with remission of the pathological signs.

  11. 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.

  12. 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.

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

    PubMed

    Harmelin, Jean-Georges

    2014-12-09

    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.

  14. 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.

  15. 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.

  16. 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

  17. 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

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

    PubMed

    Ma, Lili; Chen, Yan; Mei, Si; Liu, Chunlian; Ma, Xiaohong; Li, Yongli; Jiang, Yinzhi; Ha, Lingxia; Xu, Xian

    2015-08-01

    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, respectively), while no significant differences were observed in the occurrence of the c.447C>T and c.969C>G mutations between the two groups (60.32, vs. 50% and 50.79, vs. 55.17%, respectively). 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

  19. Geomorphology in a Rifting Environment. Can Channel Profiles from Arid Sinai, Egypt, Provide Constraints on Tectonics?

    NASA Astrophysics Data System (ADS)

    Oswald, A.; Stüwe, K.

    2012-04-01

    Significant surface uplift along rift flanks results in the formation of rift-parallel mountain belts. The combination of uplift and erosion processes characterizes fluvial systems in the vicinity of the rift. Geometry of the drainage network and channel profiles may provide information on timing and geometry of rifting. However it is not clear if traditional approaches to fluvial erosion (e.g. the stream power approach) can be used to infer aspects of landscape evolution to areas, which show fluvial geomorphology, but are arid at present, like Sinai, Egypt. In this project we set out to test this and provide a description of channels as a database for our considerations. Sinai is located at a major rift system, the Red Sea, which branches into the Gulf of Suez and the Gulf of Aqaba bordering Sinai from West and South to South East, respectively. Uplift associated with the rifting exposed bedrock in Southern Sinai and topography of up to more than 2.5km, which also acts as a drainage divide between East and West. Despite Sinai's present day aridity, the large scale geomorphology appears to be characterized by fluvial features. In contrast to channels along the northern Gulf of Aqaba, channels draining to the Gulf of Suez show a more classical profile with clear knickpoints that seem however not to have mirgrated significantly from the basin-mountain transition. As the change to arid climate may have preserved to some state a previous configuration, the knickpoints may not be used to put a time frame on the uplift, but could in combination with paleoclimate data indicate changes in the relative importance of uplift versus erosion.

  20. 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.

  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. 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.

  3. 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.

  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. Expression of TGF-beta superfamily growth factors, their receptors, the associated SMADs and antagonists in five isolated size-matched populations of pre-antral follicles from normal human ovaries.

    PubMed

    Kristensen, Stine Gry; Andersen, Kasper; Clement, Christian Alexandro; Franks, Stephen; Hardy, Kate; Andersen, Claus Yding

    2014-04-01

    In mammals, members of the transforming growth factor-beta (TGF-β) superfamily are known to have key roles in the regulation of follicular growth and development. The aim of the study was to evaluate the expression of TGF-β superfamily growth factors, their receptors, downstream SMAD signalling molecules and TGF-β/bone morphogenetic protein (BMP) antagonists during early human folliculogenesis. Human pre-antral follicles were enzymatically isolated from surplus ovarian tissue obtained from women having ovarian cortical tissue frozen for fertility preservation. A total of 348 human pre-antral follicles, ranging from 40 to 200 µm in diameter, were isolated from ovarian tissue obtained from 15 women, aged 24-34 years. Isolated pre-antral follicles were grouped according to diameter in five size-matched populations spanning the primordial, primary and secondary stage follicles and analysed by whole-genome microarray analysis. Selected proteins/genes were analysed by immunocytochemistry and quantitative RT-PCR. TGF-β superfamily genes with overall highest mRNA expressions levels included growth differentiation factors 9 (GDF9), BMP15, BMP6, BMP-receptor-2 (BMPR2), anti-Müllerian hormone receptor 2 (AMHR2), TGFβR3, inhibin-α (INHA) and intracellular SMAD3 and SMAD4. Moreover, genes which were differentially expressed from the primordial to the late secondary stage follicles included GDF9, BMP15, AMH, INHBB, TGFβR3, SMAD4 and antagonists Follistatin (FST) and GREM1. Collectively, these data indicate that the active TGF-β superfamily pathways in early human folliculogenesis consist of primarily GDF9 combined with possible synergistic effects of BMP15 through the BMPR2 and intracellular activation of SMAD3 and SMAD4, and that AMH and INHBB are engaged in intrafollicular events from the onset of follicular growth. Moreover, the presence of multiple TGF-β/BMP antagonists imply that certain growth factors are subjected to local regulation on different levels that

  6. 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

  7. No Added Value of Novel Biomarkers in the Diagnostic Assessment of Patients Suspected of Acute Coronary Syndrome

    PubMed Central

    Poldervaart, Judith M.; Röttger, Emma; Dekker, Marieke S.; Zuithoff, Nicolaas P. A.; Verheggen, Peter W. H. M.; de Vrey, Evelyn A.; Wildbergh, Thierry X.; van ‘t Hof, Arnoud W. J.; Mosterd, Arend; Hoes, Arno W.

    2015-01-01

    Background Despite the availability of high-sensitive troponin (hs-cTnT), there is still room for improvement in the diagnostic assessment of patients suspected of acute coronary syndrome (ACS). Apart from serial biomarker testing, which is time-consuming, novel biomarkers like copeptin have been proposed to expedite the early diagnosis of suspected ACS in addition to hs-cTnT. We determined whether placenta derived growth factor (PlGF), soluble Fms-like tyrosine kinase 1 (sFlt-1), myoglobin, N-terminal prohormone B-type Natriuretic Peptide (NT-proBNP), growth-differentiation factor 15 (GDF-15) and copeptin improved early assessment of chest pain patients. Methods This prospective, single centre diagnostic FAME-ER study included patients presenting to the ED with symptoms suggestive of ACS. Blood was collected to measure biomarkers, notably, hs-cTnT was retrospectively assessed. Added value of markers was judged by increase in AUC using multivariable logistic regression. Results Of 453 patients enrolled, 149 (33%) received a final diagnosis of ACS. Hs-cTnT had the highest diagnostic value in both univariable and multivariable analysis. PPVs of the biomarkers ranged from 23.5% (PlGF) to 77.9% (hs-cTnT), NPVs from 67.0% (PlGF) to 86.4% (hs-cTnT). Only myoglobin yielded diagnostic value in addition to clinical symptoms and electrocardiography (ECG) (AUC of clinical model 0.80) with AUC of 0.84 (p<0.001). However, addition of hs-cTnT was superior (AUC 0.89, p<0.001). Addition of the biomarkers to our clinical model and hs-cTnT did not or only marginally (GDF-15) improved diagnostic performance. Conclusion When assessing patients suspected of ACS, only myoglobin had added diagnostic value beyond clinical symptoms and ECG. However, when combined with hs-cTnT, it yields no additional diagnostic value. PlGF, sFlt-1, NT-proBNP, GDF-15 and copeptin had no added value to the clinical model or hs-cTnT. PMID:26177390

  8. Association of novel polymorphisms of forkhead box L2 and growth differentiation factor-9 genes with egg production traits in local Chinese Dagu hens.

    PubMed

    Qin, N; Liu, Q; Zhang, Y Y; Fan, X C; Xu, X X; Lv, Z C; Wei, M L; Jing, Y; Mu, F; Xu, R F

    2015-01-01

    Transcription factor forkhead box L2 (FOXL2) and growth differentiation factor-9 (GDF9) genes have critical roles in the regulation of hen ovarian development. In the present study, these genes were explored as possible molecular markers associated with BW, hen-housed egg production, and egg weight in Chinese Dagu hens. Samples were analyzed using the PCR-single strand conformation polymorphism (PCR-SSCP) technique followed by sequencing analysis, and two novel single nucleotide polymorphisms (SNPs) were identified within these candidate genes. Among them, an A/G transition at base position 238 in the coding region of the FOXL2 gene and a G/T transversion at base position 1609 in exon 2 of the GDF9 gene were found to be polymorphic and named SNPs A238G and G1609T, respectively. The SNP A238G (FOXL2) leads to a nonsynonymous substitution (isoleucine77-to-valine), and when the 360 Dagu hen samples were divided into genotypes AA and AB, allele A was found to be present at a higher frequency. Furthermore, the AA genotype correlated with significantly higher hen-housed egg production at 30, 43, 57, and 66 wk of age and with a higher egg weight at 43 wk (P<0.05). For the SNP G1609T (GDF9), the hens were typed into TT and TC genotypes, with the T allele shown to be dominant. The TC genotype was also markedly correlated with higher hen-housed egg production and a higher egg weight (P<0.05). Moreover, four haplotypes were reconstructed based on these two SNPs, with the AATC haplotype found to be correlated with the highest hen-housed egg production at 30 to 66 wk of age and with higher egg weights at 43 wk (P<0.05). Collectively, the two SNPs identified in this study might be used as possible genetic molecular markers to aid in the improvement of egg production traits in chicken breeding.

  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.

  10. 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

  11. 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).

  12. Myostatin rapid sequence evolution in ruminants predates domestication.

    PubMed

    Tellgren, Asa; Berglund, Ann-Charlotte; Savolainen, Peter; Janis, Christine M; Liberles, David A

    2004-12-01

    Myostatin (GDF-8) is a negative regulator of skeletal muscle development. This gene has previously been implicated in the double muscling phenotype in mice and cattle. A systematic analysis of myostatin sequence evolution in ruminants was performed in a phylogenetic context. The myostatin coding sequence was determined from duiker (Sylvicapra grimmia caffra), eland (Taurotragus derbianus), gaur (Bos gaurus), ibex (Capra ibex), impala (Aepyceros melampus rednilis), pronghorn (Antilocapra americana), and tahr (Hemitragus jemlahicus). Analysis of nonsynonymous to synonymous nucleotide substitution rate ratios (Ka/Ks) indicates that positive selection may have been operating on this gene during the time of divergence of Bovinae and Antilopinae, starting from approximately 23 million years ago, a period that appears to account for most of the sequence difference between myostatin in these groups. These periods of positive selective pressure on myostatin may correlate with changes in skeletal muscle mass during the same period. PMID:15522803

  13. 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

  14. 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

  15. 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.

  16. Intertissue control of the nucleolus via a myokine-dependent longevity pathway.

    PubMed

    Demontis, Fabio; Patel, Vishal K; Swindell, William R; Perrimon, Norbert

    2014-06-12

    Recent evidence indicates that skeletal muscle influences systemic aging, but little is known about the signaling pathways and muscle-released cytokines (myokines) responsible for this intertissue communication. Here, we show that muscle-specific overexpression of the transcription factor Mnt decreases age-related climbing defects and extends lifespan in Drosophila. Mnt overexpression in muscle autonomously decreases the expression of nucleolar components and systemically decreases rRNA levels and the size of the nucleolus in adipocytes. This nonautonomous control of the nucleolus, a regulator of ribosome biogenesis and lifespan, relies on Myoglianin, a myokine induced by Mnt and orthologous to human GDF11 and Myostatin. Myoglianin overexpression in muscle extends lifespan and decreases nucleolar size in adipocytes by activating p38 mitogen-activated protein kinase (MAPK), whereas Myoglianin RNAi in muscle has converse effects. Altogether, these findings highlight a key role for myokine signaling in the integration of signaling events in muscle and distant tissues during aging.

  17. Association of bovine meat quality traits with genes included in the PPARG and PPARGC1A networks.

    PubMed

    Sevane, N; Armstrong, E; Cortés, O; Wiener, P; Wong, R Pong; Dunner, S

    2013-07-01

    Understanding which are the genetic variants underlying the nutritional and sensory properties of beef, enables improvement in meat quality. The aim of this study is to identify new molecular markers for meat quality through an association study using candidate genes included in the PPARG and PPARGC1A networks given their master role in coordinating metabolic adaptation in fat tissue, muscle and liver. Amongst the novel associations found in this study, selection of the positive marker variants of genes such as BCL3, LPL, PPARG, SCAP, and SCD will improve meat organoleptic characteristics and health by balancing the n-6 to n-3 fatty acid ratio in meat. Also previous results on GDF8 and DGAT1 were validated, and the novel ATF4, HNF4A and PPARGC1A associations, although slightly under the significance threshold, are consistent with their physiological roles. These data contribute insights into the complex gene-networks underlying economically important traits.

  18. Metals in bulk deposition and surface waters at two upland locations in northern England.

    PubMed

    Lawlor, A J; Tipping, E

    2003-01-01

    Concentrations of aluminium and minor metals (Mn, Ni, Cu, Zn, Sr, Cd, Ba, Pb) were measured in precipitation and surface water at two upland locations (Upper Duddon Valley, UDV; Great Dun Fell, GDF) in northern England for 1 year commencing April 1998. At both locations, the loads in bulk precipitation were at the lower ends of ranges reported for other rural and remote sites, for the period 1985-1995. The deposited metals were mostly in the dissolved form, and their concentrations tended to be greatest when rainfall volumes were low. The concentrations of Cu, Zn and Pb in deposition were correlated (r2 > or = 0.40) with concentrations of non-marine sulphate. Three streams, ranging in mean pH from 5.07 to 7.07, and with mean concentrations of dissolved organic carbon (DOC) < 1 mg l(-1). were monitored at UDV, and two pools (mean pH 4.89 and 6.83, mean DOC 22 and 15 mg l(-1)) at GDF. Aluminium and the minor metals were mainly in the dissolved form, and in the following ranges (means of 49-51 samples. microg l(-1)): Al 36-530. Mn 4.4-36, Ni 0.26-2.8, Cu 0.25-1.7, Zn 2.1-30, Cd 0.03-0.16, Ba 1.9-140, Pb 0.10-4.5. Concentrations were generally higher at GDF. Differences in metal concentrations between the two locations and between waters at each location, and temporal variations in individual waters, can be explained qualitatively in terms of sorption to solid-phase soil organic matter and mineral surfaces, complexation and transport by DOC, and chemical weathering. The UDV catchments are sinks for Pb and sources of Al, Mn, Sr, Cd and Ba. The GDF catchments are sources of Al, Mn, Ni, Zn, Sr, Cd and Ba. Other metals measured at the two locations are approximately in balance. Comparison of metal:silicon ratios in the surface waters with values for silicate rocks indicates enrichment of Ni and Cu, and substantial enrichment of Zn, Cd and Pb. These enrichments, together with high metal deposition in the past, make it likely that concentrations of the metals in the surface

  19. 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.

  20. Stimulation of tendon repair: mechanical loading, GDFs and platelets. A mini-review

    PubMed Central

    2007-01-01

    The repair of subcutaneous tendon ruptures can be stimulated by a single application of one of several growth factors [e.g. platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta, insulin-like growth factor (IGF)-1, vascular endothelial growth factor (VEGF), bone morphogenetic proteins (BMPs) like growth differentiation factor (GDF)-5, -6, -7] or by a thrombocyte concentrate (PRP). The response to these measures is dependent on the mechanical microenvironment, which is crucial for repair. So far, almost all research has been limited to rodent models, mostly using the rat Achilles tendon. Ruptured human Achilles tendons appear to be mechanically loaded in spite of immobilisation. This suggests that the mechanical microenvironment might be favourable for the clinical use of growth factors or platelets for this indication. New methods to quantitate human Achilles tendon repair have been developed. PMID:17583812

  1. 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

  2. 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

  3. 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

  4. Structure and luminescence of gadolinium-doped cubic boron nitride powder

    NASA Astrophysics Data System (ADS)

    Leonchik, S. V.; Karotki, A. V.

    2012-09-01

    The structural characteristics and chemical, morphological, and optical properties of cBN and cBN:Gd micropowders are studied by x-ray diffraction, energy-dispersive electron probe microanalysis (x-ray spectral microanalysis), and photoluminescence techniques. Cubic boron nitride (cBN) micropowders were synthesized at high pressures and temperatures from hexagonal boron nitride (hBN) micropowder and Li3N catalyst. cBN:Gd micropowders were synthesized from mixtures of hBN, Li3N, and GdF3 micropowders. A lattice parameter of a~3.615 Å is calculated for both types of powder (cBN and cBN:Gd). The photoluminescence spectra of the cBN:Gd powder are found to contain emission lines attributable to intracenter optical transitions of Gd3+ ions.

  5. 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;

  6. 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.

  7. [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

  8. Lessons from rare diseases of cartilage and bone.

    PubMed

    Gallagher, James A; Ranganath, Lakshminarayan R; Boyde, Alan

    2015-06-01

    Studying severe phenotypes of rare syndromes can elucidate disease mechanisms of more common disorders and identify potential therapeutic targets. Lessons from rare bone diseases contributed to the development of the most successful class of bone active agents, the bisphosphonates. More recent research on rare bone diseases has helped elucidate key pathways and identify new targets in bone resorption and bone formation including cathepsin K and sclerostin, for which drugs are now in clinical trials. By contrast, there has been much less focus on rare cartilage diseases and osteoarthritis (OA) remains a common disease with no effective therapy. Investigation of rare cartilage syndromes is identifying new potential targets in OA including GDF5 and lubricin. Research on the arthropathy of the ultra-rare disease alkaptonuria has identified several new features of the OA phenotype, including high density mineralized protrusions (HDMPs) which constitute a newly identified mechanism of joint destruction.

  9. 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.

  10. Developmental competence and gene expression of immature oocytes following liquid helium vitrification in bovine.

    PubMed

    Chen, Jun-Yi; Li, Xiao-Xia; Xu, Ya-Kun; Wu, Hua; Zheng, Jun-Jun; Yu, Xue-Li

    2014-12-01

    The objective of this study was to develop an effective ultra-rapid vitrification method and evaluate its effect on maturation, developmental competence and development-related gene expression in bovine immature oocytes. Bovine cumulus oocyte complexes were randomly allocated into three groups: (1) controls, (2) liquid nitrogen vitrification, and (3) liquid helium vitrification. Oocytes were vitrified and then warmed, the percentage of morphologically normal oocytes in liquid helium group (89.0%) was significantly higher (P<0.05) than that of the liquid nitrogen group (81.1%). When the vitrified-thawed oocytes were matured in vitro for 24h, the maturation rate in liquid helium group (50.6%) was higher (P<0.05) than liquid nitrogen group (42.6%). Oocyte