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  1. Neuroendocrine regulation of gonadotropin secretion in seasonally breeding birds

    PubMed Central

    Ubuka, Takayoshi; Bentley, George E.; Tsutsui, Kazuyoshi

    2013-01-01

    Seasonally breeding birds detect environmental signals, such as light, temperature, food availability, and presence of mates to time reproduction. Hypothalamic neurons integrate external and internal signals, and regulate reproduction by releasing neurohormones to the pituitary gland. The pituitary gland synthesizes and releases gonadotropins which in turn act on the gonads to stimulate gametogenesis and sex steroid secretion. Accordingly, how gonadotropin secretion is controlled by the hypothalamus is key to our understanding of the mechanisms of seasonal reproduction. A hypothalamic neuropeptide, gonadotropin-releasing hormone (GnRH), activates reproduction by stimulating gonadotropin synthesis and release. Another hypothalamic neuropeptide, gonadotropin-inhibitory hormone (GnIH), inhibits gonadotropin synthesis and release directly by acting on the pituitary gland or indirectly by decreasing the activity of GnRH neurons. Therefore, the next step to understand seasonal reproduction is to investigate how the activities of GnRH and GnIH neurons in the hypothalamus and their receptors in the pituitary gland are regulated by external and internal signals. It is possible that locally-produced triiodothyronine resulting from the action of type 2 iodothyronine deiodinase on thyroxine stimulates the release of gonadotropins, perhaps by action on GnRH neurons. The function of GnRH neurons is also regulated by transcription of the GnRH gene. Melatonin, a nocturnal hormone, stimulates the synthesis and release of GnIH and GnIH may therefore regulate a daily rhythm of gonadotropin secretion. GnIH may also temporally suppress gonadotropin secretion when environmental conditions are unfavorable. Environmental and social milieus fluctuate seasonally in the wild. Accordingly, complex interactions of various neuronal and hormonal systems need to be considered if we are to understand the mechanisms underlying seasonal reproduction. PMID:23531789

  2. Hormones in Synergy: Regulation of the Pituitary Gonadotropin Genes

    PubMed Central

    Thackray, Varykina G.; Mellon, Pamela L.; Coss, Djurdjica

    2009-01-01

    The precise interplay of hormonal influences that governs gonadotropin hormone production by the pituitary includes endocrine, paracrine and autocrine actions of hypothalamic gonadotropin-releasing hormone (GnRH), activin and steroids. However, most studies of hormonal regulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the pituitary gonadotrope have been limited to analyses of the isolated actions of individual hormones. LHβ and FSHβ subunits have distinct patterns of expression during the menstrual/estrous cycle as a result of the integration of activin, GnRH, and steroid hormone action. In this review, we focus on studies that delineate the interplay among these hormones in the regulation of LHβ and FSHβ gene expression in gonadotrope cells and discuss how signaling cross-talk contributes to differential expression. We also discuss how recent technological advances will help identify additional factors involved in the differential hormonal regulation of LH and FSH. PMID:19747958

  3. Regulation of gonadotropin-releasing hormone gene expression.

    PubMed

    Kim, Helen H

    2007-09-01

    Reproductive function is influenced by several internal and external cues, which ultimately exert their effects on the gonadotropin-releasing hormone (GnRH) neuron. As the final common pathway in the brain for regulating reproduction, GnRH neurons receive signals from multiple cell types, and alterations in GnRH production impact reproductive competence. Historically, the paucity of GnRH neurons and their scattered distribution in the brain have limited the study of GnRH gene expression. With transgenic technology, newer model systems (such as immortalized GnRH-expressing cell lines and GnRH-reporter gene transgenic mice) have been developed, making molecular studies possible. This article provides an update on the molecular mechanisms responsible for the regulation of GnRH gene expression, focusing on tissue-specific expression and transcriptional regulation. After an overview of GnRH gene structure, synthesis, and secretion, the model systems for studying GnRH neurons are examined. The molecular mechanisms that translate physiologic stimuli, such as nutritional status or stress, into changes in GnRH expression will be reviewed, concentrating on the regulatory regions within the GnRH gene promoter and the critical transcription factors. PMID:17710727

  4. Gonadotropin-regulated Testicular RNA Helicase (GRTH/DDX25), a Negative Regulator of Luteinizing/Chorionic Gonadotropin Hormone-induced Steroidogenesis in Leydig Cells

    PubMed Central

    Fukushima, Masato; Villar, Joaquin; Tsai-Morris, Chon-Hwa; Dufau, Maria L.

    2011-01-01

    Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) is a testis-specific gonadotropin-regulated RNA helicase that is present in Leydig cells (LCs) and germ cells and is essential for spermatid development and completion of spermatogenesis. Normal basal levels of testosterone in serum and LCs were observed in GRTH null (GRTH−/−) mice. However, testosterone production was enhanced in LCs of GRTH−/− mice compared with WT mice by both in vivo and in vitro human chorionic gonadotropin stimulation. LCs of GRTH−/− mice had swollen mitochondria with a significantly increased cholesterol content in the inner mitochondrial membrane. Basal protein levels of SREBP2, HMG-CoA reductase, and steroidogenic acute regulatory protein (StAR; a protein that transports cholesterol to the inner mitochondrial membrane) were markedly increased in LCs of GRTH−/− mice compared with WT mice. Gonadotropin stimulation caused an increase in StAR mRNA levels and protein expression in GRTH−/− mice versus WT mice, with no further increase in SREBP2 and down-regulation of HMG-CoA reductase protein. The half-life of StAR mRNA was significantly increased in GRTH−/− mice. Moreover, association of StAR mRNA with GRTH protein was observed in WT mice. Human chorionic gonadotropin increased GRTH gene expression and its associated StAR protein at cytoplasmic sites. Taken together, these findings indicate that, through its negative role in StAR message stability, GRTH regulates cholesterol availability at the mitochondrial level. The finding of an inhibitory action of GRTH associated with gonadotropin-mediated steroidogenesis has provided insights into a novel negative autocrine molecular control mechanism of this helicase in the regulation of steroid production in the male. PMID:21719703

  5. Regulation of tonic gonadotropin release in prepubertal female hamsters

    SciTech Connect

    Smith, S.G.; Matt, K.S.; Prestowitz, W.F.; Stetson, M.H.

    1982-04-01

    Basal serum gonadotropin levels were monitored weekly in female hamsters from birth to 10 weeks of age. Hamsters raised on three different photoperiods presented uniform pre- and postpubertal patterns of serum LH and FSH, suggesting that gonadotropin release in the young hamster occurs independently of ambient photoperiod. In all groups, serum LH levels increased gradually in animals up to 4 weeks of age, after which levels plateaued at 50--100 ng/ml. Serum FSH was markedly elevated in 2- and 3-week-old hamsters (800--1200 ng/ml), but remained at 200--400 ng/ml in all other groups. We next examined the change in the responsiveness of the pituitary to exogenous gonadotropin-releasing hormone (GnRH) challenge. Female hamsters 2 days of age failed to respond to any dose (0.025--1000 ng) of GnRH, while 10-day old females responded in typical dose-dependent fashion. GnRH-stimulated LH release first occurred in 6-day-old hamsters and was maximal by day 9, whereas FSH release first occurred on day 8 and was maximal by day 9. The prepubertal pattern of gonadotropin release can, in part, be explained on the basis of the development of pituitary GnRH sensitivity, which occurs independently of photoperiod.

  6. MiR-214 suppressed ovarian cancer and negatively regulated semaphorin 4D.

    PubMed

    Liu, Yang; Zhou, Honglin; Ma, Lan; Hou, Youfang; Pan, Jing; Sun, Chunyi; Yang, Yingying; Zhang, Jie

    2016-06-01

    Ovarian cancer is one of the most common human malignancies in women. MiR-214 and semaphorin 4D (sema 4D) were found to be abhorrently expressed and involved in the progress of several kinds of malignant cancers. This study is aimed to investigate the cellular role of miR-214 and demonstrate that miR-214 negatively regulated sema 4D in ovarian cancer cells. The data showed that miR-214 expression was consistently lower in ovarian cancer tissues and cells than those in the normal controls. Over-expression of miR-214 in ovarian cancer SKOV-3 cells inhibited cell proliferation and induced apoptosis. It was suggested that miR-214 functioned as the tumor suppressor in ovarian cancer. Bioinformatic analysis indicated that miR-214 possibly regulated sema 4D by binding the sema 4D messenger RNA (mRNA) 3'-untranslated region (UTR). Sema 4D mRNA and protein levels were up-regulated in ovarian cancer tissues and SKOV-3 cells. Up-regulation of miR-214 in SKOV-3 cell line suppressed the sema 4D expression in both protein and nucleic acid levels. While, down-regulation of miR-214 in SKOV-3 cells would increase sema 4D protein and nucleic acid expression levels. The effects of miR-214 up- and down-regulation on luciferase activities of wild-type (WT) sema 4D 3'-UTR were completely removed upon introduction of mutation in 3'-UTR of WT sema 4D. Therefore, the data also demonstrated that sema 4D was the direct target of miR-214 and was negatively regulated by miR-214 in ovarian cancer cells. PMID:26718213

  7. Up-regulation of placental leptin by human chorionic gonadotropin.

    PubMed

    Maymó, Julieta L; Pérez Pérez, Antonio; Sánchez-Margalet, Víctor; Dueñas, José L; Calvo, Juan Carlos; Varone, Cecilia L

    2009-01-01

    Leptin, the 16,000 molecular weight protein product of the obese gene, was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta, in which it was found to be expressed. In the present work, we have found that recombinant human chorionic gonadotropin (hCG) added to BeWo choriocarcinoma cell line showed a stimulatory effect on endogenous leptin expression, when analyzed by Western blot. This effect was time and dose dependent. Maximal effect was achieved at hCG 100 IU/ml. Moreover, hCG treatment enhanced leptin promoter activity up to 12.9 times, evaluated by transient transfection with a plasmid construction containing different promoter regions and the reporter gene luciferase. This effect was dose dependent and evidenced with all the promoter regions analyzed, regardless of length. Similar results were obtained with placental explants, thus indicating physiological relevance. Because hCG signal transduction usually involves cAMP signaling, this pathway was analyzed. Contrarily, we found that dibutyryl cAMP counteracted hCG effect on leptin expression. Furthermore, cotransfection with the catalytic subunit of PKA and/or the transcription factor cAMP response element binding protein repressed leptin expression. Thereafter we determined that hCG effect could be partially blocked by pharmacologic inhibition of MAPK pathway with 50 microM PD98059 but not by the inhibition of the phosphatidylinositol 3-kinase pathway with 0.1 microm wortmannin. Moreover, hCG treatment promoted MAPK kinase and ERK1/ERK2 phosphorylation in placental cells. Finally, cotransfection with a dominant-negative mutant of MAPK blocked the hCG-mediated activation of leptin expression. In conclusion, we provide some evidence suggesting that hCG induces leptin expression in trophoblastic cells probably involving the MAPK signal transduction

  8. Fox Tales: Regulation of Gonadotropin Gene Expression by Forkhead Transcription Factors

    PubMed Central

    Thackray, Varykina G.

    2013-01-01

    Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are produced by pituitary gonadotrope cells and are required for steroidogenesis, the maturation of ovarian follicles, ovulation, and spermatogenesis. Synthesis of LH and FSH is tightly regulated by a complex network of signaling pathways activated by hormones including gonadotropin-releasing hormone, activin and sex steroids. Members of the forkhead box (FOX) transcription factor family have been shown to act as important regulators of development, homeostasis and reproduction. In this review, we focus on the role of four specific FOX factors (FOXD1, FOXL2, FOXO1 and FOXP3) in gonadotropin hormone production and discuss our current understanding of the molecular function of these factors derived from studies in mouse genetic and cell culture models. PMID:24099863

  9. Gonadotropins regulate ovarian germ cell mitosis/meiosis decision in the embryonic chicken.

    PubMed

    He, Bin; Mi, Yuling; Zhang, Caiqiao

    2013-05-01

    Gonadotropins are required for gametogenesis but in embryonic gonads this mechanism is not well understood. Here we use chicken embryos to investigate the mechanism that gonadotropins regulate the ovarian germ cell mitosis/meiosis decision. Treatment with follicle-stimulating hormone (FSH) delayed germ cell meiosis entry and promoted their proliferation. This action was blocked by an aromatase inhibitor. Treatment with luteinizing hormone (LH) accelerated germ cell meiosis entry and promoted transcription of 3βHSDII to increase progesterone (P4) production. In the cultured ovaries, P4 triggered meiotic initiation in germ cells. MiR181a, which acts to downregulate the NR6A1 transcript to inhibit the meiotic initiation, was upregulated by FSH and downregulated by LH. Collectively, gonadotropins regulate germ cells mitosis and meiotic initiation through steroid hormones and a miR181a-mediated pathway. In particularly, FSH delays germ cell meiosis entry and promotes cell proliferation via estrogen while LH accelerates the meiotic initiation via elevated P4 production. PMID:23422072

  10. Extracellular signal-regulated kinase mediates gonadotropin subunit gene expression and LH release responses to endogenous gonadotropin-releasing hormones in goldfish.

    PubMed

    Klausen, Christian; Booth, Morgan; Habibi, Hamid R; Chang, John P

    2008-08-01

    The possible involvement of extracellular signal-regulated kinase (ERK) in mediating the stimulatory actions of two endogenous goldfish gonadotropin-releasing hormones (salmon (s)GnRH and chicken (c)GnRH-II) on gonadotropin synthesis and secretion was examined. Western blot analysis revealed the presence of ERK and phosphorylated (p)ERK in goldfish brain, pituitary, liver, ovary, testis and muscle tissue extracts, as well as extracts of dispersed goldfish pituitary cells and HeLa cells. Interestingly, a third ERK-like immunoreactive band of higher molecular mass was detected in goldfish tissue and pituitary cell extracts in addition to the ERK1-p44- and ERK2-p42-like immunoreactive bands. Incubation of primary cultures of goldfish pituitary cells with either a PKC-activating 4beta-phorbol ester (TPA) or a synthetic diacylglycerol, but not a 4alpha-phorbol ester, elevated the ratio of pERK/total (t)ERK for all three ERK isoforms. The stimulatory effects of TPA were attenuated by the PKC inhibitor GF109203X and the MEK inhibitor PD98059. sGnRH and cGnRH-II also elevated the ratio of pERK/tERK for all three ERK isoforms, in a time-, dose- and PD98059-dependent manner. In addition, treatment with PD98059 reduced the sGnRH-, cGnRH-II- and TPA-induced increases in gonadotropin subunit mRNA levels in Northern blot studies and sGnRH- and cGnRH-II-elicited LH release in cell column perifusion studies with goldfish pituitary cells. These results indicate that GnRH and PKC can activate ERK through MEK in goldfish pituitary cells. More importantly, the present study suggests that GnRH-induced gonadotropin subunit gene expression and LH release involve MEK/ERK signaling in goldfish. PMID:18558406

  11. Identification of a calmodulin-binding domain in Sema4D that regulates its exodomain shedding in platelets.

    PubMed

    Mou, Peipei; Zeng, Zhao; Li, Qiang; Liu, Xiaohui; Xin, Xiaoran; Wannemacher, Kenneth M; Ruan, Changgeng; Li, Renhao; Brass, Lawrence F; Zhu, Li

    2013-05-16

    Semaphorin 4D (Sema4D) is a transmembrane protein that supports contact-dependent amplification of platelet activation by collagen before being gradually cleaved by the metalloprotease ADAM17, as we have previously shown. Cleavage releases a soluble 120-kDa exodomain fragment for which receptors exist on platelets and endothelial cells. Here we have examined the mechanism that regulates Sema4D exodomain cleavage. The results show that the membrane-proximal cytoplasmic domain of Sema4D contains a binding site for calmodulin within the polybasic region Arg762-Lys779. Coprecipitation studies show that Sema4D and calmodulin are associated in resting platelets, forming a complex that dissociates upon platelet activation by the agonists that trigger Sema4D cleavage. Inhibiting calmodulin with W7 or introducing a membrane-permeable peptide corresponding to the calmodulin-binding site is sufficient to trigger the dissociation of Sema4D from calmodulin and initiate cleavage. Conversely, deletion of the calmodulin-binding site causes constitutive shedding of Sema4D. These results show that (1) Sema4D is a calmodulin-binding protein with a site of interaction in its membrane-proximal cytoplasmic domain, (2) platelet agonists cause dissociation of the calmodulin-Sema4D complex, and (3) dissociation of the complex is sufficient to trigger ADAM17-dependent cleavage of Sema4D, releasing a bioactive fragment. PMID:23564909

  12. The involvement of gonadotropin inhibitory hormone and kisspeptin in the metabolic regulation of reproduction.

    PubMed

    Wahab, F; Shahab, M; Behr, R

    2015-05-01

    Recently, kisspeptin (KP) and gonadotropin inhibitory hormone (GnIH), two counteracting neuropeptides, have been acknowledged as significant regulators of reproductive function. KP stimulates reproduction while GnIH inhibits it. These two neuropeptides seem to be pivotal for the modulation of reproductive activity in response to internal and external cues. It is well-documented that the current metabolic status of the body is closely linked to its reproductive output. However, how reproductive function is regulated by the body's energy status is less clear. Recent studies have suggested an active participation of hypothalamic KP and GnIH in the modulation of reproductive function according to available metabolic cues. Expression of KISS1, the KP encoding gene, is decreased while expression of RFRP (NPVF), the gene encoding GnIH, is increased in metabolic deficiency conditions. The lower levels of KP, as suggested by a decrease in KISS1 gene mRNA expression, during metabolic deficiency can be corrected by administration of exogenous KP, which leads to an increase in reproductive hormone levels. Likewise, administration of RF9, a GnIH receptor antagonist, can reverse the inhibitory effect of fasting on testosterone in monkeys. Together, it is likely that the integrated function of both these hypothalamic neuropeptides works as a reproductive output regulator in response to a change in metabolic status. In this review, we have summarized literature from nonprimate and primate studies that demonstrate the involvement of KP and GnIH in the metabolic regulation of reproduction. PMID:25957191

  13. Characterization and steroidal regulation of gonadotropin beta subunits in the male leopard frog, Rana pipiens.

    PubMed

    Zhang, Lihong; Kessler, Ann E; Tsai, Pei-San

    2007-01-01

    In ranid frogs, the secretion of gonadotropins (GtHs), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), is potently regulated by gonadal steroids. To better understand the gonadal regulation of GtHs at the molecular level, we elucidated the full-length cDNA sequences of LH and FSH beta subunits from the leopard frog, Rana pipiens. The cDNAs for LHbeta and FSHbeta were 1084 and 667 bp in size excluding the poly (A) tail, and encoded proteins of 138 and 127 amino acids, respectively. Using reverse-transcription polymerase chain reaction (RT-PCR), the messages for LHbeta and FSHbeta were found in the pituitary, but not in the brain, heart, kidney, or the liver. Semi-quantitative RT-PCR revealed a significant elevation of FSHbeta, but not LHbeta, in mature male R. pipiens 21 days after gonadectomy (GDX). 17beta-estradiol implant for 21 days in GDX male frogs significantly suppressed the levels of both LHbeta and FSHbeta transcripts, whereas 5alpha-dihydrotestosterone implant suppressed only the latter. Together, these results laid the groundwork for investigating gonadal regulation of GtHbeta subunits in a ranid frog. Importantly, these data also revealed differential feedback effects of an androgen and an estrogen upon GtHbeta expression. PMID:16920113

  14. Gonadotropin-releasing hormone regulates spine density via its regulatory role in hippocampal estrogen synthesis

    PubMed Central

    Prange-Kiel, Janine; Jarry, Hubertus; Schoen, Michael; Kohlmann, Patrick; Lohse, Christina; Zhou, Lepu; Rune, Gabriele M.

    2008-01-01

    Spine density in the hippocampus changes during the estrus cycle and is dependent on the activity of local aromatase, the final enzyme in estrogen synthesis. In view of the abundant gonadotropin-releasing hormone receptor (GnRH-R) messenger RNA expression in the hippocampus and the direct effect of GnRH on estradiol (E2) synthesis in gonadal cells, we asked whether GnRH serves as a regulator of hippocampal E2 synthesis. In hippocampal cultures, E2 synthesis, spine synapse density, and immunoreactivity of spinophilin, a reliable spine marker, are consistently up-regulated in a dose-dependent manner at low doses of GnRH but decrease at higher doses. GnRH is ineffective in the presence of GnRH antagonists or aromatase inhibitors. Conversely, GnRH-R expression increases after inhibition of hippocampal aromatase. As we found estrus cyclicity of spine density in the hippocampus but not in the neocortex and GnRH-R expression to be fivefold higher in the hippocampus compared with the neocortex, our data strongly suggest that estrus cycle–dependent synaptogenesis in the female hippocampus results from cyclic release of GnRH. PMID:18227283

  15. Gonadotropin-releasing hormone-regulated prohibitin mediates apoptosis of the gonadotrope cells.

    PubMed

    Savulescu, Dana; Feng, Jiajun; Ping, Yueh Shyang; Mai, Oliver; Boehm, Ulrich; He, Bin; O'Malley, Bert W; Melamed, Philippa

    2013-11-01

    GnRH regulates circulating levels of the gonadotropins but has also been implicated in establishing the gonadotrope cell population. Consistent with this, GnRH induces proliferation of partially differentiated gonadotropes, while reducing the numbers of fully differentiated cells. We have previously reported that the proapoptotic protein, prohibitin (PHB) is expressed more abundantly in gonadotrope-derived LβT2 cells than in partially differentiated αT3-1 gonadotrope precursor cells, suggesting a possible role for PHB in GnRH-induced apoptosis. We show here that PHB is required for GnRH-induced apoptosis in mature gonadotropes. PHB expression and activity are regulated by GnRH: its transcription is via c-Jun NH2-terminal kinase, whereas its nuclear export follows activation of ERK. Moreover, PHB levels are down-regulated by microRNA27, which is expressed at lower levels in mature gonadotropes, possibly explaining the switch to an apoptotic response with development. PHB is required for mitochondrial import of the proapoptotic BAX, whose expression is also induced by GnRH-activated c-Jun NH2-terminal kinase, as is expression of the BH3-only protein, HRK, and this too plays a role in GnRH-induced apoptosis. Finally, we show that gonadotrope-specific PHB-knockout mice display reproductive abnormalities, including a larger gonadotrope population, increased LH levels, reduced fertility, and altered gonad development. We thus demonstrate a role for PHB in GnRH-induced cell death in mature gonadotropes, which is crucial for the normal development and function of the reproductive axis. PMID:24085822

  16. Emerging concepts regarding the integration of neuroendocrine signals that regulate gonadotropin secretion in domestic livestock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pulsatile discharge of GnRH from hypothalamic neurons is obligatory for the synthesis and release of the pituitary gonadotropins. Many conditions have been characterized that reduce gondadotropin secretion and result in anovulatory states which contribute to inefficiencies in livestock producti...

  17. The Dynamics of Connexin Expression, Degradation and Localisation Are Regulated by Gonadotropins during the Early Stages of In Vitro Maturation of Swine Oocytes

    PubMed Central

    Santiquet, Nicolas; Robert, Claude; Richard, François J.

    2013-01-01

    Gap junctional communication (GJC) plays a primordial role in oocyte maturation and meiotic resumption in mammals by directing the transfer of numerous molecules between cumulus cells and the oocyte. Gap junctions are made of connexins (Cx), proteins that regulate GJC in numerous ways. Understanding the dynamic regulation of connexin arrangements during in vitro maturation (IVM) could provide a powerful tool for controlling meiotic resumption and consequently in vitro development of fully competent oocytes. However, physiological events happening during the early hours of IVM may still be elucidated. The present study reports the dynamic regulation of connexin expression, degradation and localization during this stage. Cx43, Cx45 and Cx60 were identified as the main connexins expressed in swine COC. Cx43 and Cx45 transcripts were judged too static to be a regulator of GJC, while Cx43 protein expression was highly responsive to gonadotropins, suggesting that it might be the principal regulator of GJC. In addition, the degradation of Cx43 expressed after 4.5 h of IVM in response to equine chorionic gonadotropin appeared to involve the proteasomal complex. Cx43 localisation appeared to be associated with GJC. Taken together, these results show for the first time that gonadotropins regulate Cx43 protein expression, degradation and localisation in porcine COC during the first several hours of IVM. Regulation of Cx43 may in turn, via GJC, participate in the development of fully competent oocytes. PMID:23861906

  18. Gonadotropin-releasing hormone and gonadal steroids regulate transcription factor mRNA expression in primary pituitary and immortalized gonadotrope cells.

    PubMed

    Zheng, Weiming; Grafer, Constance M; Kim, Jonathan; Halvorson, Lisa M

    2015-03-01

    Hormonal regulation of pituitary gonadotropin gene expression has been attributed to gonadotropin-releasing hormone (GnRH)-mediated stimulation of immediate early gene expression and gonadal steroid interactions with their respective nuclear receptors. A number of orphan nuclear receptors including steroidogenic factor 1, liver receptor homologue 1, dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1, and chicken ovalbumin upstream promoter-transcription factors I/II as well as the GATA family members, GATA2 and GATA4, have also been implicated in transcriptional regulation of the gonadotropin genes. We hypothesized that hormonally mediated changes in these latter transcription factors may provide an additional mechanism for mediating hormonal effects beyond the more classically appreciated pathways. In these studies, we demonstrate significant regulation of orphan nuclear receptor and GATA messenger RNA levels by GnRH, dihydrotestosterone, estradiol, and progesterone in both cultured primary pituitary cells and gonadotrope-derived cell line, LβT2. These results advance our understanding of the complex mechanisms by which GnRH and steroid hormones achieve precise regulation of anterior pituitary function. PMID:25563755

  19. LPXRFa, the piscine ortholog of GnIH, and LPXRF receptor positively regulate gonadotropin secretion in Tilapia (Oreochromis niloticus).

    PubMed

    Biran, Jakob; Golan, Matan; Mizrahi, Naama; Ogawa, Satoshi; Parhar, Ishwar S; Levavi-Sivan, Berta

    2014-11-01

    LPXRFamide (LPXRFa) peptides have been characterized for their ability to inhibit gonadotropin (GTH) release in birds and stimulate growth hormone (GH) release in frogs. However, their involvement in regulating the reproductive hypothalamo-pituitary-gonadal axis in mammals and fish is inconclusive. To study the role of LPXRFa peptides in the regulation of GTH secretion, we cloned tilapia LPXRFa and LPXRF receptor (LPXRF-R). Processing of the tilapia preproLPXRFa liberated three mature LPXRFa peptides that varied in size and post-translational modifications. Phylogenetic analysis of LPXRFa and the closely related RFamide peptide PQRFa showed clear clustering of each peptide sequence with its orthologs from various vertebrates. Signal-transduction analysis of the tilapia LPXRF-R in COS-7 cells showed clear stimulation of CRE-dependent luciferase activity, whereas the human NPFFR1 showed suppression of forskolin-induced CRE-dependent activity in this system. Administration of the tilapia pyroglutaminated LPXRFa-2 peptide to primary cell culture of tilapia pituitaries, or to reproductive female tilapia by ip injection, positively regulated both LH and FSH release in vivo and in vitro. Using double-labeled fluorescent in-situ hybridization and immunofluorescence, βLH cells were found to co-express both tilapia lpxrf and tilapia lpxrf-r mRNA, whereas some of the βFSH cells coexpressed only lpxrf-r mRNA. No coexpression of tilapia lpxrf-r was identified in GH-positive cells. These findings suggest that the LPXRFa system is a potent positive regulator of the reproductive neuroendocrine axis of tilapia. PMID:25144920

  20. Gonadotropin Inhibitory Hormone Down-Regulates the Brain-Pituitary Reproductive Axis of Male European Sea Bass (Dicentrarchus labrax).

    PubMed

    Paullada-Salmerón, José A; Cowan, Mairi; Aliaga-Guerrero, María; Morano, Francesca; Zanuy, Silvia; Muñoz-Cueto, José A

    2016-06-01

    Gonadotropin-inhibitory hormone (GnIH) inhibits gonadotropin synthesis and release from the pituitary of birds and mammals. However, the physiological role of orthologous GnIH peptides on the reproductive axis of fish is still uncertain, and their actions on the main neuroendocrine systems controlling reproduction (i.e., GnRHs, kisspeptins) have received little attention. In a recent study performed in the European sea bass, we cloned a cDNA encoding a precursor polypeptide that contained C-terminal MPMRFamide (sbGnIH-1) and MPQRFamide (sbGnIH-2) peptide sequences, developed a specific antiserum against sbGnIH-2, and characterized its central and pituitary GnIH projections in this species. In this study, we analyzed the effects of intracerebroventricular injection of sbGnIH-1 and sbGnIH-2 on brain and pituitary expression of reproductive hormone genes (gnrh1, gnrh2, gnrh3, kiss1, kiss2, gnih, lhbeta, fshbeta), and their receptors (gnrhr II-1a, gnrhr II-2b, kiss1r, kiss2r, and gnihr) as well as on plasma Fsh and Lh levels. In addition, we determined the effects of GnIH on pituitary somatotropin (Gh) expression. The results obtained revealed the inhibitory role of sbGnIH-2 on brain gnrh2, kiss1, kiss2, kiss1r, gnih, and gnihr transcripts and on pituitary fshbeta, lhbeta, gh, and gnrhr-II-1a expression, whereas sbGnIH-1 only down-regulated brain gnrh1 expression. However, at different doses, central administration of both sbGnIH-1 and sbGnIH-2 decreased Lh plasma levels. Our work represents the first study reporting the effects of centrally administered GnIH in fish and provides evidence of the differential actions of sbGnIH-1 and sbGnIH-2 on the reproductive axis of sea bass, the main inhibitory role being exerted by the sbGnIH-2 peptide. PMID:26984999

  1. TALE homeodomain proteins regulate gonadotropin-releasing hormone gene expression independently and via interactions with Oct-1.

    PubMed

    Rave-Harel, Naama; Givens, Marjory L; Nelson, Shelley B; Duong, Hao A; Coss, Djurdjica; Clark, Melody E; Hall, Sara Barth; Kamps, Mark P; Mellon, Pamela L

    2004-07-16

    Gonadotropin-releasing hormone (GnRH) is the central regulator of reproductive function. Expression of the GnRH gene is confined to a rare population of neurons scattered throughout the hypothalamus. Restricted expression of the rat GnRH gene is driven by a multicomponent enhancer and an evolutionarily conserved promoter. Oct-1, a ubiquitous POU homeodomain transcription factor, was identified as an essential factor regulating GnRH transcription in the GT1-7 hypothalamic neuronal cell line. In this study, we conducted a two-hybrid interaction screen in yeast using a GT1-7 cDNA library to search for specific Oct-1 cofactors. Using this approach, we isolated Pbx1b, a TALE homeodomain transcription factor that specifically associates with Oct-1. We show that heterodimers containing Pbx/Prep1 or Pbx/Meis1 TALE homeodomain proteins bind to four functional elements within the GnRH regulatory region, each in close proximity to an Oct-1-binding site. Cotransfection experiments indicate that TALE proteins are essential for GnRH promoter activity in the GT1-7 cells. Moreover, Pbx1 and Oct-1, as well as Prep1 and Oct-1, form functional complexes that enhance GnRH gene expression. Finally, Pbx1 is expressed in GnRH neurons in embryonic as well as mature mice, suggesting that the associations between TALE homeodomain proteins and Oct-1 regulate neuron-specific expression of the GnRH gene in vivo. PMID:15138251

  2. SMAD1/5 Signaling in the Early Equine Placenta Regulates Trophoblast Differentiation and Chorionic Gonadotropin Secretion

    PubMed Central

    Cabrera-Sharp, Victoria; Read, Jordan E.; Richardson, Stephanie; Kowalski, Alycia A.; Antczak, Douglas F.; Cartwright, Judith E.; Mukherjee, Abir

    2014-01-01

    TGFβ superfamily proteins, acting via SMAD (Sma- and Mad-related protein)2/3 pathways, regulate placental function; however, the role of SMAD1/5/8 pathway in the placenta is unknown. This study investigated the functional role of bone morphogenetic protein (BMP)4 signaling through SMAD1/5 in terminal differentiation of primary chorionic gonadotropin (CG)-secreting trophoblast. Primary equine trophoblast cells or placental tissues were isolated from day 27–34 equine conceptuses. Detected by microarray, RT-PCR, and quantitative RT-PCR, equine chorionic girdle trophoblast showed increased gene expression of receptors that bind BMP4. BMP4 mRNA expression was 20- to 60-fold higher in placental tissues adjacent to the chorionic girdle compared with chorionic girdle itself, suggesting BMP4 acts primarily in a paracrine manner on the chorionic girdle. Stimulation of chorionic girdle-trophoblast cells with BMP4 resulted in a dose-dependent and developmental stage-dependent increase in total number and proportion of terminally differentiated binucleate cells. Furthermore, BMP4 treatment induced non-CG-secreting day 31 chorionic girdle trophoblast cells to secrete CG, confirming a specific functional response to BMP4 stimulation. Inhibition of SMAD2/3 signaling combined with BMP4 treatment further enhanced differentiation of trophoblast cells. Phospho-SMAD1/5, but not phospho-SMAD2, expression as determined by Western blotting was tightly regulated during chorionic girdle trophoblast differentiation in vivo, with peak expression of phospho-SMAD1/5 in vivo noted at day 31 corresponding to maximal differentiation response of trophoblast in vitro. Collectively, these experiments demonstrate the involvement of BMP4-dependent pathways in the regulation of equine trophoblast differentiation in vivo and primary trophoblast differentiation in vitro via activation of SMAD1/5 pathway, a previously unreported mechanism of TGFβ signaling in the mammalian placenta. PMID:24848867

  3. Architecture of GnRH-Gonadotrope-Vasculature Reveals a Dual Mode of Gonadotropin Regulation in Fish.

    PubMed

    Golan, Matan; Zelinger, Einat; Zohar, Yonathan; Levavi-Sivan, Berta

    2015-11-01

    The function and components of the hypothalamic-pituitary axis are conserved among vertebrates; however, in fish, a neuroglandular mode of delivery (direct contact between axons and endocrine cells) was considered dominant, whereas in tetrapods hypothalamic signals are relayed to their targets via the hypophysial portal blood system (neurovascular delivery mode). By using a transgenic zebrafish model we studied the functional and anatomical aspects of gonadotrope regulation thus revisiting the existing model. FSH cells were found to be situated close to the vasculature whereas the compact organization of LH cells prevented direct contact of all cells with the circulation. GnRH3 fibers formed multiple boutons upon reaching the pituitary, but most of these structures were located in the neurohypophysis rather than adjacent to gonadotropes. A close association was observed between FSH cells and GnRH3 boutons, but only a fifth of the LH cells were in direct contact with GnRH3 axons, suggesting that FSH cells are more directly regulated than LH cells. GnRH3 fibers closely followed the vasculature in the neurohypophysis and formed numerous boutons along these tracts. These vessels were found to be permeable to relatively large molecules, suggesting the uptake of GnRH3 peptides. Our findings have important implications regarding the differential regulation of LH and FSH and contradict the accepted notion that fish pituitary cells are mostly regulated directly by hypothalamic fibers. Instead, we provide evidence that zebrafish apply a dual mode of gonadotrope regulation by GnRH3 that combines both neuroglandular and neurovascular components. PMID:26261873

  4. Regulation and distribution of squirrel monkey chorionic gonadotropin and secretogranin II in the pituitary

    PubMed Central

    Vasauskas, Audrey A.; Hubler, Tina R.; Mahanic, Christina; Gibson, Susan; Kahn, Andrea G.; Scammell, Jonathan G.

    2011-01-01

    Secretogranin II (SgII) is a member of the granin family of proteins found in neuroendocrine and endocrine cells. The expression and storage of SgII in the pituitary gland of Old World primates and rodents have been linked with those of luteinizing hormone (LH). However, New World primates including squirrel monkeys do not express LH in the pituitary gland, but rather CG is expressed. If CG takes on the luteotropic role of LH in New World primates, SgII may be associated with the expression and storage of CG in the pituitary gland. The goal of this study was to evaluate the regulation and distribution of CG and SgII in the squirrel monkey. A DNA fragment containing approximately 750 bp of squirrel monkey SgII promoter was isolated from genomic DNA and found to contain a cyclic AMP response element that is also present in the human SgII promoter and important for GnRH responsiveness. The squirrel monkey and human SgII promoters were similarly activated by GnRH in luciferase reporter gene assays in LβT2 cells. Double immunofluorescence microscopy demonstrated close association of SgII and CG in gonadotrophs of squirrel monkey pituitary gland. These results suggest that CG and SgII have a similar intercellular distribution and are coregulated in squirrel monkey pituitary gland. PMID:21095191

  5. PKA and PDE4D3 anchoring to AKAP9 provides distinct regulation of cAMP signals at the centrosome

    PubMed Central

    Terrin, Anna; Monterisi, Stefania; Stangherlin, Alessandra; Zoccarato, Anna; Koschinski, Andreas; Surdo, Nicoletta C.; Mongillo, Marco; Sawa, Akira; Jordanides, Niove E.; Mountford, Joanne C.

    2012-01-01

    Previous work has shown that the protein kinase A (PKA)–regulated phosphodiesterase (PDE) 4D3 binds to A kinase–anchoring proteins (AKAPs). One such protein, AKAP9, localizes to the centrosome. In this paper, we investigate whether a PKA–PDE4D3–AKAP9 complex can generate spatial compartmentalization of cyclic adenosine monophosphate (cAMP) signaling at the centrosome. Real-time imaging of fluorescence resonance energy transfer reporters shows that centrosomal PDE4D3 modulated a dynamic microdomain within which cAMP concentration selectively changed over the cell cycle. AKAP9-anchored, centrosomal PKA showed a reduced activation threshold as a consequence of increased autophosphorylation of its regulatory subunit at S114. Finally, disruption of the centrosomal cAMP microdomain by local displacement of PDE4D3 impaired cell cycle progression as a result of accumulation of cells in prophase. Our findings describe a novel mechanism of PKA activity regulation that relies on binding to AKAPs and consequent modulation of the enzyme activation threshold rather than on overall changes in cAMP levels. Further, we provide for the first time direct evidence that control of cell cycle progression relies on unique regulation of centrosomal cAMP/PKA signals. PMID:22908311

  6. Gonadotropin-releasing hormone, estradiol, and inhibin regulation of follicle-stimulating hormone and luteinizing hormone surges: implications for follicle emergence and selection in heifers.

    PubMed

    Haughian, James M; Ginther, O J; Diaz, Francisco J; Wiltbank, Milo C

    2013-06-01

    Mechanisms regulating gonadotropin surges and gonadotropin requirements for follicle emergence and selection were studied in heifers. Experiment 1 evaluated whether follicular inhibins regulate the preovulatory luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surges elicited by gonadotropin-releasing hormone (GnRH) injection (Hour = 0) and the subsequent periovulatory FSH surge. Treatments included control (n = 6), steroid-depleted bovine follicular fluid (bFF) at Hour -4 (n = 6), and bFF at Hour 6 (n = 6). Gonadotropins in blood were assessed hourly from Hours -6 to 36, and follicle growth tracked by ultrasound. Consistent with inhibin independence, bFF at Hour -4 did not impact the GnRH-induced preovulatory FSH surge, whereas treatment at Hour 6 delayed onset of the periovulatory FSH surge and impeded growth of a new follicular wave. Experiment 2 examined GnRH and estradiol (E2) regulation of the periovulatory FSH surge. Treatment groups were control (n = 8), GnRH-receptor antagonist (GnRHr-ant, n = 8), and E2 + GnRHr-ant (n = 4). GnRHr-ant (acyline) did not reduce the concentrations of FSH during the periovulatory surge and early follicle development (<7.0 mm) was unaffected, although subsequent growth of a dominant follicle (>8.0 mm) was prevented by GnRHr-ant. Addition of E2 delayed both the onset of the periovulatory FSH surge and emergence of a follicular wave. Failure to select a dominant follicle in the GnRHr-ant group was associated with reduced concentrations of LH but not FSH. Maximum diameter of F1 in controls (13.3 ± 0.5 mm) was greater than in both GnRHr-ant (7.7 ± 0.3 mm) and E2 + GnRHr-ant (6.7 ± 0.8 mm) groups. Results indicated that the periovulatory FSH surge stems from removal of negative stimuli (follicular E2 and inhibin), but is independent of GnRH stimulation. Emergence and early growth of follicles (until about 8 mm) requires the periovulatory FSH surge but not LH pulses. However, follicular deviation and late-stage growth of

  7. Gonadotropin-Activated Androgen-Dependent and Independent Pathways Regulate Aquaporin Expression during Teleost (Sparus aurata) Spermatogenesis

    PubMed Central

    Zapater, Cinta; Cerdà, Joan

    2015-01-01

    The mediation of fluid homeostasis by multiple classes of aquaporins has been suggested to be essential during spermatogenesis and spermiation. In the marine teleost gilthead seabream (Sparus aurata), seven distinct aquaporins, Aqp0a, -1aa, -1ab, -7, -8b, -9b and -10b, are differentially expressed in the somatic and germ cell lineages of the spermiating testis, but the endocrine regulation of these channels during germ cell development is unknown. In this study, we investigated the in vivo developmental expression of aquaporins in the seabream testis together with plasma androgen concentrations. We then examined the in vitro regulatory effects of recombinant piscine gonadotropins, follicle-stimulating (rFsh) and luteinizing (rLh) hormones, and sex steroids on aquaporin mRNA levels during the spermatogenic cycle. During the resting phase, when plasma levels of androgens were low, the testis exclusively contained proliferating spermatogonia expressing Aqp1ab, whereas Aqp10b and -9b were localized in Sertoli and Leydig cells, respectively. At the onset of spermatogenesis and during spermiation, the increase of androgen plasma levels correlated with the additional appearance of Aqp0a and -7 in Sertoli cells, Aqp0a in spermatogonia and spermatocytes, Aqp1ab, -7 and -10b from spermatogonia to spermatozoa, and Aqp1aa and -8b in spermatids and spermatozoa. Short-term in vitro incubation of testis explants indicated that most aquaporins in Sertoli cells and early germ cells were upregulated by rFsh and/or rLh through androgen-dependent pathways, although Aqp1ab in proliferating spermatogonia was also activated by estrogens. However, expression of Aqp9b in Leydig cells, and of Aqp1aa and -7 in spermatocytes and spermatids, was also directly stimulated by rLh. These results reveal a complex gonadotropic control of aquaporin expression during seabream germ cell development, apparently involving both androgen-dependent and independent pathways, which may assure the fine tuning

  8. Frequency-Dependent Regulation of Follicle-Stimulating Hormone β by Pulsatile Gonadotropin-Releasing Hormone Is Mediated by Functional Antagonism of bZIP Transcription Factors ▿

    PubMed Central

    Ciccone, Nick A.; Xu, Shuyun; Lacza, Charlemagne T.; Carroll, Rona S.; Kaiser, Ursula B.

    2010-01-01

    Oscillatory synthesis and secretion of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), under the control of pulsatile hypothalamic gonadotropin-releasing hormone (GnRH), is essential for normal reproductive development and fertility. The molecular mechanisms by which various patterns of pulsatile GnRH regulate gonadotrope responsiveness remain poorly understood. In contrast to the α and LHβ subunit genes, FSHβ subunit transcription is preferentially stimulated at low rather than high frequencies of pulsatile GnRH. In this study, mutation of a cyclic AMP response element (CRE) within the FSHβ promoter resulted in the loss of preferential GnRH stimulation at low pulse frequencies. We hypothesized that high GnRH pulse frequencies might stimulate a transcriptional repressor(s) to attenuate the action of CRE binding protein (CREB) and show that inducible cAMP early repressor (ICER) fulfills such a role. ICER was not detected under basal conditions, but pulsatile GnRH stimulated ICER to a greater extent at high than at low pulse frequencies. ICER binds to the FSHβ CRE site to reduce CREB occupation and abrogates both maximal GnRH stimulation and GnRH pulse frequency-dependent effects on FSHβ transcription. These data suggest that ICER production antagonizes the stimulatory action of CREB to attenuate FSHβ transcription at high GnRH pulse frequencies, thereby playing a critical role in regulating cyclic reproductive function. PMID:20008557

  9. E2F1-Mediated Upregulation of p19INK4d Determines Its Periodic Expression during Cell Cycle and Regulates Cellular Proliferation

    PubMed Central

    Carcagno, Abel L.; Marazita, Mariela C.; Ogara, María F.; Ceruti, Julieta M.; Sonzogni, Silvina V.; Scassa, María E.; Giono, Luciana E.; Cánepa, Eduardo T.

    2011-01-01

    Background A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. Methodology/Principal Findings In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. Conclusions/Significance The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell cycle and provides an

  10. HOMOLOGOUS UP-REGULATION OF THE GONADOTROPIN-RELEASING HORMONE RECEPTOR IN A T3-1 CELLS IS ASSOCIATED WITH UNCHANGED RECEPTOR MESSENGER RNA (MRNA) LEVELS AND ALTERED MRNA ACTIVITY

    EPA Science Inventory

    Depending on the concentration and duration of agonist exposure, gonadotropin-releasing hormone (GnRH) receptor number either increases or decreases in response to GnRH. he molecular basis of this regulation could involve a combination of modulation of gene transcription, RNA pro...

  11. SET Protein Interacts with Intracellular Domains of the Gonadotropin-releasing Hormone Receptor and Differentially Regulates Receptor Signaling to cAMP and Calcium in Gonadotrope Cells*

    PubMed Central

    Avet, Charlotte; Garrel, Ghislaine; Denoyelle, Chantal; Laverrière, Jean-Noël; Counis, Raymond; Cohen-Tannoudji, Joëlle; Simon, Violaine

    2013-01-01

    In mammals, the receptor of the neuropeptide gonadotropin-releasing hormone (GnRHR) is unique among the G protein-coupled receptor (GPCR) family because it lacks the carboxyl-terminal tail involved in GPCR desensitization. Therefore, mechanisms involved in the regulation of GnRHR signaling are currently poorly known. Here, using immunoprecipitation and GST pull-down experiments, we demonstrated that SET interacts with GnRHR and targets the first and third intracellular loops. We delineated, by site-directed mutagenesis, SET binding sites to the basic amino acids 66KRKK69 and 246RK247, located next to sequences required for receptor signaling. The impact of SET on GnRHR signaling was assessed by decreasing endogenous expression of SET with siRNA in gonadotrope cells. Using cAMP and calcium biosensors in gonadotrope living cells, we showed that SET knockdown specifically decreases GnRHR-mediated mobilization of intracellular cAMP, whereas it increases its intracellular calcium signaling. This suggests that SET influences signal transfer between GnRHR and G proteins to enhance GnRHR signaling to cAMP. Accordingly, complexing endogenous SET by introduction of the first intracellular loop of GnRHR in αT3-1 cells significantly reduced GnRHR activation of the cAMP pathway. Furthermore, decreasing SET expression prevented cAMP-mediated GnRH stimulation of Gnrhr promoter activity, highlighting a role of SET in gonadotropin-releasing hormone regulation of gene expression. In conclusion, we identified SET as the first direct interacting partner of mammalian GnRHR and showed that SET contributes to a switch of GnRHR signaling toward the cAMP pathway. PMID:23233674

  12. Challenge of human Jurkat T-cells with the adenylate cyclase activator forskolin elicits major changes in cAMP phosphodiesterase (PDE) expression by up-regulating PDE3 and inducing PDE4D1 and PDE4D2 splice variants as well as down-regulating a novel PDE4A splice variant.

    PubMed Central

    Erdogan, S; Houslay, M D

    1997-01-01

    cells. Forskolin treatment led to a marked decrease of this novel PDE4A species and allowed the detection of a strong signal for an approximately 67 kDa PDE4D species, suggested to be PDE4D1, but did not induce PDE4B and PDE4C isoforms. Elevation of intracellular cAMP concentrations in Jurkat T-cells thus exerts a highly selective effect on the transcriptional activity of the genes encoding the various PDE4 isoforms. This leads to the down-regulation of a novel PDE4A splice variant and the induction of PDE4D1 and PDE4D2 splice variants, leading to a net increase in the total PDE4 activity of Jurkat T-cells. PMID:9003416

  13. A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation

    PubMed Central

    Cheong, Mei-Leng; Wang, Liang-Jie; Chuang, Pei-Yun; Chang, Ching-Wen; Lee, Yun-Shien; Lo, Hsiao-Fan; Tsai, Ming-Song

    2015-01-01

    Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGβ paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGβ promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGβ promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGβ expression and cell differentiation. PMID:26503785

  14. Down-regulation of messenger ribonucleic acid encoding an importer of sulfoconjugated steroids during human chorionic gonadotropin-induced follicular luteinization in vivo.

    PubMed

    Brown, Kristy A; Bouchard, Nadine; Lussier, Jacques G; Sirois, Jean

    2007-01-01

    Members of the organic anion transporting polypeptide (SLCO/OATP) superfamily are capable of importing anionic compounds across the lipid bilayer in a sodium-independent manner. Member 2B1 has been shown to transport few substrates, two of which are dihydroepiandrosterone-3-sulfate (DHEA-S) and estrone-3-sulfate. Steroid sulfatase (STS) catalyses the hydrolysis of these steroids into their unconjugated counterparts. The objective of this study was to investigate the regulation of SLCO2B1 and STS mRNAs during human chorionic gonadotropin (hCG)-induced ovulation/luteinization. The equine SLCO2B1 cDNA was cloned and shown to encode a 709-amino acid protein (OATP2B1) that is highly conserved when compared to mammalian orthologs. RT-PCR/Southern blot analyses were performed to study the regulation of SLCO2B1 and STS transcripts in equine preovulatory follicles isolated between 0 and 39h after hCG treatment. Results showed high levels of SLCO2B1 mRNA expression before hCG, with a marked decrease observed in follicles obtained 24-39h post-hCG (P<0.05). Analyses of isolated granulosa and theca interna cells identified high mRNA expression in both cell types prior to hCG treatment, with granulosa cells showing a more rapid SLCO2B1 mRNA down-regulation. No significant change in STS mRNA was observed in intact follicle walls. However, when both cell types were isolated, a significant decrease in STS mRNA was observed in granulosa cells 24-39h post-hCG. Collectively, these results demonstrate that the hCG-dependent induction of follicular luteinization is accompanied by the down-regulation of SLCO2B1 and STS transcripts. Considering that OATP2B1 can import sulfoconjugated DHEA and estrogens, and that STS can remove the sulfonate moiety from these steroids, their down-regulation in luteinizing preovulatory follicles may provide an additional biochemical basis for the decrease in ovarian 17beta-estradiol biosynthesis after the LH surge. PMID:17049229

  15. 4-D Photoacoustic Tomography

    PubMed Central

    Xiang, Liangzhong; Wang, Bo; Ji, Lijun; Jiang, Huabei

    2013-01-01

    Photoacoustic tomography (PAT) offers three-dimensional (3D) structural and functional imaging of living biological tissue with label-free, optical absorption contrast. These attributes lend PAT imaging to a wide variety of applications in clinical medicine and preclinical research. Despite advances in live animal imaging with PAT, there is still a need for 3D imaging at centimeter depths in real-time. We report the development of four dimensional (4D) PAT, which integrates time resolutions with 3D spatial resolution, obtained using spherical arrays of ultrasonic detectors. The 4D PAT technique generates motion pictures of imaged tissue, enabling real time tracking of dynamic physiological and pathological processes at hundred micrometer-millisecond resolutions. The 4D PAT technique is used here to image needle-based drug delivery and pharmacokinetics. We also use this technique to monitor 1) fast hemodynamic changes during inter-ictal epileptic seizures and 2) temperature variations during tumor thermal therapy. PMID:23346370

  16. 4-D Photoacoustic Tomography

    NASA Astrophysics Data System (ADS)

    Xiang, Liangzhong; Wang, Bo; Ji, Lijun; Jiang, Huabei

    2013-01-01

    Photoacoustic tomography (PAT) offers three-dimensional (3D) structural and functional imaging of living biological tissue with label-free, optical absorption contrast. These attributes lend PAT imaging to a wide variety of applications in clinical medicine and preclinical research. Despite advances in live animal imaging with PAT, there is still a need for 3D imaging at centimeter depths in real-time. We report the development of four dimensional (4D) PAT, which integrates time resolutions with 3D spatial resolution, obtained using spherical arrays of ultrasonic detectors. The 4D PAT technique generates motion pictures of imaged tissue, enabling real time tracking of dynamic physiological and pathological processes at hundred micrometer-millisecond resolutions. The 4D PAT technique is used here to image needle-based drug delivery and pharmacokinetics. We also use this technique to monitor 1) fast hemodynamic changes during inter-ictal epileptic seizures and 2) temperature variations during tumor thermal therapy.

  17. Interactions between gonadotropin-releasing hormone (GnRH) and orexin in the regulation of feeding and reproduction in goldfish (Carassius auratus).

    PubMed

    Hoskins, Leah J; Xu, Meiyu; Volkoff, Hélène

    2008-08-01

    Links between energy homeostasis and reproduction have been demonstrated in vertebrates. As a general rule, abundant food resources favor reproduction whereas low food availability induces an inhibition of reproductive processes. In both mammals and fish, gonadotropin-releasing hormone (GnRH) and orexin (OX) are hypothalamic neuropeptides that play critical roles in the regulation of sexual behavior and appetite, respectively. In order to assess possible interactions between orexin and GnRH in the control of feeding and reproduction in goldfish, we examined the effects of chicken GnRH (cGnRH-II) intracerebroventricular (ICV) injection on feeding behavior and OX brain mRNA expression as well as the effects of orexin ICV injections on spawning behavior and cGnRH-II brain mRNA expression. Treatment with cGnRH-II at doses that stimulate spawning (0.5 ng/g or 1 ng/g) resulted in a decrease in both food intake and hypothalamic orexin mRNA expression. Treatment with orexin A at doses that stimulate feeding (10 ng/g) induced an inhibition of spawning behavior and a decrease in cGnRH-II expression in the hypothalamus and optic tectum-thalamus. Our results suggest that the anorexigenic actions of cGnRH-II in goldfish might be in part mediated by OX and that orexin inhibits reproductive behavior in part via the inhibition of the GnRH system. Our data suggest the existence of a coordinated control of feeding and reproduction by the orexin and GnRH systems in goldfish. PMID:18544455

  18. Gonadotropin-releasing hormone type II (GnRH-II) agonist regulates the motility of human decidual endometrial stromal cells: possible effect on embryo implantation and pregnancy.

    PubMed

    Wu, Hsien-Ming; Huang, Hong-Yuan; Lee, Chyi-Long; Soong, Yung-Kuei; Leung, Peter C K; Wang, Hsin-Shih

    2015-04-01

    Invasion of the maternal decidua by extravillous trophoblast is an important process for embryo implantation and placentation in humans. Motile behavior of decidual endometrial stromal cells has been considered of critical importance for embryo implantation and programming of human pregnancy. The gonadotropin-releasing hormone (GnRH) effects in endometrium have raised concerns in reproduction. In the present study, we examined the action of GnRH-II agonist-promoted motility of human decidual endometrial stromal cells and the mechanisms of the action, indicating the role of GnRH-II agonist in embryo implantation and early pregnancy. Human decidual endometrial stromal cells were isolated from the decidual tissue from healthy women undergoing elective pregnancy termination of a normal pregnancy at 6- to 12-wk gestation, after informed consent. Cell motility was estimated by invasion and migration assay. Zymography and immunoblot analysis were performed to investigate the mechanisms of the GnRH-II action. The GnRH-I receptor (GnRH-IR) was expressed in human decidual tissue and endometrial stromal cells. The GnRH-II agonist promoted cell motility. Mitogen-activated protein kinase inhibitors abolished GnRH-II agonist-induced cell motility and activation of MMP-2 and MMP-9. GnRH-II agonist-mediated cell motility was suppressed by knockdown of endogenous GnRH-IR, MMP (matrix metalloproteinase)-2, and MMP-9 with small interfering RNA and MMP inhibitors. Our study demonstrates that the GnRH-II agonist promoted the cell motility of human decidual endometrial stromal cells through the GnRH-IR and the phosphorylation of extracellular signal-regulated protein kinase 1/2 and JNK-dependent activation of MMP-2 and MMP-9. Our findings represent a new concept regarding the mechanisms of GnRH-II-promoted cell motility, suggesting that GnRH-II agonist has strong effects on embryo implantation and decidual programming of human pregnancy. PMID:25761596

  19. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Serum gonadotropin and chorionic gonadotropin. 522.1079 Section 522.1079 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (i) Gilts. For induction of fertile estrus (heat) in healthy prepuberal (noncycling) gilts. (ii)...

  20. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Serum gonadotropin and chorionic gonadotropin. 522.1079 Section 522.1079 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (i) Gilts. For induction of fertile estrus (heat) in healthy prepuberal (noncycling) gilts. (ii)...

  1. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Serum gonadotropin and chorionic gonadotropin. 522.1079 Section 522.1079 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (i) Gilts. For induction of fertile estrus (heat) in healthy prepuberal (noncycling) gilts. (ii)...

  2. Gonadotropins in European sea bass: Endocrine roles and biotechnological applications.

    PubMed

    Mazón, María José; Molés, Gregorio; Rocha, Ana; Crespo, Berta; Lan-Chow-Wing, Olivier; Espigares, Felipe; Muñoz, Iciar; Felip, Alicia; Carrillo, Manuel; Zanuy, Silvia; Gómez, Ana

    2015-09-15

    Follicle stimulating hormone (Fsh) and luteinizing hormone (Lh) are central endocrine regulators of the gonadal function in vertebrates. They act through specific receptors located in certain cell types found in the gonads. In fish, the differential roles of these hormones are being progressively elucidated due to the development of suitable tools for their study. In European sea bass (Dicentrarchus labrax), isolation of the genes coding for the gonadotropin subunits and receptors allowed in first instance to conduct expression studies. Later, to overcome the limitation of using native hormones, recombinant dimeric gonadotropins, which show different functional characteristics depending on the cell system and DNA construct, were generated. In addition, single gonadotropin beta-subunits have been produced and used as antigens for antibody production. This approach has allowed the development of detection methods for native gonadotropins, with European sea bass being one of the few species where both gonadotropins can be detected in their native form. By administering recombinant gonadotropins to gonad tissues in vitro, we were able to study their effects on steroidogenesis and intracellular pathways. Their administration in vivo has also been tested for use in basic studies and as a biotechnological approach for hormone therapy and assisted reproduction strategies. In addition to the production of recombinant hormones, gene-based therapies using somatic gene transfer have been offered as an alternative. This approach has been tested in sea bass for gonadotropin delivery in vivo. The hormones produced by the genes injected were functional and have allowed studies on the action of gonadotropins in spermatogenesis. PMID:26002037

  3. 17 CFR 260.4d-8 - Content.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Content. 260.4d-8 Section 260.4d-8 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rules Under Section 304 § 260.4d-8 Content. (a)...

  4. 17 CFR 260.4d-8 - Content.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Content. 260.4d-8 Section 260.4d-8 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rules Under Section 304 § 260.4d-8 Content. (a)...

  5. 17 CFR 260.4d-8 - Content.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Content. 260.4d-8 Section 260.4d-8 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rules Under Section 304 § 260.4d-8 Content. (a)...

  6. 17 CFR 260.4d-8 - Content.

    Code of Federal Regulations, 2011 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Content. 260.4d-8 Section 260.4d-8 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rules Under Section 304 § 260.4d-8 Content. (a)...

  7. 17 CFR 260.4d-8 - Content.

    Code of Federal Regulations, 2014 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Content. 260.4d-8 Section 260.4d-8 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rules Under Section 304 § 260.4d-8 Content. (a)...

  8. 17 CFR 260.4d-8 - Content.

    Code of Federal Regulations, 2011 CFR

    2005-04-01

    ... 17 Commodity and Securities Exchanges 3 2005-04-01 2005-04-01 false Content. 260.4d-8 Section 260.4d-8 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rules Under Section 304 § 260.4d-8 Content. (a)...

  9. 17 CFR 260.4d-8 - Content.

    Code of Federal Regulations, 2014 CFR

    2000-04-01

    ... 17 Commodity and Securities Exchanges 3 2000-04-01 2000-04-01 false Content. 260.4d-8 Section 260.4d-8 Commodity and Securities Exchanges GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rules Under Section 304 § 260.4d-8 Content. (a) Each application for an order under section 304(d)...

  10. 17 CFR 260.4d-8 - Content.

    Code of Federal Regulations, 2010 CFR

    2015-04-01

    ... 17 Commodity and Securities Exchanges 4 2015-04-01 2015-04-01 false Content. 260.4d-8 Section 260.4d-8 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rules Under Section 304 § 260.4d-8 Content. (a)...

  11. HER4 D-box sequences regulate mitotic progression and degradation of the nuclear HER4 cleavage product, s80HER4

    PubMed Central

    Strunk, Karen E.; Husted, Carty; Miraglia, Leah C.; Sandahl, Melissa; Rearick, William A.; Hunter, Debra M.; Earp, H. Shelton; Muraoka-Cook, Rebecca S.

    2010-01-01

    Heregulin-mediated activation of HER4 initiates receptor cleavage (releasing an 80-kDa HER4 intracellular domain, s80HER4, containing nuclear localization sequences) and results in G2/M delay by unknown signaling mechanisms. We report herein that s80HER4 contains a functional cyclin B-like sequence known as a D-box, which targets proteins for degradation by APC/C, a multisubunit ubiquitin ligase. s80HER4 ubiquitination and ptoteosomal degradation occurred during mitosis but not during S-phase. Inhibition of an APC subunit (APC2) using siRNA knock-down impaired s80HER4 degradation. Mutation of the s80HER4 D-box sequence stabilized s80HER4 during mitosis, and s80HER4-dependent growth inhibition via G2/M delay was significantly greater with the D-box mutant. Polyomvirus middle-T antigen-transformed HC11 cells expressing s80HER4 resulted in smaller, less proliferative, more differentiated tumors in vivo than those expressing kinase-dead s80HER4 or the empty vector. Cells expressing s80HER4 with a disrupted D-box did not form tumors, instead forming differentiated ductal structures. These results suggest that cell cycle-dependent degradation of s80HER4 limits its growth inhibitory action, and stabilization of s80HER4 enhances tumor suppression, thus providing a link between HER4-mediated growth inhibition and cell cycle control. PMID:17638867

  12. Gonadotrope-specific Deletion of Dicer Results in Severely Suppressed Gonadotropins and Fertility Defects*

    PubMed Central

    Wang, Huizhen; Graham, Ian; Hastings, Richard; Gunewardena, Sumedha; Brinkmeier, Michelle L.; Conn, P. Michael; Camper, Sally A.; Kumar, T. Rajendra

    2015-01-01

    Pituitary gonadotropins follicle-stimulating hormone and luteinizing hormone are heterodimeric glycoproteins expressed in gonadotropes. They act on gonads and promote their development and functions including steroidogenesis and gametogenesis. Although transcriptional regulation of gonadotropin subunits has been well studied, the post-transcriptional regulation of gonadotropin subunits is not well understood. To test if microRNAs regulate the hormone-specific gonadotropin β subunits in vivo, we deleted Dicer in gonadotropes by a Cre-lox genetic approach. We found that many of the DICER-dependent microRNAs, predicted in silico to bind gonadotropin β subunit mRNAs, were suppressed in purified gonadotropes of mutant mice. Loss of DICER-dependent microRNAs in gonadotropes resulted in profound suppression of gonadotropin-β subunit proteins and, consequently, the heterodimeric hormone secretion. In addition to suppression of basal levels, interestingly, the post-gonadectomy-induced rise in pituitary gonadotropin synthesis and secretion were both abolished in mutants, indicating a defective gonadal negative feedback control. Furthermore, mutants lacking Dicer in gonadotropes displayed severely reduced fertility and were rescued with exogenous hormones confirming that the fertility defects were secondary to suppressed gonadotropins. Our studies reveal that DICER-dependent microRNAs are essential for gonadotropin homeostasis and fertility in mice. Our studies also implicate microRNAs in gonadal feedback control of gonadotropin synthesis and secretion. Thus, DICER-dependent microRNAs confer a new layer of transcriptional and post-transcriptional regulation in gonadotropes to orchestrate the hypothalamus-pituitary-gonadal axis physiology. PMID:25525274

  13. Side Effects of Injectable Fertility Drugs (Gonadotropins)

    MedlinePlus

    ... usually are used during fertility treatments such as intrauterine insemination (IUI) or in vitro fertilization (IVF). Injections of gonadotropins ... Gestation. When using injectable gonadotropins alone or with IUI, up to 30% of pregnancies are associated with ...

  14. MicroRNA miR-513a-3p acts as a co-regulator of luteinizing hormone/chorionic gonadotropin receptor gene expression in human granulosa cells.

    PubMed

    Troppmann, B; Kossack, N; Nordhoff, V; Schüring, A N; Gromoll, J

    2014-06-01

    The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is essential for normal male and female reproductive processes. The spatial and temporal LHCGR gene expression is controlled by a complex system of regulatory mechanisms which are crucial for normal physiological function, especially during the female cycle. In this study, we aimed to elucidate whether microRNAs are involved in this network and play a role in regulating LHCGR expression. Computational analysis predicted that miR-513a-3p interacts with the LHCGR mRNA via three binding sites located in the 3'UTR region, enabling a synergistic action. Moreover, using a luciferase-based reporter assay we found that miR-513a-3p targets the LHCGR, resulting in a significant down-regulation of its expression. In human primary granulosa cell cultures we detected a dynamic, inversely associated expression pattern of miR-513a-3p and the LHCGR. In addition, transfection with miR-513a-3p or its specific inhibitor led to a down- or up-regulation at the LHCGR mRNA level, respectively. An increased amount of miR-513a-3p resulted in the down-regulation of the LHCGR mRNA, reflected by the attenuation of cAMP synthesis after hormonal stimulation. In conclusion, these data demonstrate that miR-513a-3p is involved in the control of the LHCGR expression by an inversely regulated mechanism at the post-transcriptional level and show for the first time that this kind of post-transcriptional process contributes to the multifaceted system of the human LHCGR regulation. PMID:24747085

  15. Distribution and regulation of gonadotropin-releasing hormone, kisspeptin, RF-amide related peptide-3, and dynorphin in the bovine hypothalamus.

    PubMed

    Tanco, Valeria M; Whitlock, Brian K; Jones, Melaney A; Wilborn, Robyn R; Brandebourg, Terry D; Foradori, Chad D

    2016-01-01

    Recent work has led to the hypothesis that kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the arcuate nucleus (ARC) play a key role in gonadotropin-releasing hormone (GnRH) pulse generation and gonadal steroid feedback, with kisspeptin driving GnRH release and neurokinin B and dynorphin acting as pulse start and stop signals, respectively. A separate cell group, expressing RFamide-related peptide-3 (RFRP-3) has been shown to be a primary inhibitor of GnRH release. Very little is known regarding these cell groups in the bovine. In this study, we examined the relative immunoreactivity of kisspeptin, dynorphin, and RFRP-3 and their possible connectivity to GnRH neurons in the hypothalami of periestrus and diestrus bovine. While GnRH and RFRP-3 immunoreactivity were unchanged, kisspeptin and dynorphin immunoreactivity levels varied in relation to plasma progesterone concentrations and estrous status. Animals with higher plasma progesterone concentrations in diestrus had lower kisspeptin and increased dynorphin immunoreactivity in the ARC. The percentage of GnRH cells with kisspeptin or RFRP-3 fibers in close apposition did not differ between estrous stages. However, the proportions of GnRH cells with kisspeptin or RFRP-3 contacts (∼49.8% and ∼31.3%, respectively) suggest direct communication between kisspeptin and RFRP-3 cells to GnRH cells in the bovine. The data produced in this work support roles for kisspeptin and dynorphin, within the KNDy neural network, in controlling GnRH release over the ovarian cycle and conveying progesterone-negative feedback onto GnRH neurons in the bovine. PMID:27014517

  16. Distribution and regulation of gonadotropin-releasing hormone, kisspeptin, RF-amide related peptide-3, and dynorphin in the bovine hypothalamus

    PubMed Central

    Tanco, Valeria M.; Whitlock, Brian K.; Jones, Melaney A.; Wilborn, Robyn R.; Brandebourg, Terry D.

    2016-01-01

    Recent work has led to the hypothesis that kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the arcuate nucleus (ARC) play a key role in gonadotropin-releasing hormone (GnRH) pulse generation and gonadal steroid feedback, with kisspeptin driving GnRH release and neurokinin B and dynorphin acting as pulse start and stop signals, respectively. A separate cell group, expressing RFamide-related peptide-3 (RFRP-3) has been shown to be a primary inhibitor of GnRH release. Very little is known regarding these cell groups in the bovine. In this study, we examined the relative immunoreactivity of kisspeptin, dynorphin, and RFRP-3 and their possible connectivity to GnRH neurons in the hypothalami of periestrus and diestrus bovine. While GnRH and RFRP-3 immunoreactivity were unchanged, kisspeptin and dynorphin immunoreactivity levels varied in relation to plasma progesterone concentrations and estrous status. Animals with higher plasma progesterone concentrations in diestrus had lower kisspeptin and increased dynorphin immunoreactivity in the ARC. The percentage of GnRH cells with kisspeptin or RFRP-3 fibers in close apposition did not differ between estrous stages. However, the proportions of GnRH cells with kisspeptin or RFRP-3 contacts (∼49.8% and ∼31.3%, respectively) suggest direct communication between kisspeptin and RFRP-3 cells to GnRH cells in the bovine. The data produced in this work support roles for kisspeptin and dynorphin, within the KNDy neural network, in controlling GnRH release over the ovarian cycle and conveying progesterone-negative feedback onto GnRH neurons in the bovine. PMID:27014517

  17. 17 CFR 260.4d-8 - Content.

    Code of Federal Regulations, 2011 CFR

    1998-04-01

    ... 17 Commodity and Securities Exchanges 3 1998-04-01 1998-04-01 false Content. 260.4d-8 Section 260.4d-8 GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rules Under Section 304 § 260.4d-8 Content. (a) Each application for an order under section 304(d) of the Act (15 U.S.C. 77ddd(d))...

  18. A Novel Gonadotropin-Releasing Hormone 1 (Gnrh1) Enhancer-Derived Noncoding RNA Regulates Gnrh1 Gene Expression in GnRH Neuronal Cell Models

    PubMed Central

    Huang, Polly P.; Brusman, Liza E.; Iyer, Anita K.; Webster, Nicholas J. G.

    2016-01-01

    Gonadotropin-releasing hormone (GnRH), a neuropeptide released from a small population of neurons in the hypothalamus, is the central mediator of the hypothalamic-pituitary-gonadal axis, and is required for normal reproductive development and function. Evolutionarily conserved regulatory elements in the mouse, rat, and human Gnrh1 gene include three enhancers and the proximal promoter, which confer Gnrh1 gene expression specifically in GnRH neurons. In immortalized mouse hypothalamic GnRH (GT1-7) neurons, which show pulsatile GnRH release in culture, RNA sequencing and RT-qPCR revealed that expression of a novel long noncoding RNA at Gnrh1 enhancer 1 correlates with high levels of GnRH mRNA expression. In GT1-7 neurons, which contain a transgene carrying 3 kb of the rat Gnrh1 regulatory region, both the mouse and rat Gnrh1 enhancer-derived noncoding RNAs (GnRH-E1 RNAs) are expressed. We investigated the characteristics and function of the endogenous mouse GnRH-E1 RNA. Strand-specific RT-PCR analysis of GnRH-E1 RNA in GT1-7 cells revealed GnRH-E1 RNAs that are transcribed in the sense and antisense directions from distinct 5’ start sites, are 3’ polyadenylated, and are over 2 kb in length. These RNAs are localized in the nucleus and have a half-life of over 8 hours. In GT1-7 neurons, siRNA knockdown of mouse GnRH-E1 RNA resulted in a significant decrease in the expression of the Gnrh1 primary transcript and Gnrh1 mRNA. Over-expression of either the sense or antisense mouse GnRH-E1 RNA in immature, migratory GnRH (GN11) neurons, which do not express either GnRH-E1 RNA or GnRH mRNA, induced the transcriptional activity of co-transfected rat Gnrh1 gene regulatory elements, where the induction requires the presence of the rat Gnrh1 promoter. Together, these data indicate that GnRH-E1 RNA is an inducer of Gnrh1 gene expression. GnRH-E1 RNA may play an important role in the development and maturation of GnRH neurons. PMID:27389022

  19. Gonadotropin-releasing hormone in the ovary.

    PubMed

    Metallinou, Chryssa; Asimakopoulos, Byron; Schröer, Andreas; Nikolettos, Nikos

    2007-12-01

    Gonadotropin-releasing hormone (GnRH) plays a pivotal role in the physiology of reproduction in mammals. GnRH acts by binding to the GnRH receptor (GnRHR). In humans, only 1 conventional GnRH receptor subtype (type I GnRH receptor) has been found. In the human genome, 2 forms of GnRH have been identified, GnRH-I (mammal GnRH) and GnRH-II (chicken GnRH II). Both forms and their common receptor are expressed, apart from the hypothalamus, in various compartments of the human ovary. Gonadal steroids, gonadotropins, and GnRH itself controls the regulation of the GnRH/GnRHR system gene expression in the human ovary. The 2 types of GnRH acting paracrinally/autocrinally influence ovarian steroidogenesis, decrease the proliferation, and induce apoptosis of ovarian cells. In this review, the biology of GnRH/GnRHR system in humans, the potential roles of GnRH, and the direct effects of GnRH analogues in ovarian cells are discussed. PMID:18089592

  20. Proline-Rich Tyrosine Kinase 2 Mediates Gonadotropin-Releasing Hormone Signaling to a Specific Extracellularly Regulated Kinase-Sensitive Transcriptional Locus in the Luteinizing Hormone β-Subunit Gene

    PubMed Central

    Maudsley, Stuart; Naor, Zvi; Bonfil, David; Davidson, Lindsay; Karali, Dimitra; Pawson, Adam J.; Larder, Rachel; Pope, Caroline; Nelson, Nancy; Millar, Robert P.; Brown, Pamela

    2007-01-01

    G protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH β-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH2-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH β-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH2-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH β-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression. PMID:17327421

  1. R4D on Ramp

    NASA Technical Reports Server (NTRS)

    1956-01-01

    This Photograph taken in 1956 shows the first of three R4D Skytrain aircraft on the ramp behind the NACA High-Speed Flight Station. Note the designation 'United States NACA' on the side of the aircraft. NACA stood for the National Advisory Committee for Aeronautics, which evolved into the National Aeronautics and Space Administration (NASA) in 1958. The R4D Skytrain was one of the early workhorses for NACA and NASA at Edwards Air Force Base, California, from 1952 to 1984. Designated the R4D by the U.S. Navy, the aircraft was called the C-47 by the U.S. Army and U.S. Air Force and the DC-3 by its builder, Douglas Aircraft. Nearly everyone called it the 'Gooney Bird.' In 1962, Congress consolidated the military-service designations and called all of them the C-47. After that date, the R4D at NASA's Flight Research Center (itself redesignated the Dryden Flight Research Center in 1976) was properly called a C-47. Over the 32 years it was used at Edwards, three different R4D/C-47s were used to shuttle personnel and equipment between NACA/NASA Centers and test locations throughout the country and for other purposes. One purpose was landing on 'dry' lakebeds used as alternate landing sites for the X-15, to determine whether their surfaces were hard (dry) enough for the X-15 to land on in case an emergency occurred after its launch and before it could reach Rogers Dry Lake at Edwards Air Force Base. The R4D/C-47 served a variety of needs, including serving as the first air-tow vehicle for the M2-F1 lifting body (which was built of mahogany plywood). The C-47 (as it was then called) was used for 77 tows before the M2-F1 was retired for more advanced lifting bodies that were dropped from the NASA B-52 'Mothership.' The R4D also served as a research aircraft. It was used to conduct early research on wing-tip-vortex flow visualization as well as checking out the NASA Uplink Control System. The first Gooney Bird was at the NACA High-Speed Flight Research Station (now the Dryden

  2. Activation of the chicken gonadotropin-inhibitory hormone receptor reduces gonadotropin releasing hormone receptor signaling.

    PubMed

    Shimizu, Mamiko; Bédécarrats, Grégoy Y

    2010-06-01

    Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic peptide from the RFamide peptide family that has been identified in multiple avian species. Although GnIH has clearly been shown to reduce LH release from the anterior pituitary gland, its mechanism of action remains to be determined. The overall objectives of this study were (1) to characterize the GnIH receptor (GnIH-R) signaling pathway, (2) to evaluate potential interactions with gonadotropin releasing hormone type III receptor (GnRH-R-III) signaling, and (3) to determine the molecular mechanisms by which GnIH and GnRH regulate pituitary gonadotrope function during a reproductive cycle in the chicken. Using real-time PCR, we showed that in the chicken pituitary gland, GnIH-R mRNA levels fluctuate in an opposite manner to GnRH-R-III, with higher and lower levels observed during inactive and active reproductive stages, respectively. We demonstrated that the chicken GnIH-R signals by inhibiting adenylyl cyclase cAMP production, most likely by coupling to G(alphai). We also showed that this inhibition is sufficient to significantly reduce GnRH-induced cAMP responsive element (CRE) activation in a dose-dependent manner, and that the ratio of GnRH/GnIH receptors is a significant factor. We propose that in avian species, sexual maturation is characterized by a change in GnIH/GnRH receptor ratio, resulting in a switch in pituitary sensitivity from inhibitory (involving GnIH) to stimulatory (involving GnRH). In turn, decreasing GnIH-R signaling, combined with increasing GnRH-R-III signaling, results in significant increases in CRE activation, possibly initiating gonadotropin synthesis. PMID:20350548

  3. Regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase expression and activity in the hypophysectomized rat ovary: Interactions between the stimulatory effect of human chorionic gonadotropin and the luteolytic effect of prolactin

    SciTech Connect

    Martel, C.; Labrie, C.; Dupont, E.; Couet, J.; Trudel, C.; Rheaume, E.; Simard, J.; Luu-The, V.; Pelletier, G.; Labrie, F. )

    1990-12-01

    The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) catalyzes an obligatory step in the conversion of pregnenolone and other 5-ene-3 beta-hydroxysteroids into progesterone as well as precursors of all androgens and estrogens in the ovary. Since 3 beta-HSD is likely to be an important target for regulation by pituitary hormones, we have studied the effect of chronic treatment with LH (hCG), FSH, and PRL on ovarian 3 beta-HSD expression and activity in hypophysectomized adult female rats. Human CG (hCG) (10 IU, twice a day (bid)), ovine FSH (0.5 microgram, bid), and ovine PRL (1 mg, bid) were administered, singly or in combination, for a period of 10 days starting 15 days after hypophysectomy. In hypophysectomized rats, PRL exerted a potent inhibitory effect on all the parameters studied. In fact, PRL caused a 81% decrease in ovarian 3 beta-HSD mRNA content accompanied by a similar decrease in 3 beta-HSD activity and protein levels. In addition, ovarian weight decreased by 40% whereas serum progesterone fell dramatically from 1.92 nmol/liter to undetectable levels after treatment with PRL. Whereas hCG alone had only slight stimulatory effects on 3 beta-HSD mRNA, protein content and activity levels, treatment with the gonadotropin partially or completely reversed the potent inhibitory effects of oPRL on all the parameters measured. FSH, on the other hand, had no significant effect on 3 beta-HSD expression and activity. In situ hybridization experiments using the 35S-labeled rat ovary 3 beta-HSD cDNA probe show that the inhibitory effect of PRL is exerted primarily on luteal cell 3 beta-HSD expression and activity. On the other hand, it can be seen that hCG stimulates 3 beta-HSD mRNA accumulation in interstitial cells.

  4. Further evidence for the role of glucose as a metabolic regulator of hypothalamic gonadotropin-releasing hormone pulse generator activity in goats.

    PubMed

    Ohkura, Satoshi; Ichimaru, Toru; Itoh, Fumiaki; Matsuyama, Shuichi; Okamura, Hiroaki

    2004-07-01

    The present study examined the relative importance of blood glucose vs. free fatty acids as a metabolic signal regulating GnRH release as measured electrophysiologically by multiple-unit activity (MUA) in the arcuate nucleus/median eminence region in ovariectomized, estradiol-treated goats. MUA was recorded before, during, and after: 1) cellular glucoprivation by peripheral infusion of 2-deoxy-d-glucose (2DG; 25, 50, and 75 mg/kg.h, iv); 2) peripheral hypoglycemia in response to various doses (15-195 mU/kg.h, iv) of insulin infusion; and 3) cellular lipoprivation induced by peripheral infusion of sodium mercaptoacetate (MA; 2.4 mg/kg.h alone or combined with 25 mg/kg.h of 2DG, iv), and effects on the interval of characteristic increases in MUA (MUA volleys) were examined. Infusion of the highest dose of 2DG increased the mean interval between MUA volleys, whereas the lower doses of 2DG had no effect on volley interval. The MUA volley intervals lengthened as insulin-induced hypoglycemia became profound. There was a negative correlation between MUA volley intervals and blood glucose concentrations during insulin infusion, and coinfusion of glucose with insulin returned the MUA volley interval to a normal frequency. Infusion of MA alone or MA with 2DG did not increase MUA volley intervals. These findings demonstrate that glucose availability, but not fatty acids, regulates the GnRH pulse generator activity in the ruminant. Glucose is considered a key metabolic regulator that fine-tunes pulsatile GnRH release. PMID:15044379

  5. Monoclonal antibodies to gonadotropin subunits

    SciTech Connect

    Ehrlich, P.H.; Moyle, W.R.; Canfield, R.E.

    1985-01-01

    The production of monoclonal antibodies to peptide hormones, with their unifocal binding sites, can provide tools for understanding hormone structure and function. The paper focuses on techniques that are important for the study of monoclonal antibodies to chorionic gonadotropin (hCG), including hybridoma production, methods of screening for desired clones, properties of the monoclonal antibodies, effect of antibodies on hormone-receptor interaction, inhibition of binding of radiolabeled hCG, inhibition of hCG induced steroidogenesis, determination of relative orientation of epitopes, and synergistic actions of monoclonal antibodies to hCG.

  6. Gonadotropin therapy: a 20th century relic.

    PubMed

    Reindollar, Richard H; Goldman, Marlene B

    2012-04-01

    Gonadotropin therapy has been a cornerstone of infertility therapy for half a century. From the very beginning, its use has been associated with a high rate of multiple births, particularly high order multiples, and ovarian hyperstimulation syndrome. Initially, success rates seemed acceptable when used for superovulation (SO)/IUI therapy. However, as data from RCTs have emerged, reported outcomes suggest that we question the use of injectible gonadotropins. This manuscript examines the studies that have challenged gonadotropin use for SO/IUI and other research that supports reduced doses of gonadotropins for IVF. We examine the challenges for its continued use for SO/IUI and for moving to lower doses worldwide for IVF. We propose a future that views gonadotropins as a relic of the twentieth century. PMID:22463775

  7. The regulation of gonadotropin-releasing hormone-induced calcium signals in male rat gonadotrophs by testosterone is mediated by dihydrotestosterone.

    PubMed

    Tobin, V A; Canny, B J

    1998-03-01

    The biological effects of testosterone (T) may be mediated directly by T or indirectly by its metabolites, dihydrotestosterone (DHT) and estradiol. The present study examined whether the metabolism of T is involved in the regulation of GnRH-induced Ca2+ signaling at the pituitary. In gonadotrophs from castrated rats, a significantly greater percentage of gonadotrophs demonstrated oscillatory Ca2+ responses to 100 nM GnRH than cells from intact rats (72% vs. 24%; P < 0.05). This increase was prevented by the administration of T propionate (0.1 mg/kg x day), DHT benzoate (2 mg/kg x day,), estradiol benzoate (EB; 5 microg/kg x day), or the combination of the above doses of DHT benzoate and EB. In all cases the proportion of gonadotrophs from the steroid-treated rats having oscillatory Ca2+ responses to 100 nM GnRH was between 21-25% (P > 0.05, compared with intact rats). To assess the importance of T metabolism, intact male rats were treated with the aromatase inhibitor letrozole (1 mg/kg x day), the 5alpha-reductase inhibitor finasteride (50 mg/kg x day), or their respective vehicles for 7 days. Letrozole had no effect on GnRH-induced Ca2+ signals, serum LH concentrations, or ventral prostate or testes weight. Finasteride treatment, however, mimicked the effects of castration, with significantly more gonadotrophs exhibiting Ca2+ oscillations in response to 100 nM GnRH than gonadotrophs from the vehicle-treated group (71% vs. 20% respectively; P < 0.05). Finasteride also caused a significant (P < 0.05) decrease in prostatic weight and DHT concentration, but had no significant effect on either prostatic T or serum LH concentrations. These findings suggest that in the intact male rat, the effects of T on GnRH-induced Ca2+ signaling are preferentially mediated via DHT. The results of this study also show that in the absence of androgens, estradiol may regulate GnRH-induced Ca2+ signaling in the male rat pituitary. PMID:9492036

  8. Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility

    PubMed Central

    Diamond, M.P.; Legro, R.S.; Coutifaris, C.; Alvero, R.; Robinson, R.D.; Casson, P.; Christman, G.M.; Ager, J.; Huang, H.; Hansen, K.R.; Baker, V.; Usadi, R.; Seungdamrong, A.; Bates, G.W.; Rosen, R.M.; Haisenleder, D.; Krawetz, S.A.; Barnhart, K.; Trussell, J.C.; Ohl, D.; Jin, Y.; Santoro, N.; Eisenberg, E.; Zhang, H.

    2015-01-01

    BACKGROUND The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates. METHODS We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies. RESULTS After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P = 0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P = 0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P = 0.15) or clomiphene alone (8 of 85, 9%; P = 0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P = 0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications. CONCLUSIONS In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; Clinical

  9. Endocrine disrupting effects of dichlorodiphenyltrichloroethane analogues on gonadotropin hormones in pituitary gonadotrope cells.

    PubMed

    Zhou, Jinghua; Yang, Ye; Xiong, Kang; Liu, Jing

    2014-05-01

    It has been shown that exposure to dichlorodiphenyltrichloroethane (DDT) analogues leads to disharmony of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, the effects and mechanisms of DDT analogues on the expression of gonadotropin genes (FSHβ, LHβ and Cgα), which is the rate-limiting step of FSH and LH biosynthesis, remain unknown. In this study, we assessed the effects of p,p'-DDT, o,p'-DDT, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and methoxychlor (MXC) on gonadotropin genes expression and hormones synthesis in gonadotrope cells. p,p'-DDT and MXC at test concentrations ranging from 10(-9) to 10(-7)mol/L, stimulated gonadotropin genes expression and hormones synthesis in a dose-dependent manner. The activation of extracellular signal-regulated kinase (ERK) was required for the induction of gonadotropin genes expression and hormones synthesis by p,p'-DDT or MXC exposure. This study showed for the first time that p,p'-DDT and MXC regulated gonadotropin genes expression and hormones synthesis through ERK pathway in gonadotrope cells. PMID:24814263

  10. 4-D OCT in Developmental Cardiology

    NASA Astrophysics Data System (ADS)

    Jenkins, Michael W.; Rollins, Andrew M.

    Although strong evidence exists to suggest that altered cardiac function can lead to CHDs, few studies have investigated the influential role of cardiac function and biophysical forces on the development of the cardiovascular system due to a lack of proper in vivo imaging tools. 4-D imaging is needed to decipher the complex spatial and temporal patterns of biomechanical forces acting upon the heart. Numerous solutions over the past several years have demonstrated 4-D OCT imaging of the developing cardiovascular system. This chapter will focus on these solutions and explain their context in the evolution of 4-D OCT imaging. The first sections describe the relevant techniques (prospective gating, direct 4-D imaging, retrospective gating), while later sections focus on 4-D Doppler imaging and measurements of force implementing 4-D OCT Doppler. Finally, the techniques are summarized, and some possible future directions are discussed.

  11. Effect of nutrition during calfhood and peripubertal period on serum metabolic hormones, gonadotropins and testosterone concentrations, and on sexual development in bulls.

    PubMed

    Brito, Leonardo F C; Barth, Albert D; Rawlings, Norm C; Wilde, Randal E; Crews, Denny H; Mir, Priya S; Kastelic, John P

    2007-07-01

    The objective of the present study was to characterize the effects of nutrition on circulating concentrations of metabolic hormones, gonadotropins, and testosterone during sexual development in bulls. Nutrition regulated the hypothalamus-pituitary-testes axis through effects on the GnRH pulse generator in the hypothalamus and through direct effects on the testes. Pituitary function (gonadotropin secretion after GnRH challenge) was not affected by nutrition. However, nutrition affected LH pulse frequency and basal LH concentration during the early gonadotropin rise (10-26 weeks of age). There were close temporal associations between changes in insulin-like growth factor-I (IGF-I) concentrations and changes in LH pulse frequency, suggesting a role for IGF-I in regulating the early gonadotropin rise in bulls. The peripubertal increase in testosterone concentration was delayed in bulls with lesser serum IGF-I concentrations (low nutrition), suggesting a role for IGF-I in regulating Leydig cell function. Serum IGF-I concentrations accounted for 72 and 67% of the variation in scrotal circumference and paired-testes volume, respectively (at any given age), indicating that IGF-I may regulate testicular growth. Bulls with a more sustained elevated LH pulse frequency during the early gonadotropin rise (high nutrition) had greater testicular mass at 70 weeks of age relative to the control group (medium nutrition), despite no differences in metabolic hormone concentrations after 26 weeks of age. Therefore, gonadotropin-independent mechanism regulating testicular growth might be dependent on previous gonadotropin milieu. PMID:16677793

  12. Molecular Mechanisms of Gonadotropin-Releasing Hormone Signaling: Integrating Cyclic Nucleotides into the Network

    PubMed Central

    Perrett, Rebecca M.; McArdle, Craig A.

    2013-01-01

    Gonadotropin-releasing hormone (GnRH) is the primary regulator of mammalian reproductive function in both males and females. It acts via G-protein coupled receptors on gonadotropes to stimulate synthesis and secretion of the gonadotropin hormones luteinizing hormone and follicle-stimulating hormone. These receptors couple primarily via G-proteins of the Gq/ll family, driving activation of phospholipases C and mediating GnRH effects on gonadotropin synthesis and secretion. There is also good evidence that GnRH causes activation of other heterotrimeric G-proteins (Gs and Gi) with consequent effects on cyclic AMP production, as well as for effects on the soluble and particulate guanylyl cyclases that generate cGMP. Here we provide an overview of these pathways. We emphasize mechanisms underpinning pulsatile hormone signaling and the possible interplay of GnRH and autocrine or paracrine regulatory mechanisms in control of cyclic nucleotide signaling. PMID:24312080

  13. Central and peripheral administration of kisspeptin activates gonadotropin but not somatotropin secretion in prepubertal gilts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The role that kisspeptin might have in regulating the onset of puberty in large domestic animals is unknown. We tested the hypothesis that either central or peripheral infusion of kisspeptin would stimulate gonadotropin and growth hormone secretion in prepubertal gilts. In experiment 1, prepuberta...

  14. 77 FR 4227 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor Analog...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... regulations in 21 CFR 522.1083 are amended to reflect the approval. In accordance with the freedom of... CFR part 522 continues to read as follows: Authority: 21 U.S.C. 360b. 0 2. In Sec. 522.1083, revise paragraphs (c)(1) and (c)(3) to read as follows: Sec. 522.1083 Gonadotropin releasing factor...

  15. Los Alamos National Laboratory 4D Database

    SciTech Connect

    Atencio, Julian J.

    2014-05-02

    4D is an integrated development platform - a single product comprised of the components you need to create and distribute professional applications. You get a graphical design environment, SQL database, a programming language, integrated PHP execution, HTTP server, application server, executable generator, and much more. 4D offers multi-platform development and deployment, meaning whatever you create on a Mac can be used on Windows, and vice-versa. Beyond productive development, 4D is renowned for its great flexibility in maintenance and modification of existing applications, and its extreme ease of implementation in its numerous deployment options. Your professional application can be put into production more quickly, at a lower cost, and will always be instantly scalable. 4D makes it easy, whether you're looking to create a classic desktop application, a client-server system, a distributed solution for Web or mobile clients - or all of the above!

  16. Computing Myocardial Motion in 4D Echocardiography

    PubMed Central

    Mukherjee, Ryan; Sprouse, Chad; Pinheiro, Aurélio; Abraham, Theodore; Burlina, Philippe

    2012-01-01

    4D (3D spatial+time) echocardiography is gaining widespread acceptance at clinical institutions for its high temporal resolution and relatively low cost. We describe a novel method for computing dense 3D myocardial motion with high accuracy. The method is based on a classical variational optical flow technique, but exploits modern developments in optical flow research to utilize the full capabilities of 4D echocardiography. Using a variety of metrics, we present an in-depth performance evaluation of the method on synthetic, phantom, and intraoperative 4D Transesophageal Echocardiographic (TEE) data. When compared with state-of-the-art optical flow and speckle tracking techniques currently found in 4D echocardiography, the method we present shows notable improvements in error. We believe the performance improvements shown can have a positive impact when the method is used as input for various applications, such as strain computation, biomechanical modeling, or automated diagnostics. PMID:22677256

  17. Gonadotropin-releasing hormone receptor mRNA expression by human pituitary tumors in vitro.

    PubMed Central

    Alexander, J M; Klibanski, A

    1994-01-01

    An important question in the pathogenesis and regulation of human gonadotroph adenomas is whether heterogeneous gonadotropin responses to gonadotropin-releasing hormone (GnRH) are due to dysregulation of GnRH receptor biosynthesis and/or cell-signaling pathways. We investigated gonadotropin responsiveness to pulsatile GnRH in 13 gonadotroph adenomas. All tumors had evidence of follicle-stimulating hormone (FSH) beta and alpha subunit biosynthesis using reverse transcriptase/polymerase chain reaction (RTPCR) techniques. Four tumors significantly increased gonadotropin and/or free subunit secretion during pulsatile 10(-8) M GnRH administration. The GnRH antagonist Antide (10(-6) to 10(-8) M) blocked secretory increases in all GnRH-responsive tumors. Gonadotropin and/or free subunit secretion increased after 60 mM KCl, confirming that GnRH nonresponsiveness was not due to intracellular gonadotropin depletion. We hypothesized that GnRH nonresponsiveness in these tumors may be due to GnRH receptor (GnRH-Rc) biosynthetic defects. RTPCR analyses detected GnRH-Rc transcripts only in responsive tumors and normal human pituitary. This is the first demonstration of a cell-surface receptor biosynthetic defect in human pituitary tumors. We conclude (a) one third of gonadotroph tumors respond to pulsatile GnRH in vitro, (b) GnRH-Rc mRNA is detected in human gonadotroph adenomas and predicts GnRH responsiveness, and (c) GnRH-Rc biosynthetic defects may underlie GnRH nonresponsiveness in gonadotroph tumors. Images PMID:8200967

  18. On "new massive" 4D gravity

    NASA Astrophysics Data System (ADS)

    Bergshoeff, Eric A.; Fernández-Melgarejo, J. J.; Rosseel, Jan; Townsend, Paul K.

    2012-04-01

    We construct a four-dimensional (4D) gauge theory that propagates, unitarily, the five polarization modes of a massive spin-2 particle. These modes are described by a "dual" graviton gauge potential and the Lagrangian is 4th-order in derivatives. As the construction mimics that of 3D "new massive gravity", we call this 4D model (linearized) "new massive dual gravity". We analyse its massless limit, and discuss similarities to the Eddington-Schrödinger model.

  19. Experimental and computational study of inter- and intra- species specificity of gonadotropins for various gonadotropin receptors.

    PubMed

    Aizen, Joseph; Kowalsman, Noga; Kobayashi, Makito; Hollander, Lian; Sohn, Young Chang; Yoshizaki, Goro; Niv, Masha Y; Levavi-Sivan, Berta

    2012-11-25

    The gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and their receptors play critical roles in vertebrate reproduction. In order to study intra- and interspecies ligand promiscuity of gonadotropins, COS-7 cells were transiently transfected with one of the gonadotropin receptor genes, FSHR or LHR, and tested for activation by gonadotropins from representative fish orders: Aquilliformes (eel; e), Salmoniformes (trout; tr), and Perciformes (tilapia; ta), and of mammalian origin: porcine (p), bovine (b) and human (h). The study reveals complex relations between the gonadotropin hormones and their receptors. Each gonadotropin activated its own cognate receptor. However, taLHR was also activated by hCG and eLHR was activated by hFSH, hCG, and trFSH. For FSHR, the only cross-reactivity detected was for hFSHR, which was activated by pFSH and bFSH. These findings are of great interest and applicability in the context of activation of various GTHRs by their ligands and by ligands from other vertebrates. Analysis of the three-dimensional models of the structures highlights the importance of residues outside of the currently established hormone-receptor interface region. In addition, the interface residues in taFSHR and the effect of exon duplication, which causes an insert in the LRR domain, are suggested to affect the interaction and binding of taFSH. PMID:22954681

  20. 21 CFR 556.304 - Gonadotropin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gonadotropin. 556.304 Section 556.304 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....25 I.U. per kilogram of body weight per day. (b) Tolerances. A tolerance for residues of...

  1. 21 CFR 556.304 - Gonadotropin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gonadotropin. 556.304 Section 556.304 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....25 I.U. per kilogram of body weight per day. (b) Tolerances. A tolerance for residues of...

  2. 21 CFR 556.304 - Gonadotropin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gonadotropin. 556.304 Section 556.304 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....25 I.U. per kilogram of body weight per day. (b) Tolerances. A tolerance for residues of...

  3. 21 CFR 556.304 - Gonadotropin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gonadotropin. 556.304 Section 556.304 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs §...

  4. 21 CFR 556.304 - Gonadotropin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gonadotropin. 556.304 Section 556.304 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....25 I.U. per kilogram of body weight per day. (b) Tolerances. A tolerance for residues of...

  5. Helical 4D CT and Comparison with Cine 4D CT

    NASA Astrophysics Data System (ADS)

    Pan, Tinsu

    4D CT was one of the most important developments in radiation oncology in the last decade. Its early development in single slice CT and commercialization in multi-slice CT has radically changed our practice in radiation treatment of lung cancer, and has enabled the stereotactic radiosurgery of early stage lung cancer. In this chapter, we will document the history of 4D CT development, detail the data sufficiency condition governing the 4D CT data collection; present the design of the commercial helical 4D CTs from Philips and Siemens; compare the differences between the helical 4D CT and the GE cine 4D CT in data acquisition, slice thickness, acquisition time and work flow; review the respiratory monitoring devices; and understand the causes of image artifacts in 4D CT.

  6. Insulin Augments Gonadotropin-Releasing Hormone Induction of Translation in LβT2 Cells

    PubMed Central

    Navratil, Amy M.; Song, Hyunjin; Hernandez, Jeniffer B.; Cherrington, Brian D.; Santos, Sharon J.; Low, Janine M.; Do, Minh-Ha T.; Lawson, Mark A.

    2009-01-01

    Summary The integrated signaling of insulin and gonadotropin-releasing hormone in the pituitary gonadotropes may have a profound bearing on reproductive function, although the cross-receptor signaling mechanisms are unclear. We demonstrate that the insulin receptor is constitutively localized to non-caveolar lipid raft microdomains in the pituitary gonadotrope cell line LβT2. The localization to rafts is consistent with similar localization of the GnRH receptor. Insulin receptor phosphorylation occurs in raft domains and activates the downstream signaling targets Insulin Receptor Substrate1 and Akt/Protein Kinase B. Although insulin alone does not strongly activate the extracellular signal-regulated kinase second messenger cascade, co-stimulation potentiates the phosphorylation of the extracellular signal-regulated kinase by gonadotropin-releasing hormone. The co-stimulatory effect of insulin and gonadotropin-releasing hormone is also evident in increased activation of cap-dependent translation. In contrast, co-stimulation attenuates Akt/Protein Kinase B activation. Our results show that both gonadotropin-releasing hormone and insulin are capable of mutually altering their respective regulatory signaling cascades. We suggest that this provides a mechanism to integrate neuropeptide and energy homeostatic signals to modulate reproductive function. PMID:19632296

  7. 4D Bioprinting for Biomedical Applications.

    PubMed

    Gao, Bin; Yang, Qingzhen; Zhao, Xin; Jin, Guorui; Ma, Yufei; Xu, Feng

    2016-09-01

    3D bioprinting has been developed to effectively and rapidly pattern living cells and biomaterials, aiming to create complex bioconstructs. However, placing biocompatible materials or cells into direct contact via bioprinting is necessary but insufficient for creating these constructs. Therefore, '4D bioprinting' has emerged recently, where 'time' is integrated with 3D bioprinting as the fourth dimension, and the printed objects can change their shapes or functionalities when an external stimulus is imposed or when cell fusion or postprinting self-assembly occurs. In this review, we highlight recent developments in 4D bioprinting technology. Additionally, we review the uses of 4D bioprinting in tissue engineering and drug delivery. Finally, we discuss the major roadblocks to this approach, together with possible solutions, to provide future perspectives on this technology. PMID:27056447

  8. Establishing a framework to implement 4D XCAT Phantom for 4D radiotherapy research

    PubMed Central

    Panta, Raj K.; Segars, Paul; Yin, Fang-Fang; Cai, Jing

    2015-01-01

    Aims To establish a framework to implement the 4D integrated extended cardiac torso (XCAT) digital phantom for 4D radiotherapy (RT) research. Materials and Methods A computer program was developed to facilitate the characterization and implementation of the 4D XCAT phantom. The program can (1) generate 4D XCAT images with customized parameter files; (2) review 4D XCAT images; (3) generate composite images from 4D XCAT images; (4) track motion of selected region-of-interested (ROI); (5) convert XCAT raw binary images into DICOM format; (6) analyse clinically acquired 4DCT images and real-time position management (RPM) respiratory signal. Motion tracking algorithm was validated by comparing with manual method. Major characteristics of the 4D XCAT phantom were studied. Results The comparison between motion tracking and manual measurements of lesion motion trajectory showed a small difference between them (mean difference in motion amplitude: 1.2 mm). The maximum lesion motion decreased nearly linearly (R2 = 0.97) as its distance to the diaphragm (DD) increased. At any given DD, lesion motion amplitude increased nearly linearly (R 2 range: 0.89 to 0.95) as the inputted diaphragm motion increased. For a given diaphragm motion, the lesion motion is independent of the lesion size at any given DD. The 4D XCAT phantom can closely reproduce irregular breathing profile. The end-to-end test showed that clinically comparable treatment plans can be generated successfully based on 4D XCAT images. Conclusions An integrated computer program has been developed to generate, review, analyse, process, and export the 4D XCAT images. A framework has been established to implement the 4D XCAT phantom for 4D RT research. PMID:23361276

  9. Structural and Functional Divergence of Gonadotropin-Inhibitory Hormone from Jawless Fish to Mammals

    PubMed Central

    Ogawa, Satoshi; Parhar, Ishwar S.

    2014-01-01

    Gonadotropin-inhibitory hormone (GnIH) was discovered as a novel hypothalamic peptide that inhibits gonadotropin release in the quail. The presence of GnIH-homologous peptides and its receptors (GnIHRs) have been demonstrated in various vertebrate species including teleosts, suggesting that the GnIH-GnIHR family is evolutionarily conserved. In avian and mammalian brain, GnIH neurons are localized in the hypothalamic nuclei and their neural projections are widely distributed. GnIH acts on the pituitary and gonadotropin-releasing hormone neurons to inhibit reproductive functions by decreasing gonadotropin release and synthesis. In addition, GnIH-GnIHR signaling is regulated by various factors, such as environmental cues and stress. However, the function of fish GnIH orthologs remains inconclusive because the physiological properties of fish GnIH peptides are debatable. This review summarizes the current research progress in GnIH-GnIHR signaling and their physiological functions in vertebrates with special emphasis on non-mammalian vertebrate species. PMID:25386165

  10. 4D-Var Developement at GMAO

    NASA Technical Reports Server (NTRS)

    Pelc, Joanna S.; Todling, Ricardo; Akkraoui, Amal El

    2014-01-01

    The Global Modeling and Assimilation Offce (GMAO) is currently using an IAU-based 3D-Var data assimilation system. GMAO has been experimenting with a 3D-Var-hybrid version of its data assimilation system (DAS) for over a year now, which will soon become operational and it will rapidly progress toward a 4D-EnVar. Concurrently, the machinery to exercise traditional 4DVar is in place and it is desirable to have a comparison of the traditional 4D approach with the other available options, and evaluate their performance in the Goddard Earth Observing System (GEOS) DAS. This work will also explore the possibility for constructing a reduced order model (ROM) to make traditional 4D-Var computationally attractive for increasing model resolutions. Part of the research on ROM will be to search for a suitably acceptable space to carry on the corresponding reduction. This poster illustrates how the IAU-based 4D-Var assimilation compares with our currently used IAU-based 3D-Var.

  11. Constrained reconstructions for 4D intervention guidance

    NASA Astrophysics Data System (ADS)

    Kuntz, J.; Flach, B.; Kueres, R.; Semmler, W.; Kachelrieß, M.; Bartling, S.

    2013-05-01

    Image-guided interventions are an increasingly important part of clinical minimally invasive procedures. However, up to now they cannot be performed under 4D (3D + time) guidance due to the exceedingly high x-ray dose. In this work we investigate the applicability of compressed sensing reconstructions for highly undersampled CT datasets combined with the incorporation of prior images in order to yield low dose 4D intervention guidance. We present a new reconstruction scheme prior image dynamic interventional CT (PrIDICT) that accounts for specific image features in intervention guidance and compare it to PICCS and ASD-POCS. The optimal parameters for the dose per projection and the numbers of projections per reconstruction are determined in phantom simulations and measurements. In vivo experiments in six pigs are performed in a cone-beam CT; measured doses are compared to current gold-standard intervention guidance represented by a clinical fluoroscopy system. Phantom studies show maximum image quality for identical overall doses in the range of 14 to 21 projections per reconstruction. In vivo studies reveal that interventional materials can be followed in 4D visualization and that PrIDICT, compared to PICCS and ASD-POCS, shows superior reconstruction results and fewer artifacts in the periphery with dose in the order of biplane fluoroscopy. These results suggest that 4D intervention guidance can be realized with today’s flat detector and gantry systems using the herein presented reconstruction scheme.

  12. R4D Parked on Ramp

    NASA Technical Reports Server (NTRS)

    1956-01-01

    This Photograph taken in 1956 shows the first of three R4D Skytrain aircraft on the ramp behind the NACA High-Speed Flight Station. NACA stood for the National Advisory Committee for Aeronautics, which evolved into the National Aeronautics and Space Administration (NASA) in 1958. The R4D Skytrain was one of the early workhorses for NACA and NASA at Edwards Air Force Base, California, from 1952 to 1984. Designated the R4D by the U.S. Navy, the aircraft was called the C-47 by the U.S. Army and U.S. Air Force and the DC-3 by its builder, Douglas Aircraft. Nearly everyone called it the 'Gooney Bird.' In 1962, Congress consolidated the military-service designations and called all of them the C-47. After that date, the R4D at NASA's Flight Research Center (itself redesignated the Dryden Flight Research Center in 1976) was properly called a C-47. Over the 32 years it was used at Edwards, three different R4D/C-47s were used to shuttle personnel and equipment between NACA/NASA Centers and test locations throughout the country and for other purposes. One purpose was landing on 'dry' lakebeds used as alternate landing sites for the X-15, to determine whether their surfaces were hard (dry) enough for the X-15 to land on in case an emergency occurred after its launch and before it could reach Rogers Dry Lake at Edwards Air Force Base. The R4D/C-47 served a variety of needs, including serving as the first air-tow vehicle for the M2-F1 lifting body (which was built of mahogany plywood). The C-47 (as it was then called) was used for 77 tows before the M2-F1 was retired for more advanced lifting bodies that were dropped from the NASA B-52 'Mothership.' The R4D also served as a research aircraft. It was used to conduct early research on wing-tip-vortex flow visualization as well as checking out the NASA Uplink Control System. The first Gooney Bird was at the NACA High-Speed Flight Research Station (now the Dryden Flight Research Center) from 1952 to 1956 and flew at least one cross

  13. Absence of Sema4D improves oligodendrocyte recovery after cerebral ischemia/reperfusion injury in mice.

    PubMed

    Wada, Takenobu; Sawano, Toshinori; Tanaka, Takashi; Furuyama, Tatsuo; Fukumoto, Moe; Yamaguchi, Wataru; Saino, Orie; Takeda, Yuichi; Kogo, Mikihiko; Matsuyama, Tomohiro; Inagaki, Shinobu

    2016-07-01

    Sema4D, originally identified as a negative regulator of axon guidance during development, is involved in various physiological and pathological responses. In this study, we evaluated the effect of Sema4D-deficiency on oligodendrocyte restoration after the cerebral ischemia/reperfusion using direct ligation of the middle cerebral artery followed by reperfusion. In both Sema4D(+/+) wild-type and Sema4D(-/-) null mutant mice, the peri-infarct area showed a decrease in the number of oligodendrocytes at 3 days post-reperfusion. Subsequently, the number of oligodendrocytes was observed to gradually recover in both groups. Sema4D-deficient mice, however, showed an enhanced recovery of oligodendrocytes and an upregulation of oligodendrocyte progenitor cells at days 14 and 28 of reperfusion. Cell proliferation identified by incorporation of bromodeoxyuridine was enhanced in Sema4D(-/-) mice from days 3 to 14 post-reperfusion compared to the Sema4D(+/+) mice. Furthermore, apoptotic cell death of oligodendrocytes was reduced at days 7 post-reperfusion in Sema4D(-/-) mice compared to Sema4D(+/+) mice. These findings indicate that enhanced proliferation of progenitor cells and survival of oligodendrocytes resulted in improved oligodendrocyte recovery in Sema4D(-/-) mice. This may provide a new approach for neurorestorative treatment in patients with stroke, which aims to manipulate endogenous oligodendrogenesis and thereby to promote brain repair after stroke. PMID:26752319

  14. Neuroimmune semaphorin 4D is necessary for optimal lung allergic inflammation.

    PubMed

    Shanks, K; Nkyimbeng-Takwi, E H; Smith, E; Lipsky, M M; DeTolla, L J; Scott, D W; Keegan, A D; Chapoval, S P

    2013-12-01

    Neuroimmune semaphorin 4D (Sema4D) was found to be expressed and function in the nervous and immune systems. In the immune system, Sema4D is constitutively expressed on T cells and regulates T cell priming. In addition, it displays a stimulatory function on macrophages, DC, NK cells, and neutrophils. As all these cells are deeply involved in asthma pathology, we hypothesized that Sema4D plays a critical non-redundant regulatory role in allergic airway response. To test our hypothesis, we exposed Sema4D(-/-) and WT mice to OVA injections and challenges in the well-defined mouse model of OVA-induced experimental asthma. We observed a significant decrease in eosinophilic airway infiltration in allergen-treated Sema4D(-/-) mice relative to WT mice. This reduced allergic inflammatory response was associated with decreased BAL IL-5, IL-13, TGFβ1, IL-6, and IL-17A levels. In addition, T cell proliferation in OVA₃₂₃₋₃₃₉-restimulated Sema4D(-/-) cell cultures was downregulated. We also found increased Treg numbers in spleens of Sema4D(-/-) mice. However, airway hyperreactivity (AHR) to methacholine challenges was not affected by Sema4D deficiency in either acute or chronic experimental disease setting. Surprisingly, lung DC number and activation were not affected by Sema4D deficiency. These data provide a new insight into Sema4D biology and define Sema4D as an important regulator of Th2-driven lung pathophysiology and as a potential target for a combinatory disease immunotherapy. PMID:23911404

  15. Interactive animation of 4D performance capture.

    PubMed

    Casas, Dan; Tejera, Margara; Guillemaut, Jean-Yves; Hilton, Adrian

    2013-05-01

    A 4D parametric motion graph representation is presented for interactive animation from actor performance capture in a multiple camera studio. The representation is based on a 4D model database of temporally aligned mesh sequence reconstructions for multiple motions. High-level movement controls such as speed and direction are achieved by blending multiple mesh sequences of related motions. A real-time mesh sequence blending approach is introduced, which combines the realistic deformation of previous nonlinear solutions with efficient online computation. Transitions between different parametric motion spaces are evaluated in real time based on surface shape and motion similarity. Four-dimensional parametric motion graphs allow real-time interactive character animation while preserving the natural dynamics of the captured performance. PMID:23492379

  16. Nondipole Effects in Xe 4d Photoemission

    SciTech Connect

    Hemmers, O; Guillemin, R; Wolska, A; Lindle, D W; Rolles, D; Cheng, K T; Johnson, W R; Zhou, H L; Manson, S T

    2004-07-14

    We measured the nondipole parameters for the spin-orbit doublets Xe 4d{sub 5/2} and Xe 4d{sub 3/2} over a photon-energy range from 100 eV to 250 eV at beamline 8.0.1.3 of the Advanced Light Source at the Lawrence Berkeley National Laboratory. Significant nondipole effects are found at relatively low energies as a result of Cooper minima in dipole channels and interchannel coupling in quadrupole channels. Most importantly, sharp disagreement between experiment and theory, when otherwise excellent agreement was expected, has provided the first evidence of satellite two-electron quadrupole photoionization transitions, along with their crucial importance for a quantitatively accurate theory.

  17. 4D image reconstruction for emission tomography

    NASA Astrophysics Data System (ADS)

    Reader, Andrew J.; Verhaeghe, Jeroen

    2014-11-01

    An overview of the theory of 4D image reconstruction for emission tomography is given along with a review of the current state of the art, covering both positron emission tomography and single photon emission computed tomography (SPECT). By viewing 4D image reconstruction as a matter of either linear or non-linear parameter estimation for a set of spatiotemporal functions chosen to approximately represent the radiotracer distribution, the areas of so-called ‘fully 4D’ image reconstruction and ‘direct kinetic parameter estimation’ are unified within a common framework. Many choices of linear and non-linear parameterization of these functions are considered (including the important case where the parameters have direct biological meaning), along with a review of the algorithms which are able to estimate these often non-linear parameters from emission tomography data. The other crucial components to image reconstruction (the objective function, the system model and the raw data format) are also covered, but in less detail due to the relatively straightforward extension from their corresponding components in conventional 3D image reconstruction. The key unifying concept is that maximum likelihood or maximum a posteriori (MAP) estimation of either linear or non-linear model parameters can be achieved in image space after carrying out a conventional expectation maximization (EM) update of the dynamic image series, using a Kullback-Leibler distance metric (comparing the modeled image values with the EM image values), to optimize the desired parameters. For MAP, an image-space penalty for regularization purposes is required. The benefits of 4D and direct reconstruction reported in the literature are reviewed, and furthermore demonstrated with simple simulation examples. It is clear that the future of reconstructing dynamic or functional emission tomography images, which often exhibit high levels of spatially correlated noise, should ideally exploit these 4D

  18. Abdominal and pancreatic motion correlation using 4D CT, 4D transponders, and a gating belt.

    PubMed

    Betancourt, Ricardo; Zou, Wei; Plastaras, John P; Metz, James M; Teo, Boon-Keng; Kassaee, Alireza

    2013-01-01

    The correlation between the pancreatic and external abdominal motion due to respiration was investigated on two patients. These studies utilized four dimensional computer tomography (4D CT), a four dimensional (4D) electromagnetic transponder system, and a gating belt system. One 4D CT study was performed during simulation to quantify the pancreatic motion using computer tomography images at eight breathing phases. The motion under free breathing and breath-hold were analyzed for the 4D electromagnetic transponder system and the gating belt system during treatment. A linear curve was fitted for all data sets and correlation factors were evaluated between the 4D electromagnetic transponder system and the gating belt system data. The 4D CT study demonstrated a modest correlation between the external marker and the pancreatic motion with R-square values larger than 0.8 for the inferior-superior (inf-sup). Then, the relative pressure from the belt gating system correlated well with the 4D electromagnetic transponder system's motion in the anterior-posterior (ant-post) and the inf-post directions. These directions have a correlation value of -0.93 and 0.76, while the lateral only had a 0.03 correlation coefficient. Based on our limited study, external surrogates can be used as predictors of the pancreatic motion in the inf-sup and the ant-post directions. Although there is a low correlation on the lateral direction, its motion is significantly shorter. In conclusion, an appropriate treatment delivery can be used for pancreatic cancer when an internal tracking system, such as the 4D electromagnetic transponder system, is unavailable. PMID:23652242

  19. Gonadotropin-Dependent Precocious Puberty: Neoplastic Causes and Endocrine Considerations

    PubMed Central

    2011-01-01

    Premature activation of the hypothalamic-pituitary-gonadal (HPG) axis manifests as gonadotropin-dependent precocious puberty. The mechanisms behind HPG activation are complex and a clear etiology for early activation is often not elucidated. Though collectively uncommon, the neoplastic and developmental causes of gonadotropin-dependent precocious puberty are very important to consider, as a delay in diagnosis may lead to adverse patient outcomes. The intent of the current paper is to review the neoplastic and developmental causes of gonadotropin-dependent precocious puberty. We discuss the common CNS lesions and human chorionic gonadotropin-secreting tumors that cause sexual precocity, review the relationship between therapeutic radiation and gonadotropin-dependent precocious puberty, and finally, provide an overview of the therapies available for height preservation in this unique patient population. PMID:21603196

  20. Active origami by 4D printing

    NASA Astrophysics Data System (ADS)

    Ge, Qi; Dunn, Conner K.; Qi, H. Jerry; Dunn, Martin L.

    2014-09-01

    Recent advances in three dimensional (3D) printing technology that allow multiple materials to be printed within each layer enable the creation of materials and components with precisely controlled heterogeneous microstructures. In addition, active materials, such as shape memory polymers, can be printed to create an active microstructure within a solid. These active materials can subsequently be activated in a controlled manner to change the shape or configuration of the solid in response to an environmental stimulus. This has been termed 4D printing, with the 4th dimension being the time-dependent shape change after the printing. In this paper, we advance the 4D printing concept to the design and fabrication of active origami, where a flat sheet automatically folds into a complicated 3D component. Here we print active composites with shape memory polymer fibers precisely printed in an elastomeric matrix and use them as intelligent active hinges to enable origami folding patterns. We develop a theoretical model to provide guidance in selecting design parameters such as fiber dimensions, hinge length, and programming strains and temperature. Using the model, we design and fabricate several active origami components that assemble from flat polymer sheets, including a box, a pyramid, and two origami airplanes. In addition, we directly print a 3D box with active composite hinges and program it to assume a temporary flat shape that subsequently recovers to the 3D box shape on demand.

  1. Electrical synapses connect a network of gonadotropin releasing hormone neurons in a cichlid fish

    PubMed Central

    Ma, Yunyong; Hu, Caroline K.; Huguenard, John R.; Fernald, Russell D.

    2015-01-01

    Initiating and regulating vertebrate reproduction requires pulsatile release of gonadotropin-releasing hormone (GnRH1) from the hypothalamus. Coordinated GnRH1 release, not simply elevated absolute levels, effects the release of pituitary gonadotropins that drive steroid production in the gonads. However, the mechanisms underlying synchronization of GnRH1 neurons are unknown. Control of synchronicity by gap junctions between GnRH1 neurons has been proposed but not previously found. We recorded simultaneously from pairs of transgenically labeled GnRH1 neurons in adult male Astatotilapia burtoni cichlid fish. We report that GnRH1 neurons are strongly and uniformly interconnected by electrical synapses that can drive spiking in connected cells and can be reversibly blocked by meclofenamic acid. Our results suggest that electrical synapses could promote coordinated spike firing in a cellular assemblage of GnRH1 neurons to produce the pulsatile output necessary for activation of the pituitary and reproduction. PMID:25775522

  2. The aryl hydrocarbon receptor is required for normal gonadotropin responsiveness in the mouse ovary

    SciTech Connect

    Barnett, Kimberly R.; Tomic, Dragana; Gupta, Rupesh K.; Babus, Janice K.; Roby, Katherine F.; Terranova, Paul F.; Flaws, Jodi A.

    2007-08-15

    The aryl hydrocarbon receptor (AHR) mediates the toxicity of a variety of environmental chemicals. Although little is known about the physiological role of the AHR, studies suggest that it plays an important role in regulating ovulation because Ahr deficient (AhRKO) mice have a reduced number of ovulations compared to wild-type (WT) mice. The reasons for the reduced ability of AhRKO mice to ovulate are unknown. Normal ovulation, however, requires estrous cyclicity, appropriate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and LH and FSH responsiveness. Thus, the purpose of this study was to test the hypothesis that Ahr deletion regulates ovulation by altering cyclicity, FSH and LH levels, follicle-stimulating hormone receptor (Fshr) and luteinizing hormone receptor (Lhcgr) levels and/or gonadotropin responsiveness. The data indicate that AhRKO and WT mice have similar levels of FSH and LH, but AhRKO mice have reduced Fshr and Lhcgr mRNA levels compared to WT mice. Furthermore, AhRKO ovaries contain fewer corpora lutea compared to WT ovaries after 5 IU equine chorionic gonadotropin (eCG) treatment. Lastly, both AhRKO and WT mice ovulate a similar number of eggs in response to 5 IU human chorionic gonadotropin (hCG), but AhRKO mice ovulate fewer eggs than WT mice in response to 2.5 IU and 1.25 IU hCG. Collectively, these data indicate that AhRKO follicles have a reduced capacity to ovulate compared to WT follicles and that this is due to reduced responsiveness to gonadotropins. Thus, in addition to mediating toxicity of environmental chemicals, the Ahr is required for normal ovulation.

  3. Pituitary gonadotropin and testicular gonadotropin receptor expression in Atlantic cod (Gadusmorhua L.) during the first reproductive season: Effects of photoperiod modulation.

    PubMed

    de Almeida, Fernanda Ferreira Loureiro; Andersson, Eva; Mittelholzer, Christian; Karlsen, Orjan; Taranger, Geir Lasse; Schulz, Rüdiger W

    2011-08-01

    Pituitary mRNA levels of gonadotropin β-subunits and of their cognate receptors in the testis were studied during puberty in Atlantic cod under normal and experimental photoperiod conditions that suppressed, delayed or accelerated testis maturation. Results are discussed in context with changes in testicular histology and plasma androgen levels, considered as end points of gonadotropic regulation. Up-regulation of fshb was closely associated with the onset of puberty, decreased when spermatogenesis was completed and reached minimum levels after spawning. These results demonstrate, for the first time using an experimental approach, that activation of Fsh-dependent signaling is associated with spermatogonial proliferation and formation of spermatogenic cysts. Changes in fshr expression were less prominent and could be explained by changes in the cellular composition and RNA content of cod testis tissue. At more advanced stages of development (spermiogenesis, spermiation and spawning), lhb and, one month later, lhcgr transcript levels increased and reached peak values in spawning fish, in a positive feedback loop involving plasma androgens and Lh/Lhcgr-dependent signaling. This loop was broken by a loss of lhb expression at the end of the spawning season. Continuous light (LL) from summer solstice, ~8 months prior to spawning, suppressed the start of testis maturation and the changes in gonadotropin and receptor mRNA levels, while LL from winter solstice initially up-regulated lhb and lhcgr expression, before resulting in a precocious termination of the spawning season and low expression of all four genes. Our studies provide experimental evidence for a clear functional discrimination of cod gonadotropins. PMID:21605561

  4. Soft Route to 4D Tomography

    NASA Astrophysics Data System (ADS)

    Taillandier-Thomas, Thibault; Roux, Stéphane; Hild, François

    2016-07-01

    Based on the assumption that the time evolution of a sample observed by computed tomography requires many less parameters than the definition of the microstructure itself, it is proposed to reconstruct these changes based on the initial state (using computed tomography) and very few radiographs acquired at fixed intervals of time. This Letter presents a proof of concept that for a fatigue cracked sample its kinematics can be tracked from no more than two radiographs in situations where a complete 3D view would require several hundreds of radiographs. This 2 order of magnitude gain opens the way to a "computed" 4D tomography, which complements the recent progress achieved in fast or ultrafast computed tomography, which is based on beam brightness, detector sensitivity, and signal acquisition technologies.

  5. ICT4D: A Computer Science Perspective

    NASA Astrophysics Data System (ADS)

    Sutinen, Erkki; Tedre, Matti

    The term ICT4D refers to the opportunities of Information and Communication Technology (ICT) as an agent of development. Research in that field is often focused on evaluating the feasibility of existing technologies, mostly of Western or Far East Asian origin, in the context of developing regions. A computer science perspective is complementary to that agenda. The computer science perspective focuses on exploring the resources, or inputs, of a particular context and on basing the design of a technical intervention on the available resources, so that the output makes a difference in the development context. The modus operandi of computer science, construction, interacts with evaluation and exploration practices. An analysis of a contextualized information technology curriculum of Tumaini University in southern Tanzania shows the potential of the computer science perspective for designing meaningful information and communication technology for a developing region.

  6. Controlled Source 4D Seismic Imaging

    NASA Astrophysics Data System (ADS)

    Luo, Y.; Morency, C.; Tromp, J.

    2009-12-01

    Earth's material properties may change after significant tectonic events, e.g., volcanic eruptions, earthquake ruptures, landslides, and hydrocarbon migration. While many studies focus on how to interpret observations in terms of changes in wavespeeds and attenuation, the oil industry is more interested in how we can identify and locate such temporal changes using seismic waves generated by controlled sources. 4D seismic analysis is indeed an important tool to monitor fluid movement in hydrocarbon reservoirs during production, improving fields management. Classic 4D seismic imaging involves comparing images obtained from two subsequent seismic surveys. Differences between the two images tell us where temporal changes occurred. However, when the temporal changes are small, it may be quite hard to reliably identify and characterize the differences between the two images. We propose to back-project residual seismograms between two subsequent surveys using adjoint methods, which results in images highlighting temporal changes. We use the SEG/EAGE salt dome model to illustrate our approach. In two subsequent surveys, the wavespeeds and density within a target region are changed, mimicking possible fluid migration. Due to changes in material properties induced by fluid migration, seismograms recorded in the two surveys differ. By back propagating these residuals, the adjoint images identify the location of the affected region. An important issue involves the nature of model. For instance, are we characterizing only changes in wavespeed, or do we also consider density and attenuation? How many model parameters characterize the model, e.g., is our model isotropic or anisotropic? Is acoustic wave propagation accurate enough or do we need to consider elastic or poroelastic effects? We will investigate how imaging strategies based upon acoustic, elastic and poroelastic simulations affect our imaging capabilities.

  7. Metabolic and renal clearance rates of purified human chorionic gonadotropin.

    PubMed Central

    Wehmann, R E; Nisula, B C

    1981-01-01

    The metabolic clearance rate (MCR) and renal clearance rate (RCR) of human chorionic gonadotropin (hCG) were measured in healthy young men and women using techniques of continuous intravenous infusion and rapid intravenous injection of unlabeled, highly purified hCG. Seven subjects received 4 d of infusion at a rate of 0.2 microgram/min, followed by an additional 4 d of infusion at 0.8 microgram/min. Mean serum levels of hCG established at these rates of infusion were 61.1 +/- 3.3 and 237 +/- 16 ng/ml, respectively (mean +/- SEM). The MCR determined at the low infusion rate was not significantly different from that determined at the higher infusion rate (1.83 +/- 0.09 vs. 1.95 +/- 0.14 ml/min per m2). The mean MCR for all subjects was 1.88 +/- 0.08 ml/min per m2. The MCR was not significantly different between men amd women (2.04 +/- 0.13 vs. 1.76 +/- 0.07 ml/min per m2). The RCR also did not vary between low and high infusion rates (0.40 +/- 0.03 vs. 0.40 +/- 0.04 ml/min per m2). The mean RCR for all subjects was 0.40 +/- 0.02 ml/min per m2. There was no difference in RCR between men and women (0.42 +/- 0.05 vs. 0.39 +/- 0.03 ml/min per m2). Six subjects were given 1.0 mg of highly purified hCG by rapid intravenous injection. Initial serum levels of hCG were 300-400 ng/ml, and the subsequent disappearance curve was multiexponential over 8-10 d. The disappearance curve of hCG in each subject was fitted to a biexponential equation. The rapid component t1/2 was 5.97 +/- 0.63 h and the slow component t1/2 was 35.6 +/- 8.0 h. We conclude that the MCR of purified hCG in man is about 2 ml/min per m2 and the RCR is 0.4 ml/min per m2; these parameters are concentration independent and do not differ significantly between healthy young men and women. PMID:7251859

  8. Bacterial degradation of phenoxy herbicide mixtures 2,4-D and MCPP

    SciTech Connect

    Kyeheon Oh; Tuovinen, O.H. )

    1991-08-01

    The phenoxy herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-(2-methyl-4-chlorophenoxy)propionic acid (MCPP) have auxin-like growth regulating properties and are extensively used for the control of broad-leaf angiosperm weeds. The microbiological degradation of 2,4-D by pure and mixed cultures has been examined in a number of studies. The authors have previously evaluated the concurrent microbiological degradation of 2,4-D and MCPP in stirred tank reactors. For the present paper, they examined the utilization of the two substrates by three mixed cultures that had a previous history of growth with the respective single phenoxy herbicide.

  9. Opening the Black Box of ICT4D: Advancing Our Understanding of ICT4D Partnerships

    ERIC Educational Resources Information Center

    Park, Sung Jin

    2013-01-01

    The term, Information and Communication Technologies for Development (ICT4D), pertains to programs or projects that strategically use ICTs (e.g. mobile phones, computers, and the internet) as a means toward the socio-economic betterment for the poor in developing contexts. Gaining the political and financial support of the international community…

  10. Gonadotropin binding sites in human ovarian follicles and corpora lutea during the menstrual cycle

    SciTech Connect

    Shima, K.; Kitayama, S.; Nakano, R.

    1987-05-01

    Gonadotropin binding sites were localized by autoradiography after incubation of human ovarian sections with /sup 125/I-labeled gonadotropins. The binding sites for /sup 125/I-labeled human follicle-stimulating hormone (/sup 125/I-hFSH) were identified in the granulosa cells and in the newly formed corpora lutea. The /sup 125/I-labeled human luteinizing hormone (/sup 125/I-hLH) binding to the thecal cells increased during follicular maturation, and a dramatic increase was preferentially observed in the granulosa cells of the large preovulatory follicle. In the corpora lutea, the binding of /sup 125/I-hLH increased from the early luteal phase and decreased toward the late luteal phase. The changes in 3 beta-hydroxysteroid dehydrogenase activity in the corpora lutea corresponded to the /sup 125/I-hLH binding. Thus, the changes in gonadotropin binding sites in the follicles and corpora lutea during the menstrual cycle may help in some important way to regulate human ovarian function.

  11. Impact of gene polymorphisms of gonadotropins and their receptors on human reproductive success.

    PubMed

    Casarini, Livio; Santi, Daniele; Marino, Marco

    2015-12-01

    Gonadotropins and their receptors' genes carry several single-nucleotide polymorphisms resulting in endocrine genotypes modulating reproductive parameters, diseases, and lifespan leading to important implications for reproductive success and potential relevance during human evolution. Here we illustrate common genotypes of the gonadotropins and gonadotropin receptors' genes and their clinical implications in phenotypes relevant for reproduction such as ovarian cycle length, age of menopause, testosterone levels, polycystic ovary syndrome, and cancer. We then discuss their possible role in human reproduction and adaptation to the environment. Gonadotropins and their receptors' variants are differently distributed among human populations. Some hints suggest that they may be the result of natural selection that occurred in ancient times, increasing the individual chance of successful mating, pregnancy, and effective post-natal parental cares. The gender-related differences in the regulation of the reproductive endocrine systems imply that many of these genotypes may lead to sex-dependent effects, increasing the chance of mating and reproductive success in one sex at the expenses of the other sex. Also, we suggest that sexual conflicts within the FSH and LH-choriogonadotropin receptor genes contributed to maintain genotypes linked to subfertility among humans. Because the distribution of polymorphic markers results in a defined geographical pattern due to human migrations rather than natural selection, these polymorphisms may have had only a weak impact on reproductive success. On the contrary, such genotypes could acquire relevant consequences in the modern, developed societies in which parenthood attempts often occur at a later age, during a short, suboptimal reproductive window, making clinical fertility treatments necessary. PMID:26370242

  12. Functional organization of the human 4D Nucleome

    PubMed Central

    Chen, Haiming; Chen, Jie; Muir, Lindsey A.; Ronquist, Scott; Meixner, Walter; Ljungman, Mats; Ried, Thomas; Smale, Stephen; Rajapakse, Indika

    2015-01-01

    The 4D organization of the interphase nucleus, or the 4D Nucleome (4DN), reflects a dynamical interaction between 3D genome structure and function and its relationship to phenotype. We present initial analyses of the human 4DN, capturing genome-wide structure using chromosome conformation capture and 3D imaging, and function using RNA-sequencing. We introduce a quantitative index that measures underlying topological stability of a genomic region. Our results show that structural features of genomic regions correlate with function with surprising persistence over time. Furthermore, constructing genome-wide gene-level contact maps aided in identifying gene pairs with high potential for coregulation and colocalization in a manner consistent with expression via transcription factories. We additionally use 2D phase planes to visualize patterns in 4DN data. Finally, we evaluated gene pairs within a circadian gene module using 3D imaging, and found periodicity in the movement of clock circadian regulator and period circadian clock 2 relative to each other that followed a circadian rhythm and entrained with their expression. PMID:26080430

  13. Functional organization of the human 4D Nucleome.

    PubMed

    Chen, Haiming; Chen, Jie; Muir, Lindsey A; Ronquist, Scott; Meixner, Walter; Ljungman, Mats; Ried, Thomas; Smale, Stephen; Rajapakse, Indika

    2015-06-30

    The 4D organization of the interphase nucleus, or the 4D Nucleome (4DN), reflects a dynamical interaction between 3D genome structure and function and its relationship to phenotype. We present initial analyses of the human 4DN, capturing genome-wide structure using chromosome conformation capture and 3D imaging, and function using RNA-sequencing. We introduce a quantitative index that measures underlying topological stability of a genomic region. Our results show that structural features of genomic regions correlate with function with surprising persistence over time. Furthermore, constructing genome-wide gene-level contact maps aided in identifying gene pairs with high potential for coregulation and colocalization in a manner consistent with expression via transcription factories. We additionally use 2D phase planes to visualize patterns in 4DN data. Finally, we evaluated gene pairs within a circadian gene module using 3D imaging, and found periodicity in the movement of clock circadian regulator and period circadian clock 2 relative to each other that followed a circadian rhythm and entrained with their expression. PMID:26080430

  14. Inhibitory effect of pure 31-kilodalton bovine inhibin on gonadotropin-releasing hormone (GnRH)-induced up-regulation of GnRH binding sites in cultured rat anterior pituitary cells.

    PubMed

    Wang, Q F; Farnworth, P G; Findlay, J K; Burger, H G

    1989-01-01

    Primary cultures of enzymatically dispersed rat anterior pituitary cells were used to examine the effect of pure 31 kilodalton bovine inhibin on GnRH-induced up-regulation of GnRH binding sites. After 2 days in culture, the cells were exposed to stimuli with or without test substances for 10 h, followed by evaluation of GnRH binding sites using iodinated GnRH-A (Buserelin) as tracer. Inhibin suppressed GnRH-induced up-regulation of GnRH binding sites in a dose-dependent manner with an IC50 of 0.13 U/ml (5.5 pM). The inhibin-related peptides transforming growth factor-beta, and Müllerian inhibitory substance had no detectable effect (stimulatory or inhibitory), suggesting that the action is specific to inhibin. In addition, inhibin inhibited the calcium ionophore A23187-induced up-regulation of GnRH binding sites, indicating that this effect of inhibin can occur, at least in part, at a stage subsequent to Ca2+ mobilization. Inhibin did not compete with iodinated GnRH-A for GnRH binding sites. In conclusion, pure 31 kilodalton bovine inhibin suppressed GnRH-induced up-regulation of GnRH binding sites in cultured rat anterior pituitary cells, providing direct evidence that inhibin modulates delayed actions of GnRH. PMID:2535810

  15. Gonadotropin-releasing hormone induces miR-132 and miR-212 to regulate cellular morphology and migration in immortalized LbetaT2 pituitary gonadotrope cells.

    PubMed

    Godoy, Joseph; Nishimura, Marin; Webster, Nicholas J G

    2011-05-01

    GnRH is central to the regulation of reproductive function. It acts on pituitary gonadotropes to stimulate LH and FSH synthesis and secretion. We had previously presented evidence for translational control of LHβ synthesis; therefore we investigated whether micro-RNAs might play a role in GnRH regulation in LβT2 cells. We show here that GnRH strongly induces the AK006051 gene transcript that encodes two micro-RNAs, miR-132 and miR-212, within the first intron. We show furthermore that the AK006051 promoter region is highly GnRH responsive. We verify that the p250Rho GTPase activating protein (GAP) is a target of miR-132/212 and show that GnRH treatment leads to a decrease in mRNA and protein expression. This reduction is blocked by an anti-miR to miR-132/212 and mimicked by a pre-miR-132. GnRH inhibits p250RhoGAP expression through a miR-132/212 response element within the 3'-untranslated region. The loss of p250RhoGAP expression leads to activation of Rac and marked increases in both the number and length of neurite-like processes extending from the cell. Knockdown of p250RhoGAP by small interfering RNA induces the same morphological changes observed with GnRH treatment. In addition, loss of p250RhoGAP causes an increase in cellular motility. Our findings suggest a novel pathway regulating long-term changes in cellular motility and process formation via the GnRH induction of miR-132/212 with the subsequent down-regulation of p250RhoGAP. PMID:21372146

  16. Luteinizing hormone/human chorionic gonadotropin receptors in breast cancer.

    PubMed

    Meduri, G; Charnaux, N; Loosfelt, H; Jolivet, A; Spyratos, F; Brailly, S; Milgrom, E

    1997-03-01

    Recent studies have suggested that human choriogonadotropin (hCG), in addition to its function in regulating steroidogenesis, may also play a role as a growth factor. Immunocytochemistry using two different monoclonal antibodies (LHR29 and LHR1055) raised against the human luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor allowed us to detect this receptor in breast cancer cell lines (T47D, MCF7, and ZR75) in individual cancer biopsies and in benign breast lesions. The receptor was also present in epithelial cells of normal human and sow breast. In the latter, its concentration increased after ovulation. The presence of LH/hCG receptor mRNA was confirmed by reverse transcription-PCR using primers extending over exons 2-4, 5-11, and 9-11. The proportion of LH/hCG-receptor positive cells and the intensity of the immunolabeling varied in individual biopsies, but there was no obvious correlation with the histological type of the cancer. These results are compatible with previous studies suggesting that during pregnancy, hCG is involved in the differentiation of breast glandular epithelium and that this hormone may play an inhibitory role in mammary carcinogenesis and in the growth of breast tumors. PMID:9041186

  17. Establishment of a human nonluteinized granulosa cell line that transitions from the gonadotropin-independent to the gonadotropin-dependent status.

    PubMed

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

    2012-06-01

    The ovary is a complex endocrine organ responsible for steroidogenesis and folliculogenesis. Follicles consist of oocytes and two primary steroidogenic cell types, the granulosa cells, and the theca cells. Immortalized human granulosa cells are essential for researching the mechanism of steroidogenesis and folliculogenesis. We obtained granulosa cells from a 35-yr-old female and immortalized them by lentivirus-mediated transfer of several genes so as to establish a human nonluteinized granulosa cell line (HGrC1). We subsequently characterized HGrC1 and investigated its steroidogenic performance. HGrC1 expressed enzymes related to steroidogenesis, such as steroidogenic acute regulatory protein, CYP11A, aromatase, and gonadotropin receptors. Stimulation with FSH increased the mRNA levels of aromatase, which consequently induced the aromatization of androstenedione to estradiol. Activin A increased the mRNA levels of the FSH receptor, which were synergistically up-regulated with FSH stimulation. HGrC1 also expressed a series of ligands and receptors belonging to the TGF-β superfamily. A Western blot analysis showed that bone morphogenetic protein (BMP)-4, BMP-6, and BMP-7 phosphorylated small mother against decapentaplegic (Smad)1/5/8, whereas growth differentiation factor-9 phosphorylated Smad2/3. BMP-15 and anti-Müllerian hormone phosphorylated Smad1/5/8 while also weakly phosphorylating Smad2/3. These results indicate that HGrC1 may possess the characteristics of granulosa cells belonging to follicles in the early stage. HGrC1 might also be capable of displaying the growth transition from a gonadotropin-independent status to gonadotropin-dependent one. PMID:22467494

  18. Heterozygous mutations in cyclic AMP phosphodiesterase-4D (PDE4D) and protein kinase A (PKA) provide new insights into the molecular pathology of acrodysostosis.

    PubMed

    Kaname, Tadashi; Ki, Chang-Seok; Niikawa, Norio; Baillie, George S; Day, Jonathan P; Yamamura, Ken-Ichi; Ohta, Tohru; Nishimura, Gen; Mastuura, Nobuo; Kim, Ok-Hwa; Sohn, Young Bae; Kim, Hyun Woo; Cho, Sung Yoon; Ko, Ah-Ra; Lee, Jin Young; Kim, Hyun Wook; Ryu, Sung Ho; Rhee, Hwanseok; Yang, Kap-Seok; Joo, Keehyoung; Lee, Jooyoung; Kim, Chi Hwa; Cho, Kwang-Hyun; Kim, Dongsan; Yanagi, Kumiko; Naritomi, Kenji; Yoshiura, Ko-Ichiro; Kondoh, Tatsuro; Nii, Eiji; Tonoki, Hidefumi; Houslay, Miles D; Jin, Dong-Kyu

    2014-11-01

    Acrodysostosis without hormone resistance is a rare skeletal disorder characterized by brachydactyly, nasal hypoplasia, mental retardation and occasionally developmental delay. Recently, loss-of-function mutations in the gene encoding cAMP-hydrolyzing phosphodiesterase-4D (PDE4D) have been reported to cause this rare condition but the pathomechanism has not been fully elucidated. To understand the pathogenetic mechanism of PDE4D mutations, we conducted 3D modeling studies to predict changes in the binding efficacy of cAMP to the catalytic pocket in PDE4D mutants. Our results indicated diminished enzyme activity in the two mutants we analyzed (Gly673Asp and Ile678Thr; based on PDE4D4 residue numbering). Ectopic expression of PDE4D mutants in HEK293 cells demonstrated this reduction in activity, which was identified by increased cAMP levels. However, the cells from an acrodysostosis patient showed low cAMP accumulation, which resulted in a decrease in the phosphorylated cAMP Response Element-Binding Protein (pCREB)/CREB ratio. The reason for this discrepancy was due to a compensatory increase in expression levels of PDE4A and PDE4B isoforms, which accounted for the paradoxical decrease in cAMP levels in the patient cells expressing mutant isoforms with a lowered PDE4D activity. Skeletal radiographs of 10-week-old knockout (KO) rats showed that the distal part of the forelimb was shorter than in wild-type (WT) rats and that all the metacarpals and phalanges were also shorter in KO, as the name acrodysostosis implies. Like the G-protein α-stimulatory subunit and PRKAR1A, PDE4D critically regulates the cAMP signal transduction pathway and influences bone formation in a way that activity-compromising PDE4D mutations can result in skeletal dysplasia. We propose that specific inhibitory PDE4D mutations can lead to the molecular pathology of acrodysostosis without hormone resistance but that the pathological phenotype may well be dependent on an over-compensatory induction

  19. Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function

    PubMed Central

    Dacquin, Romain; Domenget, Chantal; Kumanogoh, Atsushi; Kikutani, Hitoshi; Jurdic, Pierre; Machuca-Gayet, Irma

    2011-01-01

    Osteoporosis is one of the most common bone pathologies, which are characterized by a decrease in bone mass. It is well established that bone mass, which results from a balanced bone formation and bone resorption, is regulated by many hormonal, environmental and genetic factors. Here we report that the immune semaphorin 4D (Sema4D) is a novel factor controlling bone resorption. Sema4D-deficient primary osteoclasts showed impaired spreading, adhesion, migration and resorption due to altered ß3 integrin sub-unit downstream signaling. In apparent accordance with these in vitro results, Sema4D deletion in sexually mature female mice led to a high bone mass phenotype due to defective bone resorption by osteoclasts. Mutant males, however, displayed normal bone mass and the female osteopetrotic phenotype was only detected at the onset of sexual maturity, indicating that, in vivo, this intrinsic osteoclast defect might be overcome in these mice. Using bone marrow cross transplantation, we confirmed that Sema4D controls bone resorption through an indirect mechanism. In addition, we show that Sema4D −/− mice were less fertile than their WT littermates. A decrease in Gnrh1 hypothalamic expression and a reduced number of ovarian follicles can explain this attenuated fertility. Interestingly, ovariectomy abrogated the bone resorption phenotype in Sema4D −/− mice, providing the evidence that the observed high bone mass phenotype is strictly dependent on ovarian function. Altogether, this study reveals that, in vivo, Sema4D is an indirect regulator of bone resorption, which acts via its effect on reproductive function. PMID:22046317

  20. Gonadotropin-releasing hormone modulates cholesterol synthesis and steroidogenesis in SH-SY5Y cells.

    PubMed

    Rosati, Fabiana; Sturli, Niccolò; Cungi, Maria Chiara; Morello, Matteo; Villanelli, Fabio; Bartolucci, Gianluca; Finocchi, Claudia; Peri, Alessandro; Serio, Mario; Danza, Giovanna

    2011-04-01

    Neurosteroids are involved in Central Nervous System development, brain functionality and neuroprotection but little is known about regulators of their biosynthesis. Recently gonadotropins, Gonadotropin-releasing Hormone (GnRH) and their receptors have been localized in different brain regions, such as hippocampus and cortex. Using human neuronal-like cells we found that GnRH up-regulates the expression of key genes of cholesterol and steroid synthesis when used in a narrow range around 1.0 nM. The expression of Hydroxysterol D24-reductase (seladin-1/DHCR24), that catalyzes the last step of cholesterol biosynthesis, is increased by 50% after 90 min of incubation with GnRH. StAR protein and P450 side chain cleavage (P450scc) are up-regulated by 3.3 times after 90 min and by 3.5 times after 3 h, respectively. GnRH action is mediated by LH and 1.0 nM GnRH enhances the expression of LHβ as well. A two fold increase of cell cholesterol is induced after 90 min of GnRH incubation and 17β-estradiol (E2) production is increased after 24, 48 and 72 h. These data indicate for the first time that GnRH regulates both cholesterol and steroid biosynthesis in human neuronal-like cells and suggest a new physiological role for GnRH in the brain. PMID:21296663

  1. Oral Progestin Priming Increases Ovarian Sensitivity to Gonadotropin Stimulation and Improves Luteal Function in the Cat1

    PubMed Central

    Stewart, Rosemary A.; Pelican, Katharine M.; Crosier, Adrienne E.; Pukazhenthi, Budhan S.; Wildt, David E.; Ottinger, Mary Ann; Howard, JoGayle

    2012-01-01

    ABSTRACT As the only domesticated species known to exhibit both induced and spontaneous ovulation, the cat is a model for understanding the nuances of ovarian control. To explore ovarian sensitivity to exogenous gonadotropins and the influence of progestin priming, we conducted a study of queens that were down-regulated with oral progestin or allowed to cycle normally, followed by low or high doses of equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG). Our metrics included 1) fecal steroid metabolite profiles before and after ovulation induction, 2) laparoscopic examination of ovarian follicles and corpora lutea (CL) on Days 2 and 17 (Day 0 = hCG administration), and 3) ovariohysterectomy (Day 17) to assess CL progesterone concentrations, morphometrics, and histology. Reproductive tracts from time-matched, naturally mated queens (n = 6) served as controls. Every progestin-primed cat (n = 12) produced the desired response of morphologically similar, fresh CL (regardless of eCG/hCG dose) by Day 2, whereas 41.7% of unprimed counterparts (n = 12) failed to ovulate or had variable-aged CL suggestive of prior spontaneous ovulation (P < 0.05). The ovarian response to low, but not high, eCG/hCG was improved (P < 0.05) in primed compared to unprimed cats, indicating increased sensitivity to gonadotropin in the progestin-primed ovary. Progestin priming prevented hyperelevated fecal steroid metabolites and normalized CL progesterone capacity, but only when combined with low eCG/hCG. However, priming failed to prevent ancillary CL formation, smaller CL mass, or abnormal luteal cell density, which were common to all eCG/hCG-treated cats. Thus, the domestic cat exposed to eCG/hCG produces CL with structural and functional aberrations. These anomalies can be partially mitigated by progestin priming, possibly due to a protective effect of progestin associated with enhanced ovarian sensitivity to gonadotropins. PMID:23100619

  2. Motion4D-library extended

    NASA Astrophysics Data System (ADS)

    Müller, Thomas

    2011-06-01

    The new version of the Motion4D-library now also includes the integration of a Sachs basis and the Jacobi equation to determine gravitational lensing of pointlike sources for arbitrary spacetimes.New version program summaryProgram title: Motion4D-libraryCatalogue identifier: AEEX_v3_0Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEEX_v3_0.htmlProgram obtainable from: CPC Program Library, Queen's University, Belfast, N. IrelandLicensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.htmlNo. of lines in distributed program, including test data, etc.: 219 441No. of bytes in distributed program, including test data, etc.: 6 968 223Distribution format: tar.gzProgramming language: C++Computer: All platforms with a C++ compilerOperating system: Linux, WindowsRAM: 61 MbytesClassification: 1.5External routines: Gnu Scientic Library (GSL) (http://www.gnu.org/software/gsl/)Catalogue identifier of previous version: AEEX_v2_0Journal reference of previous version: Comput. Phys. Comm. 181 (2010) 703Does the new version supersede the previous version?: YesNature of problem: Solve geodesic equation, parallel and Fermi-Walker transport in four-dimensional Lorentzian spacetimes. Determine gravitational lensing by integration of Jacobi equation and parallel transport of Sachs basis.Solution method: Integration of ordinary differential equations.Reasons for new version: The main novelty of the current version is the extension to integrate the Jacobi equation and the parallel transport of the Sachs basis along null geodesics. In combination, the change of the cross section of a light bundle and thus the gravitational lensing effect of a spacetime can be determined. Furthermore, we have implemented several new metrics.Summary of revisions: The main novelty of the current version is the integration of the Jacobi equation and the parallel transport of the Sachs basis along null geodesics. The corresponding set of equations readd2xμdλ2=-Γρ

  3. The 4D-TECS integration for NASA TSRV airplane

    NASA Technical Reports Server (NTRS)

    Kaminer, I.; Oshaughnessy, P. R.

    1989-01-01

    The integration of the Total Energy Control System (TECS) concept with 4D navigation is described. This integration was made to increase the operational capacity of modern aircraft and encourage incorporation of this increased capability with the evolving National Airspace System (NAS). Described herein is: 4D smoothing, the basic concepts of TECS, the spoiler integration concept, an algorithm for nulling out time error, speed and altitude profile modes, manual spoiler implementation, 4D logic, and the results of linear and nonlinear analysis.

  4. Killing Weeds with 2,4-D. Extension Bulletin 389.

    ERIC Educational Resources Information Center

    Lee, Oliver C.

    Discussed is the use of the herbicide 2,4-D. Though written for farmers and agricultural workers, the pamphlet considers turf weed control and use of 2,4-D near ornamental plants. Aspects of the use of this herbicide covered are: (1) the common forms of 2,4-D; (2) plant responses and tolerances to the herbicide; (3) dilution and concentration of…

  5. Pros and cons for C4d as a biomarker.

    PubMed

    Cohen, Danielle; Colvin, Robert B; Daha, Mohamed R; Drachenberg, Cinthia B; Haas, Mark; Nickeleit, Volker; Salmon, Jane E; Sis, Banu; Zhao, Ming-Hui; Bruijn, Jan A; Bajema, Ingeborg M

    2012-04-01

    The introduction of C4d in daily clinical practice in the late nineties aroused an ever-increasing interest in the role of antibody-mediated mechanisms in allograft rejection. As a marker of classical complement activation, C4d made it possible to visualize the direct link between anti-donor antibodies and tissue injury at sites of antibody binding in a graft. With the expanding use of C4d worldwide several limitations of C4d were identified. For instance, in ABO-incompatible transplantations C4d is present in the majority of grafts but this seems to point at 'graft accommodation' rather than antibody-mediated rejection. C4d is now increasingly recognized as a potential biomarker in other fields where antibodies can cause tissue damage, such as systemic autoimmune diseases and pregnancy. In all these fields, C4d holds promise to detect patients at risk for the consequences of antibody-mediated disease. Moreover, the emergence of new therapeutics that block complement activation makes C4d a marker with potential to identify patients who may possibly benefit from these drugs. This review provides an overview of the past, present, and future perspectives of C4d as a biomarker, focusing on its use in solid organ transplantation and discussing its possible new roles in autoimmunity and pregnancy. PMID:22297669

  6. Human chorionic gonadotropin measurements in parathyroid carcinoma

    PubMed Central

    Rubin, Mishaela R; Bilezikian, John P; Birken, Steven; Silverberg, Shonni J

    2010-01-01

    Objective Preoperatively, it is difficult to differentiate between parathyroid cancer (PtCa) and severe primary hyperparathyroidism (PHPT) due to a benign tumor. Human chorionic gonadotropin (hCG) is a tumor marker in trophoblastic and nontrophoblastic cancers and hyperglycosylated hCG is increased in hCG-secreting malignancies. We investigated whether hCG can distinguish PtCa cancer from benign disease and add prognostic information. Design Observational study. Methods Measurement of urinary hCG (total and malignant isoforms) and serum malignant hCG in 8 subjects with PtCa and in 18 subjects with PHPT (measurement of urine in ten and serum in eight). Results Total urinary hCG was normal in the benign PHPT control subjects (range: 0–17 fmol/mg Cr; nl < 50). In the PtCa subjects, three had normal total urinary hCG levels and survived complication free for at least 2 years; three had persistently elevated total urinary hCG levels (range: 217–1986 fmol/mg Cr) and sustained hip fracture (n = 3) and died (n = 2) within 3 and 6 months respectively; two had a rise in total urinary hCG and had hip fracture (n = 1) and died (n = 2) within 4 and 10 months respectively. Elevated urinary hCG was of the malignant hyperglycosylated isoform. Serum malignant hyperglycosylated hCG values in all of the cancer patients exceeded the maximal serum malignant hCG level of the PHPT subjects with benign disease (3.77 pmol/l). Conclusion hCG, especially itshyperglycosylated isoform, might add diagnostic and prognostic information in PtCa. Further studies would help to elucidate the role of hCG as a potential tumor marker in this disease. PMID:18625691

  7. Phosphodiesterase 4D Inhibitors Limit Prostate Cancer Growth Potential

    PubMed Central

    Powers, Ginny L.; Hammer, Kimberly D.P.; Domenech, Maribella; Frantskevich, Katsiaryna; Malinowski, Rita L.; Bushman, Wade; Beebe, David J.; Marker, Paul C.

    2014-01-01

    Phosphodiesterase 4D (PDE4D) has recently been implicated as a proliferation-promoting factor in prostate cancer and is over-expressed in human prostate carcinoma. However, the effects of PDE4D inhibition using pharmacological inhibitors have not been examined in prostate cancer. These studies examined the effects of selective PDE4D inhibitors, NVP-ABE171 and cilomilast, as anti-prostate cancer therapies in both in vitro and in vivo models. The effects of PDE4D inhibitors on pathways that are critical in prostate cancer and/or downstream of cyclic AMP (cAMP) were examined. Both NVP-ABE171 and cilomilast decreased cell growth. In vitro, PDE4D inhibitors lead to decreased signaling of the sonic hedgehog (SHH), Androgen Receptor (AR), and MAPK pathways, but growth inhibition was best correlated to the sonic hedgehog pathway. PDE4D inhibition also reduced proliferation of epithelial cells induced by paracrine signaling from co-cultured stromal cells that had activated hedgehog signaling. In addition, PDE4D inhibitors decreased the weight of the prostate in wild-type mice. Prostate cancer xenografts grown in nude mice that were treated with cilomilast or NVP-ABE171 had decreased wet weight and increased apoptosis compared to vehicle treated controls. These studies suggest the pharmacological inhibition of PDE4D using small molecule inhibitors is an effective option for prostate cancer therapy. Implications PDE4D inhibitors decrease the growth of prostate cancer cells in vivo and in vitro, and PDE4D inhibition has therapeutic potential in prostate cancer. PMID:25149359

  8. Biologically Active Chorionic Gonadotropin: Synthesis by the Human Fetus

    NASA Astrophysics Data System (ADS)

    McGregor, W. G.; Kuhn, R. W.; Jaffe, R. B.

    1983-04-01

    The kidney, and to a slight extent the liver, of human fetuses were found to synthesize and secrete the α subunit common to glycoprotein hormones. Fetal lung and muscle did not synthesize this protein. Since fetal kidney and liver were previously found to synthesize β chorionic gonadotropin, their ability to synthesize bioactive chorionic gonadotropin was also determined. The newly synthesized hormone bound to mouse Leydig cells and elicited a biological response: namely, the synthesis of testosterone. These results suggest that the human fetus may participate in metabolic homeostasis during its development.

  9. 32 CFR 1645.4 - Exclusion from Class 4-D.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... MINISTERS OF RELIGION § 1645.4 Exclusion from Class 4-D. A registrant is excluded from Class 4-D when his... duly ordained minister of religion in accordance with the ceremonial rite or discipline of a church... principles of religion and administer the ordinances of public worship, as embodied in the creed...

  10. 32 CFR 1645.4 - Exclusion from Class 4-D.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... MINISTERS OF RELIGION § 1645.4 Exclusion from Class 4-D. A registrant is excluded from Class 4-D when his... duly ordained minister of religion in accordance with the ceremonial rite or discipline of a church... principles of religion and administer the ordinances of public worship, as embodied in the creed...

  11. 32 CFR 1645.4 - Exclusion from Class 4-D.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... MINISTERS OF RELIGION § 1645.4 Exclusion from Class 4-D. A registrant is excluded from Class 4-D when his... duly ordained minister of religion in accordance with the ceremonial rite or discipline of a church... principles of religion and administer the ordinances of public worship, as embodied in the creed...

  12. 32 CFR 1645.4 - Exclusion from Class 4-D.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... MINISTERS OF RELIGION § 1645.4 Exclusion from Class 4-D. A registrant is excluded from Class 4-D when his... duly ordained minister of religion in accordance with the ceremonial rite or discipline of a church... principles of religion and administer the ordinances of public worship, as embodied in the creed...

  13. 32 CFR 1645.4 - Exclusion from Class 4-D.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MINISTERS OF RELIGION § 1645.4 Exclusion from Class 4-D. A registrant is excluded from Class 4-D when his... duly ordained minister of religion in accordance with the ceremonial rite or discipline of a church... principles of religion and administer the ordinances of public worship, as embodied in the creed...

  14. Fast 4D segmentation of large datasets using graph cuts

    NASA Astrophysics Data System (ADS)

    Lombaert, Herve; Sun, Yiyong; Cheriet, Farida

    2011-03-01

    In this paper, we propose to use 4D graph cuts for the segmentation of large spatio-temporal (4D) datasets. Indeed, as 4D datasets grow in popularity in many clinical areas, so will the demand for efficient general segmentation algorithms. The graph cuts method1 has become a leading method for complex 2D and 3D image segmentation in many applications. Despite a few attempts2-5 in 4D, the use of graph cuts on typical medical volume quickly exceeds today's computer capacities. Among all existing graph cuts based methods6-10 the multilevel banded graph cuts9 is the fastest and uses the least amount of memory. Nevertheless, this method has its limitation. Memory becomes an issue when using large 4D volume sequences, and small structures become hardly recoverable when using narrow bands. We thus improve the boundary refinement efficiency by using a 4D competitive region growing. First, we construct a coarse graph at a low resolution with strong temporal links to prevent the shrink bias inherent to the graph cuts method. Second, we use a competitive region growing using a priority queue to capture all fine details. Leaks are prevented by constraining the competitive region growing within a banded region and by adding a viscosity term. This strategy yields results comparable to the multilevel banded graph cuts but is faster and allows its application to large 4D datasets. We applied our method on both cardiac 4D MRI and 4D CT datasets with promising results.

  15. Identification of novel mutations confirms PDE4D as a major gene causing acrodysostosis.

    PubMed

    Lynch, Danielle C; Dyment, David A; Huang, Lijia; Nikkel, Sarah M; Lacombe, Didier; Campeau, Philippe M; Lee, Brendan; Bacino, Carlos A; Michaud, Jacques L; Bernier, Francois P; Parboosingh, Jillian S; Innes, A Micheil

    2013-01-01

    Acrodysostosis is characterized by nasal hypoplasia, peripheral dysostosis, variable short stature, and intellectual impairment. Recently, mutations in PRKAR1A were reported in patients with acrodysostosis and hormone resistance. Subsequently, mutations in a phosphodiesterase gene (PDE4D) were identified in seven sporadic cases. We sequenced PDE4D in seven acrodysostosis patients from five families. Missense mutations were identified in all cases. Families showed de novo inheritance except one family with three affected children whose father was subsequently found to have subtle features of acrodysostosis. There were no recurrent mutations. Short stature and endocrine resistance are rare in this series; however, cognitive involvement and obesity were frequent. This last finding is relevant given PDE4D is insulin responsive and potentially involved in lipolysis. PDE4D encodes a cyclic AMP regulator and places PDE4D-related acrodysostosis within the same family of diseases as pseudohypoparathyroidism, pseudopseudohypoparathyroidism, PRKAR1A-related acrodysostosis and brachydactyly-mental retardation syndrome; all characterized by cognitive impairment and short distal extremities. PMID:23033274

  16. Ovarian stimulation with human chorionic gonadotropin and equine chorionic gonadotropin affects prostacyclin and its receptor expression in the porcine oviduct.

    PubMed

    Małysz-Cymborska, I; Andronowska, A

    2015-10-01

    Prostaglandins are well-known mediators of crucial events in the female reproductive tract, eg, early embryo development and implantation. Prostacyclin (PGI2) is the most synthesized prostaglandin in the human oviduct during the postovulatory period, indicating its important role in supporting and regulating the oviductal environment. The present study was undertaken to determine the influence of insemination and ovarian stimulation with human chorionic gonadotropin (hCG)/equine chorionic gonadotropin (eCG) on PGI2 synthesis in the porcine oviduct on day 3 post coitus. Mature gilts (n = 25) were assigned into 2 experiments. In experiment I, gilts were divided into cyclic (control; n = 5) and inseminated (control; n = 5) groups. In experiment II, there were 3 groups of animals: inseminated (n = 5), induced ovulation/inseminated (750 IU eCG, 500 IU hCG; n = 5), and superovulated/inseminated (1,500 IU eCG, 1,000 IU hCG; n = 5) gilts. Parts of oviducts (isthmus and ampulla) were collected 3 days after phosphate-buffered saline treatment (cyclic gilts of experiment I) or insemination (all other groups). Expression of messenger RNA for PGI2 synthase (PGIS) and its receptor (IP) was measured by real-time reverse transcription polymerase chain reaction (real-time RT PCR) and protein levels using Western blots. Concentrations of the PGI2 metabolite 6-keto PGF1α were evaluated by enzyme immunoassay and localization of PGIS and IP in the oviductal tissues using immunohistochemical staining. Insemination by itself increased PGIS protein levels in the oviductal isthmus (P < 0.05) and IP protein expression in the ampulla (P < 0.05). The concentration of 6-keto PGF1α increased significantly in the oviductal ampulla after insemination (P < 0.05). Induction of ovulation decreased IP protein levels in the oviductal ampulla (P < 0.05), whereas superovulation reduced IP levels in both parts of the oviduct (P < 0.01). Synthesis of 6-keto PGF1α was reduced by induction of ovulation

  17. 4D-Var or Ensemble Kalman Filter

    NASA Astrophysics Data System (ADS)

    Kalnay, E.; Li, H.; Yang, S.; Miyoshi, T.; Ballabrera, J.

    2007-05-01

    We consider the relative advantages of two advanced data assimilation systems, 4D-Var and ensemble Kalman filter (EnKF), currently in use or considered for operational implementation. We explore the impact of tuning assimilation parameters such as the assimilation window length and background error covariance in 4D-Var, the variance inflation in EnKF, and the effect of model errors and reduced observation coverage in both systems. For short assimilation windows EnKF gives more accurate analyses. Both systems reach similar levels of accuracy if long windows are used for 4D-Var, and for infrequent observations, when ensemble perturbations grow nonlinearly and become non-Gaussian, 4D-Var attains lower errors than EnKF. Results obtained with variations of EnKF using operational models and both simulated and real observations are reviewed. A table summarizes the pros and cons of the two methods.

  18. Modulation of rat testes lipid composition by hormones: Effect of PRL (prolactin) and hCG (human chorionic gonadotropin)

    SciTech Connect

    Sebokova, E.; Wierzbicki, A.; Clandinin, M.T. )

    1988-10-01

    The effect of prolactin (PRL) and human chorionic gonadotropin (hCG) administration for 7 days on the composition and function of rat testicular plasma membrane was investigated. Refractory state in Leydig cells desensitized by hCG decreased the binding capacity for {sup 125}I-labeled hCG and also luteinizing hormone (LH)-induced adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) and testosterone production. In testicular membranes of hCG-treated animals, a depletion of cholesterol and an increase in total phospholipid content was observed after gonadotropin injection, thereby decreasing the cholesterol-to-phospholipid ratio. Injection of high doses of PRL had no effect on the binding capacity or affinity of the LH-hCG receptor but decreased the response of Leydig cells to LH in terms of cAMP and testosterone synthesis. PRL also increased total and esterified cholesterol and decreased free cholesterol and membrane phospholipid content. The fatty acid composition of testicular lipids was significantly and selectively influenced by both hormonal treatments. These observations suggest that metabolism of cholesterol and long-chain polyunsaturated fatty acids in testicular tissue is affected by chorionic gonadotropin and PRL and may provide the mechanism for regulating steroidogenic functions.

  19. PDE4D phosphorylation: A coincidence detector integrating multiple signaling pathways.

    PubMed

    Mika, Delphine; Conti, Marco

    2016-07-01

    In Eukaryotes, more than 100 different phosphodiesterase (PDE) proteins serve to fine-tune cyclic nucleotide (cAMP and cGMP) signals and contribute to specificity of signaling. In mammals, PDEs are divided into 11 families, of which PDE4 represents the largest family. Four genes (pde4a, pde4b, pde4c and pde4d) encode for this class of enzymes in mammals and give rise to more than 20 variants. Within this family of genes, PDE4D was discovered on the basis of its regulatory properties and its induction by hormones and cAMP. PDE4D has often been used as the prototype PDE4 and large body of work has been generated on the biochemical, pharmacological, and physiological properties of this enzyme. This review covers the regulation of PDE4D by phosphorylation, the impact of this regulation in the context of the structure of this protein, and the functional consequences of this complex pattern of posttranslational modifications. PMID:26562185

  20. 4-D-Var or ensemble Kalman filter?

    NASA Astrophysics Data System (ADS)

    Kalnay, Eugenia; Li, Hong; Miyoshi, Takemasa; Yang, Shu-Chih; Ballabrera-Poy, Joaquim

    2007-10-01

    We consider the relative advantages of two advanced data assimilation systems, 4-D-Var and ensemble Kalman filter (EnKF), currently in use or under consideration for operational implementation. With the Lorenz model, we explore the impact of tuning assimilation parameters such as the assimilation window length and background error covariance in 4-D-Var, variance inflation in EnKF, and the effect of model errors and reduced observation coverage. For short assimilation windows EnKF gives more accurate analyses. Both systems reach similar levels of accuracy if long windows are used for 4-D-Var. For infrequent observations, when ensemble perturbations grow non-linearly and become non-Gaussian, 4-D-Var attains lower errors than EnKF. If the model is imperfect, the 4-D-Var with long windows requires weak constraint. Similar results are obtained with a quasi-geostrophic channel model. EnKF experiments made with the primitive equations SPEEDY model provide comparisons with 3-D-Var and guidance on model error and `observation localization'. Results obtained using operational models and both simulated and real observations indicate that currently EnKF is becoming competitive with 4-D-Var, and that the experience acquired with each of these methods can be used to improve the other. A table summarizes the pros and cons of the two methods.

  1. Substitutional 4d and 5d impurities in graphene.

    PubMed

    Alonso-Lanza, Tomás; Ayuela, Andrés; Aguilera-Granja, Faustino

    2016-08-21

    We describe the structural and electronic properties of graphene doped with substitutional impurities of 4d and 5d transition metals. The adsorption energies and distances for 4d and 5d metals in graphene show similar trends for the later groups in the periodic table, which are also well-known characteristics of 3d elements. However, along earlier groups the 4d impurities in graphene show very similar adsorption energies, distances and magnetic moments to the 5d ones, which can be related to the influence of the 4d and 5d lanthanide contraction. Surprisingly, within the manganese group, the total magnetic moment of 3 μB for manganese is reduced to 1 μB for technetium and rhenium. We find that compared with 3d elements, the larger size of the 4d and 5d elements causes a high degree of hybridization with the neighbouring carbon atoms, reducing spin splitting in the d levels. It seems that the magnetic adjustment of graphene could be significantly different if 4d or 5d impurities are used instead of 3d impurities. PMID:27439363

  2. Exome Sequencing Identifies PDE4D Mutations as Another Cause of Acrodysostosis

    PubMed Central

    Michot, Caroline; Le Goff, Carine; Goldenberg, Alice; Abhyankar, Avinash; Klein, Céline; Kinning, Esther; Guerrot, Anne-Marie; Flahaut, Philippe; Duncombe, Alice; Baujat, Genevieve; Lyonnet, Stanislas; Thalassinos, Caroline; Nitschke, Patrick; Casanova, Jean-Laurent; Le Merrer, Martine; Munnich, Arnold; Cormier-Daire, Valérie

    2012-01-01

    Acrodysostosis is a rare autosomal-dominant condition characterized by facial dysostosis, severe brachydactyly with cone-shaped epiphyses, and short stature. Moderate intellectual disability and resistance to multiple hormones might also be present. Recently, a recurrent mutation (c.1102C>T [p.Arg368∗]) in PRKAR1A has been identified in three individuals with acrodysostosis and resistance to multiple hormones. After studying ten unrelated acrodysostosis cases, we report here de novo PRKAR1A mutations in five out of the ten individuals (we found c.1102C>T [p.Arg368∗] in four of the ten and c.1117T>C [p.Tyr373His] in one of the ten). We performed exome sequencing in two of the five remaining individuals and selected phosphodiesterase 4D (PDE4D) as a candidate gene. PDE4D encodes a class IV cyclic AMP (cAMP)-specific phosphodiesterase that regulates cAMP concentration. Exome analysis detected heterozygous PDE4D mutations (c.673C>A [p.Pro225Thr] and c.677T>C [p.Phe226Ser]) in these two individuals. Screening of PDE4D identified heterozygous mutations (c.568T>G [p.Ser190Ala] and c.1759A>C [p.Thr587Pro]) in two additional acrodysostosis cases. These mutations occurred de novo in all four cases. The four individuals with PDE4D mutations shared common clinical features, namely characteristic midface and nasal hypoplasia and moderate intellectual disability. Metabolic screening was normal in three of these four individuals. However, resistance to parathyroid hormone and thyrotropin was consistently observed in the five cases with PRKAR1A mutations. Finally, our study further supports the key role of the cAMP signaling pathway in skeletogenesis. PMID:22464250

  3. Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis.

    PubMed

    Michot, Caroline; Le Goff, Carine; Goldenberg, Alice; Abhyankar, Avinash; Klein, Céline; Kinning, Esther; Guerrot, Anne-Marie; Flahaut, Philippe; Duncombe, Alice; Baujat, Genevieve; Lyonnet, Stanislas; Thalassinos, Caroline; Nitschke, Patrick; Casanova, Jean-Laurent; Le Merrer, Martine; Munnich, Arnold; Cormier-Daire, Valérie

    2012-04-01

    Acrodysostosis is a rare autosomal-dominant condition characterized by facial dysostosis, severe brachydactyly with cone-shaped epiphyses, and short stature. Moderate intellectual disability and resistance to multiple hormones might also be present. Recently, a recurrent mutation (c.1102C>T [p.Arg368*]) in PRKAR1A has been identified in three individuals with acrodysostosis and resistance to multiple hormones. After studying ten unrelated acrodysostosis cases, we report here de novo PRKAR1A mutations in five out of the ten individuals (we found c.1102C>T [p.Arg368(∗)] in four of the ten and c.1117T>C [p.Tyr373His] in one of the ten). We performed exome sequencing in two of the five remaining individuals and selected phosphodiesterase 4D (PDE4D) as a candidate gene. PDE4D encodes a class IV cyclic AMP (cAMP)-specific phosphodiesterase that regulates cAMP concentration. Exome analysis detected heterozygous PDE4D mutations (c.673C>A [p.Pro225Thr] and c.677T>C [p.Phe226Ser]) in these two individuals. Screening of PDE4D identified heterozygous mutations (c.568T>G [p.Ser190Ala] and c.1759A>C [p.Thr587Pro]) in two additional acrodysostosis cases. These mutations occurred de novo in all four cases. The four individuals with PDE4D mutations shared common clinical features, namely characteristic midface and nasal hypoplasia and moderate intellectual disability. Metabolic screening was normal in three of these four individuals. However, resistance to parathyroid hormone and thyrotropin was consistently observed in the five cases with PRKAR1A mutations. Finally, our study further supports the key role of the cAMP signaling pathway in skeletogenesis. PMID:22464250

  4. Soil matrix and macropore biodegradation of 2,4-D

    SciTech Connect

    Pivetz, B.E.; Steenhuis, T.S.

    1995-07-01

    Preferential flow of pesticides in macropores can lead to decreased travel times through the vadose zone and increased groundwater contamination. Macropores, however, may present a favorable environment for biodegradation because of greater oxygen, nutrient, and substrate supply, and higher microbial populations in earthworm burrows, compared to the soil matrix. The biodegradation of 2,4-dichlorophenoxyacetic acid (2,4-D) was measured in macropores and soil matrix of packed soil columns (7.0-cm diam., 10-cm length) and undisturbed cores contained as well-defined artificial macropore and the undisturbed cores contained earthworm-burrow macropores. A 50 {mu}g/L 2,4-D solution was continuously applied to the unsaturated soil surface and breakthrough curves (BTCs) indicating pesticide loss in the effluent were obtained from the soil matrix and macropore flow paths. Biodegradation rates were calculated separately for each flow path by comparing the BTCs to BTCs representing abiotic conditions, and dividing the 2,4-D loss by the travel time through each flow path. The biodegradation rates increased with time in both flow paths, and the final biodegradation rate in the macropore region surpassed that of the matrix, presumably because of increased microbial populations in the macropore. Complete loss of the 2,4-D in both flow paths was observed after continuous application of 2,4-D for 400 h, with maximum column-averaged 2,4-D loss rates of 0.879 {mu}g/(L h) in the matrix and 1.073 {mu}g/(L h) in the macropore. Biodegradation of 2,4-D was also observed in the macropore and matrix regions of the undisturbed soil cores. 19 refs., 7 figs., 2 tabs.

  5. Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer

    PubMed Central

    Yang, Ying-Hua; Buhamrah, Asma; Schneider, Abraham; Lin, Yi-Ling; Zhou, Hua; Bugshan, Amr; Basile, John R.

    2016-01-01

    Bone density is controlled by interactions between osteoclasts, which resorb bone, and osteoblasts, which deposit it. The semaphorins and their receptors, the plexins, originally shown to function in the immune system and to provide chemotactic cues for axon guidance, are now known to play a role in this process as well. Emerging data have identified Semaphorin 4D (Sema4D) as a product of osteoclasts acting through its receptor Plexin-B1 on osteoblasts to inhibit their function, tipping the balance of bone homeostasis in favor of resorption. Breast cancers and other epithelial malignancies overexpress Sema4D, so we theorized that tumor cells could be exploiting this pathway to establish lytic skeletal metastases. Here, we use measurements of osteoblast and osteoclast differentiation and function in vitro and a mouse model of skeletal metastasis to demonstrate that both soluble Sema4D and protein produced by the breast cancer cell line MDA-MB-231 inhibits differentiation of MC3T3 cells, an osteoblast cell line, and their ability to form mineralized tissues, while Sema4D-mediated induction of IL-8 and LIX/CXCL5, the murine homologue of IL-8, increases osteoclast numbers and activity. We also observe a decrease in the number of bone metastases in mice injected with MDA-MB-231 cells when Sema4D is silenced by RNA interference. These results are significant because treatments directed at suppression of skeletal metastases in bone-homing malignancies usually work by arresting bone remodeling, potentially leading to skeletal fragility, a significant problem in patient management. Targeting Sema4D in these cancers would not affect bone remodeling and therefore could elicit an improved therapeutic result without the debilitating side effects. PMID:26910109

  6. Antibody Blockade of Semaphorin 4D Promotes Immune Infiltration into Tumor and Enhances Response to Other Immunomodulatory Therapies.

    PubMed

    Evans, Elizabeth E; Jonason, Alan S; Bussler, Holm; Torno, Sebold; Veeraraghavan, Janaki; Reilly, Christine; Doherty, Michael A; Seils, Jennifer; Winter, Laurie A; Mallow, Crystal; Kirk, Renee; Howell, Alan; Giralico, Susan; Scrivens, Maria; Klimatcheva, Katya; Fisher, Terrence L; Bowers, William J; Paris, Mark; Smith, Ernest S; Zauderer, Maurice

    2015-06-01

    Semaphorin 4D (SEMA4D, CD100) and its receptor plexin-B1 (PLXNB1) are broadly expressed in murine and human tumors, and their expression has been shown to correlate with invasive disease in several human tumors. SEMA4D normally functions to regulate the motility and differentiation of multiple cell types, including those of the immune, vascular, and nervous systems. In the setting of cancer, SEMA4D-PLXNB1 interactions have been reported to affect vascular stabilization and transactivation of ERBB2, but effects on immune-cell trafficking in the tumor microenvironment (TME) have not been investigated. We describe a novel immunomodulatory function of SEMA4D, whereby strong expression of SEMA4D at the invasive margins of actively growing tumors influences the infiltration and distribution of leukocytes in the TME. Antibody neutralization of SEMA4D disrupts this gradient of expression, enhances recruitment of activated monocytes and lymphocytes into the tumor, and shifts the balance of cells and cytokines toward a proinflammatory and antitumor milieu within the TME. This orchestrated change in the tumor architecture was associated with durable tumor rejection in murine Colon26 and ERBB2(+) mammary carcinoma models. The immunomodulatory activity of anti-SEMA4D antibody can be enhanced by combination with other immunotherapies, including immune checkpoint inhibition and chemotherapy. Strikingly, the combination of anti-SEMA4D antibody with antibody to CTLA-4 acts synergistically to promote complete tumor rejection and survival. Inhibition of SEMA4D represents a novel mechanism and therapeutic strategy to promote functional immune infiltration into the TME and inhibit tumor progression. PMID:25614511

  7. Inhibition of P450 aromatase enhances gonadotropin secretion in early and midpubertal boys: evidence for a pituitary site of action of endogenous E.

    PubMed

    Wickman, S; Dunkel, L

    2001-10-01

    In early pubertal boys, E concentrations are very low. We studied the role and site of action of endogenous E in the regulation of gonadotropin secretion in early and midpubertal boys by inhibiting the action of E with a potent and specific P450 aromatase inhibitor, letrozole. A total of 35 boys who were referred to us because of suspicion of delayed puberty were included in the study. The boys were in either early or midpuberty, and they composed 3 groups: 10 boys did not receive any treatment, 12 boys received T alone, and 13 boys received T and letrozole. In the untreated group during the 5-month follow-up, no changes were observed in 17beta-E2, T, basal gonadotropin, or inhibin B concentrations or in the GnRH-induced gonadotropin responses. In the T-treated group during the 5-month treatment, the T concentration increased by 55% (P < 0.05), and the 17beta-E2 concentration increased by 130% (P < 0.02). Concurrently, basal gonadotropin concentrations were suppressed, but the GnRH-induced gonadotropin responses and the inhibin B concentration remained unchanged. In the T- plus letrozole-treated group during the 5-month treatment, an increase in T concentration of 606% was observed (P < 0.001), but the 17beta-E2 concentration remained unchanged. The changes in the 17beta-E2 concentration within 5 months in the untreated and the T- plus letrozole-treated groups were different (P < 0.02), indicating significant inhibition of endogenous E synthesis during letrozole treatment. During the T plus letrozole treatment, basal gonadotropin concentration, the GnRH-induced LH response, and inhibin B concentration increased, and the GnRH-induced FSH response did not change significantly. Serum nocturnal gonadotropin pulses were determined in 5 boys treated with T and in 5 boys treated with T plus letrozole. In the T- plus letrozole-treated group, the nocturnal LH pulse amplitude increased, and the LH pulse frequency and interpulse interval remained unchanged. In conclusion, in

  8. Normal gonadotropin production and fertility in gonadotrope-specific Bmpr1a knockout mice.

    PubMed

    Zhou, Xiang; Wang, Ying; Ongaro, Luisina; Boehm, Ulrich; Kaartinen, Vesa; Mishina, Yuji; Bernard, Daniel J

    2016-06-01

    Pituitary follicle-stimulating hormone (FSH) synthesis is regulated by transforming growth factorβsuperfamily ligands, most notably the activins and inhibins. Bone morphogenetic proteins (BMPs) also regulate FSHβ subunit (Fshb) expression in immortalized murine gonadotrope-like LβT2 cells and in primary murine or ovine primary pituitary cultures. BMP2 signals preferentially via the BMP type I receptor, BMPR1A, to stimulate murine Fshb transcription in vitro Here, we used a Cre-lox approach to assess BMPR1A's role in FSH synthesis in mice in vivo Gonadotrope-specific Bmpr1a knockout animals developed normally and had reproductive organ weights comparable with those of controls. Knockouts were fertile, with normal serum gonadotropins and pituitary gonadotropin subunit mRNA expression. Cre-mediated recombination of the floxed Bmpr1a allele was efficient and specific, as indicated by PCR analysis of diverse tissues and isolated gonadotrope cells. Furthermore, BMP2 stimulation of inhibitor of DNA binding 3 expression was impaired in gonadotropes isolated from Bmpr1a knockout mice, confirming the loss of functional receptor protein in these cells. Treatment of purified gonadotropes with small-molecule inhibitors of BMPR1A (and the related receptors BMPR1B and ACVR1) suppressed Fshb mRNA expression, suggesting that an autocrine BMP-like molecule might regulate FSH synthesis. However, deletion of Bmpr1a and Acvr1 in cultured pituitary cells did not alter Fshb expression, indicating that the inhibitors had off-target effects. In sum, BMPs or related ligands acting via BMPR1A or ACVR1 are unlikely to play direct physiological roles in FSH synthesis by murine gonadotrope cells. PMID:27029473

  9. New C4D Sensor with a Simulated Inductor

    PubMed Central

    Lyu, Yingchao; Ji, Haifeng; Yang, Shijie; Huang, Zhiyao; Wang, Baoliang; Li, Haiqing

    2016-01-01

    A new capacitively coupled contactless conductivity detection (C4D) sensor with an improved simulated inductor is developed in this work. The improved simulated inductor is designed on the basis of the Riordan-type floating simulated inductor. With the improved simulated inductor, the negative influence of the coupling capacitances is overcome and the conductivity measurement is implemented by the series resonance principle. The conductivity measurement experiments are carried out in three pipes with different inner diameters of 3.0 mm, 4.6 mm and 6.4 mm, respectively. The experimental results show that the designs of the new C4D sensor and the improved simulated inductor are successful. The maximum relative error of the conductivity measurement is less than 5%. Compared with the C4D sensors using practical inductors, the measurement accuracy of the new C4D sensor is comparable. The research results also indicate that the adjustability of a simulated inductor can reduce the requirement for the AC source and guarantee the interchangeableness. Meanwhile, it is recommended that making the potential of one terminal of a simulated inductor stable is beneficial to the running stability. Furthermore, this work indirectly verifies the possibility and feasibility of the miniaturization of the C4D sensor by using the simulated inductor technique and lays a good foundation for future research work. PMID:26828493

  10. A normal cumulative conception rate after human pituitary gonadotropin.

    PubMed

    Healy, D L; Kovacs, G T; Pepperell, R J; Burger, H G

    1980-10-01

    Forty consecutive women were treated with human pituitary gonadotropin to induce ovulation. Thirty-seven patients (93%) ovulated and thirty (75%) conceived on at least one occasion. The cumulative conception rate for the series equaled that of the general population. Women with a past history of anorexia nervosa had the shortest average time to pregnancy. Of patients who did not conceive, four represented failures of patient selection in that they withdrew from treatment for a variety of psychiatric and social reasons, and six represented failures of treatment, not becoming pregnant despite the induction of ovulation. It is concluded that realistic goals for a contemporary human gonadotropin program include induction of ovulation in all patients and a cumulative conception rate equal to that of the general community. PMID:6252067

  11. Binding sites for gonadotropins in human postmenopausal ovaries

    SciTech Connect

    Nakano, R.; Shima, K.; Yamoto, M.; Kobayashi, M.; Nishimori, K.; Hiraoka, J.

    1989-02-01

    The binding of human LH and human FSH to postmenopausal ovarian tissue from 21 patients with cervical carcinoma was analyzed. The binding sites for FSH and LH were demonstrated in postmenopausal ovarian tissue. The surface-binding sites for gonadotropins were localized in the cells of cortical stroma of the postmenopausal ovary. In addition, diffuse cytoplasmic staining of endogenous estrogen and 3 beta-hydroxysteroid dehydrogenase activity were detected immunohistochemically and histochemically in the cells of the cortical stroma. Electron microscopic study also suggested steroidogenic function in the cells of the cortical stroma. The results of the present study suggest that postmenopausal ovaries contain specific binding sites for pituitary gonadotropins and play a role in ovarian steroidogenesis.

  12. Evaluating the ovarian cancer gonadotropin hypothesis: A candidate gene study

    PubMed Central

    Lee, Alice W.; Tyrer, Jonathan P.; Doherty, Jennifer A.; Stram, Douglas A.; Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Spiewankiewicz, Beata; Myers, Emily J.; Chenevix-Trench, Georgia; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Hein, Alexander; Vergote, Ignace; Van Nieuwenhuysen, Els; Lambrechts, Diether; Wicklund, Kristine G.; Eilber, Ursula; Wang-Gohrke, Shan; Chang-Claude, Jenny; Rudolph, Anja; Sucheston-Campbell, Lara; Odunsi, Kunle; Moysich, Kirsten B.; Shvetsov, Yurii B.; Thompson, Pamela J.; Goodman, Marc T.; Wilkens, Lynne R.; Dörk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo B.; Bogdanova, Natalia; Pelttari, Liisa M.; Nevanlinna, Heli; Leminen, Arto; Edwards, Robert P.; Kelley, Joseph L.; Harter, Philipp; Schwaab, Ira; Heitz, Florian; du Bois, Andreas; Orsulic, Sandra; Lester, Jenny; Walsh, Christine; Karlan, Beth Y.; Hogdall, Estrid; Kjaer, Susanne K.; Jensen, Allan; Vierkant, Robert A.; Cunningham, Julie M.; Goode, Ellen L.; Fridley, Brooke L.; Southey, Melissa C.; Giles, Graham G.; Bruinsma, Fiona; Wu, Xifeng; Hildebrandt, Michelle A.T.; Lu, Karen; Liang, Dong; Bisogna, Maria; Levine, Douglas A.; Weber, Rachel Palmieri; Schildkraut, Joellen M.; Iversen, Edwin S.; Berchuck, Andrew; Terry, Kathryn L.; Cramer, Daniel W.; Tworoger, Shelley S.; Poole, Elizabeth M.; Olson, Sara H.; Orlow, Irene; Bandera, Elisa V.; Bjorge, Line; Tangen, Ingvild L.; Salvesen, Helga B.; Krakstad, Camilla; Massuger, Leon F.A.G.; Kiemeney, Lambertus A.; Aben, Katja K.H.; van Altena, Anne M.; Bean, Yukie; Pejovic, Tanja; Kellar, Melissa; Le, Nhu D.; Cook, Linda S.; Kelemen, Linda E.; Brooks-Wilson, Angela; Lubinski, Jan; Gronwald, Jacek; Cybulski, Cezary; Jakubowska, Anna; Wentzensen, Nicolas; Brinton, Louise A.; Lissowska, Jolanta; Yang, Hannah; Nedergaard, Lotte; Lundvall, Lene; Hogdall, Claus; Song, Honglin; Campbell, Ian G.; Eccles, Diana; Glasspool, Rosalind; Siddiqui, Nadeem; Carty, Karen; Paul, James; McNeish, Iain A.; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H.; Whittemore, Alice S.; McLaughlin, John R.; Risch, Harvey A.; Phelan, Catherine M.; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Harrington, Patricia; Pike, Malcolm C.; Modugno, Francesmary; Rossing, Mary Anne; Ness, Roberta B.; Pharoah, Paul D.P.; Stram, Daniel O.; Wu, Anna H.; Pearce, Celeste Leigh

    2016-01-01

    Objective Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted. Methods Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations. Results We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some suggestion of gene-level associations for four gonadotropin signaling pathway genes: INHBB (p = 0.045, mucinous), LHCGR (p = 0.046, high-grade serous), GNRH (p = 0.041, high-grade serous), and FSHB (p = 0.036, overall invasive). There was also suggestive evidence for INHA (p = 0.060, overall invasive). Conclusions Ovarian cancer studies have limited sample numbers, thus fewer genome-wide susceptibility alleles, with only modest associations, have been identified relative to breast and prostate cancers. We have evaluated the majority of ovarian cancer studies with biological samples, to our knowledge, leaving no opportunity for replication. Using both our understanding of biology and powerful gene-level tests, we have identified four putative ovarian cancer loci near INHBB, LHCGR, GNRH, and FSHB that warrant a second look if larger sample sizes and denser genotype chips become available. PMID:25528498

  13. Pattern of human chorionic gonadotropin binding in the polycystic ovary

    SciTech Connect

    Brawer, J.; Richard, M.; Farookhi, R. )

    1989-08-01

    The histologic evolution of polycystic ovaries in the estradiol valerate-treated rat coincides with the development of a unique plasma pattern of luteinizing hormone. To assess the role of luteinizing hormone in polycystic ovaries, it is necessary to evaluate the luteinizing hormone sensitivity of the specific tissues in the polycystic ovary. Therefore, we examined the pattern of luteinizing hormone binding sites in polycystic ovaries. Rats at 4 or 8 weeks after estradiol valerate treatment each received an intrajugular injection of iodine 125-labeled human chorionic gonadotropin. Some rats also received a 1000-fold excess of unlabeled human chorionic gonadotropin in the same injection. Ovaries were prepared for autoradiography. Dense accumulations of grains occurred over the theca of normal and atretic secondary follicles in all ovaries and over clusters of secondary interstitial cells. The iodine label was variable over the typically hypertrophied theca of precystic follicles. The theca of definitive cysts showed little or no label. These results indicate that cyst formation coincides with the loss of luteinizing hormone/human chorionic gonadotropin binding to the affected follicles.

  14. Prolonged gonadotropin stimulation is associated with decreased ART success

    PubMed Central

    Chuang, Meleen; Zapantis, Athena; Taylor, Martina; Jindal, Sangita K.; Neal-Perry, Genevieve S.; Lieman, Harry J.

    2010-01-01

    Purpose To evaluate whether the duration of gonadotropin stimulation predicts the likelihood of live birth after ART. Methods All IVF or ICSI cycles using fresh autologous oocytes at our institution between January 2004 and December 2007 were analyzed. Results Out of 699 cycles resulting in oocyte retrieval, 193 produced a live birth (27.6%). Women who achieved a live birth had a significantly shorter stimulation phase (11.1 vs. 11.5 days, respectively). Multivariable analysis suggested that 13 days or longer of stimulation decreased the likelihood of a live birth by 53% as compared to cycles that were 10–12 days long (odds ratio [OR] 0.47; 95% confidence interval [CI]: 0.30–0.75) after adjustment for female age, maximum historical FSH, total dose of gonadotropin received, oocytes retrieved, embryos transferred, antagonist suppression and PCOS diagnosis. Conclusions Prolonged duration of gonadotropin stimulation is an independent negative predictor of ART success in our cohort. PMID:20821043

  15. Relative charge transfer cross section from Rb (4d)

    NASA Astrophysics Data System (ADS)

    Shah, M. H.; Camp, H. A.; Trachy, M. L.; Fléchard, X.; Gearba, M. A.; Nguyen, H.; Brédy, R.; Lundeen, S. R.; Depaola, B. D.

    2005-08-01

    Relative charge transfer cross section measurements for the excited state Rb(4d) with 7keV Na+ is reported. The specific channels reported are Na++Rb(4d5/2)→Na(nl)+Rb+ , where the dominant transfer cross sections channels were nl=3d and 4s . Using a combination of a magneto-optical trap and recoil ion momentum spectroscopy (MOTRIMS methodology), the cross sections were measured relative to the previously studied Na++Rb(5s,5p) systems at the same collision energy.

  16. Relative charge transfer cross section from Rb(4d)

    SciTech Connect

    Shah, M.H.; Camp, H.A.; Trachy, M.L.; De Paola, B.D.; Flechard, X.; Gearba, M.A.; Nguyen, H.; Bredy, R.; Lundeen, S.R.

    2005-08-15

    Relative charge transfer cross section measurements for the excited state Rb(4d) with 7 keV Na{sup +} is reported. The specific channels reported are Na{sup +}+Rb(4d{sub 5/2}){yields}Na(nl)+Rb{sup +}, where the dominant transfer cross sections channels were nl=3d and 4s. Using a combination of a magneto-optical trap and recoil ion momentum spectroscopy (MOTRIMS methodology), the cross sections were measured relative to the previously studied Na{sup +}+Rb(5s,5p) systems at the same collision energy.

  17. The 4-D approach to visual control of autonomous systems

    NASA Technical Reports Server (NTRS)

    Dickmanns, Ernst D.

    1994-01-01

    Development of a 4-D approach to dynamic machine vision is described. Core elements of this method are spatio-temporal models oriented towards objects and laws of perspective projection in a foward mode. Integration of multi-sensory measurement data was achieved through spatio-temporal models as invariants for object recognition. Situation assessment and long term predictions were allowed through maintenance of a symbolic 4-D image of processes involving objects. Behavioral capabilities were easily realized by state feedback and feed-foward control.

  18. Emerging Applications of Abdominal 4D Flow MRI

    PubMed Central

    Roldán-Alzate, Alejandro; Francois, Christopher J.; Wieben, Oliver; Reeder, Scott B.

    2016-01-01

    OBJECTIVE Comprehensive assessment of abdominal hemodynamics is crucial for many clinical diagnoses but is challenged by a tremendous complexity of anatomy, normal physiology, and a wide variety of pathologic abnormalities. This article introduces 4D flow MRI as a powerful technique for noninvasive assessment of the hemodynamics of abdominal vascular territories. CONCLUSION Four-dimensional flow MRI provides clinicians with a more extensive and straightforward approach to evaluate disorders that affect blood flow in the abdomen. This review presents a series of clinical cases to illustrate the utility of 4D flow MRI in the comprehensive assessment of the abdominal circulation. PMID:27187681

  19. 77 FR 55481 - Withdrawal of Approval of New Animal Drug Applications; Chorionic Gonadotropin; Naloxone...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-10

    ...; Chorionic Gonadotropin; Naloxone; Oxymorphone; Oxytocin AGENCY: Food and Drug Administration, HHS. ACTION... Pharmaceuticals hydrochloride) Inc., 100 Painters Injection. Dr., Chadds Ford, PA 19317. 046-822 VETOCIN...

  20. The effect of gonadotropin on glucose transport and apoptosis in rat ovary.

    PubMed

    Zhang, Cheng; Niu, Wanbao; Wang, Zhengpin; Wang, Xiaoxia; Xia, Guoliang

    2012-01-01

    Although the effects of Gonadotropin on ovarian physiology have been known for many decades, its action on glucose uptake in the rat ovary remained poorly understood. Evidence also suggests that glucose uptake is mediated by a number of glucose transporter proteins (Glut). Therefore, we examined the rat ovary for the presence of Glut1-4 and blood glucose level after eCG (equine chorionic gonadotropin) and anti-eCG antiserum treatment. All of the glucose transports were present in the ovarian oocyte, granulosa cells and theca cells in different stage follicles. The expression of Glut in ovary was up-regulated by eCG, however, anti-eCG antiserum reversed eCG action. Western blot analysis also demonstrated the content of Glut1 was higher in eCG treatment group compared with anti-eCG antiserum and control group. The same tendency was shown in other glut isoforms. Moreover, there were no significant difference between the anti-eCG antiserum and control group. In additional, the level of serum glucose in eCG treatment group was significantly higher than others, which is similar with glut expression pattern. High glucose level in blood is correlated with increased expression of glucose transporter proteins in rat ovary. Meanwhile, anti-eCG antiserum increased granulosa cell apoptosis in antral follicle compared with those in eCG group. Our observations provide potential explanation for the effects of Glut on follicular development in rat ovary and a role for eCG in the regulation of ovarian glucose uptake. PMID:22870326

  1. The Effect of Gonadotropin on Glucose Transport and Apoptosis in Rat Ovary

    PubMed Central

    Zhang, Cheng; Niu, Wanbao; Wang, Zhengpin; Wang, Xiaoxia; Xia, Guoliang

    2012-01-01

    Although the effects of Gonadotropin on ovarian physiology have been known for many decades, its action on glucose uptake in the rat ovary remained poorly understood. Evidence also suggests that glucose uptake is mediated by a number of glucose transporter proteins (Glut). Therefore, we examined the rat ovary for the presence of Glut1–4 and blood glucose level after eCG (equine chorionic gonadotropin) and anti-eCG antiserum treatment. All of the glucose transports were present in the ovarian oocyte, granulosa cells and theca cells in different stage follicles. The expression of Glut in ovary was up-regulated by eCG, however, anti-eCG antiserum reversed eCG action. Western blot analysis also demonstrated the content of Glut1 was higher in eCG treatment group compared with anti-eCG antiserum and control group. The same tendency was shown in other glut isoforms. Moreover, there were no significant difference between the anti-eCG antiserum and control group. In additional, the level of serum glucose in eCG treatment group was significantly higher than others, which is similar with glut expression pattern. High glucose level in blood is correlated with increased expression of glucose transporter proteins in rat ovary. Meanwhile, anti-eCG antiserum increased granulosa cell apoptosis in antral follicle compared with those in eCG group. Our observations provide potential explanation for the effects of Glut on follicular development in rat ovary and a role for eCG in the regulation of ovarian glucose uptake. PMID:22870326

  2. Identification and distribution of gonadotropin-releasing hormone-like peptides in the brain of horseshoe crab Tachypleus tridentatus

    NASA Astrophysics Data System (ADS)

    Huang, Huiyang; Li, Linming; Ye, Haihui; Feng, Biyun; Li, Shaojing

    2013-03-01

    Gonadotropin-releasing hormone (GnRH) is a crucial peptide for the regulation of reproduction. Using immunological techniques, we investigated the presence of GnRH in horseshoe crab Tachypleus tridentatus. Octopus GnRH-like immunoreactivity, tunicate GnRH-like immunoreactivity, and lamprey GnRH-I-like immunoreactivity were detected in the neurons and fibers of the protocerebrum. However, no mammal GnRH-like immunoreactivity or lamprey GnRH-III-like immunoreactivity was observed. Our results suggest that a GnRH-like factor, an ancient peptide, existed in the brain of T. tridentatus and may be involved in the reproductive endocrine system.

  3. Human Head and Neck Squamous Cell Carcinoma–Associated Semaphorin 4D Induces Expansion of Myeloid-Derived Suppressor Cells

    PubMed Central

    Han, Kyu Lee; Webb, Tonya J.

    2016-01-01

    One of the mechanisms by which malignancies can induce immune suppression is through the production of cytokines that affect the maturation and differentiation of inflammatory cells in the tumor microenvironment. Semaphorin 4D (Sema4D) is a proangiogenic cytokine produced by several malignancies, which has been described in the regulation of the immune system. In the present study, we examined the role of human head and neck squamous cell carcinoma (HNSCC)–secreted Sema4D on myeloid cell differentiation. CD33+ cells cultured in HNSCC cell line–derived conditioned medium differentiated into myeloid derived suppressor cells (MDSC) (CD33+CD11b+HLA-DR−/low). The addition of anti-Sema4D Ab to HNSCC conditioned medium significantly reduced the expansion of the MDSC population. Similarly, knockdown of Sema4D in an HNSCC cell line resulted in a loss of MDSC function as shown by a decrease in the production of the immune-suppressive cytokines arginase-1, TGF-β, and IL-10 by MDSC, concomitant with recovery of T cell proliferation and IFN-γ production following stimulation of CD3/CD28. Importantly, CD33+ myeloid and T cells cultured in conditioned medium of HNSCC cells in which Sema4D was knocked down promoted antitumor inflammatory profile, through recovery of the effector T cells (CD4+T-bet+ and CD8+T-bet+), as well as a decrease in regulatory T cells (CD4+CD25+FOXP3+). We also showed that Sema4D was comparable to GM-CSF in its induction of MDSC. Collectively, this study describes a novel immunosuppressive role for Sema4D in HNSCC through induction of MDSC, and it highlights Sema4D as a therapeutic target for future studies to enhance the antitumorigenic inflammatory response in HNSCC and other epithelial malignancies. PMID:26740106

  4. 2,4-Dichlorophenoxyacetic acid (2,4-D)

    Integrated Risk Information System (IRIS)

    2,4 - Dichlorophenoxyacetic acid ( 2,4 - D ) ; CASRN 94 - 75 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Asses

  5. 4D microvascular imaging based on ultrafast Doppler tomography.

    PubMed

    Demené, Charlie; Tiran, Elodie; Sieu, Lim-Anna; Bergel, Antoine; Gennisson, Jean Luc; Pernot, Mathieu; Deffieux, Thomas; Cohen, Ivan; Tanter, Mickael

    2016-02-15

    4D ultrasound microvascular imaging was demonstrated by applying ultrafast Doppler tomography (UFD-T) to the imaging of brain hemodynamics in rodents. In vivo real-time imaging of the rat brain was performed using ultrasonic plane wave transmissions at very high frame rates (18,000 frames per second). Such ultrafast frame rates allow for highly sensitive and wide-field-of-view 2D Doppler imaging of blood vessels far beyond conventional ultrasonography. Voxel anisotropy (100 μm × 100 μm × 500 μm) was corrected for by using a tomographic approach, which consisted of ultrafast acquisitions repeated for different imaging plane orientations over multiple cardiac cycles. UFT-D allows for 4D dynamic microvascular imaging of deep-seated vasculature (up to 20 mm) with a very high 4D resolution (respectively 100 μm × 100 μm × 100 μm and 10 ms) and high sensitivity to flow in small vessels (>1 mm/s) for a whole-brain imaging technique without requiring any contrast agent. 4D ultrasound microvascular imaging in vivo could become a valuable tool for the study of brain hemodynamics, such as cerebral flow autoregulation or vascular remodeling after ischemic stroke recovery, and, more generally, tumor vasculature response to therapeutic treatment. PMID:26555279

  6. 4D flow mri post-processing strategies for neuropathologies

    NASA Astrophysics Data System (ADS)

    Schrauben, Eric Mathew

    4D flow MRI allows for the measurement of a dynamic 3D velocity vector field. Blood flow velocities in large vascular territories can be qualitatively visualized with the added benefit of quantitative probing. Within cranial pathologies theorized to have vascular-based contributions or effects, 4D flow MRI provides a unique platform for comprehensive assessment of hemodynamic parameters. Targeted blood flow derived measurements, such as flow rate, pulsatility, retrograde flow, or wall shear stress may provide insight into the onset or characterization of more complex neuropathologies. Therefore, the thorough assessment of each parameter within the context of a given disease has important medical implications. Not surprisingly, the last decade has seen rapid growth in the use of 4D flow MRI. Data acquisition sequences are available to researchers on all major scanner platforms. However, the use has been limited mostly to small research trials. One major reason that has hindered the more widespread use and application in larger clinical trials is the complexity of the post-processing tasks and the lack of adequate tools for these tasks. Post-processing of 4D flow MRI must be semi-automated, fast, user-independent, robust, and reliably consistent for use in a clinical setting, within large patient studies, or across a multicenter trial. Development of proper post-processing methods coupled with systematic investigation in normal and patient populations pushes 4D flow MRI closer to clinical realization while elucidating potential underlying neuropathological origins. Within this framework, the work in this thesis assesses venous flow reproducibility and internal consistency in a healthy population. A preliminary analysis of venous flow parameters in healthy controls and multiple sclerosis patients is performed in a large study employing 4D flow MRI. These studies are performed in the context of the chronic cerebrospinal venous insufficiency hypothesis. Additionally, a

  7. 4D MR imaging using robust internal respiratory signal

    NASA Astrophysics Data System (ADS)

    Hui, CheukKai; Wen, Zhifei; Stemkens, Bjorn; Tijssen, R. H. N.; van den Berg, C. A. T.; Hwang, Ken-Pin; Beddar, Sam

    2016-05-01

    The purpose of this study is to investigate the feasibility of using internal respiratory (IR) surrogates to sort four-dimensional (4D) magnetic resonance (MR) images. The 4D MR images were constructed by acquiring fast 2D cine MR images sequentially, with each slice scanned for more than one breathing cycle. The 4D volume was then sorted retrospectively using the IR signal. In this study, we propose to use multiple low-frequency components in the Fourier space as well as the anterior body boundary as potential IR surrogates. From these potential IR surrogates, we used a clustering algorithm to identify those that best represented the respiratory pattern to derive the IR signal. A study with healthy volunteers was performed to assess the feasibility of the proposed IR signal. We compared this proposed IR signal with the respiratory signal obtained using respiratory bellows. Overall, 99% of the IR signals matched the bellows signals. The average difference between the end inspiration times in the IR signal and bellows signal was 0.18 s in this cohort of matching signals. For the acquired images corresponding to the other 1% of non-matching signal pairs, the respiratory motion shown in the images was coherent with the respiratory phases determined by the IR signal, but not the bellows signal. This suggested that the IR signal determined by the proposed method could potentially correct the faulty bellows signal. The sorted 4D images showed minimal mismatched artefacts and potential clinical applicability. The proposed IR signal therefore provides a feasible alternative to effectively sort MR images in 4D.

  8. Dissecting the Roles of Gonadotropin-Inhibitory Hormone in Mammals: Studies Using Pharmacological Tools and Genetically Modified Mouse Models

    PubMed Central

    Leon, Silvia; Tena-Sempere, Manuel

    2016-01-01

    Reproduction is essential for perpetuation of the species and, hence, is controlled by a sophisticated network of regulatory factors of central and peripheral origin that integrate at the hypothalamic–pituitary–gonadal (HPG) axis. Among the central regulators of reproduction, kisspeptins, as major stimulatory drivers of gonadotropin-releasing hormone (GnRH) neurosecretion, have drawn considerable interest in the last decade. However, the dynamic, if not cyclic (in the female), nature of reproductive function and the potency of kisspeptins and other stimulatory signals of the HPG axis make tenable the existence of counterbalance inhibitory mechanisms, which may keep stimulation at check and would allow adaptation of reproductive maturation and function to different endogenous and environmental conditions. In this context, discovery of the gonadotropin-inhibitory hormone (GnIH) in birds, and its mammalian homolog, RFRP, opened up the exciting possibility that this inhibitory signal might operate centrally to suppress, directly or indirectly, GnRH/gonadotropin secretion, thus reciprocally cooperating with other stimulatory inputs in the dynamic regulation of the reproductive hypothalamic–pituitary unit. After more than 15 years of active research, the role of GnIH/RFRP in the control of the HPG axis has been documented in different species. Yet, important aspects of the physiology of this system, especially regarding its relative importance and actual roles in the control of key facets of reproductive function, remain controversial. In the present work, we aim to provide a critical review of recent developments in this area, with special attention to studies in rodent models, using pharmacological tools and functional genomics. In doing so, we intend to endow the reader with an updated view of what is known (and what is not known) about the physiological role of GnIH/RFRP signaling in the control of mammalian reproduction. PMID:26779117

  9. Impact of incorporating visual biofeedback in 4D MRI.

    PubMed

    To, David T; Kim, Joshua P; Price, Ryan G; Chetty, Indrin J; Glide-Hurst, Carri K

    2016-01-01

    Precise radiation therapy (RT) for abdominal lesions is complicated by respiratory motion and suboptimal soft tissue contrast in 4D CT. 4D MRI offers improved con-trast although long scan times and irregular breathing patterns can be limiting. To address this, visual biofeedback (VBF) was introduced into 4D MRI. Ten volunteers were consented to an IRB-approved protocol. Prospective respiratory-triggered, T2-weighted, coronal 4D MRIs were acquired on an open 1.0T MR-SIM. VBF was integrated using an MR-compatible interactive breath-hold control system. Subjects visually monitored their breathing patterns to stay within predetermined tolerances. 4D MRIs were acquired with and without VBF for 2- and 8-phase acquisitions. Normalized respiratory waveforms were evaluated for scan time, duty cycle (programmed/acquisition time), breathing period, and breathing regularity (end-inhale coefficient of variation, EI-COV). Three reviewers performed image quality assessment to compare artifacts with and without VBF. Respiration-induced liver motion was calculated via centroid difference analysis of end-exhale (EE) and EI liver contours. Incorporating VBF reduced 2-phase acquisition time (4.7 ± 1.0 and 5.4 ± 1.5 min with and without VBF, respectively) while reducing EI-COV by 43.8% ± 16.6%. For 8-phase acquisitions, VBF reduced acquisition time by 1.9 ± 1.6 min and EI-COVs by 38.8% ± 25.7% despite breathing rate remaining similar (11.1 ± 3.8 breaths/min with vs. 10.5 ± 2.9 without). Using VBF yielded higher duty cycles than unguided free breathing (34.4% ± 5.8% vs. 28.1% ± 6.6%, respectively). Image grading showed that out of 40 paired evaluations, 20 cases had equivalent and 17 had improved image quality scores with VBF, particularly for mid-exhale and EI. Increased liver excursion was observed with VBF, where superior-inferior, anterior-posterior, and left-right EE-EI displacements were 14.1± 5.8, 4.9 ± 2.1, and 1.5 ± 1.0 mm, respectively, with VBF compared to 11.9

  10. Potential Diagnostic Utility of Intermittent Short-Acting GnRH Agonist Administration in Gonadotropin Deficiency

    PubMed Central

    Zimmer, Carrie A.; Ehrmann, David A; Rosenfield, Robert L.

    2010-01-01

    Objective The objective was to determine if intermittent, low-dose, short-acting GnRH agonist (GnRHag) administration up-regulates pituitary-gonadal function in gonadotropin deficiency (GnD) sufficiently to be of diagnostic or therapeutic value. Design/Intervention Low-dose leuprolide acetate was administered SC at 4–5 d intervals up to one year. Patients Adult volunteers and GnD patients were studied. Setting The studies were performed in a General Clinical Research Center. Main Outcome Measures LH, FSH, and sex steroid responses were determined. Results In normal men and women, low-dose GnRHag repetitively transiently stimulated gonadotropins in a gender-dimorphic manner. In congenitally GnD deficient men (n=6) and women (n=1), none of whom had a normal LH response to an initial GnRHag test dose, this regimen consistently stimulated LH to the normal baseline range within two weeks. Long-term GnRHag administration to a partially GnD man did not alleviate hypogonadism, however. Women with hypothalamic amenorrhea (n=2) responded normally to a single GnRHag injection; however, repeated dosing did not seem to induce the normal priming effect. Conclusions The subnormal LH response to GnRHag of congenital GnD normalized in response to repetitive intermittent GnRHag, but not sufficiently to improve hypogonadism. Hypothalamic amenorrhea patients lacked the priming response to repeated GnRHag, but otherwise had normal hormonal responses to GnRHag. We conclude that intermittent administration of a short-acting GnRHag is of potential diagnostic value in distinguishing hypothalamic from pituitary causes of GnD. PMID:20553679

  11. Signaling Responses to Pulsatile Gonadotropin-releasing Hormone in LβT2 Gonadotrope Cells*

    PubMed Central

    Tsutsumi, Rie; Mistry, Devendra; Webster, Nicholas J. G.

    2010-01-01

    The hypothalamic neuropeptide gonadotropin-releasing hormone (GnRH) is secreted in a pulsatile fashion by hypothalamic neurons, and alterations in pulse frequency and amplitude differentially regulate gonadotropin synthesis and release. In this study, we investigated the kinetics of Gs and Gq signaling in response to continuous or pulsatile GnRH using fluorescence resonance energy transfer reporters in live mouse LβT2 gonadotrope cells. cAMP and protein kinase A-dependent reporters showed a rapid but transient increase in fluorescence resonance energy transfer signal with increasing doses of constant GnRH, and in contrast diacylglycerol (DAG) and calcium reporters showed a rapid and sustained signal. Multiple pulses of GnRH caused multiple pulses of cAMP and protein kinase A activation without desensitization, but the DAG and calcium reporters were rapidly desensitized resulting in inhibition of calcium and DAG responses. At the transcriptional level, both a cAMP-dependent cAMP-response element reporter and a DAG/calcium-dependent AP-1 reporter showed a pulse frequency-dependent increase in luciferase activity. However, constant GnRH stimulation gave very little cAMP-response element activation but very strong AP-1 activation. Based on these data, we propose that both the GnRH-R-Gs and Gq pathways are responsive to pulses of GnRH, but only the Gq pathway is responsive to constant GnRH. Furthermore, the Gq pathway is subject to desensitization with multiple GnRH pulses, but the Gs pathway is not. PMID:20406815

  12. Three gonadotropin-releasing hormone genes in one organism suggest novel roles for an ancient peptide.

    PubMed Central

    White, S A; Kasten, T L; Bond, C T; Adelman, J P; Fernald, R D

    1995-01-01

    Gonadotropin-releasing hormone (GnRH) is known and named for its essential role in vertebrate reproduction. Release of this decapeptide from neurons in the hypothalamus controls pituitary gonadotropin levels which, in turn, regulate gonadal state. The importance of GnRH is underscored by its widespread expression and conservation across vertebrate taxa: five amino acids are invariant in all nine known forms, whereas two others show only conservative changes. In most eutherian mammals, only one form, expressed in the hypothalamus, is thought to exist, although in a recent report, antibody staining in developing primates suggests an additional form. In contrast, multiple GnRH forms and expression loci have been reported in many non-mammalian vertebrates. However, evidence based on immunological discrimination does not always agree with analysis of gene expression, since GnRH forms encoded by different genes may not be reliably distinguished by antibodies. Here we report the expression of three distinct GnRH genes in a teleost fish brain, including the sequence encoding a novel GnRH preprohormone. Using in situ hybridization, we show that this form is found only in neurons that project to the pituitary and exhibit changes in soma size depending on social and reproductive state. The other two GnRH genes are expressed in other, distinct cell populations. All three genes share the motif of encoding a polypeptide consisting of GnRH and a GnRH-associated peptide. Whereas the GnRH moiety is highly conserved, the GnRH-associated peptides are not, reflecting differential selective pressure on different parts of the gene. GnRH forms expressed in nonhypothalamic regions may serve to coordinate reproductive activities of the animal. Images Fig. 3 PMID:7667296

  13. Intelligent Vehicle Systems: A 4D/RCS Approach

    SciTech Connect

    Madhavan, Raj

    2007-04-01

    This book presents new research on autonomous mobility capabilities and shows how technological advances can be anticipated in the coming two decades. An in-depth description is presented on the theoretical foundations and engineering approaches that enable these capabilities. Chapter 1 provides a brief introduction to the 4D/RCS reference model architecture and design methodology that has proven successful in guiding the development of autonomous mobility systems. Chapters 2 through 7 provide more detailed descriptions of research that has been conducted and algorithms that have been developed to implement the various aspects of the 4D/RCS reference model architecture and design methodology. Chapters 8 and 9 discuss applications, performance measures, and standards. Chapter 10 provides a history of Army and DARPA research in autonomous ground mobility. Chapter 11 provides a perspective on the potential future developments in autonomous mobility.

  14. Quantication and analysis of respiratory motion from 4D MRI

    NASA Astrophysics Data System (ADS)

    Aizzuddin Abd Rahni, Ashrani; Lewis, Emma; Wells, Kevin

    2014-11-01

    It is well known that respiratory motion affects image acquisition and also external beam radiotherapy (EBRT) treatment planning and delivery. However often the existing approaches for respiratory motion management are based on a generic view of respiratory motion such as the general movement of organ, tissue or fiducials. This paper thus aims to present a more in depth analysis of respiratory motion based on 4D MRI for further integration into motion correction in image acquisition or image based EBRT. Internal and external motion was first analysed separately, on a per-organ basis for internal motion. Principal component analysis (PCA) was then performed on the internal and external motion vectors separately and the relationship between the two PCA spaces was analysed. The motion extracted from 4D MRI on general was found to be consistent with what has been reported in literature.

  15. Exome sequencing identifies PDE4D mutations in acrodysostosis.

    PubMed

    Lee, Hane; Graham, John M; Rimoin, David L; Lachman, Ralph S; Krejci, Pavel; Tompson, Stuart W; Nelson, Stanley F; Krakow, Deborah; Cohn, Daniel H

    2012-04-01

    Acrodysostosis is a dominantly-inherited, multisystem disorder characterized by skeletal, endocrine, and neurological abnormalities. To identify the molecular basis of acrodysostosis, we performed exome sequencing on five genetically independent cases. Three different missense mutations in PDE4D, which encodes cyclic AMP (cAMP)-specific phosphodiesterase 4D, were found to be heterozygous in three of the cases. Two of the mutations were demonstrated to have occurred de novo, providing strong genetic evidence of causation. Two additional cases were heterozygous for de novo missense mutations in PRKAR1A, which encodes the cAMP-dependent regulatory subunit of protein kinase A and which has been recently reported to be the cause of a form of acrodysostosis resistant to multiple hormones. These findings demonstrate that acrodysostosis is genetically heterogeneous and underscore the exquisite sensitivity of many tissues to alterations in cAMP homeostasis. PMID:22464252

  16. 4D, Script N = 1 supersymmetry genomics (I)

    NASA Astrophysics Data System (ADS)

    Gates, S. James, Jr.; Gonzales, James; MacGregor, Boanne; Parker, James; Polo-Sherk, Ruben; Rodgers, Vincent G. J.; Wassink, Luke

    2009-12-01

    Presented in this paper the nature of the supersymmetrical representation theory behind 4D, Script N = 1 theories, as described by component fields, is investigated using the tools of Adinkras and Garden Algebras. A survey of familiar matter multiplets using these techniques reveals they are described by two fundamental valise Adinkras that are given the names of the cis-Valise (c-V) and the trans-Valise (t-V). A conjecture is made that all off-shell 4D, Script N = 1 component descriptions of supermultiplets are associated with two integers (nc, nt) — the numbers of c-V and t-V Adinkras that occur in the representation.

  17. Brain tissue segmentation in 4D CT using voxel classification

    NASA Astrophysics Data System (ADS)

    van den Boom, R.; Oei, M. T. H.; Lafebre, S.; Oostveen, L. J.; Meijer, F. J. A.; Steens, S. C. A.; Prokop, M.; van Ginneken, B.; Manniesing, R.

    2012-02-01

    A method is proposed to segment anatomical regions of the brain from 4D computer tomography (CT) patient data. The method consists of a three step voxel classification scheme, each step focusing on structures that are increasingly difficult to segment. The first step classifies air and bone, the second step classifies vessels and the third step classifies white matter, gray matter and cerebrospinal fluid. As features the time averaged intensity value and the temporal intensity change value were used. In each step, a k-Nearest-Neighbor classifier was used to classify the voxels. Training data was obtained by placing regions of interest in reconstructed 3D image data. The method has been applied to ten 4D CT cerebral patient data. A leave-one-out experiment showed consistent and accurate segmentation results.

  18. Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech

    PubMed Central

    Leão, Rogério de Barros F.; Esteves, Sandro C.

    2014-01-01

    Gonadotropin therapy plays an integral role in ovarian stimulation for infertility treatments. Efforts have been made over the last century to improve gonadotropin preparations. Undoubtedly, current gonadotropins have better quality and safety profiles as well as clinical efficacy than earlier ones. A major achievement has been introducing recombinant technology in the manufacturing processes for follicle-stimulating hormone, luteinizing hormone, and human chorionic gonadotropin. Recombinant gonadotropins are purer than urine-derived gonadotropins, and incorporating vial filling by mass virtually eliminated batch-to-batch variations and enabled accurate dosing. Recombinant and fill-by-mass technologies have been the driving forces for launching of prefilled pen devices for more patient-friendly ovarian stimulation. The most recent developments include the fixed combination of follitropin alfa + lutropin alfa, long-acting FSH gonadotropin, and a new family of prefilled pen injector devices for administration of recombinant gonadotropins. The next step would be the production of orally bioactive molecules with selective follicle-stimulating hormone and luteinizing hormone activity. PMID:24714837

  19. 21 CFR 522.1083 - Gonadotropin releasing factor analog-diphtheria toxoid conjugate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gonadotropin releasing factor analog-diphtheria... HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1083 Gonadotropin releasing factor analog-diphtheria...

  20. 21 CFR 522.1083 - Gonadotropin releasing factor analog-diphtheria toxoid conjugate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gonadotropin releasing factor analog-diphtheria... HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1083 Gonadotropin releasing factor analog-diphtheria...

  1. 21 CFR 522.1083 - Gonadotropin releasing factor analog-diphtheria toxoid conjugate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gonadotropin releasing factor analog-diphtheria... HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1083 Gonadotropin releasing factor analog-diphtheria...

  2. Phosphodiesterase 4D gene polymorphisms in sudden sensorineural hearing loss.

    PubMed

    Chien, Chen-Yu; Tai, Shu-Yu; Wang, Ling-Feng; Hsi, Edward; Chang, Ning-Chia; Wang, Hsun-Mo; Wu, Ming-Tsang; Ho, Kuen-Yao

    2016-09-01

    The phosphodiesterase 4D (PDE4D) gene has been reported as a risk gene for ischemic stroke. The vascular factors are between the hypothesized etiologies of sudden sensorineural hearing loss (SSNHL), and this genetic effect might be attributed for its role in SSNHL. We hypothesized that genetic variants of the PDE4D gene are associated with susceptibility to SSNHL. We conducted a case-control study with 362 SSNHL cases and 209 controls. Three single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. We carried out sex-specific analysis to analyze the overall data. All three SNPs were in HWE. When subjects were stratified by sex, the genetic effect was only evident in females but not in males. The TT genotype of rs702553 exhibited an adjusted odds ratio (OR) of 3.83 (95 % confidence interval = 1.46-11.18) (p = 0.006) in female SSNHL. The TT genotype of SNP rs702553 was associated with female SSNHL under the recessive model (p = 0.004, OR 3.70). In multivariate logistic regression analysis, TT genotype of rs702553 was significantly associated with female SSNHL (p = 0.0043, OR 3.70). These results suggest that PDE4D gene polymorphisms influence the susceptibility for the development of SSNHL in the southern Taiwanese female population. PMID:26521189

  3. Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma.

    PubMed

    Ge, Xuecai; Milenkovic, Ljiljana; Suyama, Kaye; Hartl, Tom; Purzner, Teresa; Winans, Amy; Meyer, Tobias; Scott, Matthew P

    2015-01-01

    Alterations in Hedgehog (Hh) signaling lead to birth defects and cancers including medulloblastoma, the most common pediatric brain tumor. Although inhibitors targeting the membrane protein Smoothened suppress Hh signaling, acquired drug resistance and tumor relapse call for additional therapeutic targets. Here we show that phosphodiesterase 4D (PDE4D) acts downstream of Neuropilins to control Hh transduction and medulloblastoma growth. PDE4D interacts directly with Neuropilins, positive regulators of Hh pathway. The Neuropilin ligand Semaphorin3 enhances this interaction, promoting PDE4D translocation to the plasma membrane and cAMP degradation. The consequent inhibition of protein kinase A (PKA) enhances Hh transduction. In the developing cerebellum, genetic removal of Neuropilins reduces Hh signaling activity and suppresses proliferation of granule neuron precursors. In mouse medulloblastoma allografts, PDE4D inhibitors suppress Hh transduction and inhibit tumor growth. Our findings reveal a new regulatory mechanism of Hh transduction, and highlight PDE4D as a promising target to treat Hh-related tumors. PMID:26371509

  4. Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma

    PubMed Central

    Ge, Xuecai; Milenkovic, Ljiljana; Suyama, Kaye; Hartl, Tom; Purzner, Teresa; Winans, Amy; Meyer, Tobias; Scott, Matthew P

    2015-01-01

    Alterations in Hedgehog (Hh) signaling lead to birth defects and cancers including medulloblastoma, the most common pediatric brain tumor. Although inhibitors targeting the membrane protein Smoothened suppress Hh signaling, acquired drug resistance and tumor relapse call for additional therapeutic targets. Here we show that phosphodiesterase 4D (PDE4D) acts downstream of Neuropilins to control Hh transduction and medulloblastoma growth. PDE4D interacts directly with Neuropilins, positive regulators of Hh pathway. The Neuropilin ligand Semaphorin3 enhances this interaction, promoting PDE4D translocation to the plasma membrane and cAMP degradation. The consequent inhibition of protein kinase A (PKA) enhances Hh transduction. In the developing cerebellum, genetic removal of Neuropilins reduces Hh signaling activity and suppresses proliferation of granule neuron precursors. In mouse medulloblastoma allografts, PDE4D inhibitors suppress Hh transduction and inhibit tumor growth. Our findings reveal a new regulatory mechanism of Hh transduction, and highlight PDE4D as a promising target to treat Hh-related tumors. DOI: http://dx.doi.org/10.7554/eLife.07068.001 PMID:26371509

  5. Gonadotropins in doping: pharmacological basis and detection of illicit use

    PubMed Central

    Stenman, U-H; Hotakainen, K; Alfthan, H

    2008-01-01

    Parenteral administration of human chorionic gonadotropin (hCG) or luteinizing hormone (LH) stimulates the production of testosterone in males and these gonadotropins can therefore be used by athletes to enhance muscle strength. However, they are more expensive and less efficient than testosterone and anabolic steroids. Therefore their main use is probably to stimulate gonadal testosterone production during and after self-administration of testosterone or anabolic steroids. A positive effect of hCG on muscle strength has not been demonstrated in women and elevated concentrations of hCG in females are often caused by pregnancy. The use of gonadotropins is therefore prohibited only in males but not in females. HCG occurs at low but measurable concentrations in plasma and urine of healthy males and can be measured by sensitive methods. However, the characteristics of the method to be used for doping control have not been defined. Virtually all commercially available hCG assays have been designed for determination of hCG in serum rather than urine, which is used for doping control. Methods based on mass spectrometric detection of fragments derived from hCG extracted from urine by immunoadsorption have been developed but their suitability for doping control remains to be determined. The concentrations of LH in serum and urine are variable and more then 10-fold higher than those hCG. It is therefore difficult to detect illicit use of LH. The characteristics and reference values for hCG and LH assays used in doping control and the cutoff values need to be defined. PMID:18414398

  6. Abnormal gonadotropin release and carbohydrate metabolism in morbid obese women.

    PubMed

    Sheu, W H; Lee, W J

    1997-12-31

    Obese women are associated with clinical symptoms suggestive of abnormal reproductive functions including irregular menses and infertility. Previous studies of gonadotropin release in obese women, basal or after luteal hormone releasing hormone (LHRH) stimulation, are controversial. Obese women are also often characterized by glucose intolerance and hyperinsulinemia which might relate to their excessive body fat. To understand the link between abnormal gonadotropin release, carbohydrate metabolism and percent body fat, we examined 17 premenopausal morbid obese women with body mass index (BMI) 38.7 +/- 1.6 Kg/m2 (mean +/- SEM) and 16 age-matched lean controls with BMI 19.7 +/- 0.6 Kg/m2. Plasma glucose, insulin and C-peptide values were measured before and 30, 60, 90 and 120 min after a 75 gm oral glucose tolerant test (OGTT). Each individual also received LHRH test which involved determinations of serum LH and FSH values at basal, 15, 30 and 60 min after injection of LHRH for 0.1 mg intravenously. Women with morbid obesity had significantly greater responses of glucose, insulin and C-peptide values as compared with lean women (all p < 0.001, two-way ANOVA). Despite that basal concentrations were not different, serum LH, FSH and ratio of LH to FSH values in response to LHRH test showed significantly lesser increase in obese women than lean controls. Percent body fat, determined by bioelectrical impedance analysis, correlated positively with plasma glucose, insulin and C-peptide responses to OGTT while negatively with ratio of LH to FSH responses (r = -0.418, p < 0.01) to LHRH test. Body mass index also correlated inversely with ratio of LH to FSH responses (r = -0.472, p < 0.01). In conclusion, morbid obese women had glucose intolerance, hyperinsulinemia and lower responses of serum LH and FSH values as compared with lean women. Excessive body fat play an important role in mediating these carbohydrate and gonadotropin abnormalities. PMID:9551249

  7. 4D-Flow validation, numerical and experimental framework

    NASA Astrophysics Data System (ADS)

    Sansom, Kurt; Liu, Haining; Canton, Gador; Aliseda, Alberto; Yuan, Chun

    2015-11-01

    This work presents a group of assessment metrics of new 4D MRI flow sequences, an imaging modality that allows for visualization of three-dimensional pulsatile flow in the cardiovascular anatomy through time-resolved three-dimensional blood velocity measurements from cardiac-cycle synchronized MRI acquisition. This is a promising tool for clinical assessment but lacks a robust validation framework. First, 4D-MRI flow in a subject's stenotic carotid bifurcation is compared with a patient-specific CFD model using two different boundary condition methods. Second, Particle Image Velocimetry in a patient-specific phantom is used as a benchmark to compare the 4D-MRI in vivo measurements and CFD simulations under the same conditions. Comparison of estimated and measureable flow parameters such as wall shear stress, fluctuating velocity rms, Lagrangian particle residence time, will be discussed, with justification for their biomechanics relevance and the insights they can provide on the pathophysiology of arterial disease: atherosclerosis and intimal hyperplasia. Lastly, the framework is applied to a new sequence to provide a quantitative assessment. A parametric analysis on the carotid bifurcation pulsatile flow conditions will be presented and an accuracy assessment provided.

  8. 4D remote sensing image coding with JPEG2000

    NASA Astrophysics Data System (ADS)

    Muñoz-Gómez, Juan; Bartrina-Rapesta, Joan; Blanes, Ian; Jiménez-Rodríguez, Leandro; Aulí-Llinàs, Francesc; Serra-Sagristà, Joan

    2010-08-01

    Multicomponent data have become popular in several scientific fields such as forest monitoring, environmental studies, or sea water temperature detection. Nowadays, this multicomponent data can be collected more than one time per year for the same region. This generates different instances in time of multicomponent data, also called 4D-Data (1D Temporal + 1D Spectral + 2D Spatial). For multicomponent data, it is important to take into account inter-band redundancy to produce a more compact representation of the image by packing the energy into fewer number of bands, thus enabling a higher compression performance. The principal decorrelators used to compact the inter-band correlation redundancy are the Karhunen Loeve Transform (KLT) and Discrete Wavelet Transform (DWT). Because of the Temporal Dimension added, the inter-band redundancy among different multicomponent images is increased. In this paper we analyze the influence of the Temporal Dimension (TD) and the Spectral Dimension (SD) in 4D-Data in terms of coding performance for JPEG2000, because it has support to apply different decorrelation stages and transforms to the components through the different dimensions. We evaluate the influence to perform different decorrelators techniques to the different dimensions. Also we will assess the performance of the two main decorrelation techniques, KLT and DWT. Experimental results are provided, showing rate-distortion performances encoding 4D-Data using KLT and WT techniques to the different dimensions TD and SD.

  9. 4D flow imaging: current status to future clinical applications.

    PubMed

    Markl, Michael; Schnell, Susanne; Barker, Alex J

    2014-05-01

    4D flow MRI permits a comprehensive in-vivo assessment of three-directional blood flow within 3-dimensional vascular structures throughout the cardiac cycle. Given the large coverage permitted from a 4D flow acquisition, the distribution of vessel wall and flow parameters along an entire vessel of interest can thus be derived from a single measurement without being dependent on multiple predefined 2D acquisitions. In addition to qualitative 3D visualizations of complex cardiac and vascular flow patterns, quantitative flow analysis can be performed and is complemented by the ability to compute sophisticated hemodynamic parameters, such as wall shear stress or 3D pressure difference maps. These metrics can provide information previously unavailable with conventional modalities regarding the impact of cardiovascular disease or therapy on global and regional changes in hemodynamics. This review provides an introduction to the methodological aspects of 4D flow MRI to assess vascular hemodynamics and describes its potential for the assessment and understanding of altered hemodynamics in the presence of cardiovascular disease. PMID:24700368

  10. A 4D Hyperspherical Interpretation of q-Space

    PubMed Central

    Hosseinbor, A. Pasha; Chung, Moo K.; Wu, Yu-Chien; Bendlin, Barbara B.; Alexander, Andrew L.

    2015-01-01

    3D q-space can be viewed as the surface of a 4D hypersphere. In this paper, we seek to develop a 4D hyperspherical interpretation of q-space by projecting it onto a hypersphere and subsequently modeling the q-space signal via 4D hyperspherical harmonics (HSH). Using this orthonormal basis, we derive several well-established q-space indices and numerically estimate the diffusion orientation distribution function (dODF). We also derive the integral transform describing the relationship between the diffusion signal and propagator on a hypersphere. Most importantly, we will demonstrate that for hybrid diffusion imaging (HYDI) acquisitions low order linear expansion of the HSH basis is sufficient to characterize diffusion in neural tissue. In fact, the HSH basis achieves comparable signal and better dODF reconstructions than other well-established methods, such as Bessel Fourier orientation reconstruction (BFOR), using fewer fitting parameters. All in all, this work provides a new way of looking at q-space. PMID:25624043

  11. [Demonstration and evolution of chorionic gonadotropin in ewes].

    PubMed

    Lacroix, M C; Martal, J

    1979-02-26

    Occurrence of ovine Chorionic Gonadotropin (oCG) is demonstrated in placenta and amniotic fluid with the use of a radioreceptor assay (corpus luteum membranes) in ewes. Identification of oCG is possible as early as 15th day of pregnancy. It should be secreted at a constant rate, and its maximum concentration is recorded on the 130th day. This hormonal factor might be one of the major components accountable for high progesteronemia observed during the 100 last days of pregnancy. PMID:110484

  12. Ovarian Hyper-Response to Administration of an GnRH-Agonist Without Gonadotropins

    PubMed Central

    Park, Hyun Tae; Bae, Hyo Sook; Kim, Tak

    2011-01-01

    Several case reports have indicated that a small subgroup of patients may develop ovarian hyperstimulation following the administration of gonadotropin-releasing hormone agonists (GnRHa) without gonadotropins. However, since only few such cases have been published, it is unclear what course to follow in subsequent cycles after ovarian hyperstimulation in the first cycle using only GnRHa. A 33-yr-old woman was referred to in vitro fertilization for oocyte donation. A depot preparation (3.75 mg) of tryptorelin without gonadotropins induced ovarian multifollicular enlargement with high estradiol level, and was followed by human chorionic gonadotropin administration and oocyte retrieval. In a subsequent cycle of the same patient, a low dose of tryptorelin (0.05 mg) did not induce ovarian hyperstimulation, and resulted in clinical pregnancy. This report shows potential management of ovarian hyperstimulation following the administration of GnRHa without gonadotropins. PMID:22022197

  13. Cleavage pattern and fate map of the mesentoblast, 4d, in the gastropod Crepidula: a hallmark of spiralian development

    PubMed Central

    2012-01-01

    include the adult heart, internal foot tissues, and additional muscle and mesenchymal cells derived from later-born progeny of the left and right teloblasts. To test whether other cells can compensate for the loss of these tissues (that is, undergo regulation), specific cells were ablated in C. fornicata. Conclusions Our results present the first fate map of the 4d micromere sublineages in a mollusk. The fate map reveals that endodermal and mesodermal fates segregate much later than previously thought. We observed little evidence of regulation between sublineages, consistent with a lineage-driven cell specification process. Our results provide a framework for comparisons with other spiralians and lay the groundwork for investigation of the molecular mechanisms of endomesoderm formation, germ line segregation and bilateral differentiation in Crepidula. PMID:22992254

  14. 2,4-D impact on bacterial communities, and the activity and genetic potential of 2,4-D degrading communities in soil.

    PubMed

    Gonod, Laure Vieublé; Martin-Laurent, Fabrice; Chenu, Claire

    2006-12-01

    The key role of telluric microorganisms in pesticide degradation is well recognized but the possible relationships between the biodiversity of soil microbial communities and their functions still remain poorly documented. If microorganisms influence the fate of pesticides, pesticide application may reciprocally affect soil microorganisms. The objective of our work was to estimate the impact of 2,4-D application on the genetic structure of bacterial communities and the 2,4-D-degrading genetic potential in relation to 2,4-D mineralization. Experiments combined isotope measurements with molecular analyses. The impact of 2,4-D on soil bacterial populations was followed with ribosomal intergenic spacer analysis. The 2,4-D degrading genetic potential was estimated by real-time PCR targeted on tfdA sequences coding an enzyme specifically involved in 2,4-D mineralization. The genetic structure of bacterial communities was significantly modified in response to 2,4-D application, but only during the intense phase of 2,4-D biodegradation. This effect disappeared 7 days after the treatment. The 2,4-D degrading genetic potential increased rapidly following 2,4-D application. There was a concomitant increase between the tfdA copy number and the 14C microbial biomass. The maximum of tfdA sequences corresponded to the maximum rate of 2,4-D mineralization. In this soil, 2,4-D degrading microbial communities seem preferentially to use the tfd pathway to degrade 2,4-D. PMID:17117994

  15. Regulation of gonadotropin receptors, gonadotropin responsiveness, and cell multiplication by somatomedin-C and insulin in cultured pig Leydig cells

    SciTech Connect

    Bernier, M.; Chatelain, P.; Mather, J.P.; Saez, J.M.

    1986-11-01

    The author have investigated the effects of insulin and somatomedin-C/insulin like growth factor I(Sm-C) in purified porcine Leydig cells in vitro on gonadotrophins (hCG) receptor number, hCG responsiveness (cAMP and testosterone production), and thymidine incorporation into DNA. Leydig cells cultured in a serum-free medium containing transferrin, vitamin E, and insulin (5 ..mu..g/ml) maintained fairly constant both hCG receptors and hCG responsiveness. When they were cultured for 3 days in the same medium without insulin, there was a dramatic decline (more than 80%) in both hCG receptor number and hCG responsiveness. However the cAMP but not the testosterone response to forskolin was normal. Both insulin and Sm-C at nanomolar concentrations prevent the decline of both hCG receptors and hCG-induced cAMP production. At nanomolar concentrations, Sm-C and insulin enhanced hCG-induced testosterone production but the effect of Sm-C was significantly higher than that of insulin. However, the effect of insulin at higher concentrations (5 ..mu..g/ml) was significantly higher than that of Sm-C at 50 ng/ml. In contrast, at nanomolar concentrations only Sm-C stimulated (/sup 3/H)-thymidine incorporation into DNA and cell multiplication, the stimulatory effect of insulin on these parameters, was seen only at micromolar concentrations. These results indicate that both Sm-C and insulin acting through the receptors increase Leydig cell steroidogenic responsiveness to hCG by increasing hCG receptor number and improving some step beyond cAMP formation. In contrast, the mitogenic effects of insulin are mediated only through Sm-C receptors.

  16. Non-spherical particle generation from 4D optofluidic fabrication.

    PubMed

    Paulsen, Kevin S; Chung, Aram J

    2016-08-01

    Particles with non-spherical shapes can exhibit properties which are not available from spherical shaped particles. Complex shaped particles can provide unique benefits for areas such as drug delivery, tissue engineering, structural materials, and self-assembly building blocks. Current methods of creating complex shaped particles such as 3D printing, photolithography, and imprint lithography are limited by either slow speeds, shape limitations, or expensive processes. Previously, we presented a novel microfluidic flow lithography fabrication scheme combined with fluid inertia called optofluidic fabrication for the creation of complex shaped three-dimensional (3D) particles. This process was able to address the aforementioned limits and overcome two-dimensional shape limitations faced by traditional flow lithography methods; however, all of the created 3D particle shapes displayed top-down symmetry. Here, by introducing the time dimension into our existing optofluidic fabrication process, we break this top-down symmetry, generating fully asymmetric 3D particles where we termed the process: four-dimensional (4D) optofluidic fabrication. This 4D optofluidic fabrication is comprised of three sequential procedures. First, density mismatched precursor fluids flow past pillars within fluidic channels to manipulate the flow cross sections via fluid inertia. Next, the time dimension is incorporated by stopping the flow and allowing the denser fluids to settle by gravity to create asymmetric flow cross sections. Finally, the fluids are exposed to patterned ultraviolet (UV) light in order to polymerize fully asymmetric 3D-shaped particles. By varying inertial flow shaping, gravity-induced flow shaping, and UV light patterns, 4D optofluidic fabrication can create an infinite set of complex shaped asymmetric particles. PMID:27092661

  17. 4D Proton treatment planning strategy for mobile lung tumors

    SciTech Connect

    Kang Yixiu; Zhang Xiaodong; Chang, Joe Y.; Wang He; Wei Xiong; Liao Zhongxing; Komaki, Ritsuko; Cox, James D.; Balter, Peter A.; Liu, Helen; Zhu, X. Ronald; Mohan, Radhe; Dong Lei . E-mail: ldong@mdanderson.org

    2007-03-01

    Purpose: To investigate strategies for designing compensator-based 3D proton treatment plans for mobile lung tumors using four-dimensional computed tomography (4DCT) images. Methods and Materials: Four-dimensional CT sets for 10 lung cancer patients were used in this study. The internal gross tumor volume (IGTV) was obtained by combining the tumor volumes at different phases of the respiratory cycle. For each patient, we evaluated four planning strategies based on the following dose calculations: (1) the average (AVE) CT; (2) the free-breathing (FB) CT; (3) the maximum intensity projection (MIP) CT; and (4) the AVE CT in which the CT voxel values inside the IGTV were replaced by a constant density (AVE{sub R}IGTV). For each strategy, the resulting cumulative dose distribution in a respiratory cycle was determined using a deformable image registration method. Results: There were dosimetric differences between the apparent dose distribution, calculated on a single CT dataset, and the motion-corrected 4D dose distribution, calculated by combining dose distributions delivered to each phase of the 4DCT. The AVE{sub R}IGTV plan using a 1-cm smearing parameter had the best overall target coverage and critical structure sparing. The MIP plan approach resulted in an unnecessarily large treatment volume. The AVE and FB plans using 1-cm smearing did not provide adequate 4D target coverage in all patients. By using a larger smearing value, adequate 4D target coverage could be achieved; however, critical organ doses were increased. Conclusion: The AVE{sub R}IGTV approach is an effective strategy for designing proton treatment plans for mobile lung tumors.

  18. Phase and amplitude binning for 4D-CT imaging.

    PubMed

    Abdelnour, A F; Nehmeh, S A; Pan, T; Humm, J L; Vernon, P; Schöder, H; Rosenzweig, K E; Mageras, G S; Yorke, E; Larson, S M; Erdi, Y E

    2007-06-21

    We compare the consistency and accuracy of two image binning approaches used in 4D-CT imaging. One approach, phase binning (PB), assigns each breathing cycle 2pi rad, within which the images are grouped. In amplitude binning (AB), the images are assigned bins according to the breathing signal's full amplitude. To quantitate both approaches we used a NEMA NU2-2001 IEC phantom oscillating in the axial direction and at random frequencies and amplitudes, approximately simulating a patient's breathing. 4D-CT images were obtained using a four-slice GE Lightspeed CT scanner operating in cine mode. We define consistency error as a measure of ability to correctly bin over repeated cycles in the same field of view. Average consistency error mue+/-sigmae in PB ranged from 18%+/-20% to 30%+/-35%, while in AB the error ranged from 11%+/-14% to 20%+/-24%. In PB nearly all bins contained sphere slices. AB was more accurate, revealing empty bins where no sphere slices existed. As a proof of principle, we present examples of two non-small cell lung carcinoma patients' 4D-CT lung images binned by both approaches. While AB can lead to gaps in the coronal images, depending on the patient's breathing pattern, PB exhibits no gaps but suffers visible artifacts due to misbinning, yielding images that cover a relatively large amplitude range. AB was more consistent, though often resulted in gaps when no data existed due to patients' breathing pattern. We conclude AB is more accurate than PB. This has important consequences to treatment planning and diagnosis. PMID:17664557

  19. Localization of 4D gravity on pure geometrical thick branes

    SciTech Connect

    Barbosa-Cendejas, Nandinii; Herrera-Aguilar, Alfredo

    2006-04-15

    We consider the generation of thick brane configurations in a pure geometric Weyl integrable 5D spacetime which constitutes a non-Riemannian generalization of Kaluza-Klein (KK) theory. In this framework, we show how 4D gravity can be localized on a scalar thick brane which does not necessarily respect reflection symmetry, generalizing in this way several previous models based on the Randall-Sundrum (RS) system and avoiding both, the restriction to orbifold geometries and the introduction of the branes in the action by hand. We first obtain a thick brane solution that preserves 4D Poincare invariance and breaks Z{sub 2}-symmetry along the extra dimension which, indeed, can be either compact or extended, and supplements brane solutions previously found by other authors. In the noncompact case, this field configuration represents a thick brane with positive energy density centered at y=c{sub 2}, whereas pairs of thick branes arise in the compact case. Remarkably, the Weylian scalar curvature is nonsingular along the fifth dimension in the noncompact case, in contraposition to the RS thin brane system. We also recast the wave equations of the transverse traceless modes of the linear fluctuations of the classical background into a Schroedinger's equation form with a volcano potential of finite bottom in both the compact and the extended cases. We solve Schroedinger equation for the massless zero mode m{sup 2}=0 and obtain a single bound wave function which represents a stable 4D graviton. We also get a continuum gapless spectrum of KK states with m{sup 2}>0 that are suppressed at y=c{sub 2} and turn asymptotically into plane waves.

  20. Multicolor 4D Fluorescence Microscopy using Ultrathin Bessel Light Sheets

    PubMed Central

    Zhao, Teng; Lau, Sze Cheung; Wang, Ying; Su, Yumian; Wang, Hao; Cheng, Aifang; Herrup, Karl; Ip, Nancy Y.; Du, Shengwang; Loy, M. M. T.

    2016-01-01

    We demonstrate a simple and efficient method for producing ultrathin Bessel (‘non-diffracting’) light sheets of any color using a line-shaped beam and an annulus filter. With this robust and cost-effective technology, we obtained two-color, 3D images of biological samples with lateral/axial resolution of 250 nm/400 nm, and high-speed, 4D volume imaging of 20 μm sized live sample at 1 Hz temporal resolution. PMID:27189786

  1. Oblique sounding using the DPS-4D stations in Europe

    NASA Astrophysics Data System (ADS)

    Mosna, Zbysek; Kouba, Daniel; Koucka Knizova, Petra; Arikan, Feza; Arikan, Orhan; Gok, Gokhan; Rejfek, Lubos

    2016-07-01

    The DPS-4D Digisondes are capable of detection of echoes from neighbouring European stations. Currently, a campaign with high-temporal resolution of 5 min is being run. Further, ionograms from regular vertical sounding with 15 min resolution provide us with oblique reflections together with vertical reflections. We analyzed profiles of electron concentration and basic ionospheric parameters derived from the ionograms. We compared results derived from reflections from the ionosphere above the stations (vertical sounding) with information derived from oblique reflections between the stations. This study is supported by the Joint TUBITAK 114E092 and AS CR 14/001 projects.

  2. All the supersymmetric configurations of N=4, d=4 supergravity

    NASA Astrophysics Data System (ADS)

    Bellorín, Jorge; Ortín, Tomás

    2005-10-01

    All the supersymmetric configurations of pure, ungauged, N=4, d=4 supergravity are classified in a formalism that keeps manifest the S and T dualities of the theory. We also find simple equations that need to be satisfied by the configurations to be classical solutions of the theory. While the solutions associated to null Killing vectors were essentially classified by Tod (a classification that we refine), we find new configurations and solutions associated to timelike Killing vectors that do not satisfy Tod's rigidity hypothesis (hence, they have a nontrivial U(1) connection) and whose supersymmetry projector is associated to 1-dimensional objects (strings), although they have a trivial axion field.

  3. Multielectron Spectroscopy: The Xenon 4d Hole Double Auger Decay

    SciTech Connect

    Penent, F.; Palaudoux, J.; Lablanquie, P.; Andric, L.; Feifel, R.; Eland, J.H.D.

    2005-08-19

    A magnetic bottle spectrometer of the type recently developed by Eland et al. [Phys. Rev. Lett. 90, 053003 (2003).] has been implemented for use with synchrotron radiation, allowing multidimensional electron spectroscopy. Its application to the Xe 4d double Auger decay reveals all the energy pathways involved. The dominant path is a cascade process with a rapid (6 fs) ejection of a first Auger electron followed by the slower (>23 fs) emission of a second Auger electron. Weaker processes implying 3 electron processes are also revealed, namely, direct double Auger and associated Rydberg series.

  4. Founding Gravitation in 4D Euclidean Space-Time Geometry

    SciTech Connect

    Winkler, Franz-Guenter

    2010-11-24

    The Euclidean interpretation of special relativity which has been suggested by the author is a formulation of special relativity in ordinary 4D Euclidean space-time geometry. The natural and geometrically intuitive generalization of this view involves variations of the speed of light (depending on location and direction) and a Euclidean principle of general covariance. In this article, a gravitation model by Jan Broekaert, which implements a view of relativity theory in the spirit of Lorentz and Poincare, is reconstructed and shown to fulfill the principles of the Euclidean approach after an appropriate reinterpretation.

  5. Actively triggered 4d cone-beam CT acquisition

    SciTech Connect

    Fast, Martin F.; Wisotzky, Eric; Oelfke, Uwe; Nill, Simeon

    2013-09-15

    Purpose: 4d cone-beam computed tomography (CBCT) scans are usually reconstructed by extracting the motion information from the 2d projections or an external surrogate signal, and binning the individual projections into multiple respiratory phases. In this “after-the-fact” binning approach, however, projections are unevenly distributed over respiratory phases resulting in inefficient utilization of imaging dose. To avoid excess dose in certain respiratory phases, and poor image quality due to a lack of projections in others, the authors have developed a novel 4d CBCT acquisition framework which actively triggers 2d projections based on the forward-predicted position of the tumor.Methods: The forward-prediction of the tumor position was independently established using either (i) an electromagnetic (EM) tracking system based on implanted EM-transponders which act as a surrogate for the tumor position, or (ii) an external motion sensor measuring the chest-wall displacement and correlating this external motion to the phase-shifted diaphragm motion derived from the acquired images. In order to avoid EM-induced artifacts in the imaging detector, the authors devised a simple but effective “Faraday” shielding cage. The authors demonstrated the feasibility of their acquisition strategy by scanning an anthropomorphic lung phantom moving on 1d or 2d sinusoidal trajectories.Results: With both tumor position devices, the authors were able to acquire 4d CBCTs free of motion blurring. For scans based on the EM tracking system, reconstruction artifacts stemming from the presence of the EM-array and the EM-transponders were greatly reduced using newly developed correction algorithms. By tuning the imaging frequency independently for each respiratory phase prior to acquisition, it was possible to harmonize the number of projections over respiratory phases. Depending on the breathing period (3.5 or 5 s) and the gantry rotation time (4 or 5 min), between ∼90 and 145

  6. 4D micro-CT using fast prospective gating

    NASA Astrophysics Data System (ADS)

    Guo, Xiaolian; Johnston, Samuel M.; Qi, Yi; Johnson, G. Allan; Badea, Cristian T.

    2012-01-01

    Micro-CT is currently used in preclinical studies to provide anatomical information. But, there is also significant interest in using this technology to obtain functional information. We report here a new sampling strategy for 4D micro-CT for functional cardiac and pulmonary imaging. Rapid scanning of free-breathing mice is achieved with fast prospective gating (FPG) implemented on a field programmable gate array. The method entails on-the-fly computation of delays from the R peaks of the ECG signals or the peaks of the respiratory signals for the triggering pulses. Projection images are acquired for all cardiac or respiratory phases at each angle before rotating to the next angle. FPG can deliver the faster scan time of retrospective gating (RG) with the regular angular distribution of conventional prospective gating for cardiac or respiratory gating. Simultaneous cardio-respiratory gating is also possible with FPG in a hybrid retrospective/prospective approach. We have performed phantom experiments to validate the new sampling protocol and compared the results from FPG and RG in cardiac imaging of a mouse. Additionally, we have evaluated the utility of incorporating respiratory information in 4D cardiac micro-CT studies with FPG. A dual-source micro-CT system was used for image acquisition with pulsed x-ray exposures (80 kVp, 100 mA, 10 ms). The cardiac micro-CT protocol involves the use of a liposomal blood pool contrast agent containing 123 mg I ml-1 delivered via a tail vein catheter in a dose of 0.01 ml g-1 body weight. The phantom experiment demonstrates that FPG can distinguish the successive phases of phantom motion with minimal motion blur, and the animal study demonstrates that respiratory FPG can distinguish inspiration and expiration. 4D cardiac micro-CT imaging with FPG provides image quality superior to RG at an isotropic voxel size of 88 µm and 10 ms temporal resolution. The acquisition time for either sampling approach is less than 5 min. The

  7. Multicolor 4D Fluorescence Microscopy using Ultrathin Bessel Light Sheets.

    PubMed

    Zhao, Teng; Lau, Sze Cheung; Wang, Ying; Su, Yumian; Wang, Hao; Cheng, Aifang; Herrup, Karl; Ip, Nancy Y; Du, Shengwang; Loy, M M T

    2016-01-01

    We demonstrate a simple and efficient method for producing ultrathin Bessel ('non-diffracting') light sheets of any color using a line-shaped beam and an annulus filter. With this robust and cost-effective technology, we obtained two-color, 3D images of biological samples with lateral/axial resolution of 250 nm/400 nm, and high-speed, 4D volume imaging of 20 μm sized live sample at 1 Hz temporal resolution. PMID:27189786

  8. Familial idiopathic gonadotropin deficiency not linked to gene for gonadotropin-releasing hormone (GnRH) in Brazilian kindred

    SciTech Connect

    Faraco, J.; Francke, U.; Toledo, S.

    1994-09-01

    Familial idiopathic gonadotropin deficiency (FIGD) is an autosomal recessive disorder which results in failure to develop secondary sexual characteristics. The origin is a hypothalamic defect resulting in insufficient secretion of gonadotropin-releasing hormone GnRH (also called LHRH, luteinizing hormone releasing hormone) and follicle-stimuating hormone (FSH). FIGD has been determined to be a separate entity from Kallmann syndrome which presents with hypogonadism as well as anosmia. The FIGD phenotype appears to be analogous to the phenotype of the hpg (hypogonadal) mouse. Because the hpg phenotype is the result of a structurally abnormal GnRH gene, we have studied the GnRH gene in individuals from a previously reported Brazilian FIGD family. An informative dimorphic marker in the signal peptide sequence of the GnRH gene allowed assessment of linkage between the disease gene and the GnRH locus in this pedigree. We have concluded that the GnRH locus is not linked to the disease-causing mutation in these hypogonadal individuals. Recent evidence suggests that neuropeptide Y (NPY) may play a role in the initiation of puberty. We hypothesize that mutations in NPY may result in failure to secrete GnRH. We have characterized three diallelic frequent-cutter restriction fragment length polymorphisms within the human NPY locus, and are currently using these markers to determine if the NPY gene is linked to, and possibly the site of the disease mutation in this kindred.

  9. Perspective: 4D ultrafast electron microscopy--Evolutions and revolutions.

    PubMed

    Shorokhov, Dmitry; Zewail, Ahmed H

    2016-02-28

    In this Perspective, the evolutionary and revolutionary developments of ultrafast electron imaging are overviewed with focus on the "single-electron concept" for probing methodology. From the first electron microscope of Knoll and Ruska [Z. Phys. 78, 318 (1932)], constructed in the 1930s, to aberration-corrected instruments and on, to four-dimensional ultrafast electron microscopy (4D UEM), the developments over eight decades have transformed humans' scope of visualization. The changes in the length and time scales involved are unimaginable, beginning with the micrometer and second domains, and now reaching the space and time dimensions of atoms in matter. With these advances, it has become possible to follow the elementary structural dynamics as it unfolds in real time and to provide the means for visualizing materials behavior and biological functions. The aim is to understand emergent phenomena in complex systems, and 4D UEM is now central for the visualization of elementary processes involved, as illustrated here with examples from past achievements and future outlook. PMID:26931672

  10. Complete valvular heart apparatus model from 4D cardiac CT.

    PubMed

    Grbic, Sasa; Ionasec, Razvan; Vitanovski, Dime; Voigt, Ingmar; Wang, Yang; Georgescu, Bogdan; Navab, Nassir; Comaniciu, Dorin

    2012-07-01

    The cardiac valvular apparatus, composed of the aortic, mitral, pulmonary and tricuspid valves, is an essential part of the anatomical, functional and hemodynamic characteristics of the heart and the cardiovascular system as a whole. Valvular heart diseases often involve multiple dysfunctions and require joint assessment and therapy of the valves. In this paper, we propose a complete and modular patient-specific model of the cardiac valvular apparatus estimated from 4D cardiac CT data. A new constrained Multi-linear Shape Model (cMSM), conditioned by anatomical measurements, is introduced to represent the complex spatio-temporal variation of the heart valves. The cMSM is exploited within a learning-based framework to efficiently estimate the patient-specific valve parameters from cine images. Experiments on 64 4D cardiac CT studies demonstrate the performance and clinical potential of the proposed method. Our method enables automatic quantitative evaluation of the complete valvular apparatus based on non-invasive imaging techniques. In conjunction with existent patient-specific chamber models, the presented valvular model enables personalized computation modeling and realistic simulation of the entire cardiac system. PMID:22481023

  11. 488-4D ASH LANDFILL CLOSURE CAP HELP MODELING

    SciTech Connect

    Phifer, M.

    2014-11-17

    At the request of Area Completion Projects (ACP) in support of the 488-4D Landfill closure, the Savannah River National Laboratory (SRNL) has performed Hydrologic Evaluation of Landfill Performance (HELP) modeling of the planned 488-4D Ash Landfill closure cap to ensure that the South Carolina Department of Health and Environmental Control (SCDHEC) limit of no more than 12 inches of head on top of the barrier layer (saturated hydraulic conductivity of no more than 1.0E-05 cm/s) in association with a 25-year, 24-hour storm event is not projected to be exceeded. Based upon Weber 1998 a 25-year, 24-hour storm event at the Savannah River Site (SRS) is 6.1 inches. The results of the HELP modeling indicate that the greatest peak daily head on top of the barrier layer (i.e. geosynthetic clay liner (GCL) or high density polyethylene (HDPE) geomembrane) for any of the runs made was 0.079 inches associated with a peak daily precipitation of 6.16 inches. This is well below the SCDHEC limit of 12 inches.

  12. Perspective: 4D ultrafast electron microscopy—Evolutions and revolutions

    NASA Astrophysics Data System (ADS)

    Shorokhov, Dmitry; Zewail, Ahmed H.

    2016-02-01

    In this Perspective, the evolutionary and revolutionary developments of ultrafast electron imaging are overviewed with focus on the "single-electron concept" for probing methodology. From the first electron microscope of Knoll and Ruska [Z. Phys. 78, 318 (1932)], constructed in the 1930s, to aberration-corrected instruments and on, to four-dimensional ultrafast electron microscopy (4D UEM), the developments over eight decades have transformed humans' scope of visualization. The changes in the length and time scales involved are unimaginable, beginning with the micrometer and second domains, and now reaching the space and time dimensions of atoms in matter. With these advances, it has become possible to follow the elementary structural dynamics as it unfolds in real time and to provide the means for visualizing materials behavior and biological functions. The aim is to understand emergent phenomena in complex systems, and 4D UEM is now central for the visualization of elementary processes involved, as illustrated here with examples from past achievements and future outlook.

  13. 4D Dynamic Required Navigation Performance Final Report

    NASA Technical Reports Server (NTRS)

    Finkelsztein, Daniel M.; Sturdy, James L.; Alaverdi, Omeed; Hochwarth, Joachim K.

    2011-01-01

    New advanced four dimensional trajectory (4DT) procedures under consideration for the Next Generation Air Transportation System (NextGen) require an aircraft to precisely navigate relative to a moving reference such as another aircraft. Examples are Self-Separation for enroute operations and Interval Management for in-trail and merging operations. The current construct of Required Navigation Performance (RNP), defined for fixed-reference-frame navigation, is not sufficiently specified to be applicable to defining performance levels of such air-to-air procedures. An extension of RNP to air-to-air navigation would enable these advanced procedures to be implemented with a specified level of performance. The objective of this research effort was to propose new 4D Dynamic RNP constructs that account for the dynamic spatial and temporal nature of Interval Management and Self-Separation, develop mathematical models of the Dynamic RNP constructs, "Required Self-Separation Performance" and "Required Interval Management Performance," and to analyze the performance characteristics of these air-to-air procedures using the newly developed models. This final report summarizes the activities led by Raytheon, in collaboration with GE Aviation and SAIC, and presents the results from this research effort to expand the RNP concept to a dynamic 4D frame of reference.

  14. Positive Energy Conditions in 4D Conformal Field Theory

    NASA Astrophysics Data System (ADS)

    Farnsworth, Kara; Luty, Markus; Prilepina, Valentina

    2016-03-01

    We argue that all consistent 4D quantum field theories obey a spacetime-averaged weak energy inequality avgT00 >= - C /L4 , where L is the size of the smearing region, and C is a positive constant that depends on the theory. If this condition is violated, the theory has states that are indistinguishable from states of negative total energy by any local measurement, and we expect instabilities or other inconsistencies. We apply this condition to 4D conformal field theories, and find that it places constraints on the OPE coefficients of the theory. The constraints we find are weaker than the ``conformal collider'' constraints of Hofman and Maldacena. We speculate that there may be theories that violate the Hofman-Maldacena bounds, but satisfy our bounds. In 3D CFTs, the only constraint we find is equivalent to the positivity of 2-point function of the energy-momentum tensor, which follows from unitarity. Our calculations are performed using momentum-space Wightman functions, which are remarkably simple functions of momenta, and may be of interest in their own right.

  15. Abdominal organ motion measured using 4D CT

    SciTech Connect

    Brandner, Edward D.; Wu, Andrew . E-mail: andrew.wu@jefferson.edu; Chen, Hungcheng; Heron, Dwight; Kalnicki, Shalom; Komanduri, Krishna; Gerszten, Kristina; Burton, Steve; Ahmed, Irfan; Shou, Zhenyu

    2006-06-01

    Purpose: To measure respiration-induced abdominal organ motion using four-dimensional computed tomography (4D CT) scanning and to examine the organ paths. Methods and Materials: During 4D CT scanning, consecutive CT images are acquired of the patient at each couch position. Simultaneously, the patient's respiratory pattern is recorded using an external marker block taped to the patient's abdomen. This pattern is used to retrospectively organize the CT images into multiple three-dimensional images, each representing one breathing phase. These images are analyzed to measure organ motion between each phase. The displacement from end expiration is compared to a displacement limit that represents acceptable dosimetric results (5 mm). Results: The organs measured in 13 patients were the liver, spleen, and left and right kidneys. Their average superior to inferior absolute displacements were 1.3 cm for the liver, 1.3 cm for the spleen, 1.1 cm for the left kidney, and 1.3 cm for the right kidney. Although the organ paths varied among patients, 5 mm of superior to inferior displacement from end expiration resulted in less than 5 mm of displacement in the other directions for 41 of 43 organs measured. Conclusions: Four-dimensional CT scanning can accurately measure abdominal organ motion throughout respiration. This information may result in greater organ sparing and planning target volume coverage.

  16. 4-D XRD for strain in many grains using triangulation

    SciTech Connect

    Bale, Hrishikesh A.; Hanan, Jay C.; Tamura, Nobumichi

    2006-12-31

    Determination of the strains in a polycrystalline materialusing 4-D XRD reveals sub-grain and grain-to-grain behavior as a functionof stress. Here 4-D XRD involves an experimental procedure usingpolychromatic micro-beam X-radiation (micro-Laue) to characterizepolycrystalline materials in spatial location as well as with increasingstress. The in-situ tensile loading experiment measured strain in a modelaluminum-sapphire metal matrix composite using the Advanced Light Source,Beam-line 7.3.3. Micro-Laue resolves individual grains in thepolycrystalline matrix. Results obtained from a list of grains sorted bycrystallographic orientation depict the strain states within and amongindividual grains. Locating the grain positions in the planeperpendicular to the incident beam is trivial. However, determining theexact location of grains within a 3-D space is challenging. Determiningthe depth of the grains within the matrix (along the beam direction)involved a triangulation method tracing individual rays that producespots on the CCD back to the point of origin. Triangulation wasexperimentally implemented by simulating a 3-D detector capturingmultiple diffraction images while increasing the camera to sampledistance. Hence by observing the intersection of rays from multiple spotsbelonging to the corresponding grain, depth is calculated. Depthresolution is a function of the number of images collected, grain to beamsize ratio, and the pixel resolution of the CCD. The 4DXRD methodprovides grain morphologies, strain behavior of each grain, andinteractions of the matrix grains with each other and the centrallylocated single crystal fiber.

  17. 2D/4D marker-free tumor tracking using 4D CBCT as the reference image

    PubMed Central

    Wang, Mengjiao; Rit, Simon; Delmon, Vivien; Wang, Guangzhi

    2014-01-01

    Tumor motion caused by respiration is an important issue in image guided radiotherapy. A 2D/4D matching method between 4D volumes derived from cone beam computed tomography (CBCT) and 2D fluoroscopic images was implemented to track the tumor motion without the use of implanted markers. In this method, firstly, 3DCBCT and phase-rebinned 4DCBCT are reconstructed from cone beam acquisition. Secondly, 4DCBCT volumes and streak free 3DCBCT volume are combined to improve the image quality of the DRRs. Finally, the 2D/4D matching problem is converted into a 2D/2D matching between incoming projections and DRR images from each phase of the 4DCBCT. The diaphragm is used as a target surrogate for matching instead of using the tumor position directly. This relies on the assumption that if a patient has the same breathing phase and diaphragm position as the reference 4DCBCT, then the tumor position is the same. From the matching results, the phase information, diaphragm position and tumor position at the time of each incoming projection acquisition can be derived. The accuracy of this method was verified using 16 candidate datasets, representing lung and liver applications and 1-minute and 2-minute acquisitions. The criteria for the eligibility of datasets were described: 11 eligible datasets were selected to verify the accuracy of diaphragm tracking, and one eligible dataset was chosen to verify the accuracy of tumor tracking. Diaphragm matching accuracy was 1.88±1.35mm in the isocenter plane, the 2D tumor tracking accuracy was 2.13±1.26mm in the isocenter plane. These features make this method feasible for real-time marker-free tumor motion tracking purpose. PMID:24710793

  18. 2D/4D marker-free tumor tracking using 4D CBCT as the reference image

    NASA Astrophysics Data System (ADS)

    Wang, Mengjiao; Sharp, Gregory C.; Rit, Simon; Delmon, Vivien; Wang, Guangzhi

    2014-05-01

    Tumor motion caused by respiration is an important issue in image-guided radiotherapy. A 2D/4D matching method between 4D volumes derived from cone beam computed tomography (CBCT) and 2D fluoroscopic images was implemented to track the tumor motion without the use of implanted markers. In this method, firstly, 3DCBCT and phase-rebinned 4DCBCT are reconstructed from cone beam acquisition. Secondly, 4DCBCT volumes and a streak-free 3DCBCT volume are combined to improve the image quality of the digitally reconstructed radiographs (DRRs). Finally, the 2D/4D matching problem is converted into a 2D/2D matching between incoming projections and DRR images from each phase of the 4DCBCT. The diaphragm is used as a target surrogate for matching instead of using the tumor position directly. This relies on the assumption that if a patient has the same breathing phase and diaphragm position as the reference 4DCBCT, then the tumor position is the same. From the matching results, the phase information, diaphragm position and tumor position at the time of each incoming projection acquisition can be derived. The accuracy of this method was verified using 16 candidate datasets, representing lung and liver applications and one-minute and two-minute acquisitions. The criteria for the eligibility of datasets were described: 11 eligible datasets were selected to verify the accuracy of diaphragm tracking, and one eligible dataset was chosen to verify the accuracy of tumor tracking. The diaphragm matching accuracy was 1.88 ± 1.35 mm in the isocenter plane and the 2D tumor tracking accuracy was 2.13 ± 1.26 mm in the isocenter plane. These features make this method feasible for real-time marker-free tumor motion tracking purposes.

  19. WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling.

    PubMed

    Abedini, Atefeh; Zamberlam, Gustavo; Lapointe, Evelyne; Tourigny, Catherine; Boyer, Alexandre; Paquet, Marilène; Hayashi, Kanako; Honda, Hiroaki; Kikuchi, Akira; Price, Christopher; Boerboom, Derek

    2016-04-01

    Whereas the roles of the canonical wingless-type MMTV (mouse mammary tumor virus) integration site family (WNT) signaling pathway in the regulation of ovarian follicle growth and steroidogenesis are now established, noncanonical WNT signaling in the ovary has been largely overlooked. Noncanonical WNTs, including WNT5a and WNT11, are expressed in granulosa cells (GCs) and are differentially regulated throughout follicle development, but their physiologic roles remain unknown. Using conditional gene targeting, we found that GC-specific inactivation ofWnt5a(but notWnt11) results in the female subfertility associated with increased follicular atresia and decreased rates of ovulation. Microarray analyses have revealed that WNT5a acts to down-regulate the expression of FSH-responsive genesin vitro, and corresponding increases in the expression of these genes have been found in the GCs of conditional knockout mice. Unexpectedly, we found that WNT5a regulates its target genes not by signalingviathe WNT/Ca(2+)or planar cell polarity pathways, but rather by inhibiting the canonical pathway, causing both β-catenin (CTNNB1) and cAMP responsive element binding (CREB) protein levels to decreaseviaa glycogen synthase kinase-3β-dependent mechanism. We further found that WNT5a prevents follicle-stimulating hormone and luteinizing protein from up-regulating the CTNNB1 and CREB proteins and their target genes, indicating that WNT5a functions as a physiologic inhibitor of gonadotropin signaling. Together, these findings identify WNT5a as a key regulator of follicle development and gonadotropin responsiveness.-Abedini, A., Zamberlam, G., Lapointe, E., Tourigny, C., Boyer, A., Paquet, M., Hayashi, K., Honda, H., Kikuchi, A., Price, C., Boerboom, D. WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling. PMID:26667040

  20. RACK1 and β-arrestin2 attenuate dimerization of PDE4 cAMP phosphodiesterase PDE4D5.

    PubMed

    Bolger, Graeme B

    2016-07-01

    PDE4 family cAMP-selective cyclic nucleotide phosphodiesterases are important in the regulation of cAMP abundance in numerous systems, and thereby play an important role in the regulation of PKA and EPAC activity and the phosphorylation of CREB. We have used the yeast 2-hybrid system to demonstrate recently that long PDE4 isoforms form homodimers, consistent with data obtained recently by structural studies. The long PDE4 isoform PDE4D5 interacts selectively with β-arrestin2, implicated in the regulation of G-protein-coupled receptors and other cell signaling components, and also with the β-propeller protein RACK1. In the present study, we use 2-hybrid approaches to demonstrate that RACK1 and β-arrestin2 inhibit the dimerization of PDE4D5. We also show that serine-to-alanine mutations at PKA and ERK1/2 phosphorylation sites on PDE4D5 detectably ablate dimerization. Conversely, phospho-mimic serine-to-aspartate mutations at the MK2 and oxidative stress kinase sites ablate dimerization. Analysis of PDE4D5 that is locked into the dimeric configuration by the formation of a trans disulfide bond between Ser261 and Ser602 shows that RACK1 interacts strongly with both the monomeric and dimeric forms, but that β-arrestin2 interacts exclusively with the monomeric form. This is consistent with the concept that β-arrestin2 can preferentially recruit the monomeric, or "open," form of PDE4D5 to β2-adrenergic receptors, where it can regulate cAMP signaling. PMID:26257302

  1. Molecular characterization of three gonadotropin subunits and their expression patterns during ovarian maturation in Cynoglossus semilaevis.

    PubMed

    Shi, Bao; Liu, Xuezhou; Xu, Yongjiang; Wang, Shanshan

    2015-01-01

    The endocrine regulation of reproduction in a multiple spawning flatfish with an ovary of asynchronous development remains largely unknown. The objectives of this study were to monitor changes in mRNA expression patterns of three gonadotropin hormone (GTH) subunits (FSHβ, LHβ and CGα) and plasma GTH levels during ovarian maturation of half-smooth tongue sole Cynoglossus semilaevis. Cloning and sequence analysis revealed that the cDNAs of FSHβ, LHβ and CGα were 541, 670 and 685 bp in length, and encode for peptides of 130, 158 and 127 amino acids, respectively. The number of cysteine residues and potential N-linked glycosylation sites of the flatfish GTHs were conserved among teleosts. However, the primary structure of GTHs in Pleuronectiformes appeared to be highly divergent. The FSHβ transcriptional level in the pituitary remained high during the vitellogenic stage while plasma levels of FSH peaked and oocyte development was stimulated. The LHβ expression in the pituitary and ovary reached the maximum level during oocyte maturation stages when the plasma levels of LH peaked. The brain GTHs were expressed at the different ovarian stages. These results suggested that FSH and LH may simultaneously regulate ovarian development and maturation through the brain-pituitary-ovary axis endocrine system in tongue sole. PMID:25633101

  2. Gonadotropin releasing hormone and brooding behavior in the native Thai hen.

    PubMed

    Chaiyachet, Orn-anong; Chokchaloemwong, Duangsuda; Prakobsaeng, Nattiya; Sartsoongnoen, Natagarn; Kosonsiriluk, Sunantha; Chaiseha, Yupaporn

    2013-07-01

    Changes in the number of hypothalamic gonadotropin releasing hormone-I (GnRH-I) neurons within the Nucleus commissurae pallii (nCPa) were associated with the reproductive cycle of native Thai chickens. In order to further understand the association of GnRH-I in the regulation of brooding behavior in this bird, the native Thai chickens were divided into two groups; chick-rearing (R) and non-chick-rearing (NR) hens. Numbers of visible of GnRH-I-immunoreactive (GnRH-I-ir) neurons in the hypothalamus of R and NR hens were compared utilizing immunohistochemistry. Numbers of visible GnRH-I-ir neurons within the Nucleus anterior medialis hypothalami, Nucleus suprachaiasmaticus, pars medialis, Nucleus septalis lateralis, Nucleus paraventricularis magnocellularis, and Regio lateralis hypothalami areas were observed in both groups, but no differences were seen between R and NR hens. The number of visible GnRH-I neurons in the nCPa was higher (P<0.05) in the NR than in R hens, and increased in NR hens by day 14 after chick removal. These findings suggest, for the first time, an association of the GnRH system with brooding behavior in continuously breeding birds. Furthermore, the expression of brooding behavior of native Thai chickens might be regulated, in part, by GnRH-I neurons in the nCPa. PMID:23466257

  3. Androgen receptor repression of gonadotropin-releasing hormone gene transcription via enhancer 1.

    PubMed

    Brayman, Melissa J; Pepa, Patricia A; Mellon, Pamela L

    2012-11-01

    Gonadotropin-releasing hormone (GnRH) plays a major role in the hypothalamic-pituitary-gonadal (HPG) axis, and synthesis and secretion of GnRH are regulated by gonadal steroid hormones. Disruptions in androgen levels are involved in a number of reproductive defects, including hypogonadotropic hypogonadism and polycystic ovarian syndrome. Androgens down-regulate GnRH mRNA synthesis in vivo and in vitro via an androgen receptor (AR)-dependent mechanism. Methyltrienolone (R1881), a synthetic AR agonist, represses GnRH expression through multiple sites in the proximal promoter. In this study, we show AR also represses GnRH transcription via the major enhancer (GnRH-E1). A multimer of the -1800/-1766 region was repressed by R1881 treatment. Mutation of two bases, -1792 and -1791, resulted in decreased basal activity and a loss of AR-mediated repression. AR bound to the -1796/-1791 sequence in electrophoretic mobility shift assays, indicating a direct interaction with DNA or other transcription factors in this region. We conclude that AR repression of GnRH-E1 acts via multiple AR-responsive regions, including the site at -1792/-1791. PMID:22877652

  4. Molecular Characterization of Three Gonadotropin Subunits and Their Expression Patterns during Ovarian Maturation in Cynoglossus semilaevis

    PubMed Central

    Shi, Bao; Liu, Xuezhou; Xu, Yongjiang; Wang, Shanshan

    2015-01-01

    The endocrine regulation of reproduction in a multiple spawning flatfish with an ovary of asynchronous development remains largely unknown. The objectives of this study were to monitor changes in mRNA expression patterns of three gonadotropin hormone (GTH) subunits (FSHβ, LHβ and CGα) and plasma GTH levels during ovarian maturation of half-smooth tongue sole Cynoglossus semilaevis. Cloning and sequence analysis revealed that the cDNAs of FSHβ, LHβ and CGα were 541, 670 and 685 bp in length, and encode for peptides of 130, 158 and 127 amino acids, respectively. The number of cysteine residues and potential N-linked glycosylation sites of the flatfish GTHs were conserved among teleosts. However, the primary structure of GTHs in Pleuronectiformes appeared to be highly divergent. The FSHβ transcriptional level in the pituitary remained high during the vitellogenic stage while plasma levels of FSH peaked and oocyte development was stimulated. The LHβ expression in the pituitary and ovary reached the maximum level during oocyte maturation stages when the plasma levels of LH peaked. The brain GTHs were expressed at the different ovarian stages. These results suggested that FSH and LH may simultaneously regulate ovarian development and maturation through the brain-pituitary-ovary axis endocrine system in tongue sole. PMID:25633101

  5. 4D Light Field Imaging System Using Programmable Aperture

    NASA Technical Reports Server (NTRS)

    Bae, Youngsam

    2012-01-01

    Complete depth information can be extracted from analyzing all angles of light rays emanated from a source. However, this angular information is lost in a typical 2D imaging system. In order to record this information, a standard stereo imaging system uses two cameras to obtain information from two view angles. Sometimes, more cameras are used to obtain information from more angles. However, a 4D light field imaging technique can achieve this multiple-camera effect through a single-lens camera. Two methods are available for this: one using a microlens array, and the other using a moving aperture. The moving-aperture method can obtain more complete stereo information. The existing literature suggests a modified liquid crystal panel [LC (liquid crystal) panel, similar to ones commonly used in the display industry] to achieve a moving aperture. However, LC panels cannot withstand harsh environments and are not qualified for spaceflight. In this regard, different hardware is proposed for the moving aperture. A digital micromirror device (DMD) will replace the liquid crystal. This will be qualified for harsh environments for the 4D light field imaging. This will enable an imager to record near-complete stereo information. The approach to building a proof-ofconcept is using existing, or slightly modified, off-the-shelf components. An SLR (single-lens reflex) lens system, which typically has a large aperture for fast imaging, will be modified. The lens system will be arranged so that DMD can be integrated. The shape of aperture will be programmed for single-viewpoint imaging, multiple-viewpoint imaging, and coded aperture imaging. The novelty lies in using a DMD instead of a LC panel to move the apertures for 4D light field imaging. The DMD uses reflecting mirrors, so any light transmission lost (which would be expected from the LC panel) will be minimal. Also, the MEMS-based DMD can withstand higher temperature and pressure fluctuation than a LC panel can. Robotics need

  6. 4D XCAT phantom for multimodality imaging research

    SciTech Connect

    Segars, W. P.; Sturgeon, G.; Mendonca, S.; Grimes, Jason; Tsui, B. M. W.

    2010-09-15

    Purpose: The authors develop the 4D extended cardiac-torso (XCAT) phantom for multimodality imaging research. Methods: Highly detailed whole-body anatomies for the adult male and female were defined in the XCAT using nonuniform rational B-spline (NURBS) and subdivision surfaces based on segmentation of the Visible Male and Female anatomical datasets from the National Library of Medicine as well as patient datasets. Using the flexibility of these surfaces, the Visible Human anatomies were transformed to match body measurements and organ volumes for a 50th percentile (height and weight) male and female. The desired body measurements for the models were obtained using the PEOPLESIZE program that contains anthropometric dimensions categorized from 1st to the 99th percentile for US adults. The desired organ volumes were determined from ICRP Publication 89 [ICRP, ''Basic anatomical and physiological data for use in radiological protection: reference values,'' ICRP Publication 89 (International Commission on Radiological Protection, New York, NY, 2002)]. The male and female anatomies serve as standard templates upon which anatomical variations may be modeled in the XCAT through user-defined parameters. Parametrized models for the cardiac and respiratory motions were also incorporated into the XCAT based on high-resolution cardiac- and respiratory-gated multislice CT data. To demonstrate the usefulness of the phantom, the authors show example simulation studies in PET, SPECT, and CT using publicly available simulation packages. Results: As demonstrated in the pilot studies, the 4D XCAT (which includes thousands of anatomical structures) can produce realistic imaging data when combined with accurate models of the imaging process. With the flexibility of the NURBS surface primitives, any number of different anatomies, cardiac or respiratory motions or patterns, and spatial resolutions can be simulated to perform imaging research. Conclusions: With the ability to produce

  7. 4D XCAT phantom for multimodality imaging research

    PubMed Central

    Segars, W. P.; Sturgeon, G.; Mendonca, S.; Grimes, Jason; Tsui, B. M. W.

    2010-01-01

    Purpose: The authors develop the 4D extended cardiac-torso (XCAT) phantom for multimodality imaging research. Methods: Highly detailed whole-body anatomies for the adult male and female were defined in the XCAT using nonuniform rational B-spline (NURBS) and subdivision surfaces based on segmentation of the Visible Male and Female anatomical datasets from the National Library of Medicine as well as patient datasets. Using the flexibility of these surfaces, the Visible Human anatomies were transformed to match body measurements and organ volumes for a 50th percentile (height and weight) male and female. The desired body measurements for the models were obtained using the PEOPLESIZE program that contains anthropometric dimensions categorized from 1st to the 99th percentile for US adults. The desired organ volumes were determined from ICRP Publication 89 [ICRP, ‘‘Basic anatomical and physiological data for use in radiological protection: reference values,” ICRP Publication 89 (International Commission on Radiological Protection, New York, NY, 2002)]. The male and female anatomies serve as standard templates upon which anatomical variations may be modeled in the XCAT through user-defined parameters. Parametrized models for the cardiac and respiratory motions were also incorporated into the XCAT based on high-resolution cardiac- and respiratory-gated multislice CT data. To demonstrate the usefulness of the phantom, the authors show example simulation studies in PET, SPECT, and CT using publicly available simulation packages. Results: As demonstrated in the pilot studies, the 4D XCAT (which includes thousands of anatomical structures) can produce realistic imaging data when combined with accurate models of the imaging process. With the flexibility of the NURBS surface primitives, any number of different anatomies, cardiac or respiratory motions or patterns, and spatial resolutions can be simulated to perform imaging research. Conclusions: With the ability to produce

  8. Profiles of gonadotropin-inhibitory hormone and melatonin during the sex change and maturation of cinnamon clownfish, Amphiprion melanopus.

    PubMed

    Choi, Young Jae; Habibi, Hamid R; Choi, Cheol Young

    2016-06-24

    The present study aimed to determine the relationship between melatonin and gonadotropin-inhibitory hormone (GnIH) and their effect on reproduction in cinnamon clownfish, Amphiprion melanopus. Accordingly, we investigated the expression pattern of GnIH, GnIH receptor (GnIH-R), and melatonin receptor (MT-R1) mRNA and protein, as well as the plasma levels of melatonin, during sex change in cinnamon clownfish. We found that GnIH and MT-R1 mRNA and melatonin activity were higher in fish with mature brain than in fish with developing gonads, and using double immunofluorescence staining, we found that both GnIH and MT-R1 proteins were co-expressed in the hypothalamus of cinnamon clownfish. These findings support the hypothesis that melatonin plays an important role in the negative regulation of maturation and GnIH regulation during reproduction. PMID:27208779

  9. Neurotrophic effect of gonadotropin-releasing hormone on neurite extension and neuronal migration of embryonic gonadotropin-releasing hormone neurons in chick olfactory nerve bundle culture.

    PubMed

    Kanaho, Yoh-Ichiro; Enomoto, Masahiro; Endo, Daisuke; Maehiro, Sayaka; Park, Min Kyun; Murakami, Shizuko

    2009-08-01

    Hypothalamic gonadotropin-releasing hormone (GnRH) neurons play a pivotal role in regulating the reproductive function of vertebrates. These neurons are known to originate in the olfactory placode and migrate along olfactory-related axons to reach the forebrain during embryonic development. Although GnRH is suggested to be secreted during such migration, its physiological significance is unknown. This point is difficult to explore in vivo because recent studies suggest that GnRH is an important factor for normal brain development and that modification of the embryonic GnRH system by exogenous GnRH analogue or genetic methods would result in dysgenesis of the brain. Therefore, to study the role of GnRH in the migratory process of GnRH neurons, we established an in vitro chick embryonic olfactory nerve bundle explant model. Embryonic day 7.5-8 olfactory nerve bundles were cultured in a mixture of Matrigel and collagen gel. At day 3 of culture, GnRH neurons extended their unbranched neurites and migrated out from both edges of the explant. The nature of neurite extension and migratory behavior of GnRH neurons was well maintained in the gel containing 25% Matrigel and 50% collagen. With this culture system, we examined the effect of GnRH on the migrating GnRH neurons. Cetrorelix, a GnRH antagonist, was found to inhibit significantly neurite growth and neuronal migration of GnRH neurons, the effects of which were repressed by the addition of chicken GnRH-I. These results suggest that GnRH functions as one of the regulating factors of GnRH neuronal development by promoting neurite extension and neuronal migration. PMID:19301422

  10. Mapping motion from 4D-MRI to 3D-CT for use in 4D dose calculations: A technical feasibility study

    SciTech Connect

    Boye, Dirk; Lomax, Tony; Knopf, Antje

    2013-06-15

    Purpose: Target sites affected by organ motion require a time resolved (4D) dose calculation. Typical 4D dose calculations use 4D-CT as a basis. Unfortunately, 4D-CT images have the disadvantage of being a 'snap-shot' of the motion during acquisition and of assuming regularity of breathing. In addition, 4D-CT acquisitions involve a substantial additional dose burden to the patient making many, repeated 4D-CT acquisitions undesirable. Here the authors test the feasibility of an alternative approach to generate patient specific 4D-CT data sets. Methods: In this approach motion information is extracted from 4D-MRI. Simulated 4D-CT data sets [which the authors call 4D-CT(MRI)] are created by warping extracted deformation fields to a static 3D-CT data set. The employment of 4D-MRI sequences for this has the advantage that no assumptions on breathing regularity are made, irregularities in breathing can be studied and, if necessary, many repeat imaging studies (and consequently simulated 4D-CT data sets) can be performed on patients and/or volunteers. The accuracy of 4D-CT(MRI)s has been validated by 4D proton dose calculations. Our 4D dose algorithm takes into account displacements as well as deformations on the originating 4D-CT/4D-CT(MRI) by calculating the dose of each pencil beam based on an individual time stamp of when that pencil beam is applied. According to corresponding displacement and density-variation-maps the position and the water equivalent range of the dose grid points is adjusted at each time instance. Results: 4D dose distributions, using 4D-CT(MRI) data sets as input were compared to results based on a reference conventional 4D-CT data set capturing similar motion characteristics. Almost identical 4D dose distributions could be achieved, even though scanned proton beams are very sensitive to small differences in the patient geometry. In addition, 4D dose calculations have been performed on the same patient, but using 4D-CT(MRI) data sets based on

  11. Assessing Gonadotropin Receptor Function by Resonance Energy Transfer-Based Assays.

    PubMed

    Ayoub, Mohammed Akli; Landomiel, Flavie; Gallay, Nathalie; Jégot, Gwenhael; Poupon, Anne; Crépieux, Pascale; Reiter, Eric

    2015-01-01

    Gonadotropin receptors belong to the super family of G protein-coupled receptors and mediate the physiological effects of follicle-stimulating hormone (FSHR) and luteinizing hormone (LHR). Their central role in the control of reproductive function has made them the focus of intensive studies. Upon binding to their cognate hormone, they trigger complex signaling and trafficking mechanisms that are tightly regulated in concentration, time, and space. Classical cellular assays often fail to capture all these dynamics. Here, we describe the use of various bioluminescence and fluorescence resonance energy transfer (BRET and FRET) assays to investigate the activation and regulation of FSHR and LHR in real-time, in living cells (i.e., transiently expressed in human embryonic kidney 293 cells). Indeed, the dynamics of hormone-mediated heterotrimeric G protein activation, cyclic adenosine-monophosphate (cAMP) production, calcium release, β-arrestin 2 recruitment, and receptor internalization/recycling was assessed. Kinetics and dose-response analyses confirmed the expected pharmacological and signaling properties of hFSHR and hLHR but revealed interesting characteristics when considering the two major pathways (cAMP and β-arrestin 2) of the two receptors assessed by BRET. Indeed, the EC50 values were in picomolar range for cAMP production while nanomolar range was observed for β-arrestin 2 recruitment as well as receptor internalization. Interestingly, the predicted receptor occupancy indicates that the maximal G protein activation and cAMP response occur at <10% of receptor occupancy whereas >90% of activated receptors is required to achieve full β-arrestin 2 recruitment and subsequent receptor internalization. The rapid receptor internalization was also followed by a recycling phase. Collectively, our data reveal that β-arrestin-mediated desensitization, internalization, and the subsequent fast recycling of receptors at the plasma membrane may provide a mechanistic

  12. Assessing Gonadotropin Receptor Function by Resonance Energy Transfer-Based Assays

    PubMed Central

    Ayoub, Mohammed Akli; Landomiel, Flavie; Gallay, Nathalie; Jégot, Gwenhael; Poupon, Anne; Crépieux, Pascale; Reiter, Eric

    2015-01-01

    Gonadotropin receptors belong to the super family of G protein-coupled receptors and mediate the physiological effects of follicle-stimulating hormone (FSHR) and luteinizing hormone (LHR). Their central role in the control of reproductive function has made them the focus of intensive studies. Upon binding to their cognate hormone, they trigger complex signaling and trafficking mechanisms that are tightly regulated in concentration, time, and space. Classical cellular assays often fail to capture all these dynamics. Here, we describe the use of various bioluminescence and fluorescence resonance energy transfer (BRET and FRET) assays to investigate the activation and regulation of FSHR and LHR in real-time, in living cells (i.e., transiently expressed in human embryonic kidney 293 cells). Indeed, the dynamics of hormone-mediated heterotrimeric G protein activation, cyclic adenosine-monophosphate (cAMP) production, calcium release, β-arrestin 2 recruitment, and receptor internalization/recycling was assessed. Kinetics and dose–response analyses confirmed the expected pharmacological and signaling properties of hFSHR and hLHR but revealed interesting characteristics when considering the two major pathways (cAMP and β-arrestin 2) of the two receptors assessed by BRET. Indeed, the EC50 values were in picomolar range for cAMP production while nanomolar range was observed for β-arrestin 2 recruitment as well as receptor internalization. Interestingly, the predicted receptor occupancy indicates that the maximal G protein activation and cAMP response occur at <10% of receptor occupancy whereas >90% of activated receptors is required to achieve full β-arrestin 2 recruitment and subsequent receptor internalization. The rapid receptor internalization was also followed by a recycling phase. Collectively, our data reveal that β-arrestin-mediated desensitization, internalization, and the subsequent fast recycling of receptors at the plasma membrane may provide a mechanistic

  13. 4D prediction of protein (1)H chemical shifts.

    PubMed

    Lehtivarjo, Juuso; Hassinen, Tommi; Korhonen, Samuli-Petrus; Peräkylä, Mikael; Laatikainen, Reino

    2009-12-01

    A 4D approach for protein (1)H chemical shift prediction was explored. The 4th dimension is the molecular flexibility, mapped using molecular dynamics simulations. The chemical shifts were predicted with a principal component model based on atom coordinates from a database of 40 protein structures. When compared to the corresponding non-dynamic (3D) model, the 4th dimension improved prediction by 6-7%. The prediction method achieved RMS errors of 0.29 and 0.50 ppm for Halpha and HN shifts, respectively. However, for individual proteins the RMS errors were 0.17-0.34 and 0.34-0.65 ppm for the Halpha and HN shifts, respectively. X-ray structures gave better predictions than the corresponding NMR structures, indicating that chemical shifts contain invaluable information about local structures. The (1)H chemical shift prediction tool 4DSPOT is available from http://www.uku.fi/kemia/4dspot . PMID:19876601

  14. Chaos in a 4D dissipative nonlinear fermionic model

    NASA Astrophysics Data System (ADS)

    Aydogmus, Fatma

    2015-12-01

    Gursey Model is the only possible 4D conformally invariant pure fermionic model with a nonlinear self-coupled spinor term. It has been assumed to be similar to the Heisenberg's nonlinear generalization of Dirac's equation, as a possible basis for a unitary description of elementary particles. Gursey Model admits particle-like solutions for the derived classical field equations and these solutions are instantonic in character. In this paper, the dynamical nature of damped and forced Gursey Nonlinear Differential Equations System (GNDES) are studied in order to get more information on spinor type instantons. Bifurcation and chaos in the system are observed by constructing the bifurcation diagrams and Poincaré sections. Lyapunov exponent and power spectrum graphs of GNDES are also constructed to characterize the chaotic behavior.

  15. Data representation and visualization in 4-D microscopy

    NASA Astrophysics Data System (ADS)

    Kriete, Andres; Rohrbach, Steffen; Schwebel, Tim; Wagner, Hans-Joachim; Behrens, Uwe

    1992-09-01

    Computer representation in biological microscopy is progressing from the well established modeling of three-dimensional (3-D) structural information towards the visualization of spatio- temporal (4-D) information. This paper describes two new methods to process sequential volumes, where each data set corresponds to a time sample. The first technique is based on surface rendering to study organ and tissue development. Contour stacks are rendered and in- between stages are interpolated. This technique allows the analysis and simulation of growth following different mathematical models and relates them with experimental findings. The second technique got appreciation for volume rendering of morphogenesis in living tissue. Sequences scanned with a confocal microscope are packed. The combination of ray-casting reconstructions within a color model allows for a rendering of morphogenetic activity.

  16. 4D Script N = 2 supergravity and projective superspace

    NASA Astrophysics Data System (ADS)

    Kuzenko, S. M.; Lindström, U.; Rocek, M.; Tartaglino-Mazzucchelli, G.

    2008-09-01

    This paper presents a projective superspace formulation for 4D Script N = 2 matter-coupled supergravity. We first describe a variant superspace realization for the Script N = 2 Weyl multiplet. It differs from that proposed by Howe in 1982 by the choice of the structure group (SO(3,1) × SU(2) versus SO(3,1) × U(2)), which implies that the super-Weyl transformations are generated by a covariantly chiral parameter instead of a real unconstrained one. We introduce various off-shell supermultiplets which are curved superspace analogues of the superconformal projective multiplets in global supersymmetry and which describe matter fields coupled to supergravity. A manifestly locally supersymmetric and super-Weyl invariant action principle is given. Off-shell locally supersymmetric nonlinear sigma models are presented in this new superspace.

  17. Mechanical properties of 4d transition metals in molten state

    NASA Astrophysics Data System (ADS)

    Singh, Deobrat; Sonvane, Yogesh; Thakor, P. B.

    2016-05-01

    Mechanical properties of 4d transition metals in molten state have been studied in the present study. We have calculated mechanical properties such as isothermal bulk modulus (B), modulus of rigidity (G), Young's modulus (Y) and Hardness have also been calculated from the elastic part of the Phonon dispersion curve (PDC). To describe the structural information, we have used different structure factor S(q) using Percus-Yevick hard sphere (PYHS) reference systems along with our newly constructed parameter free model potential.To see the influence of exchange and correlation effect on the above said properties of 3d liquid transition metals, we have used Sarkar et al (S)local field correction functions. Present results have been found good in agreement with available experimental data.

  18. Immersive 4-D Interactive Visualization of Large-Scale Simulations

    NASA Astrophysics Data System (ADS)

    Teuben, P. J.; Hut, P.; Levy, S.; Makino, J.; McMillan, S.; Portegies Zwart, S.; Shara, M.; Emmart, C.

    In dense clusters a bewildering variety of interactions between stars can be observed, ranging from simple encounters to collisions and other mass-transfer encounters. With faster and special-purpose computers like GRAPE, the amount of data per simulation is now exceeding 1 TB. Visualization of such data has now become a complex 4-D data-mining problem, combining space and time, and finding interesting events in these large datasets. We have recently starting using the virtual reality simulator, installed in the Hayden Planetarium in the American Museum for Natural History, to tackle some of these problem. This work reports on our first ``observations,'' modifications needed for our specific experiments, and perhaps field ideas for other fields in science which can benefit from such immersion. We also discuss how our normal analysis programs can be interfaced with this kind of visualization.

  19. Parallel Wavefront Analysis for a 4D Interferometer

    NASA Technical Reports Server (NTRS)

    Rao, Shanti R.

    2011-01-01

    This software provides a programming interface for automating data collection with a PhaseCam interferometer from 4D Technology, and distributing the image-processing algorithm across a cluster of general-purpose computers. Multiple instances of 4Sight (4D Technology s proprietary software) run on a networked cluster of computers. Each connects to a single server (the controller) and waits for instructions. The controller directs the interferometer to several images, then assigns each image to a different computer for processing. When the image processing is finished, the server directs one of the computers to collate and combine the processed images, saving the resulting measurement in a file on a disk. The available software captures approximately 100 images and analyzes them immediately. This software separates the capture and analysis processes, so that analysis can be done at a different time and faster by running the algorithm in parallel across several processors. The PhaseCam family of interferometers can measure an optical system in milliseconds, but it takes many seconds to process the data so that it is usable. In characterizing an adaptive optics system, like the next generation of astronomical observatories, thousands of measurements are required, and the processing time quickly becomes excessive. A programming interface distributes data processing for a PhaseCam interferometer across a Windows computing cluster. A scriptable controller program coordinates data acquisition from the interferometer, storage on networked hard disks, and parallel processing. Idle time of the interferometer is minimized. This architecture is implemented in Python and JavaScript, and may be altered to fit a customer s needs.

  20. Gonadotropin-Releasing Hormone Agonist Therapy and Obesity in Girls

    PubMed Central

    Shiasi Arani, Kobra; Heidari, Fatemeh

    2015-01-01

    Background: Depot preparations of gonadotropin-releasing hormone agonists (GnRHa) are the gold standard drugs for the treatment of central precocious puberty. A concern about these drugs is obesity. Objectives: This study aimed to investigate the effect of gonadotropin-releasing hormone agonists (GnRHa) therapy on body mass index (BMI) in girls with central precocious puberty (CPP). Patients and Methods: The girls with onset of puberty before eight years of age or menarche before nine years of age were studied. The weight, height, BMI, and pubertal stage were determined before and at sixth and 12th months of treatment. The GnRHa (Triptorelin) was administered intramuscularly for patients with rapidly progressive forms of CPP. Patients with slowly progressive forms of CPP were considered as control group. Results: From 110 subjects with CPP, 46 girls (41.8%) were considered as intervention and 64 (58.2%) as control groups. The mean age at initial visit was 7.46 ± 1.03 years. The BMI standard deviation scores in both groups was not significantly different at sixth and 12th months of treatment compared with baseline (P = 0.257 and P = 0.839, respectively). The prevalence of obesity was not significantly different between study groups at baseline and at and sixth and 12th months of therapy (P = 0.11, P = 0.068, and P = 0.052, respectively). Conclusions: The GnRHa therapy has no effect on BMI and the prevalence of obesity. PMID:26401141

  1. Gonadotropin-releasing hormone agonist-induced pituitary apoplexy

    PubMed Central

    Keane, Fergus; Navin, Patrick; Brett, Francesca; Dennedy, Michael C

    2016-01-01

    Summary Pituitary apoplexy represents an uncommon endocrine emergency with potentially life-threatening consequences. Drug-induced pituitary apoplexy is a rare but important consideration when evaluating patients with this presentation. We describe an unusual case of a patient with a known pituitary macroadenoma presenting with acute-onset third nerve palsy and headache secondary to tumour enlargement and apoplexy. This followed gonadotropin-releasing hormone (GNRH) agonist therapy used to treat metastatic prostate carcinoma. Following acute management, the patient underwent transphenoidal debulking of his pituitary gland with resolution of his third nerve palsy. Subsequent retrospective data interpretation revealed that this had been a secretory gonadotropinoma and GNRH agonist therapy resulted in raised gonadotropins and testosterone. Hence, further management of his prostate carcinoma required GNRH antagonist therapy and external beam radiotherapy. This case demonstrates an uncommon complication of GNRH agonist therapy in the setting of a pituitary macroadenoma. It also highlights the importance of careful, serial data interpretation in patients with pituitary adenomas. Finally, this case presents a unique insight into the challenges of managing a hormonal-dependent prostate cancer in a patient with a secretory pituitary tumour. Learning points While non-functioning gonadotropinomas represent the most common form of pituitary macroadenoma, functioning gonadotropinomas are exceedingly rare. Acute tumour enlargement, with potential pituitary apoplexy, is a rare but important adverse effect arising from GNRH agonist therapy in the presence of both functioning and non-functioning pituitary gonadotropinomas. GNRH antagonist therapy represents an alternative treatment option for patients with hormonal therapy-requiring prostate cancer, who also have diagnosed with a pituitary gonadotropinoma. PMID:27284452

  2. Oocyte and cumulus cell transcripts from cultured mouse follicles are induced to deviate from normal in vivo conditions by combinations of insulin, follicle-stimulating hormone, and human chorionic gonadotropin.

    PubMed

    Sánchez, Flor; Romero, Sergio; Smitz, Johan

    2011-09-01

    Gonadotropins and insulin are major regulators of cell proliferation, differentiation, and survival in cultured mouse ovarian follicles. Applications of variable doses of insulin in combination with follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were studied at the gene expression level in oocytes and cumulus cells. Early preantral follicles grown over 9 days were sequentially exposed to combinations of doses of insulin, FSH, and human chorionic gonadotropin (hCG). From culture Day 1 to 6 (preantral stage), two insulin concentrations (5 ng/ml and 5 μg/ml) were combined with 10 mIU/ml FSH. From Days 6 to 9 (antral stage), the three variable gonadotropin treatments set under each insulin condition were 10 mIU/ml FSH, 25 mIU/ml FSH, and 25 mIU/ml FSH plus 3 mIU/ml hCG. The Gdf9, Bmp15, Fgf8, Dazl, Pou5f1, and Pik3ca mRNA transcripts were quantified in oocytes, and the Amh, Lhcgr, Hsd3b1, Vegfa, and Insig1 mRNA transcripts were quantified in cumulus cells. In vivo controls were unprimed and eCG (equine chorionic gonadotropin)-primed prepubertal female mice. During the preantral stage, none except the Amh transcripts was regulated by insulin. Oocyte transcripts were not affected by the variable gonadotropin treatments on the last culture day but were upregulated in the combination of high insulin plus 25 mIU/ml FSH. Under low insulin conditions, high FSH levels increased levels of Lhcgr and Vegfa expression, and hCG abated this effect. However, under high insulin conditions, hCG upregulated levels of Lhcgr, Vegfa, and Insig1 mRNA. High insulin concentrations upregulated Hsd3b1 transcripts. These results demonstrate that in an in vitro follicle culture, a near physiological insulin background yields oocyte and cumulus cell transcript levels that are more similar to those in vivo. PMID:21565993

  3. 4D Dynamic RNP Annual Interim Report-Year 1

    NASA Technical Reports Server (NTRS)

    Finkelsztein, Daniel M.; Sturdy, James L.; Alaverdi, Omeed; Chung, William W.; Salvano, Daniel; Klooster, Joel; Hochwarth, Joachim K.

    2010-01-01

    This Annual Interim Report summarizes the activities led by Raytheon, in collaboration with GE Aviation and SAIC, and presents the results obtained during the first year of this research effort to expand the RNP concept to 4 dimensions relative to a dynamic frame of reference. Joint Program Development Office (JPDO)Concepts of Operations for the Next Generation Air Transportation System (NextGen) considers 4 Dimension Trajectory (4DT) procedures a key enabler to Trajectory Based Operations (TBO). The JPDO defines 4DT as a precise description of an aircraft path in space and time . While NextGen assumes that this path is defined within an Earth-reference frame, many 4DT procedure implementations will require an aircraft to precisely navigate relative to a moving reference such as another aircraft to form aggregate flows or a weather cell to allow for flows to shift. Current methods of implementing routes and flight paths rely on aircraft meeting a Required Navigation Performance (RNP) specification and being equipped with a monitoring and alerting capability to annunciate when the aircraft system is unable to meet the performance specification required for the operation. Since all aircraft today operate within the NAS relative to fixed reference points, the current RNP definition is deemed satisfactory. However, it is not well understood how the current RNP construct will support NextGen 4DT procedures where aircraft operate relative to each other or to other dynamic frames of reference. The objective of this research effort is to analyze candidate 4DT procedures from both an Air Navigation Service Provider (ANSP) and aircraft perspective, to identify their specific navigational requirements, assess the shortcomings of the current RNP construct to meet these requirements, to propose an extended 4 Dimensional Dynamic RNP (4D Dynamic RNP) construct that accounts for the dynamic spatial and temporal nature of the selected 4DT procedures, and finally, to design an

  4. 4D multiple-cathode ultrafast electron microscopy

    PubMed Central

    Baskin, John Spencer; Liu, Haihua; Zewail, Ahmed H.

    2014-01-01

    Four-dimensional multiple-cathode ultrafast electron microscopy is developed to enable the capture of multiple images at ultrashort time intervals for a single microscopic dynamic process. The dynamic process is initiated in the specimen by one femtosecond light pulse and probed by multiple packets of electrons generated by one UV laser pulse impinging on multiple, spatially distinct, cathode surfaces. Each packet is distinctly recorded, with timing and detector location controlled by the cathode configuration. In the first demonstration, two packets of electrons on each image frame (of the CCD) probe different times, separated by 19 picoseconds, in the evolution of the diffraction of a gold film following femtosecond heating. Future elaborations of this concept to extend its capabilities and expand the range of applications of 4D ultrafast electron microscopy are discussed. The proof-of-principle demonstration reported here provides a path toward the imaging of irreversible ultrafast phenomena of materials, and opens the door to studies involving the single-frame capture of ultrafast dynamics using single-pump/multiple-probe, embedded stroboscopic imaging. PMID:25006261

  5. Reduced order POD/DEIM 4-D Var data assimilation

    NASA Astrophysics Data System (ADS)

    Navon, Michael; Stefanescu, Razvan

    2014-05-01

    The computational cost of realistic ensemble and hybrid variational/ensemble data assimilation is typically dominated by the cost of ensemble forecasting. The high computational cost of ensemble forecasting limits the number of ensembles, eventually creating a severe rank reduction. Consequently, the efficiency and quality of ensemble-based data assimilation are greatly reduced. With the ever-increasing spatiotemporal resolution and complexity of numerical weather prediction (NWP) models, the room for ensemble forecasting is getting even smaller, creating a paradox: Although the NWP generally benefits from increased resolution and complexity of the models, the quality of their data assimilation is getting worse due to additional computational restrictions. We propose POD model order reduction substantially improving computational efficiency of NWP models. We present recent advances in this domain and the state-of the art of hyper reduction addressing issues of turbulence closure and nonlinearities allowing CPU speed -ups of orders of magnitude, reduced order 4-D VAR and future prospects of implementation to operational NMP models.

  6. Multimaterial 4D Printing with Tailorable Shape Memory Polymers

    PubMed Central

    Ge, Qi; Sakhaei, Amir Hosein; Lee, Howon; Dunn, Conner K.; Fang, Nicholas X.; Dunn, Martin L.

    2016-01-01

    We present a new 4D printing approach that can create high resolution (up to a few microns), multimaterial shape memory polymer (SMP) architectures. The approach is based on high resolution projection microstereolithography (PμSL) and uses a family of photo-curable methacrylate based copolymer networks. We designed the constituents and compositions to exhibit desired thermomechanical behavior (including rubbery modulus, glass transition temperature and failure strain which is more than 300% and larger than any existing printable materials) to enable controlled shape memory behavior. We used a high resolution, high contrast digital micro display to ensure high resolution of photo-curing methacrylate based SMPs that requires higher exposure energy than more common acrylate based polymers. An automated material exchange process enables the manufacture of 3D composite architectures from multiple photo-curable SMPs. In order to understand the behavior of the 3D composite microarchitectures, we carry out high fidelity computational simulations of their complex nonlinear, time-dependent behavior and study important design considerations including local deformation, shape fixity and free recovery rate. Simulations are in good agreement with experiments for a series of single and multimaterial components and can be used to facilitate the design of SMP 3D structures. PMID:27499417

  7. 4D MRI of renal function in the developing mouse

    PubMed Central

    Xie, Luke; Subashi, Ergys; Qi, Yi; Knepper, Mark A.; Johnson, G. Allan

    2014-01-01

    The major roles of filtration, metabolism, and high blood flow make the kidney highly vulnerable to drug-induced toxicity and other renal injuries. A method to follow kidney function is essential for early screening of toxicity and malformations. In this study, we acquired high spatiotemporal resolution (4D) datasets of normal mice to follow changes in kidney structure and function during development. The data were acquired with dynamic contrast-enhanced MRI (via keyhole imaging) and a cryogenic surface coil, allowing us to obtain a full 3D image (125-micron isotropic resolution) every 7.7 seconds over a 50-minute scan. This time course permitted demonstration of both contrast enhancement and clearance. Functional changes were measured over a 17-week course (at 3, 5, 7, 9, 13, and 17 weeks). The time dimension of the MRI dataset was processed to produce unique image contrasts for segmenting the 4 regions of the kidney: cortex (CO), outer stripe (OS) of the outer medulla (OM), inner stripe (IS) of the OM, and inner medulla (IM). Local volumes, time-to-peak (TTP) values, and decay constants (DC) were measured in each renal region. These metrics increased significantly with age, with the exception of DC values in the IS and OS. These data will serve as a foundation for studies of normal renal physiology and future studies of renal diseases that require early detection and intervention. PMID:25066408

  8. Multimaterial 4D Printing with Tailorable Shape Memory Polymers

    NASA Astrophysics Data System (ADS)

    Ge, Qi; Sakhaei, Amir Hosein; Lee, Howon; Dunn, Conner K.; Fang, Nicholas X.; Dunn, Martin L.

    2016-08-01

    We present a new 4D printing approach that can create high resolution (up to a few microns), multimaterial shape memory polymer (SMP) architectures. The approach is based on high resolution projection microstereolithography (PμSL) and uses a family of photo-curable methacrylate based copolymer networks. We designed the constituents and compositions to exhibit desired thermomechanical behavior (including rubbery modulus, glass transition temperature and failure strain which is more than 300% and larger than any existing printable materials) to enable controlled shape memory behavior. We used a high resolution, high contrast digital micro display to ensure high resolution of photo-curing methacrylate based SMPs that requires higher exposure energy than more common acrylate based polymers. An automated material exchange process enables the manufacture of 3D composite architectures from multiple photo-curable SMPs. In order to understand the behavior of the 3D composite microarchitectures, we carry out high fidelity computational simulations of their complex nonlinear, time-dependent behavior and study important design considerations including local deformation, shape fixity and free recovery rate. Simulations are in good agreement with experiments for a series of single and multimaterial components and can be used to facilitate the design of SMP 3D structures.

  9. "4D Biology for health and disease" workshop report.

    PubMed

    Abrahams, Jan-Pieter; Apweiler, Rolf; Balling, Rudi; Bertero, Michela G; Bujnicki, Janusz M; Chayen, Naomi E; Chène, Patrick; Corthals, Gary L; Dyląg, Tomasz; Förster, Friedrich; Heck, Albert J R; Henderson, Peter J F; Herwig, Ralf; Jehenson, Philippe; Kokalj, Sasa Jenko; Laue, Ernest; Legrain, Pierre; Martens, Lennart; Migliorini, Cristiano; Musacchio, Andrea; Podobnik, Marjetka; Schertler, Gebhard F X; Schreiber, Gideon; Sixma, Titia K; Smit, August B; Stuart, David; Svergun, Dmitri I; Taussig, Michael J

    2011-07-01

    The "4D Biology Workshop for Health and Disease", held on 16-17th of March 2010 in Brussels, aimed at finding the best organising principles for large-scale proteomics, interactomics and structural genomics/biology initiatives, and setting the vision for future high-throughput research and large-scale data gathering in biological and medical science. Major conclusions of the workshop include the following. (i) Development of new technologies and approaches to data analysis is crucial. Biophysical methods should be developed that span a broad range of time/spatial resolution and characterise structures and kinetics of interactions. Mathematics, physics, computational and engineering tools need to be used more in biology and new tools need to be developed. (ii) Database efforts need to focus on improved definitions of ontologies and standards so that system-scale data and associated metadata can be understood and shared efficiently. (iii) Research infrastructures should play a key role in fostering multidisciplinary research, maximising knowledge exchange between disciplines and facilitating access to diverse technologies. (iv) Understanding disease on a molecular level is crucial. System approaches may represent a new paradigm in the search for biomarkers and new targets in human disease. (v) Appropriate education and training should be provided to help efficient exchange of knowledge between theoreticians, experimental biologists and clinicians. These conclusions provide a strong basis for creating major possibilities in advancing research and clinical applications towards personalised medicine. PMID:20951846

  10. Analytical and numerical manifolds in a symplectic 4-D map

    NASA Astrophysics Data System (ADS)

    Delis, N.; Contopoulos, G.

    2016-05-01

    We study analytically the orbits along the asymptotic manifolds from a complex unstable periodic orbit in a symplectic 4-D Froeschlé map. The orbits are given as convergent series. We compare the analytic results by truncating the series at various orders with the corresponding numerical results and we find agreement along a more extended length, as the order of truncation increases. The agreement is improved when the parameters approach those of the stability domain. Along the manifolds no terms with small divisors appear in the series. The same result is found if we use a parametrization method along the asymptotic curves. In the case of orbits starting close to the manifolds small divisors appear, but the orbits remain close to the manifolds for an extended period of time. If the parameters of the map are close to the stable domain the orbits recede and approach the origin several times and remain confined in a certain volume around the origin for a long time before escaping to large distances. For special sets of parameters we see resonance phenomena and the orbits take particular forms near every resonance.

  11. Multimaterial 4D Printing with Tailorable Shape Memory Polymers.

    PubMed

    Ge, Qi; Sakhaei, Amir Hosein; Lee, Howon; Dunn, Conner K; Fang, Nicholas X; Dunn, Martin L

    2016-01-01

    We present a new 4D printing approach that can create high resolution (up to a few microns), multimaterial shape memory polymer (SMP) architectures. The approach is based on high resolution projection microstereolithography (PμSL) and uses a family of photo-curable methacrylate based copolymer networks. We designed the constituents and compositions to exhibit desired thermomechanical behavior (including rubbery modulus, glass transition temperature and failure strain which is more than 300% and larger than any existing printable materials) to enable controlled shape memory behavior. We used a high resolution, high contrast digital micro display to ensure high resolution of photo-curing methacrylate based SMPs that requires higher exposure energy than more common acrylate based polymers. An automated material exchange process enables the manufacture of 3D composite architectures from multiple photo-curable SMPs. In order to understand the behavior of the 3D composite microarchitectures, we carry out high fidelity computational simulations of their complex nonlinear, time-dependent behavior and study important design considerations including local deformation, shape fixity and free recovery rate. Simulations are in good agreement with experiments for a series of single and multimaterial components and can be used to facilitate the design of SMP 3D structures. PMID:27499417

  12. Insight into water molecules bonding on 4d metal surfaces

    NASA Astrophysics Data System (ADS)

    Carrasco, Javier; Michaelides, Angelos; Scheffler, Matthias

    2008-03-01

    Water-metal interactions are of capital importance to a wide variety of phenomena in materials science, catalysis, corrosion, electrochemistry, etc. Here we address the nature of the bond between water molecules and metal surfaces through a careful systematic study. Specifically, the bonding of isolated water molecules to a series of close-packed transition metal surfaces - Ru(0001), Rh(111), Pd(111) and Ag(111) - has been examined in detail with density functional theory (DFT). Aiming to understand the origin behind energetic and structural trends along the 4d series we employ a range of analysis tools, such as decomposition of the density of states, electron density differences, electronic reactivity function and inspection of individual Kohn-Sham orbitals. The results obtained allow us to rationalize the bonding between water and transition metal surfaces as a balance of covalent and electrostatic interactions. A frontier orbital scheme based on so-called two-center four-electron interactions between molecular orbitals of water and d band states of the surface proves incisive in understanding these systems.

  13. Estimating Myocardial Motion by 4D Image Warping

    PubMed Central

    Sundar, Hari; Litt, Harold; Shen, Dinggang

    2009-01-01

    A method for spatio-temporally smooth and consistent estimation of cardiac motion from MR cine sequences is proposed. Myocardial motion is estimated within a 4-dimensional (4D) registration framework, in which all 3D images obtained at different cardiac phases are simultaneously registered. This facilitates spatio-temporally consistent estimation of motion as opposed to other registration-based algorithms which estimate the motion by sequentially registering one frame to another. To facilitate image matching, an attribute vector (AV) is constructed for each point in the image, and is intended to serve as a “morphological signature” of that point. The AV includes intensity, boundary, and geometric moment invariants (GMIs). Hierarchical registration of two image sequences is achieved by using the most distinctive points for initial registration of two sequences and gradually adding less-distinctive points to refine the registration. Experimental results on real data demonstrate good performance of the proposed method for cardiac image registration and motion estimation. The motion estimation is validated via comparisons with motion estimates obtained from MR images with myocardial tagging. PMID:20379351

  14. Temporally coherent 4D video segmentation for teleconferencing

    NASA Astrophysics Data System (ADS)

    Ehmann, Jana; Guleryuz, Onur G.

    2013-09-01

    We develop an algorithm for 4-D (RGB+Depth) video segmentation targeting immersive teleconferencing ap- plications on emerging mobile devices. Our algorithm extracts users from their environments and places them onto virtual backgrounds similar to green-screening. The virtual backgrounds increase immersion and interac- tivity, relieving the users of the system from distractions caused by disparate environments. Commodity depth sensors, while providing useful information for segmentation, result in noisy depth maps with a large number of missing depth values. By combining depth and RGB information, our work signi¯cantly improves the other- wise very coarse segmentation. Further imposing temporal coherence yields compositions where the foregrounds seamlessly blend with the virtual backgrounds with minimal °icker and other artifacts. We achieve said improve- ments by correcting the missing information in depth maps before fast RGB-based segmentation, which operates in conjunction with temporal coherence. Simulation results indicate the e±cacy of the proposed system in video conferencing scenarios.

  15. 2,4-D and IAA Amino Acid Conjugates Show Distinct Metabolism in Arabidopsis

    PubMed Central

    Eyer, Luděk; Vain, Thomas; Pařízková, Barbora; Oklestkova, Jana; Barbez, Elke; Kozubíková, Hana; Pospíšil, Tomáš; Wierzbicka, Roksana; Kleine-Vehn, Jürgen; Fránek, Milan; Strnad, Miroslav; Robert, Stéphanie

    2016-01-01

    The herbicide 2,4-D exhibits an auxinic activity and therefore can be used as a synthetic and traceable analog to study auxin-related responses. Here we identified that not only exogenous 2,4-D but also its amide-linked metabolite 2,4-D-Glu displayed an inhibitory effect on plant growth via the TIR1/AFB auxin-mediated signaling pathway. To further investigate 2,4-D metabolite conversion, identity and activity, we have developed a novel purification procedure based on the combination of ion exchange and immuno-specific sorbents combined with a sensitive liquid chromatography-mass spectrometry method. In 2,4-D treated samples, 2,4-D-Glu and 2,4-D-Asp were detected at 100-fold lower concentrations compared to 2,4-D levels, showing that 2,4-D can be metabolized in the plant. Moreover, 2,4-D-Asp and 2,4-D-Glu were identified as reversible forms of 2,4-D homeostasis that can be converted to free 2,4-D. This work paves the way to new studies of auxin action in plant development. PMID:27434212

  16. Development of Gonadotropin-Releasing Hormone-Secreting Neurons from Human Pluripotent Stem Cells.

    PubMed

    Lund, Carina; Pulli, Kristiina; Yellapragada, Venkatram; Giacobini, Paolo; Lundin, Karolina; Vuoristo, Sanna; Tuuri, Timo; Noisa, Parinya; Raivio, Taneli

    2016-08-01

    Gonadotropin-releasing hormone (GnRH) neurons regulate human puberty and reproduction. Modeling their development and function in vitro would be of interest for both basic research and clinical translation. Here, we report a three-step protocol to differentiate human pluripotent stem cells (hPSCs) into GnRH-secreting neurons. Firstly, hPSCs were differentiated to FOXG1, EMX2, and PAX6 expressing anterior neural progenitor cells (NPCs) by dual SMAD inhibition. Secondly, NPCs were treated for 10 days with FGF8, which is a key ligand implicated in GnRH neuron ontogeny, and finally, the cells were matured with Notch inhibitor to bipolar TUJ1-positive neurons that robustly expressed GNRH1 and secreted GnRH decapeptide into the culture medium. The protocol was reproducible both in human embryonic stem cells and induced pluripotent stem cells, and thus provides a translational tool for investigating the mechanisms of human puberty and its disorders. PMID:27426041

  17. Adrenocorticotropic Hormone Suppresses Gonadotropin-Stimulated Estradiol Release from Zebrafish Ovarian Follicles

    PubMed Central

    Alsop, Derek; Ings, Jennifer S.; Vijayan, Mathilakath M.

    2009-01-01

    While stress is known to impact reproductive performance, the pathways involved are not entirely understood. Corticosteroid effects on the functioning of the hypothalamus-pituitary-gonadal axis are thought to be a key aspect of stress-mediated reproductive dysfunction. A vital component of the stress response is the pituitary secretion of adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. We recently reported MC2R mRNA abundance in fish gonads leading to the hypothesis that ACTH may be directly involved in gonadal steroid modulation. Using zebrafish (Danio rerio) ovarian follicles, we tested the hypothesis that acute ACTH stimulation modulates cortisol and estradiol (E2) secretion. ACTH neither affected cortisol nor unstimulated E2 release from ovarian follicles. However, ACTH suppressed human chorionic gonadotropin (hCG)-stimulated E2 secretion in a dose-related manner, with a maximum decrease of 62% observed at 1 I.U. ACTH mL−1. This effect of ACTH on E2 release was not observed in the presence of either 8-bromo-cAMP or forskolin, suggesting that the mechanism(s) involved in steroid attenuation was upstream of adenylyl cyclase activation. Overall, our results suggest that a stress-induced rise in plasma ACTH levels may initiate a rapid down-regulation of acute stimulated E2 biosynthesis in the zebrafish ovary, underscoring a novel physiological role for this pituitary peptide in modulating reproductive activity. PMID:19649243

  18. Evolution of gonadotropin-inhibitory hormone receptor and its ligand.

    PubMed

    Ubuka, Takayoshi; Tsutsui, Kazuyoshi

    2014-12-01

    Gonadotropin-inhibitory hormone (GnIH) is a neuropeptide inhibitor of gonadotropin secretion, which was first identified in the Japanese quail hypothalamus. GnIH peptides share a C-terminal LPXRFamide (X=L or Q) motif in most vertebrates. The receptor for GnIH (GnIHR) is the seven-transmembrane G protein-coupled receptor 147 (GPR147) that inhibits cAMP production. GPR147 is also named neuropeptide FF (NPFF) receptor 1 (NPFFR1), because it also binds NPFF that has a C-terminal PQRFamide motif. To understand the evolutionary history of the GnIH system in the animal kingdom, we searched for receptors structurally similar to GnIHR in the genome of six mammals (human, mouse, rat, cattle, cat, and rabbit), five birds (pigeon, chicken, turkey, budgerigar, and zebra finch), one reptile (green anole), one amphibian (Western clawed flog), six fishes (zebrafish, Nile tilapia, Fugu, coelacanth, spotted gar, and lamprey), one hemichordate (acorn worm), one echinoderm (purple sea urchin), one mollusk (California sea hare), seven insects (pea aphid, African malaria mosquito, honey bee, buff-tailed bumblebee, fruit fly, jewel wasp, and red flour beetle), one cnidarian (hydra), and constructed phylogenetic trees by neighbor joining (NJ) and maximum likelihood (ML) methods. A multiple sequence alignment of the receptors showed highly conserved seven-transmembrane domains as well as disulfide bridge sites between the first and second extracellular loops, including the receptor of hydra. Both NJ and ML analyses grouped the receptors of vertebrates into NPFFR1 and NPFFR2 (GPR74), and the receptors of insects into the receptor for SIFamide peptides that share a C-terminal YRKPPFNGSIFamide motif. Although human, quail and zebrafish GnIHR (NPFFR1) were most structurally similar to SIFamide receptor of fruit fly in the Famide peptide (FMRFamide, neuropeptide F, short neuropeptide F, drosulfakinin, myosuppressin, SIFamide) receptor families, the amino acid sequences and the peptide coding

  19. GRAM 88 - 4D GLOBAL REFERENCE ATMOSPHERE MODEL-1988

    NASA Technical Reports Server (NTRS)

    Johnson, D. L.

    1994-01-01

    the Jacchia values. Below 25km the atmospheric parameters are computed by the 4-D worldwide atmospheric model of Spiegler and Fowler (1972). This data set is not included. GRAM-88 incorporates a hydrostatic/gas law check in the 0-30 km altitude range to flag and change any bad data points. Between 5km and 30km, an interpolation scheme is used between the 4-D results and the modified Groves values. The output parameters consist of components for: (1) latitude, longitude, and altitude dependent monthly and annual means, (2) quasi-biennial oscillations (QBO), and (3) random perturbations to partially simulate the variability due to synoptic, diurnal, planetary wave, and gravity wave variations. Quasi-biennial and random variation perturbations are computed from parameters determined by various empirical studies and are added to the monthly mean values. The GRAM-88 program is for batch execution on the IBM 3084. It is written in STANDARD FORTRAN 77 under the MVS/XA operating system. The IBM DISPLA graphics routines are necessary for graphical output. The program was developed in 1988.

  20. Plasma kisspeptin levels are elevated in cord blood and present sexual dimorphism in the adult population: relation with leptin, gonadotropins and anthropometrical data.

    PubMed

    Pita, Jimena; Rado-Peralta, Sandra; Gavela-Pérez, Teresa; Aragón, Isabel; Barrios, Vicente; Rovira, Adela; Argente, Jesús; Soriano-Guillén, Leandro

    2011-05-01

    Kisspeptin, the product of the hypothalamic KISS1 gene, is a main regulator of the hypothalamic-pituitary-gonadal axis and could be a link between metabolism and reproduction through its interaction with leptin. Kisspeptin could be involved in gonadotropin regulation and responsive to leptin levels from the first stages of life, exhibiting, as does leptin, sexual dimorphism. To test our hypothesis, we have analyzed plasma kisspeptin levels and their possible relationship with gonadotropins and leptin in a cohort composed of newborns (n = 86) and adults (n = 55). Plasma kisspeptin, gonadotropin and leptin levels were measured by RIA and multiplexed bead immunoassays, respectively. We have built a multivariate linear regression model (analyzing kisspeptin and LH separately as dependent variables) by stepwise analysis, incorporating the variables that had shown significant correlation in the univariate analysis. Cord blood samples exhibited high kisspeptin levels 127.01(113-141.02 pmol/l), but these were not sexually dimorphic. The adult population exhibited sexual dimorphism (3.72(2.95-4.49) vs. 1.77(1.23-2.31)pmol/l women vs. men, p<0.05). Leptin levels showed sexual dimorphism in cord blood samples and also in the adult population. Furthermore, there was a significant interaction between LH and kisspeptin levels and kisspeptin was negatively correlated with age. The high kisspeptin levels observed in cord blood, with no sexual dimorphism, suggest a placental source. The sexual dimorphism exhibited in adulthood supports the notion that there are different sources and/or differential kisspeptin regulation between men and women. PMID:21295095

  1. Infrared PINEM developed by diffraction in 4D UEM

    PubMed Central

    Liu, Haihua; Baskin, John Spencer; Zewail, Ahmed H.

    2016-01-01

    The development of four-dimensional ultrafast electron microscopy (4D UEM) has enabled not only observations of the ultrafast dynamics of photon–matter interactions at the atomic scale with ultrafast resolution in image, diffraction, and energy space, but photon–electron interactions in the field of nanoplasmonics and nanophotonics also have been captured by the related technique of photon-induced near-field electron microscopy (PINEM) in image and energy space. Here we report a further extension in the ongoing development of PINEM using a focused, nanometer-scale, electron beam in diffraction space for measurements of infrared-light-induced PINEM. The energy resolution in diffraction mode is unprecedented, reaching 0.63 eV under the 200-keV electron beam illumination, and separated peaks of the PINEM electron-energy spectrum induced by infrared light of wavelength 1,038 nm (photon energy 1.2 eV) have been well resolved for the first time, to our knowledge. In a comparison with excitation by green (519-nm) pulses, similar first-order PINEM peak amplitudes were obtained for optical fluence differing by a factor of more than 60 at the interface of copper metal and vacuum. Under high fluence, the nonlinear regime of IR PINEM was observed, and its spatial dependence was studied. In combination with PINEM temporal gating and low-fluence infrared excitation, the PINEM diffraction method paves the way for studies of structural dynamics in reciprocal space and energy space with high temporal resolution. PMID:26848135

  2. Fast interactive exploration of 4D MRI flow data

    NASA Astrophysics Data System (ADS)

    Hennemuth, A.; Friman, O.; Schumann, C.; Bock, J.; Drexl, J.; Huellebrand, M.; Markl, M.; Peitgen, H.-O.

    2011-03-01

    1- or 2-directional MRI blood flow mapping sequences are an integral part of standard MR protocols for diagnosis and therapy control in heart diseases. Recent progress in rapid MRI has made it possible to acquire volumetric, 3-directional cine images in reasonable scan time. In addition to flow and velocity measurements relative to arbitrarily oriented image planes, the analysis of 3-dimensional trajectories enables the visualization of flow patterns, local features of flow trajectories or possible paths into specific regions. The anatomical and functional information allows for advanced hemodynamic analysis in different application areas like stroke risk assessment, congenital and acquired heart disease, aneurysms or abdominal collaterals and cranial blood flow. The complexity of the 4D MRI flow datasets and the flow related image analysis tasks makes the development of fast comprehensive data exploration software for advanced flow analysis a challenging task. Most existing tools address only individual aspects of the analysis pipeline such as pre-processing, quantification or visualization, or are difficult to use for clinicians. The goal of the presented work is to provide a software solution that supports the whole image analysis pipeline and enables data exploration with fast intuitive interaction and visualization methods. The implemented methods facilitate the segmentation and inspection of different vascular systems. Arbitrary 2- or 3-dimensional regions for quantitative analysis and particle tracing can be defined interactively. Synchronized views of animated 3D path lines, 2D velocity or flow overlays and flow curves offer a detailed insight into local hemodynamics. The application of the analysis pipeline is shown for 6 cases from clinical practice, illustrating the usefulness for different clinical questions. Initial user tests show that the software is intuitive to learn and even inexperienced users achieve good results within reasonable processing

  3. 4D measurement system for automatic location of anatomical structures

    NASA Astrophysics Data System (ADS)

    Witkowski, Marcin; Sitnik, Robert; Kujawińska, Małgorzata; Rapp, Walter; Kowalski, Marcin; Haex, Bart; Mooshake, Sven

    2006-04-01

    Orthopedics and neurosciences are fields of medicine where the analysis of objective movement parameters is extremely important for clinical diagnosis. Moreover, as there are significant differences between static and dynamic parameters, there is a strong need of analyzing the anatomical structures under functional conditions. In clinical gait analysis the benefits of kinematical methods are undoubted. In this paper we present a 4D (3D + time) measurement system capable of automatic location of selected anatomical structures by locating and tracing the structures' position and orientation in time. The presented system is designed to help a general practitioner in diagnosing selected lower limbs' dysfunctions (e.g. knee injuries) and also determine if a patient should be directed for further examination (e.g. x-ray or MRI). The measurement system components are hardware and software. For the hardware part we adapt the laser triangulation method. In this way we can evaluate functional and dynamic movements in a contact-free, non-invasive way, without the use of potentially harmful radiation. Furthermore, opposite to marker-based video-tracking systems, no preparation time is required. The software part consists of a data acquisition module, an image processing and point clouds (point cloud, set of points described by coordinates (x, y, z)) calculation module, a preliminary processing module, a feature-searching module and an external biomechanical module. The paper briefly presents the modules mentioned above with the focus on the feature-searching module. Also we present some measurement and analysis results. These include: parameters maps, landmarks trajectories in time sequence and animation of a simplified model of lower limbs.

  4. Vessels as 4-D curves: global minimal 4-D paths to extract 3-D tubular surfaces and centerlines.

    PubMed

    Li, Hua; Yezzi, Anthony

    2007-09-01

    In this paper, we propose an innovative approach to the segmentation of tubular structures. This approach combines all of the benefits of minimal path techniques such as global minimizers, fast computation, and powerful incorporation of user input, while also having the capability to represent and detect vessel surfaces directly which so far has been a feature restricted to active contour and surface techniques. The key is to represent the trajectory of a tubular structure not as a 3-D curve but to go up a dimension and represent the entire structure as a 4-D curve. Then we are able to fully exploit minimal path techniques to obtain global minimizing trajectories between two user supplied endpoints in order to reconstruct tubular structures from noisy or low contrast 3-D data without the sensitivity to local minima inherent in most active surface techniques. In contrast to standard purely spatial 3-D minimal path techniques, however, we are able to represent a full tubular surface rather than just a curve which runs through its interior. Our representation also yields a natural notion of a tube's "central curve." We demonstrate and validate the utility of this approach on magnetic resonance (MR) angiography and computed tomography (CT) images of coronary arteries. PMID:17896594

  5. 49 CFR 178.53 - Specification 4D welded steel cylinders for aircraft use.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Specification 4D welded steel cylinders for...) SPECIFICATIONS FOR PACKAGINGS Specifications for Cylinders § 178.53 Specification 4D welded steel cylinders for aircraft use. (a) Type, size, and service pressure. A DOT 4D cylinder is a welded steel sphere...

  6. 49 CFR 178.53 - Specification 4D welded steel cylinders for aircraft use.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Specification 4D welded steel cylinders for...) SPECIFICATIONS FOR PACKAGINGS Specifications for Cylinders § 178.53 Specification 4D welded steel cylinders for aircraft use. (a) Type, size, and service pressure. A DOT 4D cylinder is a welded steel sphere...

  7. 49 CFR 178.53 - Specification 4D welded steel cylinders for aircraft use.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Specification 4D welded steel cylinders for...) SPECIFICATIONS FOR PACKAGINGS Specifications for Cylinders § 178.53 Specification 4D welded steel cylinders for aircraft use. (a) Type, size, and service pressure. A DOT 4D cylinder is a welded steel sphere...

  8. 32 CFR 1630.43 - Class 4-D: Minister of religion.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 6 2011-07-01 2011-07-01 false Class 4-D: Minister of religion. 1630.43 Section... CLASSIFICATION RULES § 1630.43 Class 4-D: Minister of religion. In accord with part 1645 of this chapter any registrant shall be placed in Class 4-D who is a: (a) Duly ordained minister of religion; or (b)...

  9. 32 CFR 1630.43 - Class 4-D: Minister of religion.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false Class 4-D: Minister of religion. 1630.43 Section... CLASSIFICATION RULES § 1630.43 Class 4-D: Minister of religion. In accord with part 1645 of this chapter any registrant shall be placed in Class 4-D who is a: (a) Duly ordained minister of religion; or (b)...

  10. 32 CFR 1630.43 - Class 4-D: Minister of religion.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false Class 4-D: Minister of religion. 1630.43 Section... CLASSIFICATION RULES § 1630.43 Class 4-D: Minister of religion. In accord with part 1645 of this chapter any registrant shall be placed in Class 4-D who is a: (a) Duly ordained minister of religion; or (b)...

  11. 32 CFR 1630.43 - Class 4-D: Minister of religion.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 6 2012-07-01 2012-07-01 false Class 4-D: Minister of religion. 1630.43 Section... CLASSIFICATION RULES § 1630.43 Class 4-D: Minister of religion. In accord with part 1645 of this chapter any registrant shall be placed in Class 4-D who is a: (a) Duly ordained minister of religion; or (b)...

  12. 32 CFR 1630.43 - Class 4-D: Minister of religion.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Class 4-D: Minister of religion. 1630.43 Section... CLASSIFICATION RULES § 1630.43 Class 4-D: Minister of religion. In accord with part 1645 of this chapter any registrant shall be placed in Class 4-D who is a: (a) Duly ordained minister of religion; or (b)...

  13. Human chorionic gonadotropin induces human macrophages to form intracytoplasmic vacuoles mimicking Hofbauer cells in human chorionic villi.

    PubMed

    Yamaguchi, Munekage; Ohba, Takashi; Tashiro, Hironori; Yamada, Gen; Katabuchi, Hidetaka

    2013-01-01

    The most characteristic morphological feature of macrophages in the stroma of placental villi, known as Hofbauer cells, is their highly vacuolated appearance. They also show positive immunostaining for human chorionic gonadotropin (hCG) and express messenger ribonucleic acid of the luteinizing hormone/chorionic gonadotropin receptor with a deletion of exon 9 (LH/CG-R Δ9). Maternal hCG enters fetal plasma through the mesenchyme of the placental villi and promotes male sexual differentiation in early pregnancy; therefore, excess hCG may induce aberrant genital differentiation and hCG must be adjusted at the fetomaternal interface. We hypothesized that hCG is regulated by Hofbauer cells and that their peculiar vacuoles are involved in a cell-specific function. To assess the morphological modification and expression of LH/CG-R Δ9 in human macrophages after hCG exposure, the present study examined phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells, a human monocyte-macrophage cell line. hCG induced transient vacuole formation in PMA-treated THP-1 cells, morphologically mimicking Hofbauer cells. Immunocytochemistry showed that PMA-treated THP-1 cells incorporated hCG but not luteinizing hormone or follicle-stimulating hormone. Western blotting analyses demonstrated that PMA-treated THP-1 cells expressed an immunoreactive 60-kDa protein, designated as endogenous LH/CG-R Δ9. hCG induced a transient reduction in the LH/CG-R Δ9, which was synchronous with the appearance of cytoplasmic vacuoles. In conclusion, human macrophages regulating hCG via cytoplasmic LH/CG-R Δ9 mimic the morphological characteristics of Hofbauer cells. Their vacuoles may be associated with their cell-specific function to protect the fetus from exposure to excess maternal hCG during pregnancy. PMID:23128164

  14. Life and death before birth: 4D ultrasound and the shifting frontiers of the abortion debate.

    PubMed

    Savell, Kristin

    2007-08-01

    The development of 4D ultrasound technology has democratised fetal imagery by offering direct visual access to realistic images of the fetus in utero. These images, which purport to show a responsive being capable of complex behaviour, have renewed debate about the personhood of the fetus and the adequacy of current abortion regulation. This article considers recent abortion law reform initiatives in the United Kingdom and the United States and observes two shifts in the frontiers of these debates. The first concerns a shift from viability to sentience as a criterion of legal significance. The second concerns a shift toward constructing abortion in terms of feticide as distinct from the termination of pregnancy. Both strategies seek to deploy morphological similarities between the sentient fetus and newborn baby as a basis for extending law's dominion over the fetus. PMID:17902493

  15. Segmentation of 4D cardiac images: investigation on statistical shape models.

    PubMed

    Renno, Markus S; Shang, Yan; Sweeney, James; Dossel, Olaf

    2006-01-01

    The purpose of this research was two-fold: (1) to investigate the properties of statistical shape models constructed from manually segmented cardiac ventricular chambers to confirm the validity of an automatic 4-dimensional (4D) segmentation model that uses gradient vector flow (GVF) images of the original data and (2) to develop software to further automate the steps necessary in active shape model (ASM) training. These goals were achieved by first constructing ASMs from manually segmented ventricular models by allowing the user to cite entire datasets for processing using a GVF-based landmarking procedure and principal component analysis (PCA) to construct the statistical shape model. The statistical shape model of one dataset was used to regulate the segmentation of another dataset according to its GVF, and these results were then analyzed and found to accurately represent the original cardiac data when compared to the manual segmentation results as the golden standard. PMID:17947007

  16. Mineralization of 2,4-dichlorophenoxyacetic acid (2,4-D) and mixtures of 2,4-D and 2,4,5-trichlorophenoxyacetic acid by Phanerochaete chrysosporium

    SciTech Connect

    Yadav, J.S.; Reddy, C.A. )

    1993-09-01

    2,4-dichloropheonxyacetic Acid (2,4-D) is one of the most commonly used phenoxyalkanoic herbicides for selective control of weeds and for defoliation. Since these toxic chemical are manufactured and used each year in massive quantities, effective handling of their production wastes and the contaminated environment is needed. A number of bacterial general are known to degrade 2,4-D, but no naturally occuring bacterium is know to be capable of mineralizing 2,4,5-trichlorophenoxyacetic acid. Mutual inhibition of degradation has been reported when 2,4-D and 2,4,5-T are presented in a mixture to degrading bacteria. This paper investigates the ability of Pseudomonas chrysosporium to mineralize 2,4-D individually and in combination with 2,4,5-T. Results indicate that P. chrysosporium effectively mineralizes 2,4-D alone as well as in combination with 2,4,5-T. 31 refs., 4 figs., 1 tab.

  17. Altered ovarian responsiveness to gonadotropins in neonatally irradiated immature rats

    SciTech Connect

    Freud, A.; Sod-Moriah, U.A.

    1988-01-01

    Female rats which were exposed to a single low dose of gamma irradiation (6R or 15R) at the age of 8 days produce smaller litters when mature than untreated controls. In order to study the possibility that such an impaired reproductive performance could result from a reduced ovulation rate, neonatally irradiated females were treated with PMSG (12 iu/rat) at the age of 26 days. Another group of rats, similarly treated, was further injected with hCG (5 iu/rat) 48 hours later. Animals were killed 48, 55, 60 and 72 hours after PMSG treatment or 72 and 120 after hCG injection. The results indicated that PMSG treatment increased the ovarian weight of non-irradiated controls as well as of irradiated rats and in all animals induced a proestrus like profile of LH. Only a combined treatment of PMSG and hCG resulted in ovulation and corpora lutea formation with significantly increased numbers of corpora lutea in the ovaries of the irradiated rats. The latter was associated with higher progesterone plasma levels not correlated to the number of corpora lutea. The gradual decrease in the number of ovarian binding sites for hCG with increased radiation dose and the increased association constant in the 15R group could not explain the increased sensitivity of the ovary to exogenous gonadotropins which results from neonatal exposure to low doses of gamma irradiation.

  18. Pharmacological Chaperones for Misfolded Gonadotropin-Releasing Hormone Receptors

    PubMed Central

    Conn, P. Michael; Ulloa-Aguirre, Alfredo

    2011-01-01

    Structural alterations provoked by mutations or genetic variations in the gene sequence of G protein-coupled receptors may lead to abnormal function of the receptor molecule and, ultimately, to disease. While some mutations lead to changes in domains involved in agonist binding, receptor activation or coupling to effectors, others may cause misfolding and lead to retention/degradation of the protein molecule by the quality control system of the cell. Several strategies, including genetic, chemical and pharmacological approaches have been shown to rescue function of trafficking-defective misfolded G protein-coupled receptors. Among these, pharmacological strategies offer the most promising therapeutic tool to promote proper trafficking of misfolded proteins to the plasma membrane. Pharmacological chaperones or “pharmacoperones,” are small compounds that permeate the plasma membrane, enter cells, and bind selectively to misfolded proteins and correct folding allowing routing of the target protein to the plasma membrane, where the receptor may bind and respond to agonist stimulation. In this review we describe new therapeutic opportunities based on misfolding of otherwise functional human gonadotropin-releasing hormone receptors. This particular receptor is highly sensitive to single changes in chemical charge and its intracellular traffic is delicately balanced between expression at the plasma membrane or retention/degradation in the endoplasmic reticulum; it is, therefore, a particularly instructive model to understand both protein routing and the molecular mechanisms whereby pharmacoperones rescue misfolded intermediates or conformationally defective receptors. PMID:21907908

  19. Transdermal iontophoresis of gonadotropin releasing hormone (LHRH) and two analogues.

    PubMed

    Miller, L L; Kolaskie, C J; Smith, G A; Rivier, J

    1990-06-01

    Gonadotropin releasing hormone (GnRH), as well as an antagonist [Ac-D2Nal,1 D4ClPhe,2 D3Pal,3 NicLys,5 DNicLys,6 ILys,8 DAla10] GnRH.HOAc (1) and a superagonist [DTrp6, Pro9-NHEt]GnRH (2), have been electrochemically driven across excised hairless mouse skin. Determined by HPLC analysis, the delivery rate from aqueous solution into isotonic saline at 0.5 mA cm-2 was as high as 19 nM cm-2 h-1 for 2. Because of its insolubility in water, analogue 1 could only be delivered from an acidic donor solution. Analogue 2 was also delivered in pulsatile fashion using current on/off cycles. For all three peptides, passive transport was negligible and stability is evident when in contact with the stratum corneum. Slow metabolism occurs when GnRH contacts the dermal side of hairless mouse skin. PMID:2203894

  20. Rapid Anti-Inflammatory Effects of Gonadotropin-Releasing Hormone Antagonism in Rheumatoid Arthritis Patients with High Gonadotropin Levels in the AGRA Trial

    PubMed Central

    Kåss, Anita; Hollan, Ivana; Fagerland, Morten Wang; Gulseth, Hans Christian; Torjesen, Peter Abusdal; Førre, Øystein Torleiv

    2015-01-01

    Objectives Gonadotropin-releasing hormone (GnRH) and pituitary gonadotropins, which appear to be proinflammatory, undergo profound secretory changes during events associated with rheumatoid arthritis (RA) onset, flares, or improvement e.g. menopausal transition, postpartum, or pregnancy. Potential anti-inflammatory effects of GnRH-antagonists may be most pronounced in patients with high GnRH and gonadotropin levels. Therefore, we investigated the efficacy and safety of a GnRH-antagonist, cetrorelix, in RA patients with high gonadotropin levels. Methods We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99). Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1–2; 3mg days 3–5) or placebo, were followed through day 15. Only predefined primary and secondary endpoints were analyzed. Results The primary endpoint, Disease Activity Score of 28-joint counts with C-reactive protein (DAS28-CRP), improved with cetrorelix compared with placebo by day 5 (-1.0 vs. -0.4, P = 0∙010). By day 5, more patients on cetrorelix achieved at least a 20% improvement in the American College of Rheumatology scale (44% vs. 19%, P = 0.049), DAS28-CRP≤3.2 (24% vs. 0%, P = 0.012), and European League against Rheumatism ‘Good-responses’ (19% vs. 0%, P = 0.026). Tumor necrosis factor-α, interleukin-1β, interleukin-10, and CRP decreased with cetrorelix (P = 0.045, P = 0.034, P = 0.020 and P = 0.042 respectively) compared with placebo by day 15. Adverse event rates were similar between groups. Conclusions GnRH-antagonism produced rapid anti-inflammatory effects in RA patients with high gonadotropin levels. GnRH should be investigated further in RA. Trial Registration ClinicalTrials.gov NCT00667758 PMID:26460564

  1. 4D motion animation of coronary arteries from rotational angiography

    NASA Astrophysics Data System (ADS)

    Holub, Wolfgang; Rohkohl, Christopher; Schuldhaus, Dominik; Prümmer, Marcus; Lauritsch, Günter; Hornegger, Joachim

    2011-03-01

    Time-resolved 3-D imaging of the heart is a major research topic in the medical imaging community. Recent advances in the interventional cardiac 3-D imaging from rotational angiography (C-arm CT) are now also making 4-D imaging feasible during procedures in the catheter laboratory. State-of-the-art reconstruction algorithms try to estimate the cardiac motion and utilize the motion field to enhance the reconstruction of a stable cardiac phase (diastole). The available data offers a handful of opportunities during interventional procedures, e.g. the ECG-synchronized dynamic roadmapping or the computation and analysis of functional parameters. In this paper we will demonstrate that the motion vector field (MVF) that is output by motion compensated image reconstruction algorithms is in general not directly usable for animation and motion analysis. Dependent on the algorithm different defects are investigated. A primary issue is that the MVF needs to be inverted, i.e. the wrong direction of motion is provided. A second major issue is the non-periodicity of cardiac motion. In algorithms which compute a non-periodic motion field from a single rotation the in depth motion information along viewing direction is missing, since this cannot be measured in the projections. As a result, while the MVF improves reconstruction quality, it is insufficient for motion animation and analysis. We propose an algorithm to solve both problems, i.e. inversion and missing in-depth information in a unified framework. A periodic version of the MVF is approximated. The task is formulated as a linear optimization problem where a parametric smooth motion model based on B-splines is estimated from the MVF. It is shown that the problem can be solved using a sparse QR factorization within a clinical feasible time of less than one minute. In a phantom experiment using the publicly available CAVAREV platform, the average quality of a non-periodic animation could be increased by 39% by applying the

  2. A dose error evaluation study for 4D dose calculations

    NASA Astrophysics Data System (ADS)

    Milz, Stefan; Wilkens, Jan J.; Ullrich, Wolfgang

    2014-10-01

    Previous studies have shown that respiration induced motion is not negligible for Stereotactic Body Radiation Therapy. The intrafractional breathing induced motion influences the delivered dose distribution on the underlying patient geometry such as the lung or the abdomen. If a static geometry is used, a planning process for these indications does not represent the entire dynamic process. The quality of a full 4D dose calculation approach depends on the dose coordinate transformation process between deformable geometries. This article provides an evaluation study that introduces an advanced method to verify the quality of numerical dose transformation generated by four different algorithms. The used transformation metric value is based on the deviation of the dose mass histogram (DMH) and the mean dose throughout dose transformation. The study compares the results of four algorithms. In general, two elementary approaches are used: dose mapping and energy transformation. Dose interpolation (DIM) and an advanced concept, so called divergent dose mapping model (dDMM), are used for dose mapping. The algorithms are compared to the basic energy transformation model (bETM) and the energy mass congruent mapping (EMCM). For evaluation 900 small sample regions of interest (ROI) are generated inside an exemplary lung geometry (4DCT). A homogeneous fluence distribution is assumed for dose calculation inside the ROIs. The dose transformations are performed with the four different algorithms. The study investigates the DMH-metric and the mean dose metric for different scenarios (voxel sizes: 8 mm, 4 mm, 2 mm, 1 mm 9 different breathing phases). dDMM achieves the best transformation accuracy in all measured test cases with 3-5% lower errors than the other models. The results of dDMM are reasonable and most efficient in this study, although the model is simple and easy to implement. The EMCM model also achieved suitable results, but the approach requires a more complex

  3. 4D Visualization of Experimental Procedures in Rock Physics

    NASA Astrophysics Data System (ADS)

    Vanorio, T.; di Bonito, C.

    2010-12-01

    Engaging students in laboratory classes in geophysics is becoming more and more difficult. This is primarily because of an ever-widening gap between the less appealing aspects that characterize these courses (e.g., lengthiness of the experimental operations, high student/instrument ratio, limited time associated with lack of previous hands-on experiences, and logistical and safety concerns) and the life style of the 21st century generations (i.e., extensive practice to high-tech tools, high-speed communications and computing, 3D graphics and HD videos). To bridge the gap and enhance the teaching strategy of laboratory courses in geophysics, we have created simulator-training tools for use in preparation for the actual experimental phase. We are using a modeling, animation, and rendering package to create (a) 3D models that accurately reproduce actual scenarios and instruments used for the measurement of rock physics properties and (b) 4D interactive animations that simulate hands-on demonstrations of the experimental procedures. We present here a prototype describing step-by-step the experimental protocol and the principles behind the measurement of rock porosity. The tool reproduces an actual helium porosimeter and makes use of interactive animations, guided text, and a narrative voice guiding the audience through the different phases of the experimental process. Our strategy is to make the most of new technologies while preserving the accuracy of classical laboratory methods and practices. These simulations are not intended to replace traditional lab work; rather they provide students with the opportunity for review and repetition. The primary goal is thus to help students familiarize themselves during their earlier curricula with lab methodologies, thus minimizing apparent hesitation and frustration in later classes. This may also increase the level of interest and involvement of undergraduate students and, in turn, enhance their keenness to pursue their

  4. Experimenting with the GMAO 4D Data Assimilation

    NASA Technical Reports Server (NTRS)

    Todling, R.; El Akkraoui, A.; Errico, R. M.; Guo, J.; Kim, J.; Kliest, D.; Parrish, D. F.; Suarez, M.; Trayanov, A.; Tremolet, Yannick; Whitaker, J.

    2012-01-01

    The Global Modeling and Assimilation Office (GMAO) has been working to promote its prototype four-dimensional variational (4DVAR) system to a version that can be exercised at operationally desirable configurations. Beyond a general circulation model (GeM) and an analysis system, traditional 4DV AR requires availability of tangent linear (TL) and adjoint (AD) models of the corresponding GeM. The GMAO prototype 4DVAR uses the finite-volume-based GEOS GeM and the Grid-point Statistical Interpolation (GSI) system for the first two, and TL and AD models derived ITom an early version of the finite-volume hydrodynamics that is scientifically equivalent to the present GEOS nonlinear GeM but computationally rather outdated. Specifically, the TL and AD models hydrodynamics uses a simple (I-dimensional) latitudinal MPI domain decomposition, which has consequent low scalability and prevents the prototype 4DV AR ITom being used in realistic applications. In the near future, GMAO will be upgrading its operational GEOS GCM (and assimilation system) to use a cubed-sphere-based hydrodynamics. This versions of the dynamics scales to thousands of processes and has led to a decision to re-derive the TL and AD models for this more modern dynamics, thus taking advantage of a two-dimensional MPI decomposition and improved scalability properties. With the aid of the Transformation of Algorithms in FORTRAN (l'AF) automatic adjoint generation tool and some hand-coding, a version of the cubed-sphere-based TL and AD models, with a simplified vertical diffusion scheme, is now available, enabling multiple configurations of standard implementations of 4DV AR in GEOS. Concurrent to this development, collaboration with the National Centers for Environmental Prediction (NCEP) and the Earth System Research Laboratory (ESRL) has allowed GMAO to implement a hybrid-ensemble capability within the GEOS data assimilation system. Both 3Dand 4D-ensemble capabilities are presently available thus allowing

  5. Interactive 4D Visualization of Sediment Transport Models

    NASA Astrophysics Data System (ADS)

    Butkiewicz, T.; Englert, C. M.

    2013-12-01

    Coastal sediment transport models simulate the effects that waves, currents, and tides have on near-shore bathymetry and features such as beaches and barrier islands. Understanding these dynamic processes is integral to the study of coastline stability, beach erosion, and environmental contamination. Furthermore, analyzing the results of these simulations is a critical task in the design, placement, and engineering of coastal structures such as seawalls, jetties, support pilings for wind turbines, etc. Despite the importance of these models, there is a lack of available visualization software that allows users to explore and perform analysis on these datasets in an intuitive and effective manner. Existing visualization interfaces for these datasets often present only one variable at a time, using two dimensional plan or cross-sectional views. These visual restrictions limit the ability to observe the contents in the proper overall context, both in spatial and multi-dimensional terms. To improve upon these limitations, we use 3D rendering and particle system based illustration techniques to show water column/flow data across all depths simultaneously. We can also encode multiple variables across different perceptual channels (color, texture, motion, etc.) to enrich surfaces with multi-dimensional information. Interactive tools are provided, which can be used to explore the dataset and find regions-of-interest for further investigation. Our visualization package provides an intuitive 4D (3D, time-varying) visualization of sediment transport model output. In addition, we are also integrating real world observations with the simulated data to support analysis of the impact from major sediment transport events. In particular, we have been focusing on the effects of Superstorm Sandy on the Redbird Artificial Reef Site, offshore of Delaware Bay. Based on our pre- and post-storm high-resolution sonar surveys, there has significant scour and bedform migration around the

  6. Predicting lower mantle heterogeneity from 4-D Earth models

    NASA Astrophysics Data System (ADS)

    Flament, Nicolas; Williams, Simon; Müller, Dietmar; Gurnis, Michael; Bower, Dan J.

    2016-04-01

    basal layer ˜ 4% denser than ambient mantle. Increasing convective vigour (Ra ≈ 5 x 108) or decreasing the density of the basal layer decreases both the accuracy and sensitivity of the predicted lower mantle structure. References: D. J. Bower, M. Gurnis, N. Flament, Assimilating lithosphere and slab history in 4-D Earth models. Phys. Earth Planet. Inter. 238, 8-22 (2015). V. Lekic, S. Cottaar, A. Dziewonski, B. Romanowicz, Cluster analysis of global lower mantle tomography: A new class of structure and implications for chemical heterogeneity. Earth Planet. Sci. Lett. 357, 68-77 (2012).

  7. Gonadotropin-releasing hormone 2 suppresses food intake in the zebrafish, Danio rerio.

    PubMed

    Nishiguchi, Ryo; Azuma, Morio; Yokobori, Eri; Uchiyama, Minoru; Matsuda, Kouhei

    2012-01-01

    Gonadotropin-releasing hormone (GnRH) is an evolutionarily conserved neuropeptide with 10 amino acid residues, of which several structural variants exist. A molecular form known as GnRH2 ([His(5) Trp(7) Tyr(8)]GnRH, also known as chicken GnRH II) is widely distributed in vertebrates except for rodents, and has recently been implicated in the regulation of feeding behavior in goldfish. However, the influence of GnRH2 on feeding behavior in other fish has not yet been studied. In the present study, therefore, we investigated the role of GnRH2 in the regulation of feeding behavior in a zebrafish model, and examined its involvement in food intake after intracerebroventricular (ICV) administration. ICV injection of GnRH2 at 0.1 and 1 pmol/g body weight (BW) induced a marked decrease of food consumption in a dose-dependent manner during 30 min after feeding. Cumulative food intake was significantly decreased by ICV injection of GnRH2 at 1 pmol/g BW during the 30-min post-treatment observation period. The anorexigenic action of GnRH2 was completely blocked by treatment with the GnRH type I receptor antagonist Antide at 25 pmol/g BW. We also examined the effect of feeding condition on the expression level of the GnRH2 transcript in the hypothalamus. Levels of GnRH2 mRNA obtained from fish that had been provided excess food for 7 days were higher than those in fish that had been fed normally. These results suggest that, in zebrafish, GnRH2 acts as an anorexigenic factor, as is the case in goldfish. PMID:23087673

  8. The general and comparative biology of gonadotropin-inhibitory hormone (GnIH).

    PubMed

    Tsutsui, Kazuyoshi; Bentley, George E; Ubuka, Takayoshi; Saigoh, Etsuko; Yin, Hong; Osugi, Tomohiro; Inoue, Kazuhiko; Chowdhury, Vishwajit S; Ukena, Kazuyoshi; Ciccone, Nick; Sharp, Peter J; Wingfield, John C

    2007-01-01

    The decapeptide gonadotropin-releasing hormone (GnRH) is the primary factor responsible for the hypothalamic control of gonadotropin secretion. Gonadal sex steroids and inhibin inhibit gonadotropin secretion via feedback from the gonads, but a neuropeptide inhibitor of gonadotropin secretion was, until recently, unknown in vertebrates. In 2000, we identified a novel hypothalamic dodecapeptide that inhibits gonadotropin release in cultured quail pituitaries and termed it gonadotropin-inhibitory hormone (GnIH). To elucidate the mode of action of GnIH, we then identified a novel G protein-coupled receptor for GnIH in quail. The GnIH receptor possesses seven transmembrane domains and specifically binds to GnIH. The GnIH receptor is expressed in the pituitary and several brain regions including the hypothalamus. These results indicate that GnIH acts directly on the pituitary via GnIH receptor to inhibit gonadotropin release. GnIH may also act on the hypothalamus to inhibit GnRH release. To demonstrate the functional significance of GnIH and its potential role as a key regulatory neuropeptide in avian reproduction, we investigated GnIH actions on gonadal development and maintenance in quail. Chronic treatment with GnIH inhibited gonadal development and maintenance by decreasing gonadotropin synthesis and release. GnIH was also found in the hypothalamus of other avian species including sparrows and chickens and also inhibited gonadotropin synthesis and release. The pineal hormone melatonin may be a key factor controlling GnIH neural function, since quail GnIH neurons express melatonin receptor and melatonin treatment stimulates the expression of GnIH mRNA and mature GnIH peptide. Thus, GnIH is capable of transducing photoperiodic information via changes in the melatonin signal, thereby influencing the reproductive axis. It is concluded that GnIH, a newly discovered hypothalamic neuropeptide, is a key factor controlling avian reproduction. The discovery of avian GnIH opens

  9. Restoration of Dioxin-Induced Damage to Fetal Steroidogenesis and Gonadotropin Formation by Maternal Co-Treatment with α-Lipoic Acid

    PubMed Central

    Koga, Takayuki; Ishida, Takumi; Takeda, Tomoki; Ishii, Yuji; Uchi, Hiroshi; Tsukimori, Kiyomi; Yamamoto, Midori; Himeno, Masaru; Furue, Masutaka; Yamada, Hideyuki

    2012-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an endocrine disruptor, causes reproductive and developmental toxic effects in pups following maternal exposure in a number of animal models. Our previous studies have demonstrated that TCDD imprints sexual immaturity by suppressing the expression of fetal pituitary gonadotropins, the regulators of gonadal steroidogenesis. In the present study, we discovered that all TCDD-produced damage to fetal production of pituitary gonadotropins as well as testicular steroidogenesis can be repaired by co-treating pregnant rats with α-lipoic acid (LA), an obligate co-factor for intermediary metabolism including energy production. While LA also acts as an anti-oxidant, other anti-oxidants; i.e., ascorbic acid, butylated hydroxyanisole and edaravone, failed to exhibit any beneficial effects. Neither wasting syndrome nor CYP1A1 induction in the fetal brain caused through the activation of aryl hydrocarbon receptor (AhR) could be attenuated by LA. These lines of evidence suggest that oxidative stress makes only a minor contribution to the TCDD-induced disorder of fetal steroidogenesis, and LA has a restorative effect by targeting on mechanism(s) other than AhR activation. Following a metabolomic analysis, it was found that TCDD caused a more marked change in the hypothalamus, a pituitary regulator, than in the pituitary itself. Although the components of the tricarboxylic acid cycle and the ATP content of the fetal hypothalamus were significantly changed by TCDD, all these changes were again rectified by exogenous LA. We also provided evidence that the fetal hypothalamic content of endogenous LA is significantly reduced following maternal exposure to TCDD. Thus, the data obtained strongly suggest that TCDD reduces the expression of fetal pituitary gonadotropins to imprint sexual immaturity or disturb development by suppressing the level of LA, one of the key players serving energy production. PMID:22911699

  10. Research resource: Gonadotropin-releasing hormone receptor-mediated signaling network in LbetaT2 cells: a pathway-based web-accessible knowledgebase.

    PubMed

    Fink, Marc Y; Pincas, Hanna; Choi, Soon Gang; Nudelman, German; Sealfon, Stuart C

    2010-09-01

    The GnRH receptor (GnRHR), expressed at the cell surface of the anterior pituitary gonadotrope, is critical for normal secretion of gonadotropins LH and FSH, pubertal development, and reproduction. The signaling network downstream of the GnRHR and the molecular bases of the regulation of gonadotropin expression have been the subject of intense research. The murine LbetaT2 cell line represents a mature gonadotrope and therefore is an important model for the study of GnRHR-signaling pathways and modulation of the gonadotrope cell by physiological regulators. In order to facilitate access to the information contained in this complex and evolving literature, we have developed a pathway-based knowledgebase that is web hosted. At present, using 106 relevant primary publications, we curated a comprehensive knowledgebase of the GnRHR signaling in the LbetaT2 cell in the form of a process diagram. Positive and negative controls of gonadotropin gene expression, which included GnRH itself, hypothalamic factors, gonadal steroids and peptides, as well as other hormones, were illustrated. The knowledgebase contains 187 entities and 206 reactions. It was assembled using CellDesigner software, which provides an annotated graphic representation of interactions, stored in Systems Biology Mark-up Language. We then utilized Biological Pathway Publisher, a software suite previously developed in our laboratory, to host the knowledgebase in a web-accessible format as a public resource. In addition, the network entities were linked to a public wiki, providing a forum for discussion, updating, and error correction. The GnRHR-signaling network is openly accessible at http://tsb.mssm.edu/pathwayPublisher/GnRHR_Pathway/GnRHR_Pathway_ index.html. PMID:20592162

  11. Effect of prenatal and neonatal exposure to lead on gonadotropin receptors and steroidogenesis in rat ovaries

    SciTech Connect

    Wiebe, J.P.; Barr, K.J.; Buckingham, K.D.

    1988-01-01

    Sprague-Dawley rats were treated with lead chloride (20 or 200 ppm) or sodium chloride (controls) in their drinking water, either prior to pregnancy or during pregnancy and lactation, and female offspring were examined at weaning (21 d) or at 150 d. Other female rats were treated from d 21 to 35. Tissue (blood, kidney, bone) lead levels, body, ovary, and uterus weights, ovarian steroidogenesis, and gonadotropin (luteinizing hormone and follicle-stimulating hormone) levels, and gonadotropin-receptor binding were determined. Prenatal and/or postnatal exposure to lead at these levels (20 and 200 ppm) did not affect tissue weights but did cause a significant decrease in gonadotropin-receptor binding in the prepubertal, pubertal and adult females. Conversion of progesterone to androstenedione and dihydrotestosterone was significantly decreased in 21-d-old rats; in 150-d-old females, the prenatal and/or postnatal exposure to lead resulted in significantly increased conversion to the 5-alpha-reduced steroid, normally high during puberty. The results demonstrate that lead exposure prior to mating may affect gonadotropin-receptor binding in the offspring and that lead exposure (in utero, via mother's milk, or post weaning) may significantly alter steroid production and gonadotropin binding in ovaries of the prepubertal, pubertal, and adult female.

  12. Targeted disruption of the heat shock protein 20-phosphodiesterase 4D (PDE4D) interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy.

    PubMed

    Martin, Tamara P; Hortigon-Vinagre, Maria P; Findlay, Jane E; Elliott, Christina; Currie, Susan; Baillie, George S

    2014-01-01

    Phosphorylated heat shock protein 20 (HSP20) is cardioprotective. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and a mouse model of pressure overload mediated hypertrophy, we show that peptide disruption of the HSP20-phosphodiesterase 4D (PDE4D) complex results in attenuation of action potential prolongation and protection against adverse cardiac remodelling. The later was evidenced by improved contractility, decreased heart weight to body weight ratio, and reduced interstitial and perivascular fibrosis. This study demonstrates that disruption of the specific HSP20-PDE4D interaction leads to attenuation of pathological cardiac remodelling. PMID:25426411

  13. Gonadotropin-Inhibitory Hormone Reduces Sexual Motivation But Not Lordosis Behavior In Female Syrian Hamsters (Mesocricetus auratus)

    PubMed Central

    Piekarski, David J.; Zhao, Sheng; Jennings, Kimberly J.; Iwasa, Takeshi; Legan, Sandra J.; Mikkelsen, Jens D.; Tsutsui, Kazuyoshi; Kriegsfeld, Lance J.

    2014-01-01

    Reproductive success is maximized when female sexual motivation and behavior coincide with the time of optimal fertility. Both processes depend upon coordinated hormonal events, beginning with signaling by the gonadotropin-releasing hormone (GnRH) neuronal system. Two neuropeptidergic systems that lie upstream of GnRH, gonadotropin-inhibitory hormone (GnIH; also known as RFamide related peptide-3) and kisspeptin, are potent inhibitory and excitatory modulators of GnRH, respectively, participate in the timing of the preovulatory luteinizing hormone (LH) surge and ovulation. Whether these neuropeptides serve as neuromodulators to coordinate female sexual behavior with the limited window of fertility has not been thoroughly explored. In the present study, either intact or ovariectomized, hormonetreated female hamsters were implanted for fifteen days with chronic release osmotic pumps filled with GnIH or saline. The effect of GnIH on sexual motivation, vaginal scent marking, and lordosis was examined. Following mating, FOS activation was quantified in brain regions implicated in the regulation of female sexual behavior. Intracerebroventricular administration of GnIH reduced sexual motivation and vaginal scent marking, but not lordosis behavior. GnIH administration altered FOS expression in key neural loci implicated in female reproductive behavior, including the medial preoptic area, medial amygdala and bed nucleus of the stria terminalis, independent of changes in circulating gonadal steroids and kisspeptin cell activation. Together, these data point to GnIH as an important modulator of female proceptive sexual behavior and motivation, independent of downstream alterations in sex steroid production. PMID:23827890

  14. Early-Life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats

    PubMed Central

    Soga, Tomoko; Teo, Chuin Hau; Cham, Kai Lin; Idris, Marshita Mohd; Parhar, Ishwar S.

    2015-01-01

    Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH) neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinizing hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic–GnIH neuronal system using enhanced green fluorescent protein (EGFP)-tagged GnIH transgenic rats. Socially isolated rats were observed for anxious and depressive behaviors. Using immunohistochemistry, we examined c-Fos protein expression in EGFP–GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group housing. We also inspected serotonergic fiber juxtapositions in EGFP–GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviors. The total number of EGFP–GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fiber juxtapositions on EGFP–GnIH neurons were also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early-life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure. PMID:26617573

  15. Molecular cloning and gene expression of the gonadotropin-releasing hormone receptor in the orange-spotted grouper, Epinephelus coioides.

    PubMed

    Hsieh, S L; Chuang, H C; Nan, F H; Ruan, Y H; Kuo, C M

    2007-06-01

    The objective of this study was to investigate the molecular mechanisms of gonadotropin-releasing hormone receptor (GnRH-R) involved in the endocrine regulation of reproduction in the orange-spotted grouper, Epinephelus coioides. The full-length cDNA encoding GnRH-R type I was successfully cloned from the pituitary by reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA end (RACE) methods in the grouper. The complete GnRH-R type I cDNA is 1607 bp, which includes an open reading frame of 1092 bp encoding a protein of 364 amino acids, a seven-alpha helix transmembrane domain, a N-terminal extracellular domain, and a C-terminal cytoplasmic domain. The expression of GnRH-R type I was found to be highest in the pituitary. An intramuscular injection of various GnRH types in vivo was attempted. The expression of GnRH-R type I was stimulated by a single injection of salmon GnRH, while in the case of chicken GnRH II treatment, the expression of GnRH-R type I was inhibited. This suggests that the action of chick GnRH II is probably enhanced through the GnRH receptor of different forms. Furthermore, none of them were expressed by an injection of seabream GnRH, and this is likely attributed to the injection dose being below the threshold level, and this remains to be further examined. In conclusion, GnRHs of various types are effective in stimulating the expression of gonadotropins through various forms of the GnRH-R, and multiple forms of the receptor gene likely exist in teleosts. PMID:17329139

  16. Effect of gonadotropin-releasing hormone II receptor (GnRHR-II) knockdown on testosterone secretion in the boar

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Unlike the classical gonadotropin-releasing hormone (GnRH-I), the second mammalian GnRH isoform (GnRH-II; His5, Trp7, Tyr8) is a poor stimulator of gonadotropin secretion. In addition, GnRH-II is ubiquitously expressed, with transcript levels highest in tissues outside of the brain. A receptor speci...

  17. Effect of gonadotropin secretion rate on the radiosensitivity of the rat luteinizing hormone-releasing hormone neuron and gonadotroph

    SciTech Connect

    Winterer, J.; Barnes, K.M.; Lichter, A.S.; Deluca, A.M.; Loriaux, D.L.; Cutler, G.B. Jr.

    1988-03-01

    To test the hypothesis that the functional state of hypothalamic LHRH neurons and pituitary gonadotrophs might alter their radiosensitivity, we determined the experimental conditions under which the gonadotropin response to castration could be impaired by a single dose of cranial irradiation. Single doses of cranial irradiation greater than 2000 rads were lethal to unshielded rats. Shielding of the oropharynx and esophagus allowed the animals to survive doses up to 5000 rads. Doses between 2000 and 5000 rads had no effect on basal gonadotropin levels for as long as 3 months after irradiation. Irradiation caused a dose- and time-dependent impairment, however, in the gonadotropin response to castration. Impairment of the gonadotropin levels of castrate animals occurred in animals that were irradiated either before or after castration. However, rats irradiated in the castrate state showed a decreased susceptibility to irradiation damage. Additionally, stimulation of the pituitary by LHRH agonist (LHRHa) 3 h before irradiation significantly reduced the impairment of gonadotropin secretion 12-20 weeks after irradiation (P less than 0.05). Thus, increased functional activity of the rat hypothalamus or pituitary at the time of irradiation, induced by either castration or acute LHRHa administration, was associated with some protection against the gonadotropin-lowering effect of irradiation. Based upon these data, we hypothesize that stimulation of gonadotropin secretion at the time of therapeutic cranial irradiation in humans might protect against subsequent impairment of gonadotropin secretion.

  18. SEMA4D compromises blood-brain barrier, activates microglia, and inhibits remyelination in neurodegenerative disease.

    PubMed

    Smith, Ernest S; Jonason, Alan; Reilly, Christine; Veeraraghavan, Janaki; Fisher, Terrence; Doherty, Michael; Klimatcheva, Ekaterina; Mallow, Crystal; Cornelius, Chad; Leonard, John E; Marchi, Nicola; Janigro, Damir; Argaw, Azeb Tadesse; Pham, Trinh; Seils, Jennifer; Bussler, Holm; Torno, Sebold; Kirk, Renee; Howell, Alan; Evans, Elizabeth E; Paris, Mark; Bowers, William J; John, Gareth; Zauderer, Maurice

    2015-01-01

    Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by immune cell infiltration of CNS, blood-brain barrier (BBB) breakdown, localized myelin destruction, and progressive neuronal degeneration. There exists a significant need to identify novel therapeutic targets and strategies that effectively and safely disrupt and even reverse disease pathophysiology. Signaling cascades initiated by semaphorin 4D (SEMA4D) induce glial activation, neuronal process collapse, inhibit migration and differentiation of oligodendrocyte precursor cells (OPCs), and disrupt endothelial tight junctions forming the BBB. To target SEMA4D, we generated a monoclonal antibody that recognizes mouse, rat, monkey and human SEMA4D with high affinity and blocks interaction between SEMA4D and its cognate receptors. In vitro, anti-SEMA4D reverses the inhibitory effects of recombinant SEMA4D on OPC survival and differentiation. In vivo, anti-SEMA4D significantly attenuates experimental autoimmune encephalomyelitis in multiple rodent models by preserving BBB integrity and axonal myelination and can be shown to promote migration of OPC to the site of lesions and improve myelin status following chemically-induced demyelination. Our study underscores SEMA4D as a key factor in CNS disease and supports the further development of antibody-based inhibition of SEMA4D as a novel therapeutic strategy for MS and other neurologic diseases with evidence of demyelination and/or compromise to the neurovascular unit. PMID:25461192

  19. Geometric validation of self-gating k-space-sorted 4D-MRI vs 4D-CT using a respiratory motion phantom

    SciTech Connect

    Yue, Yong Yang, Wensha; McKenzie, Elizabeth; Tuli, Richard; Wallace, Robert; Fraass, Benedick; Fan, Zhaoyang; Pang, Jianing; Deng, Zixin; Li, Debiao

    2015-10-15

    Purpose: MRI is increasingly being used for radiotherapy planning, simulation, and in-treatment-room motion monitoring. To provide more detailed temporal and spatial MR data for these tasks, we have recently developed a novel self-gated (SG) MRI technique with advantage of k-space phase sorting, high isotropic spatial resolution, and high temporal resolution. The current work describes the validation of this 4D-MRI technique using a MRI- and CT-compatible respiratory motion phantom and comparison to 4D-CT. Methods: The 4D-MRI sequence is based on a spoiled gradient echo-based 3D projection reconstruction sequence with self-gating for 4D-MRI at 3 T. Respiratory phase is resolved by using SG k-space lines as the motion surrogate. 4D-MRI images are reconstructed into ten temporal bins with spatial resolution 1.56 × 1.56 × 1.56 mm{sup 3}. A MRI-CT compatible phantom was designed to validate the performance of the 4D-MRI sequence and 4D-CT imaging. A spherical target (diameter 23 mm, volume 6.37 ml) filled with high-concentration gadolinium (Gd) gel is embedded into a plastic box (35 × 40 × 63 mm{sup 3}) and stabilized with low-concentration Gd gel. The phantom, driven by an air pump, is able to produce human-type breathing patterns between 4 and 30 respiratory cycles/min. 4D-CT of the phantom has been acquired in cine mode, and reconstructed into ten phases with slice thickness 1.25 mm. The 4D images sets were imported into a treatment planning software for target contouring. The geometrical accuracy of the 4D MRI and CT images has been quantified using target volume, flattening, and eccentricity. The target motion was measured by tracking the centroids of the spheres in each individual phase. Motion ground-truth was obtained from input signals and real-time video recordings. Results: The dynamic phantom has been operated in four respiratory rate (RR) settings, 6, 10, 15, and 20/min, and was scanned with 4D-MRI and 4D-CT. 4D-CT images have target

  20. A new model of Pde4d deficiency: genetic knock-down of PDE4D enzyme in rats produces an antidepressant phenotype without spatial cognitive effects.

    PubMed

    Schaefer, T L; Braun, A A; Amos-Kroohs, R M; Williams, M T; Ostertag, E; Vorhees, C V

    2012-07-01

    Phosphodiesterases (PDEs) are a superfamily of intracellular second messenger cyclic nucleotide hydrolyzing enzymes composed of 12 families. The Pde4 family has been implicated in depression and cognition, and PDE4 inhibitors have been evaluated as antidepressants and possible cognitive enhancers. Pde4d(-/-) mice show an antidepressant phenotype and learning enhancement on some tests, but not others as do mice treated with PDE4 inhibitors. Here, we report for the first time the behavioral phenotype of a new Pde4d knock-down (KD) rat model of PDE4D deficiency. Consistent with other data on PDE4D deficiency, Pde4d KD rats showed depression resistance in the Porsolt forced swim test and hyperreactivity of the acoustic startle response with no differential response on prepulse inhibition, suggesting no sensorimotor gating defect. Pde4d KD rats also exhibited a small exploratory activity reduction but no difference following habituation, and no enhanced spatial learning or reference memory in the Morris water maze. A selective improvement in route-based learning in the Cincinnati water maze was seen as well as enhanced contextual and cued fear conditioning and a more rapid rate of cued extinction from their higher freezing level that declined to wild-type (WT) levels only after ∼20 extinction trials. The rat model confirms Pde4d's role in depression but not in spatial learning or memory enhancement and shows for the first time higher fear conditioning and altered extinction compared with controls. The new model provides a tool by which to better understand the role of PDE4D in neuropsychiatric disorders and for the development of alternate treatment approaches. PMID:22487514

  1. 4D MRI for the Localization of Parathyroid Adenoma: A Novel Method in Evolution.

    PubMed

    Merchavy, Shlomo; Luckman, Judith; Guindy, Michal; Segev, Yoram; Khafif, Avi

    2016-03-01

    The sestamibi scan (MIBI) and ultrasound (US) are used for preoperative localization of parathyroid adenoma (PTA), with sensitivity as high as 90%. We developed 4-dimensional magnetic resonance imaging (4D MRI) as a novel tool for identifying PTAs. Eleven patients with PTA were enrolled. 4D MRI from the mandible to the aortic arch was used. Optimization of the timing of image acquisition was obtained by changing dynamic and static sequences. PTAs were identified in all except 1 patient. In 9 patients, there was a complete match between the 4D MRI and the US and MIBI, as well as with the operative finding. In 1 patient, the adenoma was correctly localized by 4D MRI, in contrast to the US and MIBI scan. The sensitivity of the 4D MRI was 90% and after optimization, 100%. Specificity was 100%. We concluded that 4D MRI is a reliable technique for identification of PTAs, although more studies are needed. PMID:26598499

  2. Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty

    PubMed Central

    Sun, Qi-Hong; Zheng, Yu; Zhang, Xiao-Lin; Mu, Yi-Ming

    2015-01-01

    Background: Delayed puberty can result either from constitutional delay of growth and puberty (CDP) or idiopathic hypogonadotropic hypogonadism (IHH). Gonadotropin-releasing hormone (GnRH) stimulation test has been generally accepted as a current method for diagnosing delayed puberty. The objective of this research was to assess the cut-off values and the efficacy of GnRH stimulation test in the diagnosis of delayed puberty in both males and females. Methods: A study of 91 IHH, 27 CDP patients, 6 prepubertal children, and 20 pubertal adults was undertaken. Blood samples were obtained at 0, 30, 60, and 120 min after GnRH administration and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured. For each parameter, the sensitivities and specificities were estimated, and the receiver operating characteristic (ROC) curves were constructed. Results: The ROC curves indicated that a serum basal LH <0.6 IU/L or peak LH <9.74 IU/L resulted in moderate sensitivity (73.8% or 80.0%) and specificity (90.9% or 86.4%) in the diagnosis of HH in males. Serum basal LH <0.85 IU/L or basal FSH <2.43 IU/L resulted in moderate sensitivity (80.0% or 100.0%) and specificity (75.0% or 50.0%) in the diagnosis of HH in females. Conclusions: Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males, but unnecessary in females. The most useful predictor is serum basal or peak LH to differentiate these two disorders in males, but serum basal LH or FSH in females. PMID:26365959

  3. Immunological properties of prolactin and studies on a gonadotropin binding inhibitor

    SciTech Connect

    Chang, Y.S.

    1985-01-01

    The physiological role of prolactin in horses has not yet been well defined. With the availability of highly purified ePRL for inducing antibody formation in rabbits and for radiolabeling with Na/sup 125/I, a very sensitive (0.4-0.6 ng/ml) and highly specific homologous RIA for ePRL was developed. A heterologous RIA using /sup 125/I-labeled ovine PRL and anti-ePRL antiserum was also developed and compared to the homologous RIA for ePRL. Of the two systems, it is concluded that this homologous RIA system is more suitable and more reliable for measuring prolactin concentration in horse serum samples. Until now, biochemical information on PRL has not been available for reptilian species. Sea turtle (Chelonia mydas) prolactin was purified from pituitary extracts by selective precipitation, DEAE-cellulose chromatography and gel filtration. Similar to other species of PRL, sea turtle PRL is a 22,000-24,000 daltons protein and contains a high content of glutamic acid, aspartic acid, serine and leucine, the N-terminal amino acid residue. Gonadotropin (FSH) binding inhibitor was partially purified from sheep testes by ammonium sulfate fractionation and ion exchange chromatography. The FSH-BI (molecular weight: 50,000 daltons, estimated by gel filtration) contains a protein moiety necessary for binding inhibitory activity. The inhibition of the binding of /sup 125/I-labeled ovine FSH to its receptor by the FSH-BI is not competitive. Both in vivo and in vitro biological studies of FSH-BI preparations in rats indicated various effects on FSH and LH activities at the gonadal level. These findings suggest a physiological role for FSH-BI in the regulation of reproduction.

  4. Progestin increases the expression of gonadotropins in pituitaries of male zebrafish.

    PubMed

    Wang, Cuili; Liu, Dongteng; Chen, Weiting; Ge, Wei; Hong, Wanshu; Zhu, Yong; Chen, Shi X

    2016-07-01

    Our previous study showed that the in vivo positive effects of 17α,20β-dihydroxy-4-pregnen-3-one (DHP), the major progestin in zebrafish, on early spermatogenesis was much stronger than the ex vivo ones, which may suggest an effect of DHP on the expression of gonadotropins. In our present study, we first observed that fshb and lhb mRNA levels in the pituitary of male adult zebrafish were greatly inhibited by 3 weeks exposure to 10nM estradiol (E2). However, an additional 24h 100nM DHP exposure not only reversed the E2-induced inhibition, but also significantly increased the expression of fshb and lhb mRNA. These stimulatory effects were also observed in male adult fish without E2 pretreatment, and a time course experiment showed that it took 24h for fshb and 12h for lhb to respond significantly. Because these stimulatory activities were partially antagonized by a nuclear progesterone receptor (Pgr) antagonist mifepristone, we generated a Pgr-knockout (pgr(-/-)) model using the TALEN technique. With and without DHP in vivo treatment, fshb and lhb mRNA levels of pgr(-/-) were significantly lower than those of pgr(+/+) Furthermore, ex vivo treatment of pituitary fragments of pgr(-/-) with DHP stimulated lhb, but not fshb mRNA expression. Results from double-colored fluorescent in situ hybridization showed that pgr mRNA was expressed only in fshb-expressing cells. Taken together, our results indicated that DHP participated in the regulation of neuroendocrine control of reproduction in male zebrafish, and exerted a Pgr-mediated direct stimulatory effect on fshb mRNA at pituitary level. PMID:27113852

  5. Characterization of rat leydig cell gonadotropin receptor structure by affinity cross-linking

    SciTech Connect

    Zhang, Q.Y.; Hwang, J.; Menon, K.M.J.

    1986-05-01

    The gonadotropin receptor from rat leydig cell has been characterized with respect to binding kinetics and physiological regulation. The present study was intended to examine the structure of the receptor. Leydig cell suspension was prepared by either collagenase digestion or by mechanical disruption of the testis. The cells were incubated with /sup 125/I-hCG and the unreacted hCG was removed by centrifugation. The /sup 125/I-hCG was then covalently linked to the cell surface receptor using cleavable (dithiobis (succinimidyl propionate)) and non-cleavable (disuccinimidyl suberate) cross-linking reagents. The extracted cross-linked membrane proteins were resolved on SDS-polyacrylamide gels under reducing and non-reducing conditions and subjected to autoradiographic analysis. Under non-reducing conditions, two labeled species with M/sub r/ = 87,000 and 120,000 were detected. However, only one labeled band was detected under reducing conditions with M/sub r/ = 64,000. The binding of /sup 125/I-hCG to the receptor was inhibited by hCG and LH, but not by a number of peptides and proteins. The data suggest that hCG receptor in leydig cell is an oligomeric complex consisting of four subunits, ..cap alpha cap alpha beta gamma... The ..beta.. and ..gamma.. subunits are each linked to an ..cap alpha.. subunit through disulfide linkage and the hormone binds to each ..cap alpha.. subunit. The two dimers formed (..cap alpha beta cap alpha gamma..) are associated by noncovalent interactions.

  6. Information Transfer in Gonadotropin-releasing Hormone (GnRH) Signaling

    PubMed Central

    Garner, Kathryn L.; Perrett, Rebecca M.; Voliotis, Margaritis; Bowsher, Clive; Pope, George R.; Pham, Thanh; Caunt, Christopher J.; Tsaneva-Atanasova, Krasimira; McArdle, Craig A.

    2016-01-01

    Cell signaling pathways are noisy communication channels, and statistical measures derived from information theory can be used to quantify the information they transfer. Here we use single cell signaling measures to calculate mutual information as a measure of information transfer via gonadotropin-releasing hormone (GnRH) receptors (GnRHR) to extracellular signal-regulated kinase (ERK) or nuclear factor of activated T-cells (NFAT). This revealed mutual information values <1 bit, implying that individual GnRH-responsive cells cannot unambiguously differentiate even two equally probable input concentrations. Addressing possible mechanisms for mitigation of information loss, we focused on the ERK pathway and developed a stochastic activation model incorporating negative feedback and constitutive activity. Model simulations revealed interplay between fast (min) and slow (min-h) negative feedback loops with maximal information transfer at intermediate feedback levels. Consistent with this, experiments revealed that reducing negative feedback (by expressing catalytically inactive ERK2) and increasing negative feedback (by Egr1-driven expression of dual-specificity phosphatase 5 (DUSP5)) both reduced information transfer from GnRHR to ERK. It was also reduced by blocking protein synthesis (to prevent GnRH from increasing DUSP expression) but did not differ for different GnRHRs that do or do not undergo rapid homologous desensitization. Thus, the first statistical measures of information transfer via these receptors reveals that individual cells are unreliable sensors of GnRH concentration and that this reliability is maximal at intermediate levels of ERK-mediated negative feedback but is not influenced by receptor desensitization. PMID:26644469

  7. Estradiol Restrains Prepubertal Gonadotropin Secretion in Female Mice via Activation of ERα in Kisspeptin Neurons.

    PubMed

    Dubois, Sharon L; Wolfe, Andrew; Radovick, Sally; Boehm, Ulrich; Levine, Jon E

    2016-04-01

    Elimination of estrogen receptorα (ERα) from kisspeptin (Kiss1) neurons results in premature LH release and pubertal onset, implicating these receptors in 17β-estradiol (E2)-mediated negative feedback regulation of GnRH release during the prepubertal period. Here, we tested the dependency of prepubertal negative feedback on ERα in Kiss1 neurons. Prepubertal (postnatal d 14) and peripubertal (postnatal d 34) wild-type (WT) and Kiss1 cell-specific ERα knockout (KERαKO) female mice were sham operated or ovariectomized and treated with either vehicle- or E2-containing capsules. Plasma and tissues were collected 2 days after surgery for analysis. Ovariectomy increased LH and FSH levels, and E2 treatments completely prevented these increases in WT mice of both ages. However, in prepubertal KERαKO mice, basal LH levels were elevated vs WT, and both LH and FSH levels were not further increased by ovariectomy or affected by E2 treatment. Similarly, Kiss1 mRNA levels in the medial basal hypothalamus, which includes the arcuate nucleus, were suppressed with E2 treatment in ovariectomized prepubertal WT mice but remained unaffected by any treatment in KERαKO mice. In peripubertal KERαKO mice, basal LH and FSH levels were not elevated vs WT and were unaffected by ovariectomy or E2. In contrast to our previous findings in adult animals, these results demonstrate that suppression of gonadotropins and Kiss1 mRNA by E2 in prepubertal animals depends upon ERα activation in Kiss1 neurons. Our observations are consistent with the hypothesis that these receptors play a critical role in restraining GnRH release before the onset and completion of puberty. PMID:26824364

  8. SU-D-17A-04: The Impact of Audiovisual Biofeedback On Image Quality During 4D Functional and Anatomic Imaging: Results of a Prospective Clinical Trial

    SciTech Connect

    Keall, P; Pollock, S; Yang, J; Diehn, M; Berger, J; Graves, E; Loo, B; Yamamoto, T

    2014-06-01

    Purpose: The ability of audiovisual (AV) biofeedback to improve breathing regularity has not previously been investigated for functional imaging studies. The purpose of this study was to investigate the impact of AV biofeedback on 4D-PET and 4D-CT image quality in a prospective clinical trial. We hypothesized that motion blurring in 4D-PET images and the number of artifacts in 4D-CT images are reduced using AV biofeedback. Methods: AV biofeedback is a real-time, interactive and personalized system designed to help a patient self-regulate his/her breathing using a patient-specific representative waveform and musical guides. In an IRB-approved prospective clinical trial, 4D-PET and 4D-CT images of 10 lung cancer patients were acquired with AV biofeedback (AV) and free breathing (FB). The 4D-PET images in 6 respiratory bins were analyzed for motion blurring by: (1) decrease of GTVPET and (2) increase of SUVmax in 4-DPET compared to 3D-PET. The 4D-CT images were analyzed for artifacts by: (1) comparing normalized cross correlation-based scores (NCCS); and (2) quantifying a visual assessment score (VAS). A two-tailed paired t-test was used to test the hypotheses. Results: The impact of AV biofeedback on 4D-PET and 4D-CT images varied widely between patients, suggesting inconsistent patient comprehension and capability. Overall, the 4D-PET decrease of GTVPET was 2.0±3.0cm3 with AV and 2.3±3.9cm{sup 3} for FB (p=0.61). The 4D-PET increase of SUVmax was 1.6±1.0 with AV and 1.1±0.8 with FB (p=0.002). The 4D-CT NCCS were 0.65±0.27 with AV and 0.60±0.32 for FB (p=0.32). The 4D-CT VAS was 0.0±2.7 (p=ns). Conclusion: A 10-patient study demonstrated a statistically significant reduction of motion blurring of AV over FB for 1/2 functional 4D-PET imaging metrics. No difference between AV and FB was found for 2 anatomic 4D-CT imaging metrics. Future studies will focus on optimizing the human-computer interface and including patient training sessions for improved

  9. The Relationship Between Digit Ratio (2D:4D) and Sexual Orientation in Men from China.

    PubMed

    Xu, Yin; Zheng, Yong

    2016-04-01

    We examined the relationship between 2D:4D digit ratio and sexual orientation in men from China and analyzed the influences of the components used to assess sexual orientation and the criteria used to classify individuals as homosexual on this relationship. A total of 309 male and 110 female participants took part in a web-based survey. Our results showed that heterosexual men had a significantly lower 2D:4D than heterosexual women and exclusively homosexual men had a significantly higher left 2D:4D than heterosexual men whereas only exclusively homosexual men had a significantly higher right 2D:4D than heterosexual men when sexual orientation was assessed via sexual attraction. The left 2D:4D showed a significant positive correlation with sexual identity, sexual attraction, and sexual behavior, and the right 2D:4D showed a significant positive correlation with sexual attraction. The effect sizes for differences in 2D:4D between homosexual and heterosexual men varied according to criteria used to classify individuals as homosexual and sexual orientation components; the more stringent the criteria (scores closer to the homosexual category), the larger the effect sizes; further, sexual attraction yielded the largest effect size. There were no significant effects of age and latitude on Chinese 2D:4D. This study contributes to the current understanding of the relationship between 2D:4D and male sexual orientation. PMID:25957135

  10. 4D VMAT, gated VMAT, and 3D VMAT for stereotactic body radiation therapy in lung

    NASA Astrophysics Data System (ADS)

    Chin, E.; Loewen, S. K.; Nichol, A.; Otto, K.

    2013-02-01

    Four-dimensional volumetric modulated arc therapy (4D VMAT) is a treatment strategy for lung cancers that aims to exploit relative target and tissue motion to improve organ at risk (OAR) sparing. The algorithm incorporates the entire patient respiratory cycle using 4D CT data into the optimization process. Resulting treatment plans synchronize the delivery of each beam aperture to a specific phase of target motion. Stereotactic body radiation therapy treatment plans for 4D VMAT, gated VMAT, and 3D VMAT were generated on three patients with non-small cell lung cancer. Tumour motion ranged from 1.4-3.4 cm. The dose and fractionation scheme was 48 Gy in four fractions. A B-spline transformation model registered the 4D CT images. 4D dose volume histograms (4D DVH) were calculated from total dose accumulated at the maximum exhalation. For the majority of OARs, gated VMAT achieved the most radiation sparing but treatment times were 77-148% longer than 3D VMAT. 4D VMAT plan qualities were comparable to gated VMAT, but treatment times were only 11-25% longer than 3D VMAT. 4D VMAT's improvement of healthy tissue sparing can allow for further dose escalation. Future study could potentially adapt 4D VMAT to irregular patient breathing patterns.

  11. The role of semaphorin 4D as a potential biomarker for antiangiogenic therapy in colorectal cancer

    PubMed Central

    Ding, Xiaojie; Qiu, Lijuan; Zhang, Lijuan; Xi, Juemin; Li, Duo; Huang, Xinwei; Zhao, Yujiao; Wang, Xiaodang; Sun, Qiangming

    2016-01-01

    Background Semaphorin 4D (Sema4D) belongs to the class IV semaphorins, and accumulating evidence has indicated that its elevated level may be one strategy by which tumors evade current anti-angiogenic therapies. The biological roles of Sema4D in colorectal cancer (CRC), however, remain largely undefined. This study was designed to investigate the effects of Sema4D on tumor angiogenesis and growth in CRC, especially in different vascular endothelial growth factor (VEGF) backgrounds. Methods The expression of Sema4D in human CRC was evaluated by immunohistochemical analysis of tumors and their matching normal control tissues. The expression level of Sema4D and VEGF was investigated in different CRC cell lines. To evaluate the contributions of Sema4D to tumor-induced angiogenesis, two CRC cell lines with opposite VEGF backgrounds were infected with lentiviruses expressing Sema4D or Sema4D short hairpin RNA, followed by in vitro migration and in vivo tumor angiogenic assays. Results Immunohistochemical analysis of human CRC revealed high levels of Sema4D in a cell surface pattern. In all, 84.85% of CRC samples analyzed exhibited moderate to strong Sema4D expression. The positive ratios of Sema4D staining for well, moderately, and poorly differentiated cancers were 71.43%, 96.67%, and 77.27%, respectively. Sema4D is highly expressed in five different CRC cell lines, while VEGF expression level varies among these cell lines. HCT-116 showed the lowest VEGF level, while Caco-2 showed the maximum VEGF level. In vitro migration results show that regardless of cell type and VEGF background, Sema4D showed an enhanced in vitro proangiogenic effect to induce the migration of human umbilical vein endothelial cells. Finally, in vivo tumor angiogenic assays demonstrated that Sema4D alone can elicit a significant angiogenic response to promote tumor growth independently of VEGF. Conclusion Targeting Sema4D might serve as a parallel option for antiangiogenic therapy for CRC

  12. A sinogram warping strategy for pre-reconstruction 4D PET optimization.

    PubMed

    Gianoli, Chiara; Riboldi, Marco; Fontana, Giulia; Kurz, Christopher; Parodi, Katia; Baroni, Guido

    2016-03-01

    A novel strategy for 4D PET optimization in the sinogram domain is proposed, aiming at motion model application before image reconstruction ("sinogram warping" strategy). Compared to state-of-the-art 4D-MLEM reconstruction, the proposed strategy is able to optimize the image SNR, avoiding iterative direct and inverse warping procedures, which are typical of the 4D-MLEM algorithm. A full-count statistics sinogram of the motion-compensated 4D PET reference phase is generated by warping the sinograms corresponding to the different PET phases. This is achieved relying on a motion model expressed in the sinogram domain. The strategy was tested on the anthropomorphic 4D PET-CT NCAT phantom in comparison with the 4D-MLEM algorithm, with particular reference to robustness to PET-CT co-registrations artefacts. The MLEM reconstruction of the warped sinogram according to the proposed strategy exhibited better accuracy (up to +40.90 % with respect to the ideal value), whereas images reconstructed according to the 4D-MLEM reconstruction resulted in less noisy (down to -26.90 % with respect to the ideal value) but more blurred. The sinogram warping strategy demonstrates advantages with respect to 4D-MLEM algorithm. These advantages are paid back by introducing approximation of the deformation field, and further efforts are required to mitigate the impact of such an approximation in clinical 4D PET reconstruction. PMID:26126871

  13. Lung Segmentation in 4D CT Volumes Based on Robust Active Shape Model Matching

    PubMed Central

    Gill, Gurman; Beichel, Reinhard R.

    2015-01-01

    Dynamic and longitudinal lung CT imaging produce 4D lung image data sets, enabling applications like radiation treatment planning or assessment of response to treatment of lung diseases. In this paper, we present a 4D lung segmentation method that mutually utilizes all individual CT volumes to derive segmentations for each CT data set. Our approach is based on a 3D robust active shape model and extends it to fully utilize 4D lung image data sets. This yields an initial segmentation for the 4D volume, which is then refined by using a 4D optimal surface finding algorithm. The approach was evaluated on a diverse set of 152 CT scans of normal and diseased lungs, consisting of total lung capacity and functional residual capacity scan pairs. In addition, a comparison to a 3D segmentation method and a registration based 4D lung segmentation approach was performed. The proposed 4D method obtained an average Dice coefficient of 0.9773 ± 0.0254, which was statistically significantly better (p value ≪0.001) than the 3D method (0.9659 ± 0.0517). Compared to the registration based 4D method, our method obtained better or similar performance, but was 58.6% faster. Also, the method can be easily expanded to process 4D CT data sets consisting of several volumes. PMID:26557844

  14. Equine Chorionic Gonadotropin and Human Chorionic Gonadotropin Stimulation Increase the Number of Luteinized Follicles and the Progesterone Level Compared with Cabergoline Stimulation in Anoestrus Bitches.

    PubMed

    Jurczak, A; Domosławska, A; Bukowska, B; Janowski, T

    2016-08-01

    In this study, ovarian morphologies and blood progesterone concentrations following oestrous induction in bitches were examined. Fifty-three clinically healthy anoestrus bitches received cabergoline at a daily dose of 5 μg/kg of body weight per os for 21 days (group I) or subcutaneous equine chorionic gonadotropin at a dose of 20 IU/kg of body weight for five consecutive days with an additional 500 IU s.c. per bitch of human chorionic gonadotropin on the last day of treatment (group II). Twenty bitches that spontaneously displayed oestrous signs were left untreated and served as controls (group III). The induced oestrous rates and ovulation rates in groups I and II were 60.0% vs 64.3% and 86.7% vs 83.3%, respectively. Morphological assessments of the ovarian structures after ovariohysterectomy revealed an increase in the number of luteinized follicles and cysts in group II compared with the two other groups (p < 0.001). In contrast, the numbers of corpora lutea and follicles were similar in all groups. In accordance with the above-mentioned alteration, the progesterone concentration in the gonadotropin group (II) was increased (p < 0.001) in the periovulatory period compared with the other two groups. During the entire sampling period, the progesterone profiles in the cabergoline (I) and control (III) groups were similar and typical of normally cycling bitches. In conclusion, gonadotropin treatment is associated with an increased progesterone level during the periovulatory period that probably originates from luteinized follicles, whereas cabergoline treatment induces cycles with both physiological progesterone concentrations and ovarian morphologies. PMID:27321641

  15. Anterior Cingulate Cortex Gray Matter Volume Mediates an Association between 2D:4D Ratio and Trait Aggression in Women but not Men

    PubMed Central

    Gorka, Adam X.; Norman, Rachel E.; Radtke, Spenser R.; Carré, Justin M.; Hariri, Ahmad R.

    2015-01-01

    Previous research demonstrates that prenatal testosterone exposure increases aggression, possibly through its effects on the structure and function of neural circuits supporting threat detection and emotion regulation. Here we examined associations between regional gray matter volume, trait aggression, and the ratio of the second and fourth digit of the hand (2D:4D ratio) as a putative index of prenatal testosterone exposure in 464 healthy young adult volunteers. Our analyses revealed a significant positive correlation between 2D:4D ratio and gray matter volume of the dorsal anterior cingulate cortex (dACC), a brain region supporting, emotion regulation, conflict monitoring, and behavioral inhibition. Subsequent analyses demonstrated that reduced (i.e., masculinized) gray matter volume in the dACC mediated the relationship between 2D:4D ratio and aggression in women, but not men. Expanding on this gender-specific mediation, additional analyses demonstrated that the shared variance between 2D:4D ratio, dACC gray matter volume, and aggression in women reflected the tendency to engage in cognitive reappraisal of emotionally provocative stimuli. Our results provide novel evidence that 2D:4D ratio is associated with masculinization of dACC gray matter volume, and that this neural phenotype mediates, in part, the expression of trait aggression in women. PMID:25827959

  16. Rapid enlargement of an intracranial germ cell tumor after gonadotropin hormone therapy.

    PubMed

    Sasagawa, Yasuo; Tachibana, Osamu; Nakagawa, Athushi; Nakada, Satoko; Nojima, Takayuki; Koya, Daisuke; Iizuka, Hideaki

    2016-09-01

    We report a case of an intracranial germ cell tumor (iGCT) that showed rapid enlargement after human chorionic gonadotropin (hCG) hormone therapy for pituitary hypogonadism. A 16-year-old boy presented with headache and was diagnosed with a suprasellar tumor. He was initially observed without surgery. Intranasal desmopressin therapy was started for central diabetes insipidus, but there was no change in the tumor size on MRI. The diagnosis of the tumor remained unknown for 4years. Levels of serum gonadotropin hormones (follicle-stimulating and luteinizing hormone) and testosterone progressively decreased, and the patient developed pituitary hypogonadism and complained about his undeveloped beard, lack of underarm hair, and erectile dysfunction. Intramuscular gonadotropin injection (hCG 5000U×2/week) was started at age 20. Eight months after the first gonadotropin injection, the MRI showed tumor growth with vivid enhancement. Craniotomy was performed and the tumor was partially resected. The histological diagnosis was immature teratoma. After surgery, the patient was treated with 5 cycles of chemotherapy with carboplatin and etoposide. He also received radiation therapy of 50Gy (20Gy tumor bed and 30Gy whole ventricles) to the residual tumor, after which the tumor decreased in size. We postulate that iGCT may be at risk of progression during hCG hormone therapy. Thus, careful monitoring is required for a patient with iGCT who receives this therapy. PMID:27050912

  17. A review of luteinising hormone and human chorionic gonadotropin when used in assisted reproductive technology.

    PubMed

    Ezcurra, Diego; Humaidan, Peter

    2014-01-01

    Gonadotropins extracted from the urine of post-menopausal women have traditionally been used to stimulate folliculogenesis in the treatment of infertility and in assisted reproductive technology (ART). Products, such as human menopausal gonadotropin (hMG), consist not only of a mixture of the hormones, follicle-stimulating hormone (FSH), luteinising hormone (LH) and human chorionic gonadotropin (hCG), but also other biologically active contaminants, such as growth factors, binding proteins and prion proteins. The actual amount of molecular LH in hMG preparations varies considerably due to the purification process, thus hCG, mimicking LH action, is added to standardise the product. However, unlike LH, hCG plays a different role during the natural human menstrual cycle. It is secreted by the embryo and placenta, and its main role is to support implantation and pregnancy. More recently, recombinant gonadotropins (r-hFSH and r-hLH) have become available for ART therapies. Recombinant LH contains only LH molecules. In the field of reproduction there has been controversy in recent years over whether r-hLH or hCG should be used for ART. This review examines the existing evidence for molecular and functional differences between LH and hCG and assesses the clinical implications of hCG-supplemented urinary therapy compared with recombinant therapies used for ART. PMID:25280580

  18. 21 CFR 862.1155 - Human chorionic gonadotropin (HCG) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Human chorionic gonadotropin (HCG) test system. 862.1155 Section 862.1155 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  19. 21 CFR 862.1155 - Human chorionic gonadotropin (HCG) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Human chorionic gonadotropin (HCG) test system. 862.1155 Section 862.1155 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  20. 21 CFR 862.1155 - Human chorionic gonadotropin (HCG) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Human chorionic gonadotropin (HCG) test system. 862.1155 Section 862.1155 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  1. Ovarian refractoriness to gonadotropins in cases of inappropriate lactation: restoration of ovarian function with bromocryptine.

    PubMed

    Mroueh, A M; Siler-Khodr, T M

    1976-12-01

    In ten patients with amenorrhea-galactorrhea who had hyperprolactinemia, ovulation could not be induced clomiphene citrate or exogenous gonadotropins. Treatment with bromocryptine in eight of these patients resulted in suppression of PRL in all, cessation of galactorrhea and ovulation in seven and conception in five. PMID:1036743

  2. Metabolic status, gonadotropin secretion, and ovarian function during acute nutrient restriction of beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of acute nutritional restriction on metabolic status, gonadotropin secretion, and ovarian function of heifers was determined in 2 experiments. In Exp. 1, 14-mo-old heifers were fed a diet supplying 1.2 × maintenance energy requirements (1.2M). After 10 d, heifers were fed 1.2M or were res...

  3. The Stimulatory Actions of Kisspeptin on Gonadotropin Secretion in Prepubertal Swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine the effects of kisspeptin on gonadotropin secretion in prepubertal gilts were surgically fitted with a lateral intracerebralventricular (ICV) cannula using a steriotaxic procedure. Animals randomly received an ICV infusion of 150 ul sterile phosphate buffered (PBS) saline, or either 1...

  4. INHIBIN INCREASES AND PROGESTERONE DECREASES RECEPTORS FOR GONADOTROPIN-RELEASING HORMONE IN OVINE PITUITARY CULTURE

    EPA Science Inventory

    The effects of progesterone (P4) and inhibin on gonadotropin-releasing hormone receptor number (GnRH-R) and binding affinity were investigated using ovine pituitary cells in culture. ollowing treatment with P4 or porcine inhibin, GnRH binding was analyzed using a radioligand-rece...

  5. Effects of estrogens, clomiphene and castration in a male transsexual with as compared to those without hypersecretion of gonadotropins.

    PubMed

    Goh, H H; Ratnam, S S

    1990-06-01

    A 24-year-old male-to-female transsexual with hypersecretion of gonadotropins was studied with regard to his recovery from sex steroid hormone treatment before his sex change operation and the effects of castration, clomiphene tests and estrogens on the hypersecretion of gonadotropins. Computer-assisted tomography and X-ray results indicated that the possibility that the hypersecretion of gonadotropins was not associated with a pituitary adenoma could not be ruled out. After a period of recovery from previous sex steroid hormone therapy, inappropriately high FSH and LH levels in the presence of normal male levels of testosterone and estradiol were found. The latter normal levels failed to suppress both the FSH and LH levels. From the clomiphene challenge tests carried out before and after the sex reassignment operation, the estradiol infusion studies and treatment with ethinyl estradiol after the sex reassignment operation, it appears that the hypersecretion of gonadotropins was responsive to the negative feedback effect of estrogens. However, the sensitivity, especially that of FSH, was very attenuated. Even after 23 weeks of ethinyl estradiol treatment FSH remained well above the upper limit for normal men. The results showed that before his sex change operation the hypersecretion of gonadotropins in the patient was probably under autonomous control. Testicular factors at normal male concentrations appear to have a minimal negative feedback effect on the hypersecretion of gonadotropins. However, hypersecretion of gonadotropins can be suppressed by prolonged exposure to estrogens. PMID:2118708

  6. Actions of pregnant mare serum gonadotropin in the immature female rat: correlative changes in blood steroids, gonadotropins, and cytoplasmic estradiol receptors of the anterior pituitary and hypothalamus.

    PubMed

    Parker, C R; Costoff, A; Muldoon, T G; Mahesh, V B

    1976-01-01

    Several blood steroids, serum gonadotropins and cytosol estradiol receptors of the anterior pituitary and hypothalamus were quantified in immature female rats which were induced to ovulate with pregnant mare's serum gonadotropin (PMSG). Studies revealed that serum levels of progesterone, 17-hydroxyprogesterone, testosterone, androstenedione and estradiol were initially elevated at 6 PM (day 30) after administration of 8 IU of PMSG at 10 AM day 30. Serum levels of estradiol and testosterone rose progressively from day 30 through the AM of day 32. A further increase in serum concentrations of progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, and dehydroepiandrosterone occurred on the PM of day 32 whereas serum estradiol levels declined. Serum levels of all steroids declined on the day of estrus (33) and only progesterone levels were further elevated on day 34 (diestrus). Dihydrotestosterone concentrations were minimally altered by PMSG treatment. Saline administration resulted in no significant alterations in levels of any steroid quantified from day 29 to 34 in control animals. A progressive decline in cytosol estradiol receptor content of the anterior pituitary and hypothalamus was documented following PMSG treatment of intact female rats; there was no depletion of receptors following PMSG administration to ovariectomized immature rats. Maximal depletion of cytosol estradiol receptors occurred on day 32 with replenishment of cytosol estradiol receptor levels on estrus (day 33). The preovulatory gonadotropin surge was found to occur on the PM of day 32 after maximal receptor depletion. The cycle of depletion and replenishment of receptors was repeated during a second spontaneous estrous cycle four days later which coincided with a rise and fall in serum estradiol levels. It is suggested that the depletion of cytosol estradiol receptors of the anterior pituitary/hypothalamic unit may be causally related to the preovulatory gonadotropin surge

  7. Curves of AW(k)-type in 4D Galilean space

    NASA Astrophysics Data System (ADS)

    Külahci, Mihriban

    2016-04-01

    In this paper, we investigate curves of AW(k)-type (1 ≤ k ≤ 3) in 4D Galilean space and we give curvature conditions of these kind of curves. Also, we study weak AW(2)-type curves. Furthermore, we express mannheim curves of AW(k)-type in 4D Galilean space.

  8. Elite collegiate tennis athletes have lower 2D: 4D ratios than those of nonathlete controls.

    PubMed

    Hsu, Cheng-Chen; Su, Borcherng; Kan, Nai-Wen; Lai, Su-Ling; Fong, Tsorng-Harn; Chi, Chung-Pu; Chang, Ching-Chyuan; Hsu, Mei-Chich

    2015-03-01

    The ratio of the length of the second finger (index finger) to the fourth finger (ring finger) (2D:4D ratio) is a putative marker for prenatal hormones. Physiological research has suggested a low 2D:4D ratio correlates with high athletic ability. Athletes of specific sports (e.g., American football) have lower 2D:4D ratios than those of nonathletes, whereas athletes of some sports (e.g., rowing, gymnastics, and soccer) do not. This study investigated the 2D:4D ratios among collegiate tennis athletes, elite collegiate tennis athletes, and nonelite collegiate tennis athletes and compared them with nonathletes of both sexes. The participants included 43 elite collegiate tennis athletes (Level I intercollegiate athletes in Taiwan; 27 males and 16 females), 107 nonelite collegiate tennis athletes (Level II athletes; 55 males and 52 females), and 166 nonathlete college students (80 males and 86 females). The principle findings suggest that (a) regardless of sex, collegiate tennis athletes have lower 2D:4D values than those of nonathletes; (b) elite collegiate tennis athletes have lower 2D:4D values than those of nonathletes; (c) among females but not males, athletes and nonelite athletes have lower 2D:4D values than those of nonathletes; and (d) males have lower 2D:4D values than those of females. PMID:25226321

  9. In Vivo Evaluation of the Genotoxic Effects of Gonadotropins on Rat Reticulocytes

    PubMed Central

    Duran, Bulent; Koc, Onder; Ozdemirci, Safak; Topcuoglu, Ata; Ozdemir, Ozturk

    2011-01-01

    Background Gonadotropins, as ovulation-inducing drugs, have been used widely to treat infertility. An epidemiologic correlation between infertility therapy and ovarian cancer development has been reported. However, the effect of gonadotropins in the formation of reproductive tract cancers is controversial. Objective The aim of the study was to determine the in vivo genotoxic effects of gonadotropins on rat reticulocytes. Methods In this prospective, randomized, controlled study, rats were randomly assigned to 1 of 5 groups. The calculated rat doses of 0.65 human menopausal gonadotropin (hMG), 0.95 hMG, 0.65 follitropin beta (FB), 0.95 FB, or normal saline (control group) were injected, respectively. These calculated rat doses (U/g) are based on average human gonadotropin doses of 150 and 225 IU/d for a 70-kg woman given in 2-mL saline (the control group received 2 mL of saline). Injections were administered once per day for 5 days, followed by 5 days of rest. Each treatment was repeated for 6 estrus cycles in the rats for a total of 12 estrus cycles. Six months after the last day of the 12th cycle, the rats were euthanized. Bone marrow tissues were removed, and pluripotent reticulocyte cells with micronuclei, nuclear buds, and binuclear abnormalities were analyzed using an in situ micronuclei assay under light microscopy. The proportion of micronucleated cells, cells with anaphase bridge, nuclear buds, and other nuclear abnormalities were measured. Results The number of cells with nuclear buds and binuclear abnormalities in the hMG 225 and FB 225 groups was significantly higher (P < 0.05) than that from the hMG 150, FB 150, and control groups in the cytogenetic analysis of bone marrow stem cells. An increased rate of genotoxicity in all gonadotropin groups versus that of placebo was found. Conclusion In rats, the micronucleus genotoxicity assay suggests a dose-dependent gonadotropin effect on genomic instability in bone marrow stem cells in vivo. PMID:24648576

  10. A piloted simulator evaluation of a ground-based 4D descent advisor algorithm

    NASA Technical Reports Server (NTRS)

    Green, Steven M.; Davis, Thomas J.; Erzberger, Heinz

    1987-01-01

    A ground-based, four-dimensional (4D) descent-advisor algorithm is under development at NASA Ames Research Center. The algorithm combines detailed aerodynamic, propulsive, and atmospheric models with an efficient numerical integration scheme to generate 4D descent advisories. This paper investigates the ability of the 4D descent advisor algorithm to provide adequate control of arrival time for aircraft not equipped with on-board 4D guidance systems. A piloted simulation was conducted to determine the precision with which the descent advisor could predict the 4D trajectories of typical straight-in descents flown by airline pilots under different wind conditions. The effects of errors in the estimation of wind and initial aircraft weight were also studied. A description of the descent advisor as well as the results of the simulation studies are presented.

  11. A piloted simulator evaluation of a ground-based 4-D descent advisor algorithm

    NASA Technical Reports Server (NTRS)

    Davis, Thomas J.; Green, Steven M.; Erzberger, Heinz

    1990-01-01

    A ground-based, four dimensional (4D) descent-advisor algorithm is under development at NASA-Ames. The algorithm combines detailed aerodynamic, propulsive, and atmospheric models with an efficient numerical integration scheme to generate 4D descent advisories. The ability is investigated of the 4D descent advisor algorithm to provide adequate control of arrival time for aircraft not equipped with on-board 4D guidance systems. A piloted simulation was conducted to determine the precision with which the descent advisor could predict the 4D trajectories of typical straight-in descents flown by airline pilots under different wind conditions. The effects of errors in the estimation of wind and initial aircraft weight were also studied. A description of the descent advisor as well as the result of the simulation studies are presented.

  12. Clear evidence of a continuum theory of 4D Euclidean simplicial quantum gravity

    NASA Astrophysics Data System (ADS)

    Egawa, H. S.; Horata, S.; Yukawa, T.

    2002-03-01

    Four-dimensional (4D) simplicial quantum gravity coupled to both scalar fields ( NX) and gauge fields ( NA) has been studied using Monte-Carlo simulations. The matter dependence of the string susceptibility exponent γ (4) is estimated. Furthermore, we compare our numerical results with Background-Metric-Indepenent (BMI) formulation conjectured to describe the quantum field theory of gravity in 4D. The numerical results suggest that the 4D simplicial quantum gravity is related to the conformal gravity in 4D. Therefore, we propose a phase structure in detail with adding both scalar and gauge fields and discuss the possibility and the property of a continuum theory of 4D Euclidean simplicial quantum gravity.

  13. Clear evidence of a continuum theory of 4D Euclidean simplicial quantum gravity

    NASA Astrophysics Data System (ADS)

    Egawa, H. S.; Horata, S.; Yukawa, T.

    Four-dimensional (4D) simplicial quantum gravity coupled to both scalar fields (NX) and gauge fields (NA) has been studied using Monte-Carlo simulations. The matter dependence of the string susceptibility exponent γ(4) is estimated. Furthermore, we compare our numerical results with Background-Metric-Indepenent (BMI) formulation conjectured to describe the quantum field theory of gravity in 4D. The numerical results suggest that the 4D simplicial quantum gravity is related to the conformal gravity in 4D. Therefore, we propose a phase structure in detail with adding both scalar and gauge fields and discuss the possibility and the property of a continuum theory of 4D Euclidean simplicial quantum gravity.

  14. Use of incremental analysis updates in 4D-Var data assimilation

    NASA Astrophysics Data System (ADS)

    Zhang, Banglin; Tallapragada, Vijay; Weng, Fuzhong; Sippel, Jason; Ma, Zaizhong

    2015-12-01

    The four-dimensional variational (4D-Var) data assimilation systems used in most operational and research centers use initial condition increments as control variables and adjust initial increments to find optimal analysis solutions. This approach may sometimes create discontinuities in analysis fields and produce undesirable spin ups and spin downs. This study explores using incremental analysis updates (IAU) in 4D-Var to reduce the analysis discontinuities. IAU-based 4D-Var has almost the same mathematical formula as conventional 4D-Var if the initial condition increments are replaced with time-integrated increments as control variables. The IAU technique was implemented in the NASA/GSFC 4D-Var prototype and compared against a control run without IAU. The results showed that the initial precipitation spikes were removed and that other discontinuities were also reduced, especially for the analysis of surface temperature.

  15. The Influence of Facial Characteristics on the Relation between Male 2D:4D and Dominance

    PubMed Central

    Ryckmans, Jan; Millet, Kobe; Warlop, Luk

    2015-01-01

    Although relations between 2D:4D and dominance rank in both baboons and rhesus macaques have been observed, evidence in humans is mixed. Whereas behavioral patterns in humans have been discovered that are consistent with these animal findings, the evidence for a relation between dominance and 2D:4D is weak or inconsistent. The present study provides experimental evidence that male 2D:4D is related to dominance after (fictitious) male-male interaction when the other man has a dominant, but not a submissive or neutral face. This finding provides evidence that the relationship between 2D:4D and dominance emerges in particular, predictable situations and that merely dominant facial characteristics of another person are enough to activate supposed relationships between 2D:4D and dominance. PMID:26600255

  16. Heritability of digit ratio (2D:4D) in rhesus macaques (Macaca mulatta).

    PubMed

    Nelson, Emma; Voracek, Martin

    2010-01-01

    The second-to-fourth digit ratio (2D:4D) is a putative biomarker for prenatal androgen effects, which has been widely employed to study androgenic-programming effects on shaping sex-linked traits and behaviours in humans. This approach is now increasingly applied to non-human species. Heritability studies of 2D:4D in both humans and zebra finches indicate substantial genetic contributions to the expression of this trait. This study examines the heritability of 2D:4D in rhesus macaques, based on the resemblance of mother-infant dyads, to see how these compare with human values. Results suggest that familial resemblance in 2D:4D is also strong in rhesus monkeys. Heritability estimates were within the range of estimates from human studies. These preliminary results suggest that the strength of heritability of 2D:4D may generalize across taxa. PMID:19882209

  17. Bioavailability of 2,4-D sorbed to a chlorite-like complex.

    PubMed

    McGhee, I; Sannino, F; Gianfreda, L; Burns, R G

    1999-07-01

    An Al(OH)x-montmorillonite (chlorite) complex (AM18) was prepared and 2,4-dichlorophenoxyacetic acid (2,4-D) sorbed to saturation. After several washing cycles the 'strongly sorbed' 2,4-D was 507 micrograms g-1 AM18. The bioavailability of sorbed 2,4-D was assessed in a minimal salts medium with the AM18-2,4-D as the sole C and energy source. Over a 28-day period a Pseudomonas sp. degraded 23% more of the sorbed 2,4-D than could be accounted for by desorption from AM18 in the non-inoculated controls. Possible explanations for the increase in bioavailability are presented. PMID:10399845

  18. The Influence of Facial Characteristics on the Relation between Male 2D:4D and Dominance.

    PubMed

    Ryckmans, Jan; Millet, Kobe; Warlop, Luk

    2015-01-01

    Although relations between 2D:4D and dominance rank in both baboons and rhesus macaques have been observed, evidence in humans is mixed. Whereas behavioral patterns in humans have been discovered that are consistent with these animal findings, the evidence for a relation between dominance and 2D:4D is weak or inconsistent. The present study provides experimental evidence that male 2D:4D is related to dominance after (fictitious) male-male interaction when the other man has a dominant, but not a submissive or neutral face. This finding provides evidence that the relationship between 2D:4D and dominance emerges in particular, predictable situations and that merely dominant facial characteristics of another person are enough to activate supposed relationships between 2D:4D and dominance. PMID:26600255

  19. Simultaneous motion estimation and image reconstruction (SMEIR) for 4D cone-beam CT

    SciTech Connect

    Wang, Jing; Gu, Xuejun

    2013-10-15

    Purpose: Image reconstruction and motion model estimation in four-dimensional cone-beam CT (4D-CBCT) are conventionally handled as two sequential steps. Due to the limited number of projections at each phase, the image quality of 4D-CBCT is degraded by view aliasing artifacts, and the accuracy of subsequent motion modeling is decreased by the inferior 4D-CBCT. The objective of this work is to enhance both the image quality of 4D-CBCT and the accuracy of motion model estimation with a novel strategy enabling simultaneous motion estimation and image reconstruction (SMEIR).Methods: The proposed SMEIR algorithm consists of two alternating steps: (1) model-based iterative image reconstruction to obtain a motion-compensated primary CBCT (m-pCBCT) and (2) motion model estimation to obtain an optimal set of deformation vector fields (DVFs) between the m-pCBCT and other 4D-CBCT phases. The motion-compensated image reconstruction is based on the simultaneous algebraic reconstruction technique (SART) coupled with total variation minimization. During the forward- and backprojection of SART, measured projections from an entire set of 4D-CBCT are used for reconstruction of the m-pCBCT by utilizing the updated DVF. The DVF is estimated by matching the forward projection of the deformed m-pCBCT and measured projections of other phases of 4D-CBCT. The performance of the SMEIR algorithm is quantitatively evaluated on a 4D NCAT phantom. The quality of reconstructed 4D images and the accuracy of tumor motion trajectory are assessed by comparing with those resulting from conventional sequential 4D-CBCT reconstructions (FDK and total variation minimization) and motion estimation (demons algorithm). The performance of the SMEIR algorithm is further evaluated by reconstructing a lung cancer patient 4D-CBCT.Results: Image quality of 4D-CBCT is greatly improved by the SMEIR algorithm in both phantom and patient studies. When all projections are used to reconstruct a 3D-CBCT by FDK, motion

  20. Interpreting digit ratio (2D:4D)-behavior correlations: 2D:4D sex difference, stability, and behavioral correlates and their replicability in young children.

    PubMed

    Wong, Wang I; Hines, Melissa

    2016-02-01

    The popularity of using the ratio of the second to the fourth digit (2D:4D) to study influences of early androgen exposure on human behavior relies, in part, on a report that the ratio is sex-dimorphic and stable from age 2 years (Manning etal., 1998). However, subsequent research has rarely replicated this finding. Moreover, although 2D:4D has been correlated with many behaviors, these correlations are often inconsistent. Young children's 2D:4D-behavior correlations may be more consistent than those of older individuals, because young children have experienced fewer postnatal influences. To evaluate the usefulness of 2D:4D as a biomarker of prenatal androgen exposure in studies of 2D:4D-behavior correlations, we assessed its sex difference, temporal stability, and behavioral correlates over a 6- to 8-month period in 126, 2- to 3-year-old children, providing a rare same-sample replicability test. We found a moderate sex difference on both hands and high temporal stability. However, between-sex overlap and within-sex variability were also large. Only 3 of 24 correlations with sex-typed behaviors-scores on the Preschool Activities Inventory (PSAI), preference for a boy-typical toy, preference for a girl-typical toy, were significant and in the predicted direction, all of which involved the PSAI, partially confirming findings from another study. Correlation coefficients were larger for behaviors that showed larger sex differences. But, as in older samples, the overall pattern showed inconsistency across time, sex, and hand. Therefore, although sex-dimorphic and stable, 2D:4D-behavior correlations are no more consistent for young children than for older samples. Theoretical and methodological implications are discussed. PMID:26542674

  1. Serum Soluble Semaphorin 4D is Associated with Left Atrial Diameter in Patients with Atrial Fibrillation

    PubMed Central

    Xiang, Li; You, Tao; Chen, Jianchang; Xu, Weiting; Jiao, Yang

    2015-01-01

    Background The aim of this study was to evaluate the serum soluble semaphorin 4D (sSema4D) in patients with atrial fibrillation and to investigate the relationship of serum sSema4D with left atrial diameter (LAD). Material/Methods We studied a total of 113 patients who were subdivided into paroxysmal and non-paroxysmal (included persistent and permanent) atrial fibrillation groups, respectively. Another 55 subjects without atrial fibrillation were enrolled as the healthy control group. Serum levels of soluble semaphorin 4D (Sema4D) were measured in all subjects using the enzyme-labeled immunosorbent assay method. We also evaluated the coagulation parameters and left atrial diameters. Results Patients with paroxysmal and non-paroxysmal atrial fibrillation had significantly higher sSema4D level compared with controls (8.50±2.19 ng/mL and 9.30±2.28 ng/mL vs. 6.56±1.27 ng/ml, P<0.05). Serum sSema4D concentrations were elevated in patients with non-paroxysmal atrial fibrillation compared to those with paroxysmal atrial fibrillation (P<0.001). The level of sSema4D was positively correlated with LAD (r=0.606, P<0.001). Multivariate logistic regression analysis revealed that serum sSema4D, LAD, male sex, heart rate, hypertension, and coronary artery disease were associated with atrial fibrillation (P<0.05). Conclusions Serum sSema4D levels are increased in patients with atrial fibrillation and are independently associated with atrial remodeling. PMID:26417899

  2. TU-C-BRD-01: Image Guided SBRT I: Multi-Modality 4D Imaging

    SciTech Connect

    Cai, J; Mageras, G; Pan, T

    2014-06-15

    Motion management is one of the critical technical challenges for radiation therapy. 4D imaging has been rapidly adopted as essential tool to assess organ motion associated with respiratory breathing. A variety of 4D imaging techniques have been developed and are currently under development based on different imaging modalities such as CT, MRI, PET, and CBCT. Each modality provides specific and complementary information about organ and tumor respiratory motion. Effective use of each different technique or combined use of different techniques can introduce a comprehensive management of tumor motion. Specifically, these techniques have afforded tremendous opportunities to better define and delineate tumor volumes, more accurately perform patient positioning, and effectively apply highly conformal therapy techniques such as IMRT and SBRT. Successful implementation requires good understanding of not only each technique, including unique features, limitations, artifacts, imaging acquisition and process, but also how to systematically apply the information obtained from different imaging modalities using proper tools such as deformable image registration. Furthermore, it is important to understand the differences in the effects of breathing variation between different imaging modalities. A comprehensive motion management strategy using multi-modality 4D imaging has shown promise in improving patient care, but at the same time faces significant challenges. This session will focuses on the current status and advances in imaging respiration-induced organ motion with different imaging modalities: 4D-CT, 4D-MRI, 4D-PET, and 4D-CBCT/DTS. Learning Objectives: Understand the need and role of multimodality 4D imaging in radiation therapy. Understand the underlying physics behind each 4D imaging technique. Recognize the advantages and limitations of each 4D imaging technique.

  3. Gonadotropin ratio affects the in vitro growth of rhesus ovarian preantral follicles.

    PubMed

    Kim, Yoon Young; Yun, Jun-Won; Kim, Jong Min; Park, Chung Gyu; Rosenwaks, Zev; Liu, Hung Ching; Kang, Byeong-Cheol; Ku, Seung-Yup

    2016-04-01

    In vitro follicle growth (IVFG) strategy is critical in the fertility preservation of cancer survivors; however, its optimal protocol needs to be developed using primate models since the availability of human samples is limited. Only a few previous studies have reported the successful IVFG of rhesus monkey ovaries using low-dose follicle-stimulating hormone (FSH) (0.3 or 3 ng/mL) and long-term culture (up to 5 weeks) and it is still uncertain in regard to the optimal culture duration and effective dose of treated gonadotropins applicable to the IVFG of rhesus preantral follicles. Recently, we have reported that the FSH to luteinizing hormone (LH) ratio affects the in vitro growth of murine ovarian follicles. We aimed to investigate whether gonadotropin ratios affect the efficiency of rhesus follicular growth in vitro Ovaries were collected from six necropsied rhesus macaques (4-9 years) and preantral follicles were retrieved and cultured for 14 days using 200 mIU/mL FSH. The characteristics of follicular growth were compared between the FSH:LH=1:1 (n=24) and FSH:LH=2:1 (n=24) groups. High concentration gonadotropin treatment shortened the duration required for in vitro maturation of rhesus preantral follicles. The FSH:LH=2:1 group showed a faster follicular growth and enabled the acquisition of mature oocytes, although the expression of growth differentiation factor (GDF)-9 and anti-Müllerian hormone (AMH) did not differ significantly between the two groups. Taken together, high dose gonadotropin treatment can shorten the duration of IVFG and the gonadotropin ratio is important in the IVFG of rhesus monkey ovaries. PMID:26980777

  4. Gonadotropin ratio affects the in vitro growth of rhesus ovarian preantral follicles

    PubMed Central

    Kim, Yoon Young; Yun, Jun-Won; Kim, Jong Min; Park, Chung Gyu; Rosenwaks, Zev; Liu, Hung Ching; Kang, Byeong-Cheol; Ku, Seung-Yup

    2016-01-01

    In vitro follicle growth (IVFG) strategy is critical in the fertility preservation of cancer survivors; however, its optimal protocol needs to be developed using primate models since the availability of human samples is limited. Only a few previous studies have reported the successful IVFG of rhesus monkey ovaries using low-dose follicle-stimulating hormone (FSH) (0.3 or 3 ng/mL) and long-term culture (up to 5 weeks) and it is still uncertain in regard to the optimal culture duration and effective dose of treated gonadotropins applicable to the IVFG of rhesus preantral follicles. Recently, we have reported that the FSH to luteinizing hormone (LH) ratio affects the in vitro growth of murine ovarian follicles. We aimed to investigate whether gonadotropin ratios affect the efficiency of rhesus follicular growth in vitro. Ovaries were collected from six necropsied rhesus macaques (4–9 years) and preantral follicles were retrieved and cultured for 14 days using 200 mIU/mL FSH. The characteristics of follicular growth were compared between the FSH:LH=1:1 (n=24) and FSH:LH=2:1 (n=24) groups. High concentration gonadotropin treatment shortened the duration required for in vitro maturation of rhesus preantral follicles. The FSH:LH=2:1 group showed a faster follicular growth and enabled the acquisition of mature oocytes, although the expression of growth differentiation factor (GDF)-9 and anti-Müllerian hormone (AMH) did not differ significantly between the two groups. Taken together, high dose gonadotropin treatment can shorten the duration of IVFG and the gonadotropin ratio is important in the IVFG of rhesus monkey ovaries. PMID:26980777

  5. A virilizing Leydig cell tumor of the ovary associated with stromal hyperplasia under gonadotropin control.

    PubMed

    Marcondes, J A; Nery, M; Mendonça, B B; Hayashida, S A; Halbe, H W; Carvalho, F M; Wajchenberg, B L

    1997-12-01

    A 34-yr-old nulliparous black woman presented with hair loss, facial hirsutism, irregular menses and infertility associated with greatly increased serum total testosterone levels. The adrenal glands and the ovaries were normal on radiological and ultrasonographic investigation. Catheterization of the veins draining from the adrenal glands and the ovaries yielded testosterone levels of 20.3 nmol/L and 20.0 nmol/L in the right and the left adrenal veins, respectively, and 17.9 nmol/L and 27.4 nmol/L in the right and left ovaries venous plexus, respectively. Sequencial dexamethasone and ethynyl estradiol suppression test showed a decrease in cortisol level with no change in total testosterone level on dexamethasone while an increase in testosterone from 10.5 nmol/L to 20.1 nmol/L was observed ten days after ethynil estradiol had been associated to dexamethasone. When a gonadotropin-releasing hormone agonist (gonadorelin 3.5 mg i.m.) was administered for 2 months, serum gonadotropins levels decreased to less than 2 IU/L, total testosterone to 3.8 nmol/L and estradiol to less than 36 pmol/L. The patient was submitted to a pelvic exploratory laparotomy and a left salpingo-oophorectomy was performed. A solid and circumscribed ovarian tumor of 1.0 cm in diameter was found. The pathological diagnosis was a Leydig cell tumor with surrounding stromal hyperplasia. These findings may suggest that this tumor was gonadotropin-dependent being indirectly stimulated by ethynil estradiol, through a sensitization of the pituitary gonadotropes and increase in gonadotropin levels and suppressed by a gonadotropin-releasing hormone agonist. PMID:9492110

  6. 4D subject-specific inverse modeling of the chick embryonic heart outflow tract hemodynamics.

    PubMed

    Goenezen, Sevan; Chivukula, Venkat Keshav; Midgett, Madeline; Phan, Ly; Rugonyi, Sandra

    2016-06-01

    Blood flow plays a critical role in regulating embryonic cardiac growth and development, with altered flow leading to congenital heart disease. Progress in the field, however, is hindered by a lack of quantification of hemodynamic conditions in the developing heart. In this study, we present a methodology to quantify blood flow dynamics in the embryonic heart using subject-specific computational fluid dynamics (CFD) models. While the methodology is general, we focused on a model of the chick embryonic heart outflow tract (OFT), which distally connects the heart to the arterial system, and is the region of origin of many congenital cardiac defects. Using structural and Doppler velocity data collected from optical coherence tomography, we generated 4D ([Formula: see text]) embryo-specific CFD models of the heart OFT. To replicate the blood flow dynamics over time during the cardiac cycle, we developed an iterative inverse-method optimization algorithm, which determines the CFD model boundary conditions such that differences between computed velocities and measured velocities at one point within the OFT lumen are minimized. Results from our developed CFD model agree with previously measured hemodynamics in the OFT. Further, computed velocities and measured velocities differ by [Formula: see text]15 % at locations that were not used in the optimization, validating the model. The presented methodology can be used in quantifications of embryonic cardiac hemodynamics under normal and altered blood flow conditions, enabling an in-depth quantitative study of how blood flow influences cardiac development. PMID:26361767

  7. 3′, 5′-Cyclic Adenosine 5′-Monophosphate Response Element-Dependent Transcriptional Regulation of the Secretogranin II Gene Promoter Depends on Gonadotropin-Releasing Hormone-Induced Mitogen-Activated Protein Kinase Activation and the Transactivator Activating Transcription Factor 3

    PubMed Central

    Xie, Jianjun; Roberson, Mark S.

    2008-01-01

    Previous studies demonstrated that GnRH-induced secretogranin II (SgII) promoter regulation required a consensus cAMP response element (CRE) and protein kinase A/CRE binding protein. The present studies examined the role of additional components of the GnRH signaling network on SgII promoter activity with particular attention devoted to CRE-dependent gene regulation. Disruption of the SgII CRE by mutagenesis resulted in inhibition of GnRH agonist (GnRHa) induction of this promoter in αT3-1 cells. Pharmacological and dominant-negative inhibition of the ERK and c-Jun N-terminal kinase (JNK) signaling pathways revealed that GnRHa-induced SgII promoter activity required functional JNK and ERK modules. Combined inhibition of both pathways nearly abolished GnRHa-induced SgII promoter activity. Specific induction of the ERK cascade alone using overexpression of Raf-CAAX was not sufficient to activate the SgII gene promoter. In contrast, overexpression of the catalytic domain of the more pleiotropic MAPK activator, MAPK/ERK kinase-1, was sufficient to induce SgII promoter activity. The effect(s) of mitogen-activated protein/ERK kinase-1 on SgII promoter activity was CRE dependent and was reversed by the combined pharmacological inhibition of both JNK and ERK modules. CRE DNA binding studies demonstrated the recruitment of activating transcription factor (ATF)-3 and c-Jun to the CRE after administration of GnRHa to αT3-1 cells. Specific small interfering RNA knockdown of ATF3 reduced ATF3 DNA binding and the effect of GnRHa on the SgII promoter. These studies support the conclusion that MAPK signaling and ATF3 action are essential for full SgII promoter activation by GnRHa through a canonical CRE. Moreover, we suggest that within the GnRH signaling network, CRE-dependent gene regulation in general may be mediated primarily through the immediate early response gene ATF3. PMID:17962349

  8. Identification and localization of gonadotropin-inhibitory hormone (GnIH) orthologs in the hypothalamus of the red-eared slider turtle, Trachemys scripta elegans.

    PubMed

    Ukena, Kazuyoshi; Iwakoshi-Ukena, Eiko; Osugi, Tomohiro; Tsutsui, Kazuyoshi

    2016-02-01

    Gonadotropin-inhibitory hormone (GnIH) was discovered in 2000 as a novel hypothalamic neuropeptide that inhibited gonadotropin release in the Japanese quail. GnIH and its orthologs have a common C-terminal LPXRFamide (X=L or Q) motif, and have been identified in vertebrates from agnathans to humans, apart from reptiles. In the present study, we characterized a cDNA encoding GnIH orthologs in the brain of the red-eared slider turtle. The deduced precursor protein consisted of 205 amino-acid residues, encoding three putative peptide sequences that included the LPXRFamide motif at their C-termini. In addition, the precursor sequence was most similar to those of avian species. Immunoaffinity purification combined with mass spectrometry confirmed that three mature peptides were produced in the brain. In situ hybridization and immunohistochemistry showed that turtle GnIH-containing cells were restricted to the periventricular hypothalamic nucleus. Immunoreactive fibers were densely distributed in the median eminence. Thus, GnIH and related peptides may act on the pituitary to regulate pituitary hormone release in turtles as well as other vertebrates. PMID:26130239

  9. The enhancing effects of alcoholic extract of Nigella sativa seed on fertility potential, plasma gonadotropins and testosterone in male rats

    PubMed Central

    Parandin, Rahmatollah; Yousofvand, Namdar; Ghorbani, Rostam

    2012-01-01

    Background: The task force on plants for fertility regulation in men continued with its program to identify novel prototypes in plants alleged to have fertility regulating properties. Nigella Sativa seeds are frequently used in folk medicine in the Middle East and some Asian countries for the promotion of good health and treatment of many ailments. Objective: To evaluated the role of alcoholic extract of Nigella sativa on fertility potential, Pituitary-testicular axis hormones and Testosterone in male rats. Materials and Methods: 24 male rats were randomly divided into 3 groups; control, group A and group B, each group comprising of 8 rats. Animals in control group received 1 ml of normal saline and treatment groups (A and B) received (gavage) graded doses of 200 and 400 mg/kg body weight of alcoholic extract of Nigella sativa seeds on a daily basis for 60 days. At the end of treatment period, fertility parameters such as body and reproductive organs weight, sperm motility, viability and count, epididymal sperm reserve (ESR), daily sperm production (DSP), blood testosterone concentration, Gonadotropins levels and fertility index were measured. Results: There was a significant difference in testes and epididymidis weight, sperm count, ESR, DSP, blood testosterone concentration, LH and fertility index in both the lower dose group and the higher group as compared to the control group. Conclusion: The results of this study showed that alcoholic extract of Nigella sativa seed especially in higher doses could increase fertility potential, LH and testosterone concentration in male rats. PMID:25246898

  10. Generation and preclinical characterization of an antibody specific for SEMA4D.

    PubMed

    Fisher, Terrence L; Reilly, Christine A; Winter, Laurie A; Pandina, Tracy; Jonason, Alan; Scrivens, Maria; Balch, Leslie; Bussler, Holm; Torno, Sebold; Seils, Jennifer; Mueller, Loretta; Huang, He; Klimatcheva, Ekaterina; Howell, Alan; Kirk, Renee; Evans, Elizabeth; Paris, Mark; Leonard, John E; Smith, Ernest S; Zauderer, Maurice

    2016-01-01

    Semaphorin 4D (SEMA4D or CD100) is a member of the semaphorin family of proteins and an important mediator of the movement and differentiation of multiple cell types, including those of the immune, vascular, and nervous systems. Blocking the binding of SEMA4D to its receptors can result in physiologic changes that may have implications in cancer, autoimmune, and neurological disease. To study the effects of blocking SEMA4D, we generated, in SEMA4D-deficient mice, a panel of SEMA4D-specific hybridomas that react with murine, primate, and human SEMA4D. Utilizing the complementarity-determining regions from one of these hybridomas (mAb 67-2), we generated VX15/2503, a humanized IgG4 monoclonal antibody that is currently in clinical development for the potential treatment of various malignancies and neurodegenerative disorders, including multiple sclerosis and Huntington's disease. This work describes the generation and characterization of VX15/2503, including in vitro functional testing, epitope mapping, and an in vivo demonstration of efficacy in an animal model of rheumatoid arthritis. PMID:26431358

  11. 2,4-D resistance in wild radish: reduced herbicide translocation via inhibition of cellular transport

    PubMed Central

    Goggin, Danica E.; Cawthray, Gregory R.; Powles, Stephen B.

    2016-01-01

    Resistance to auxinic herbicides is increasing in a range of dicotyledonous weed species, but in most cases the biochemical mechanism of resistance is unknown. Using 14C-labelled herbicide, the mechanism of resistance to 2,4-dichlorophenoxyacetic acid (2,4-D) in two wild radish (Raphanus raphanistrum L.) populations was identified as an inability to translocate 2,4-D out of the treated leaf. Although 2,4-D was metabolized in wild radish, and in a different manner to the well-characterized crop species wheat and bean, there was no difference in metabolism between the susceptible and resistant populations. Reduced translocation of 2,4-D in the latter was also not due to sequestration of the herbicide, or to reduced uptake by the leaf epidermis or mesophyll cells. Application of auxin efflux or ABCB transporter inhibitors to 2,4-D-susceptible plants caused a mimicking of the reduced-translocation resistance phenotype, suggesting that 2,4-D resistance in the populations under investigation could be due to an alteration in the activity of a plasma membrane ABCB-type auxin transporter responsible for facilitating long-distance transport of 2,4-D. PMID:26994475

  12. Finger length ratios (2D:4D) in anthropoids implicate reduced prenatal androgens in social bonding.

    PubMed

    Nelson, Emma; Shultz, Susanne

    2010-03-01

    The second-to-fourth digit ratio (2D:4D) has been proposed as a biomarker reflecting prenatal androgen effects (PAE), such that individuals with lower ratios have experienced higher PAE than those with higher ratios. 2D:4D has been correlated with a number of sex-linked traits in humans such as aggression, promiscuity, and competitiveness. In addition, polygynous societies reportedly have lower 2D:4D (higher PAE) than more monogamous populations. This evidence suggests that PAE may be implicated in the development of sexually selected behaviors in humans. To place 2D:4D research into a broader context, we test the relationship between digit ratios and behavior across nonhuman anthropoids; polygynous species, with higher levels of intrasexual competition, should have more pronounced markers of PAE (lower 2D:4D) than pair-bonded species. Our results accord with those found in humans: 2D:4D is lower in polygynous species and higher (lower PAE) in pair-bonded species. Old World monkeys have low, and relatively invariant 2D:4D (high PAE), which is coupled with high levels of intrasexual competition. This contrasts with higher and more variable ratios in both great apes and New World monkeys. In addition, both male and female ratios decrease with increasing levels of intrasexual competition. Human ratios are intermediate between pair-bonded and more promiscuous hominoids. We propose that PAE may be involved in promoting species characteristic social behavior in anthropoids. PMID:19862809

  13. Generation and preclinical characterization of an antibody specific for SEMA4D

    PubMed Central

    Fisher, Terrence L.; Reilly, Christine A.; Winter, Laurie A.; Pandina, Tracy; Jonason, Alan; Scrivens, Maria; Balch, Leslie; Bussler, Holm; Torno, Sebold; Seils, Jennifer; Mueller, Loretta; Huang, He; Klimatcheva, Ekaterina; Howell, Alan; Kirk, Renee; Evans, Elizabeth; Paris, Mark; Leonard, John E.; Smith, Ernest S.; Zauderer, Maurice

    2016-01-01

    Semaphorin 4D (SEMA4D or CD100) is a member of the semaphorin family of proteins and an important mediator of the movement and differentiation of multiple cell types, including those of the immune, vascular, and nervous systems. Blocking the binding of SEMA4D to its receptors can result in physiologic changes that may have implications in cancer, autoimmune, and neurological disease. To study the effects of blocking SEMA4D, we generated, in SEMA4D-deficient mice, a panel of SEMA4D-specific hybridomas that react with murine, primate, and human SEMA4D. Utilizing the complementarity-determining regions from one of these hybridomas (mAb 67-2), we generated VX15/2503, a humanized IgG4 monoclonal antibody that is currently in clinical development for the potential treatment of various malignancies and neurodegenerative disorders, including multiple sclerosis and Huntington's disease. This work describes the generation and characterization of VX15/2503, including in vitro functional testing, epitope mapping, and an in vivo demonstration of efficacy in an animal model of rheumatoid arthritis. PMID:26431358

  14. 2,4-D resistance in wild radish: reduced herbicide translocation via inhibition of cellular transport.

    PubMed

    Goggin, Danica E; Cawthray, Gregory R; Powles, Stephen B

    2016-05-01

    Resistance to auxinic herbicides is increasing in a range of dicotyledonous weed species, but in most cases the biochemical mechanism of resistance is unknown. Using (14)C-labelled herbicide, the mechanism of resistance to 2,4-dichlorophenoxyacetic acid (2,4-D) in two wild radish (Raphanus raphanistrum L.) populations was identified as an inability to translocate 2,4-D out of the treated leaf. Although 2,4-D was metabolized in wild radish, and in a different manner to the well-characterized crop species wheat and bean, there was no difference in metabolism between the susceptible and resistant populations. Reduced translocation of 2,4-D in the latter was also not due to sequestration of the herbicide, or to reduced uptake by the leaf epidermis or mesophyll cells. Application of auxin efflux or ABCB transporter inhibitors to 2,4-D-susceptible plants caused a mimicking of the reduced-translocation resistance phenotype, suggesting that 2,4-D resistance in the populations under investigation could be due to an alteration in the activity of a plasma membrane ABCB-type auxin transporter responsible for facilitating long-distance transport of 2,4-D. PMID:26994475

  15. Clinical evaluation of 4D PET motion compensation strategies for treatment verification in ion beam therapy.

    PubMed

    Gianoli, Chiara; Kurz, Christopher; Riboldi, Marco; Bauer, Julia; Fontana, Giulia; Baroni, Guido; Debus, Jürgen; Parodi, Katia

    2016-06-01

    A clinical trial named PROMETHEUS is currently ongoing for inoperable hepatocellular carcinoma (HCC) at the Heidelberg Ion Beam Therapy Center (HIT, Germany). In this framework, 4D PET-CT datasets are acquired shortly after the therapeutic treatment to compare the irradiation induced PET image with a Monte Carlo PET prediction resulting from the simulation of treatment delivery. The extremely low count statistics of this measured PET image represents a major limitation of this technique, especially in presence of target motion. The purpose of the study is to investigate two different 4D PET motion compensation strategies towards the recovery of the whole count statistics for improved image quality of the 4D PET-CT datasets for PET-based treatment verification. The well-known 4D-MLEM reconstruction algorithm, embedding the motion compensation in the reconstruction process of 4D PET sinograms, was compared to a recently proposed pre-reconstruction motion compensation strategy, which operates in sinogram domain by applying the motion compensation to the 4D PET sinograms. With reference to phantom and patient datasets, advantages and drawbacks of the two 4D PET motion compensation strategies were identified. The 4D-MLEM algorithm was strongly affected by inverse inconsistency of the motion model but demonstrated the capability to mitigate the noise-break-up effects. Conversely, the pre-reconstruction warping showed less sensitivity to inverse inconsistency but also more noise in the reconstructed images. The comparison was performed by relying on quantification of PET activity and ion range difference, typically yielding similar results. The study demonstrated that treatment verification of moving targets could be accomplished by relying on the whole count statistics image quality, as obtained from the application of 4D PET motion compensation strategies. In particular, the pre-reconstruction warping was shown to represent a promising choice when combined with intra

  16. Clinical evaluation of 4D PET motion compensation strategies for treatment verification in ion beam therapy

    NASA Astrophysics Data System (ADS)

    Gianoli, Chiara; Kurz, Christopher; Riboldi, Marco; Bauer, Julia; Fontana, Giulia; Baroni, Guido; Debus, Jürgen; Parodi, Katia

    2016-06-01

    A clinical trial named PROMETHEUS is currently ongoing for inoperable hepatocellular carcinoma (HCC) at the Heidelberg Ion Beam Therapy Center (HIT, Germany). In this framework, 4D PET-CT datasets are acquired shortly after the therapeutic treatment to compare the irradiation induced PET image with a Monte Carlo PET prediction resulting from the simulation of treatment delivery. The extremely low count statistics of this measured PET image represents a major limitation of this technique, especially in presence of target motion. The purpose of the study is to investigate two different 4D PET motion compensation strategies towards the recovery of the whole count statistics for improved image quality of the 4D PET-CT datasets for PET-based treatment verification. The well-known 4D-MLEM reconstruction algorithm, embedding the motion compensation in the reconstruction process of 4D PET sinograms, was compared to a recently proposed pre-reconstruction motion compensation strategy, which operates in sinogram domain by applying the motion compensation to the 4D PET sinograms. With reference to phantom and patient datasets, advantages and drawbacks of the two 4D PET motion compensation strategies were identified. The 4D-MLEM algorithm was strongly affected by inverse inconsistency of the motion model but demonstrated the capability to mitigate the noise-break-up effects. Conversely, the pre-reconstruction warping showed less sensitivity to inverse inconsistency but also more noise in the reconstructed images. The comparison was performed by relying on quantification of PET activity and ion range difference, typically yielding similar results. The study demonstrated that treatment verification of moving targets could be accomplished by relying on the whole count statistics image quality, as obtained from the application of 4D PET motion compensation strategies. In particular, the pre-reconstruction warping was shown to represent a promising choice when combined with intra

  17. Luteinizing hormone, a reproductive regulator that modulates the processing of amyloid-beta precursor protein and amyloid-beta deposition.

    PubMed

    Bowen, Richard L; Verdile, Giuseppe; Liu, Tianbing; Parlow, Albert F; Perry, George; Smith, Mark A; Martins, Ralph N; Atwood, Craig S

    2004-05-01

    Hormonal changes associated with the dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis following menopause/andropause have been implicated in the pathogenesis of Alzheimer's disease (AD). Experimental support for this has come from studies demonstrating an increase in amyloid-beta (Abeta) deposition following ovariectomy/castration. Because sex steroids and gonadotropins are both part of the HPG feedback loop, any loss in sex steroids results in a proportionate increase in gonadotropins. To assess whether Abeta generation was due to the loss of serum 17beta-estradiol or to the up-regulation of serum gonadotropins, we treated C57Bl/6J mice with the anti-gonadotropin leuprolide acetate, which suppresses both sex steroids and gonadotropins. Leuprolide acetate treatment resulted in a 3.5-fold (p < 0.0001) and a 1.5-fold (p < 0.024) reduction in total brain Abeta1-42 and Abeta1-40 concentrations, respectively, after 8 weeks of treatment. To further explore the role of gonadotropins in promoting amyloidogenesis, M17 neuroblastoma cells were treated with the gonadotropin luteinizing hormone (LH) at concentrations equivalent to early adulthood (10 mIU/ml) or post-menopause/andropause (30 mIU/ml). LH did not alter amyloid-beta precursor protein (AbetaPP) expression but did alter AbetaPP processing toward the amyloidogenic pathway as evidenced by increased secretion and insolubility of Abeta, decreased alphaAbetaPP secretion, and increased AbetaPP-C99 levels. These results suggest the marked increases in serum LH following menopause/andropause as a physiologically relevant signal that could promote Abeta secretion and deposition in the aging brain. Suppression of the age-related increase in serum gonadotropins using anti-gonadotropin agents may represent a novel therapeutic strategy for AD. PMID:14871891

  18. Passing to an effective 4D phantom cosmology from 5D vacuum theory of gravity

    NASA Astrophysics Data System (ADS)

    Aguilar, José Edgar Madriz; Bellini, Mauricio

    2008-02-01

    Starting from a five-dimensional (5D) vacuum theory of gravity where the extra coordinate is considered as non-compact, we investigate the possibility of inducing four-dimensional (4D) phantom scenarios by applying form-invariance symmetry transformations. In particular we obtain phantom scenarios for two cosmological frameworks. In the first framework we deal with an induced 4D de Sitter expansion and in the second one a 4D induced model where the expansion of the universe is dominated by a decreasing cosmological parameter Λ(t) is discussed.

  19. SU-E-J-241: Creation of Ventilation CT From Daily 4D CTs Or 4D Conebeam CTs Acquired During IGRT for Thoracic Cancers

    SciTech Connect

    Tai, A; Ahunbay, E; Li, X

    2014-06-01

    Purpose: To develop a method to create ventilation CTs from daily 4D CTs or 4D KV conebeam CTs (4DCBCT) acquired during image-guided radiation therapy (IGRT) for thoracic tumors, and to explore the potential for using the ventilation CTs as a means for early detection of lung injury during radiation treatment. Methods: 4DCT acquired using an in-room CT (CTVision, Siemens) and 4DCBCT acquired using the X-ray Volume Imaging (XVI) system (Infinity, Elekta) for representative lung cancer patients were analyzed. These 4D data sets were sorted into 10 phase images. A newly-available deformable image registration tool (ADMIRE, Elekta) is used to deform the phase images at the end of exhale (EE) to the phase images at the end of inhale (EI). The lung volumes at EI and EE were carefully contoured using an intensity-based auto-contour tool and then manually edited. The ventilation images were calculated from the variations of CT numbers of those voxels masked by the lung contour at EI between the registered phase images. The deformable image registration is also performed between the daily 4D images and planning 4DCT, and the resulting deformable field vector (DFV) is used to deform the planning doses to the daily images by an in-house Matlab program. Results: The ventilation images were successfully created. The tide volumes calculated using the ventilation images agree with those measured through volume difference of contours at EE and EI, indicating the accuracy of ventilation images. The association between the delivered doses and the change of lung ventilation from the daily ventilation CTs is identified. Conclusions: A method to create the ventilation CT using daily 4DCTs or 4D KV conebeam CTs was developed and demonstrated.

  20. Efficacy and Outcome Predictors of Gonadotropin Treatment for Male Congenital Hypogonadotropic Hypogonadism

    PubMed Central

    Liu, Zhaoxiang; Mao, Jangfeng; Wu, Xueyan; Xu, Hongli; Wang, Xi; Huang, Bingkun; Zheng, Junjie; Nie, Min; Zhang, Hongbing

    2016-01-01

    Abstract Gonadotropin induces masculinization and spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). However, large cohort studies for the efficacy and reliable predictors of this therapy need to be conducted. The aim of this study was to investigate the efficacy of gonadotropin treatment in a large cohort of male CHH patients and analyze putative predictors for successful spermatogenesis. This retrospective study included 223 CHH azoospermic patients without puberty development treated between 2005 and 2014. All patients received combined human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) and were followed up for >6 months (5109 person-months). Serum total testosterone level, testicular size, spermatogenesis, and pregnancy outcome were recorded at each visit. After gonadotropin therapy, testicular size was enlarged from 2.1 ± 1.6 to 8.1 ± 4.6 mL (P < 0.001) and serum total testosterone was elevated from 0.9 ± 0.5 to 15.1 ± 8.2 nmol/L (P < 0.001). Spermatogenesis (>0/mL) occurred at a median period of 15 months (95% confidence interval 13.5–16.5). Larger basal testicular volume (P = 0.012) and noncryptorchidism history (P = 0.028) are independent predictors for earlier sperm appearance. Sixty four percent (143/223) of patients succeeded in producing sperms and the average time for initial sperm detection was 14 ± 8 months. However, their sperm concentrations (11.7 [2.1, 24.4] million/mL) and sperm progressive motility (A + B 36.9% ± 20.2%) are significantly lower than World Health Organization standards. Of the 34 patients who desired for fathering children, 19 patients impregnanted their partners during the treatment. Gonadotropin therapy induces spermatogenesis in male CHH patients. A larger basal testicular size and noncryptorchidism history are favorable indicators for earlier spermatogenesis. PMID:26945370

  1. Kisspeptin depolarizes gonadotropin-releasing hormone neurons through activation of TRPC-like cationic channels.

    PubMed

    Zhang, Chunguang; Roepke, Troy A; Kelly, Martin J; Rønnekleiv, Oline K

    2008-04-23

    Kisspeptin and its cognate receptor, GPR54, are critical for reproductive development and for the regulation of gonadotropin-releasing hormone (GnRH) secretion. Although kisspeptin has been found to depolarize GnRH neurons, the underlying ionic mechanism has not been elucidated. Presently, we found that kisspeptin depolarized GnRH neurons in a concentration-dependent manner with a maximum depolarization of 22.6 +/- 0.6 mV and EC(50) of 2.8 +/- 0.2 nM. Under voltage-clamp conditions, kisspeptin induced an inward current of 18.2 +/- 1.6 pA (V(hold) = -60 mV) that reversed near -115 mV in GnRH neurons. The more negative reversal potential than E(K)(+) (-90 mV) was caused by the concurrent inhibition of barium-sensitive, inwardly rectifying (Kir) potassium channels and activation of sodium-dependent, nonselective cationic channels (NSCCs). Indeed, reducing extracellular Na(+) (to 5 mM) essentially eliminated the kisspeptin-induced inward current. The current-voltage relationships of the kisspeptin-activated NSCC currents exhibited double rectification with negative slope conductance below -40 mV in the majority of the cells. Pharmacological examination showed that the kisspeptin-induced inward currents were blocked by TRPC (canonical transient receptor potential) channel blockers 2-APB (2-aminoethyl diphenylborinate), flufenamic acid, SKF96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride), and Cd(2+), but not by lanthanum (100 microM). Furthermore, single-cell reverse transcription-PCR analysis revealed that TRPC1, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7 subunits were expressed in GnRH neurons. Therefore, it appears that kisspeptin depolarizes GnRH neurons through activating TRPC-like channels and, to a lesser extent, inhibition of Kir channels. These actions of kisspeptin contribute to the pronounced excitation of GnRH neurons that is critical for mammalian reproduction. PMID:18434521

  2. Identification of a gonadotropin-releasing hormone receptor orthologue in Caenorhabditis elegans

    PubMed Central

    Vadakkadath Meethal, Sivan; Gallego, Miguel J; Haasl, Ryan J; Petras, Stephen J; Sgro, Jean-Yves; Atwood, Craig S

    2006-01-01

    Background The Caenorhabditis elegans genome is known to code for at least 1149 G protein-coupled receptors (GPCRs), but the GPCR(s) critical to the regulation of reproduction in this nematode are not yet known. This study examined whether GPCRs orthologous to human gonadotropin-releasing hormone receptor (GnRHR) exist in C. elegans. Results Our sequence analyses indicated the presence of two proteins in C. elegans, one of 401 amino acids [GenBank: NP_491453; WormBase: F54D7.3] and another of 379 amino acids [GenBank: NP_506566; WormBase: C15H11.2] with 46.9% and 44.7% nucleotide similarity to human GnRHR1 and GnRHR2, respectively. Like human GnRHR1, structural analysis of the C. elegans GnRHR1 orthologue (Ce-GnRHR) predicted a rhodopsin family member with 7 transmembrane domains, G protein coupling sites and phosphorylation sites for protein kinase C. Of the functionally important amino acids in human GnRHR1, 56% were conserved in the C. elegans orthologue. Ce-GnRHR was actively transcribed in adult worms and immunoanalyses using antibodies generated against both human and C. elegans GnRHR indicated the presence of a 46-kDa protein, the calculated molecular mass of the immature Ce-GnRHR. Ce-GnRHR staining was specifically localized to the germline, intestine and pharynx. In the germline and intestine, Ce-GnRHR was localized specifically to nuclei as revealed by colocalization with a DNA nuclear stain. However in the pharynx, Ce-GnRHR was localized to the myofilament lattice of the pharyngeal musculature, suggesting a functional role for Ce-GnRHR signaling in the coupling of food intake with reproduction. Phylogenetic analyses support an early evolutionary origin of GnRH-like receptors, as evidenced by the hypothesized grouping of Ce-GnRHR, vertebrate GnRHRs, a molluscan GnRHR, and the adipokinetic hormone receptors (AKHRs) and corazonin receptors of arthropods. Conclusion This is the first report of a GnRHR orthologue in C. elegans, which shares significant

  3. Oxygen-Sensitive K+ Channels Modulate Human Chorionic Gonadotropin Secretion from Human Placental Trophoblast

    PubMed Central

    Díaz, Paula; Sibley, Colin P.; Greenwood, Susan L.

    2016-01-01

    Human chorionic gonadotropin (hCG) is a key autocrine/paracrine regulator of placental syncytiotrophoblast, the transport epithelium of the human placenta. Syncytiotrophoblast hCG secretion is modulated by the partial pressure of oxygen (pO2), reactive oxygen species (ROS) and potassium (K+) channels. Here we test the hypothesis that K+ channels mediate the effects of pO2 and ROS on hCG secretion. Placental villous explants from normal term pregnancies were cultured for 6 days at 6% (normoxia), 21% (hyperoxia) or 1% (hypoxia) pO2. On days 3–5, explants were treated with 5mM 4-aminopyridine (4-AP) or tetraethylammonium (TEA), blockers of pO2-sensitive voltage-gated K+ (KV) channels, or ROS (10–1000μM H2O2). hCG secretion and lactate dehydrogenase (LDH) release, a marker of necrosis, were determined daily. At day 6, hCG and LDH were measured in tissue lysate and 86Rb (K+) efflux assessed to estimate syncytiotrophoblast K+ permeability. hCG secretion and 86Rb efflux were significantly greater in explants maintained in 21% pO2 than normoxia. 4-AP/TEA inhibited hCG secretion to a greater extent at 21% than 6% and 1% pO2, and reduced 86Rb efflux at 21% but not 6% pO2. LDH release and tissue LDH/hCG were similar in 6%, 21% and 1% pO2 and unaffected by 4-AP/TEA. H2O2 stimulated 86Rb efflux and hCG secretion at normoxia but decreased 86Rb efflux, without affecting hCG secretion, at 21% pO2. 4-AP/TEA-sensitive K+ channels participate in pO2-sensitive hCG secretion from syncytiotrophoblast. ROS effects on both hCG secretion and 86Rb efflux are pO2-dependent but causal links between the two remain to be established. PMID:26863525

  4. Oxygen-Sensitive K+ Channels Modulate Human Chorionic Gonadotropin Secretion from Human Placental Trophoblast.

    PubMed

    Díaz, Paula; Sibley, Colin P; Greenwood, Susan L

    2016-01-01

    Human chorionic gonadotropin (hCG) is a key autocrine/paracrine regulator of placental syncytiotrophoblast, the transport epithelium of the human placenta. Syncytiotrophoblast hCG secretion is modulated by the partial pressure of oxygen (pO2), reactive oxygen species (ROS) and potassium (K+) channels. Here we test the hypothesis that K+ channels mediate the effects of pO2 and ROS on hCG secretion. Placental villous explants from normal term pregnancies were cultured for 6 days at 6% (normoxia), 21% (hyperoxia) or 1% (hypoxia) pO2. On days 3-5, explants were treated with 5mM 4-aminopyridine (4-AP) or tetraethylammonium (TEA), blockers of pO2-sensitive voltage-gated K+ (KV) channels, or ROS (10-1000μM H2O2). hCG secretion and lactate dehydrogenase (LDH) release, a marker of necrosis, were determined daily. At day 6, hCG and LDH were measured in tissue lysate and 86Rb (K+) efflux assessed to estimate syncytiotrophoblast K+ permeability. hCG secretion and 86Rb efflux were significantly greater in explants maintained in 21% pO2 than normoxia. 4-AP/TEA inhibited hCG secretion to a greater extent at 21% than 6% and 1% pO2, and reduced 86Rb efflux at 21% but not 6% pO2. LDH release and tissue LDH/hCG were similar in 6%, 21% and 1% pO2 and unaffected by 4-AP/TEA. H2O2 stimulated 86Rb efflux and hCG secretion at normoxia but decreased 86Rb efflux, without affecting hCG secretion, at 21% pO2. 4-AP/TEA-sensitive K+ channels participate in pO2-sensitive hCG secretion from syncytiotrophoblast. ROS effects on both hCG secretion and 86Rb efflux are pO2-dependent but causal links between the two remain to be established. PMID:26863525

  5. Effect of pH and Electrolytes on Adsorption of 2,4-D onto Kaolinite

    NASA Astrophysics Data System (ADS)

    Sharma, A.; Kawamoto, K.; Komatsu, T.; Moldrup, P.

    2006-12-01

    The fate and transport of pesticides in soil can be greatly influenced by adsorption onto clay minerals such as kaolinite. The ionic pesticide 2,4-D (2,4-dichlorophenoxyacetic acid) is one of the most commonly used herbicides. The purpose of this study is to investigate the effect of electrolytes and pH on the adsorption of 2,4- D onto kaolinite. The adsorption coefficient (Kd) of 2,4-D on two types of kaolinite was measured in batch experiments using water and 4 different electrolytes (0.005M CaSO4, 0.005M CaCl2, 0.01M KCl, and 0.01M NaCl). The experiments were carried out with 0.5 g kaolinite at a solid:liquid ratio of 1:20 and at different pH (1.9-6.3). The pH of the solution was controlled by addition of 0.2N of HCl. X-ray diffraction analysis of both kaolinite with and without adsorbed 2,4-D was also done to understand the location of 2,4-D adsorption. The effects of pH and electrolytes on Kd were compared and possible adsorption mechanisms were revealed for 2,4-D adsorption onto the two different types of kaolinite. The results implied that 2,4-D adsorption was higher for an electrolyte solution with monovalent cation than with divalent cation for one type of kaolinite, while no such trend was observed for the other kaolinite. The adsorption of 2,4-D increased significantly with decreasing pH for both types of kaolinite.

  6. Geometry and dynamics of a coupled 4 D-2 D quantum field theory

    NASA Astrophysics Data System (ADS)

    Bolognesi, Stefano; Chatterjee, Chandrasekhar; Evslin, Jarah; Konishi, Kenichi; Ohashi, Keisuke; Seveso, Luigi

    2016-01-01

    Geometric and dynamical aspects of a coupled 4 D-2 D interacting quantum field theory — the gauged nonAbelian vortex — are investigated. The fluctuations of the internal 2 D nonAbelian vortex zeromodes excite the massless 4 D Yang-Mills modes and in general give rise to divergent energies. This means that the well-known 2 D C{P}^{N-1} zeromodes associated with a nonAbelian vortex become nonnormalizable.

  7. Changes in plasma gonadotropin concentrations and urethral closure pressure in the bitch during the 12 months following ovariectomy.

    PubMed

    Reichler, Iris Margaret; Pfeiffer, Esther; Piché, Claude A; Jöchle, Wolfgang; Roos, Malgorzata; Hubler, Madeleine; Arnold, Susi

    2004-11-01

    Urinary incontinence due to acquired urethral sphincter incompetence is a common side effect of spaying, for which the underlying cause remains unknown. Spaying not only results in a significant reduction in the urethral closure pressure within 1 year but also in an increase in the plasma gonadotropin concentrations. To investigate the possible link between the post-ovariectomy changes in plasma gonadotropins and in urethral closure pressure, gonadotropin and urodynamic measurements were performed in 10 Beagle bitches before and for a period of 1 year after spaying. Plasma gonadotropin concentrations rose quickly after ovariectomy and peak levels were seen within 3-5 weeks, followed by a sharp drop until week 10. A steady increase was observed subsequently until week 42, when a plateau was reached. One year after spaying, the mean FSH concentration was 75.3 +/- 32.1 ng/ml, a 17-fold increase, and the LH was 8.3 +/- 3.8 ng/ml, an eightfold increase over the pre-spaying values. Ten months after spaying, the mean urethral closure pressure (9.7 cm H2O) was significantly reduced when compared to the mean pre-operative value of 15.4 cm H2O. However, there was no clear relationship between the gonadotropin concentrations and the urethral closure pressure. From these results it seems unlikely that chronically elevated gonadotropins are the underlying cause for reduced urethral closure pressure after spaying resulting in urinary incontinence. PMID:15451248

  8. Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages

    PubMed Central

    Sierra, Jose Rafael; Corso, Simona; Caione, Luisa; Cepero, Virna; Conrotto, Paolo; Cignetti, Alessandro; Piacibello, Wanda; Kumanogoh, Atsushi; Kikutani, Hitoshi; Comoglio, Paolo Maria; Tamagnone, Luca; Giordano, Silvia

    2008-01-01

    Increased evidence suggests that cancer-associated inflammation supports tumor growth and progression. We have previously shown that semaphorin 4D (Sema4D), a ligand produced by different cell types, is a proangiogenic molecule that acts by binding to its receptor, plexin B1, expressed on endothelial cells (Conrotto, P., D. Valdembri, S. Corso, G. Serini, L. Tamagnone, P.M. Comoglio, F. Bussolino, and S. Giordano. 2005. Blood. 105:4321–4329). The present work highlights the role of Sema4D produced by the tumor microenvironment on neoplastic angiogenesis. We show that in an environment lacking Sema4D, the ability of cancer cells to generate tumor masses and metastases is severely impaired. This condition can be explained by a defective vascularization inside the tumor. We demonstrate that tumor-associated macrophages (TAMs) are the main cells producing Sema4D within the tumor stroma and that their ability to produce Sema4D is critical for tumor angiogenesis and vessel maturation. This study helps to explain the protumoral role of inflammatory cells of the tumor stroma and leads to the identification of an angiogenic molecule that might be a novel therapeutic target. PMID:18559453

  9. Respiratory regularity gated 4D CT acquisition: concepts and proof of principle.

    PubMed

    Keall, P J; Vedam, S S; George, R; Williamson, J F

    2007-09-01

    Four-dimensional CT images are generally sorted through a post-acquisition procedure correlating images with a time-synchronized external respiration signal. The patient's ability to maintain reproducible respiration is the limiting factor during 4D CT, where artifacts occur in approximately 85% of scans with current technology. To reduce these artifacts and their subsequent effects during radiotherapy planning, a method for improved 4D CT image acquisition that relies on gating 4D CT acquisition based on the real time monitoring of the respiration signal has been proposed. The respiration signal and CT data acquisition are linked, such that data from irregular breathing cycles, which cause artifacts, are not acquired by gating CT acquisition by the respiratory signal. A proof-of-principle application of the respiratory regularity gated 4D CT method using patient respiratory signals demonstrates the potential of this method to reduce artifacts currently found in 4D CT scans. Numerical simulations indicate a potential reduction in motion within a respiratory phase bin by 20-40% depending on tolerances chosen. Additional advantages of the proposed method are dose reduction by eliminating unnecessary oversampling and obviating the need for post-processing to create the 4D CT data set. PMID:18044305

  10. Low Digit Ratio 2D∶4D in Alcohol Dependent Patients

    PubMed Central

    Lenz, Bernd; Kraus, Thomas; Sperling, Wolfgang; Bayerlein, Kristina; Biermann, Teresa; Stoessel, Christina

    2011-01-01

    The ratio of the lengths of the second and fourth finger (2D∶4D) has been described as reflecting the degree of prenatal androgen exposure in humans. 2D∶4D is smaller for males than females and is associated with traits such as left-handedness, physical aggression, attention-deficit-hyperactivity disorder and a genetic polymorphism of the androgen receptor. All of these traits are known to be correlated to the vulnerability for alcohol dependency. We therefore hypothesized low 2D∶4D in patients with alcohol dependency. In the present study on 131 patients suffering from alcohol dependency and 185 healthy volunteers, we found that alcohol dependent patients had smaller 2D∶4D ratios compared to controls with preserved sexual dimorphism but with reduced right-left differences. The detection of alcohol dependency based on 2D∶4D ratios was most accurate using the right hand of males (ROC-analysis: AUC 0.725, sensitivity 0.667, specificity 0.723). These findings provide novel insights into the role of prenatal androgen exposure in the development of alcohol dependency and for the use of 2D∶4D as a possible trait marker in identifying patients with alcohol dependency. PMID:21547078

  11. Low digit ratio 2D:4D in alcohol dependent patients.

    PubMed

    Kornhuber, Johannes; Erhard, Gabriele; Lenz, Bernd; Kraus, Thomas; Sperling, Wolfgang; Bayerlein, Kristina; Biermann, Teresa; Stoessel, Christina

    2011-01-01

    The ratio of the lengths of the second and fourth finger (2D∶4D) has been described as reflecting the degree of prenatal androgen exposure in humans. 2D∶4D is smaller for males than females and is associated with traits such as left-handedness, physical aggression, attention-deficit-hyperactivity disorder and a genetic polymorphism of the androgen receptor. All of these traits are known to be correlated to the vulnerability for alcohol dependency. We therefore hypothesized low 2D∶4D in patients with alcohol dependency. In the present study on 131 patients suffering from alcohol dependency and 185 healthy volunteers, we found that alcohol dependent patients had smaller 2D∶4D ratios compared to controls with preserved sexual dimorphism but with reduced right-left differences. The detection of alcohol dependency based on 2D∶4D ratios was most accurate using the right hand of males (ROC-analysis: AUC 0.725, sensitivity 0.667, specificity 0.723). These findings provide novel insights into the role of prenatal androgen exposure in the development of alcohol dependency and for the use of 2D∶4D as a possible trait marker in identifying patients with alcohol dependency. PMID:21547078

  12. Increased complement C4d deposition at the maternal-fetal interface in unexplained recurrent miscarriage.

    PubMed

    Meuleman, Tess; Cohen, Danielle; Swings, Godelieve M J S; Veraar, Kimberly; Claas, Frans H J; Bloemenkamp, Kitty W M

    2016-02-01

    C4d is a footprint of antibody-mediated classical complement activation, and has evolved as a useful diagnostic marker of antibody-mediated rejection. It is unknown if complement activation, as reflected by C4d deposition plays a role in unexplained recurrent miscarriage. In a case-control study products of conception of 35 women with three or more unexplained consecutive miscarriages within 20 weeks of gestation with the same partner (case group), 22 women with one spontaneous sporadic miscarriage and no history of complicated pregnancy(ies) (control group 1), and 40 women who underwent an elective abortion for psychosocial reasons (control group 2) were included. Immunohistochemical staining for C4d was performed on products of conception. Positivity for C4d was scored semi-quantitatively. C4d deposition was present in products of conception of 14 out of 35 women with unexplained recurrent miscarriage (40.0%), compared to 6 out of 22 women with a sporadic miscarriage (27.3%), and 4 out of 40 women with an elective abortion (10.0%) (p=0.020). C4d is increased at the maternal-fetal interface in women with unexplained recurrent miscarriage, which may reflect an aberrant anti-fetal immunity in these women. Further knowledge of the specific pathogenic mechanism may lead to the development of new treatment strategies for this group of women. PMID:26759961

  13. Differential expression of three types of gonadotropin-releasing hormone genes during the spawning season in grass puffer, Takifugu niphobles.

    PubMed

    Shahjahan, Md; Hamabata, Tomoko; Motohashi, Eiji; Doi, Hiroyuki; Ando, Hironori

    2010-05-15

    Grass puffer, Takifugu niphobles, has unique spawning behavior; spawning occurs on beach only for several days around new moon and full moon from spring to early summer. To investigate the role of gonadotropin-releasing hormone (GnRH) in the reproductive function, genes encoding three types of GnRHs, namely seabream GnRH (sbGnRH), chicken GnRH-II (cGnRH-II) and salmon GnRH (sGnRH), were cloned and changes in their mRNA amounts were examined over the spawning season. In addition, changes in the pituitary gonadotropin subunit mRNAs and the plasma steroid hormones were examined over the spawning season. Fishes were assessed at four reproductive stages, i.e., in December (early maturation), in April (maturing), in May (spawning), and in July (post-spawning). Moreover, spawning fish just after releasing eggs and sperm were taken at a spawning bed. The amounts of sbGnRH mRNA were substantially elevated in May and the spawning fish in both sexes, concomitant with considerable elevations of follicle-stimulating hormone and luteinizing hormone beta subunit mRNAs and plasma estradiol-17beta (E(2)) and testosterone (T) levels. There were strong positive correlations between the sbGnRH mRNA and the plasma E(2) and T levels over the spawning season in both sexes. The amounts of cGnRH-II mRNA showed no noticeable changes except for an increase in the post-spawning females. The amounts of sGnRH mRNA in the males were significantly increased in May, but they were low in the spawning males. In the females, sGnRH mRNA increased from the maturing stage and reached a maximum in the post-spawning stage, in which a positive correlation with the plasma cortisol levels was observed. These specific changes suggest that the expression of three types of GnRH genes is differentially regulated during the spawning season, and sex steroids may be important for the differential expression of GnRH genes. PMID:20138178

  14. Secondary treatment failure without anti-human chorionic gonadotropin antibody in a patient with Kallmann syndrome.

    PubMed

    Kitahara, S; Yoshida, K; Ishizaka, K; Higashi, Y; Takagi, K; Oshima, H

    1998-07-01

    A 29-year-old man with Kallmann syndrome suddenly developed decreased semen volume, azoospermia, and facial hair loss after 11 years of successful human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) treatment. Anti-hCG antibody was not detected in the patient's serum. A high serum level of luteinizing hormone (LH) with nasal LH-releasing hormone analogue administration failed to increase serum testosterone to a sufficient level. Testosterone injection after cessation of hCG and hMG therapy was able to improve semen volume, but not azoospermia. Resumption of hCG and hMG therapy after 6 months cessation partially restored spermatogenesis. The secondary failure of hCG and hMG therapy suggests a decrease of testicular sensitivity to LH as well as hCG. PMID:9712456

  15. Treatment of canine pyometra with the gonadotropin-releasing hormone antagonist acyline: a case series.

    PubMed

    Batista, Pablo R; Blanco, Paula G; Gobello, Cristina

    2015-03-01

    To describe the effect of the third-generation gonadotropin-releasing hormone antagonist acyline in the treatment of 4 diestrous bitches with the cystic endometrial hyperplasia-pyometra complex. The 4 bitches were treated with 330 μg/kg of subcutaneous acyline on day 0 and antibiotics, and followed up for 2 weeks. One closed-cervix case showed cervical dilatation 36 hours after treatment, and all the 4 animals showed resolution of clinical signs starting on day 3 posttreatment. Ultrasonographic uterine diameters and luminal contents decreased in the bitches having high progesterone serum concentrations before treatment but not in those with low levels. Serum progesterone importantly decreased from high to basal concentrations in the 3 "ultrasonographically cured" animals. No local or systemic side effects related to the treatment were observed. The gonadotropin-releasing hormone antagonist acyline may have a promising place for the medical treatment of cystic endometrial hyperplasia-pyometra complex in dogs. PMID:26041594

  16. Role of p19ink4d in the pathogenesis of hearing loss

    PubMed Central

    Lai, Ruosha; Li, Jingkun; Hu, Peng; Wen, Jie; Jie, Qing; Dong, Yunpeng; Peng, Tao; Liu, Xuezhong; Xie, Dinghua

    2015-01-01

    This study aimed to investigate the p19 expression in cisplatin-treated rats and the role of p19 in the degeneration of inner ear cells. It also searched for p19 gene alterations in patients with profound sensorineural deafness. P19ink4d is essential for the postmitotic maintenance of hair cells. It is presumed that a mutation in the functional homolog of p19 or a disturbance in its regulated expression can be the underlying cause of hearing loss. Experiments were conducted on male and female Sprague-Dawley rats (aged 6-7 weeks, 280-320 g) with thresholds of auditory brainstem responses <30 dB in the sound pressure level, and signs of middle ear infection were used for the experiment. For clinical evaluation, 400 children (age less than 13 years) from unrelated families with severe or profound sensorineural hearing loss (SNHL) were recruited at the second Xiangya Hospital of Central South University between 2005 and 2013, and genomic DNA for deafness gene analysis was obtained from peripheral blood samples of the patients and their lineal relatives. It was found that the p19 expression increased over time in the inner ear cells after cisplatin administration, but the p19 mRNA and protein levels significantly decreased in rats with manifested hearing loss induced by cisplatin. However, no mutation existed within the coding exons of p19 in the patients with profound sensorineural deafness. To conclude, the results support the concept that p19 may play an important role in the ototoxic effects of cisplatin and is probably involved in the pathogenesis of hearing loss. PMID:26722409

  17. Stimulation of Spermiation by Human Chorionic Gonadotropin and Carp Pituitary Extract in Grass Puffer, Takifugu niphobles

    PubMed Central

    Goo, In Bon; Park, In-Seok; Gil, Hyun Woo; Im, Jae Hyun

    2015-01-01

    Spermiation was stimulated in the mature grass puffer, Takifugu niphobles, with an injection of human chorionic gonadotropin (HCG) or carp pituitary extract (CPE). Spermatocrit and sperm density were reduced, but milt production was increased in both the HCG and CPE treatment groups relative to those in the control group (P <0.05). These results should be useful for increasing the fertilization efficiency in grass puffer breeding programs. PMID:26973977

  18. Gamma scintigraphy using Tc-99m labeled antibody to human chorionic gonadotropin

    SciTech Connect

    Morrison, R.T.; Lyster, D.M.; Alcorn, L.N.; Rhodes, B.A.; Breslow, K.; Burchiel, S.W.

    1984-01-01

    A case report is presented describing a 27-year-old woman with invasive trophoblastic hydatidiform mole metastatic to the lung. Gamma scintiscanning, using a polyclonal and monoclonal antibody specific to human chorionic gonadotropin, hCG, and labeled with Tc-99m, is described. The area of the primary lesion in the uterus was demonstrated with both antibodies tested without computer subtraction techniques; metastatic deposits in the lung were detected only with the aid of blood pool subtraction techniques.

  19. Partial hypopituitarism and hyperprolactinemia: successful induction of ovulation with bromocriptine and human menopausal gonadotropins.

    PubMed

    Dawood, M Y; Jarrett, J C; Choe, J K

    1982-10-01

    The case of a patient who developed partial hypopituitarism (hypogonadotropism and growth hormone deficiency) following transphenoidal removal of a prolactinoma is described. Hypogonadotropism persisted despite restoration of normoprolactinemia with bromocriptine therapy. Successful induction of ovulation with human menopausal gonadotropin (hMG) and bromocriptine suppression of the hyperprolactinemia was carried out, resulting in a pregnancy. The pros and cons of operative and nonoperative management of hyperprolactinemia are discussed. PMID:6811337

  20. Low external pH replaces 2,4-D in maintaining and multiplying 2,4-D-initiated embryogenic cells of carrot

    NASA Technical Reports Server (NTRS)

    Smith, D. L.; Krikorian, A. D.

    1990-01-01

    A mixed culture comprised of both embryonic globules and nonembryogenic callus was derived from seedling hypocotyls of Daucus carota cv. Scarlet Nantes on 2,4-D- containing medium using well-established methods. Then the mixed cultures were transferred to, and serially subcultured on, a hormone-free medium near pH 4. The medium contained 1 mM NH4+ as the sole nitrogen source. When cultured in this way, embryonic globules were able to multiply without development into later embryo stages. Nonembryogenic callus did not survive. Continuous culture of embryonic globules on this low pH hormone-free medium yielded cultures consisting entirely of preglobular stage proembryos (PGSPs). PGSP cultures have been maintained as such with continuous multiplication for nearly 2 years without loss of embryogenic potential. These hormone-free-maintained PGSPs continue their development to later embryo stages when cultured on the same hormone-free medium buffered at pH 5.8. We show that hormone-free medium near pH 4 can replace 2,4-D in its ability to sustain multiplication of 2,4-D-initiated embryogenic cells of carrot at an acceptable growth rate without their development into later embryo stages. This procedure provides selective conditions that do not permit the growth of non-embryogenic cells while providing an adequate environment for embryogenic cell proliferation and should prove invaluable in studying habituation.

  1. An unexpected reason for elevated human chorionic gonadotropin in a young woman. Cervical squamous carcinoma.

    PubMed

    Mustafa, Aynur; Bozdag, Zehra; Tepe, Neslihan B; Ozcan, Husiyen C

    2016-08-01

    Human chorionic gonadotropin has been used for decades, in addition to specific investigations, to detect pregnancy, trophoblastic tumors, as well as congenital defects. Rarely, it can be elevated in  non-trophoblastic tumors such as squamous cell cancers and germ cell tumors. A 33-year-old Asian Syrian female had irregular menses accompanied with feelings of heaviness in the vagina. In addition to routine investigations, we measured the serum beta human chorionic gonadotropin (ß-HCG) level (based on the patient's complaint of amenorrhea), which was 50.05 ml UI/ml. Cervical biopsy revealed a non-keratinized large cell squamous carcinoma. After excluding other causes, ß-hCG elevation was explained by the ectopic secretion of cancer cells line. Cervical biopsy was suggestive of large cell non-keratinizing squamous cell carcinoma and positive for human chorionic gonadotropin on immunohistochemistry. As a result, we manage the possibility of ectopic secretion of ß-HCG from non- trophoblastic disease. PMID:27464870

  2. Effect of Withania somnifera (L.) Dunal on Sex Hormone and Gonadotropin Levels in Addicted Male Rats

    PubMed Central

    Rahmati, Batool; Ghosian Moghaddam, Mohammad Hassan; Khalili, Mohsen; Enayati, Ehsan; Maleki, Maryam; Rezaeei, Saeedeh

    2016-01-01

    Background Opioid consumption has been widely increasing across the globe; how- ever, it can cause adverse effects on the body. Morphine, an opioid, can reduce sex hor- mones and fertility. Withania somnifera (WS) is a traditional herb used to improve sexual activities. This study strives to investigate the effect of WS on sex hormones and gonado- tropins in addicted male rats. Materials and Methods In this experimental study, forty-eight male National Maritime Research Institute (NMRI) rats were randomly divided into four groups: i. Control group, ii. WS-treated control group, iii. Addicted group, and iv. WS-treated addicted group. Wa- ter-soluble morphine was given to rats for 21 days to induce addiction, concurrently the treated groups (2 and 4) also received WS plant-mixed pelleted food (6.25%). At the end of the treatment, the sex hormone and gonadotropin levels of the rats’ sera were deter- mined in all the groups. Results Except for follicle-stimulating hormone (FSH), morphine reduced most of the gonadotropin and sex hormone levels. Whereas WS caused a considerable increase in the hormones in the treated addicted group, there was only a slight increase in the treated control group. Conclusion WS increased sex hormones and gonadotropins-especially testosterone, es- trogen, and luteinizing hormone-in the addicted male rats and even increased the proges- terone level, a stimulant of most sex hormones in addicted male rats. PMID:27441058

  3. mRNA expression pattern of gonadotropin receptors in bovine follicular cysts.

    PubMed

    Marelli, Belkis E; Diaz, Pablo U; Salvetti, Natalia R; Rey, Florencia; Ortega, Hugo H

    2014-12-01

    Follicular growth and steroidogenesis are dependent on gonadotropin binding to their receptors in granulosa and theca cells of ovarian follicles. The aim of the present study was to evaluate the expression patterns of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHCGR) in ovarian follicular structures from cows with cystic ovarian disease (COD) as compared with those of regularly cycling cows. Relative real-time RT-PCR analysis showed that the expression of FSHR mRNA in granulosa cells was highest in small antral follicles, then decreased significantly as follicles increased in size, and was lowest in cysts. FSHR mRNA was not detected in the theca cells of any follicular category, including cysts. LHCGR mRNA expression in granulosa cells was significantly higher in large antral follicles than in cysts, and not detected in granulosa cells of small and medium antral follicles. In theca cells, the expression level of LHCGR mRNA in medium antral follicles was higher than in small and large antral follicles, whereas that in follicular cysts it was similar to those in small and medium antral follicles, but higher than that in large antral follicles. Our findings provide evidence that there is an altered gonadotropin receptor expression in bovine cystic follicles, and suggest that in conditions characterized by altered ovulation, such as COD, changes in the signaling system of gonadotropins may play a fundamental role in their pathogenesis. PMID:25454493

  4. Comparative gene expression profiling in human cumulus cells according to ovarian gonadotropin treatments.

    PubMed

    Assou, Said; Haouzi, Delphine; Dechaud, Hervé; Gala, Anna; Ferrières, Alice; Hamamah, Samir

    2013-01-01

    In in vitro fertilization cycles, both HP-hMG and rFSH gonadotropin treatments are widely used to control human follicle development. The objectives of this study are (i) to characterize and compare gene expression profiles in cumulus cells (CCs) of periovulatory follicles obtained from patients stimulated with HP-hMG or rFSH in a GnRH antagonist cycle and (ii) to examine their relationship with in vitro embryo development, using Human Genome U133 Plus 2.0 microarrays. Genes that were upregulated in HP-hMG-treated CCs are involved in lipid metabolism (GM2A) and cell-to-cell interactions (GJA5). Conversely, genes upregulated in rFSH-treated CCs are implicated in cell assembly and organization (COL1A1 and COL3A1). Interestingly, some genes specific to each gonadotropin treatment (NPY1R and GM2A for HP-hMG; GREM1 and OSBPL6 for rFSH) were associated with day 3 embryo quality and blastocyst grade at day 5, while others (STC2 and PTX3) were related to in vitro embryo quality in both gonadotropin treatments. These genes may prove valuable as biomarkers of in vitro embryo quality. PMID:24151596

  5. Control of puberty onset and fertility by gonadotropin-releasing hormone neurons.

    PubMed

    Herbison, Allan E

    2016-08-01

    The gonadotropin-releasing hormone (GnRH) neuronal network generates pulse and surge modes of gonadotropin secretion critical for puberty and fertility. The arcuate nucleus kisspeptin neurons that innervate the projections of GnRH neurons in and around their neurosecretory zone are key components of the pulse generator in all mammals. By contrast, kisspeptin neurons located in the preoptic area project to GnRH neuron cell bodies and proximal dendrites and are involved in surge generation in female rodents (and possibly other species). The hypothalamic-pituitary-gonadal axis develops embryonically but, apart from short periods of activation immediately after birth, remains suppressed through a combination of gonadal and non-gonadal mechanisms. At puberty onset, the pulse generator reactivates, probably owing to progressive stimulatory influences on GnRH neurons from glial and neurotransmitter signalling, and the re-emergence of stimulatory arcuate kisspeptin input. In females, the development of pulsatile gonadotropin secretion enables final maturation of the surge generator that ultimately triggers the first ovulation. Representation of the GnRH neuronal network as a series of interlocking functional modules could help conceptualization of its functioning in different species. Insights into pulse and surge generation are expected to aid development of therapeutic strategies ameliorating pubertal disorders and infertility in the clinic. PMID:27199290

  6. Modulatory Effect of Gonadotropins on Rats’ Ovaries after Nandrolone Decanoate Administration: A Stereological Study

    PubMed Central

    Bordbar, Hossein; Mesbah, Fakhroddin; Talaei, Tahereh; Dehghani, Farzaneh; Mirkhani, Hossein

    2014-01-01

    Background: Nandrolone decanoate (ND) is an anabolic androgenic steroid (AAS) which influences the ovarian structure and function. We assessed the effects of ND on the ovarian volume, number of primordial follicles, and level of hormones and also evaluated the modulatory effects of gonadotropins on the histopathological changes imposed by the administration of ND. Methods: Six groups of Sprague-Dawley adult female rats (n=30) were used. The experimental rats were injected intraperitoneally with 3 and 10 mg/kg ND with or without human menopausal gonadotropin (hMG), 10 IU weekly for one month. The vehicle and control rats were administered olive oil and saline, respectively, for the same period of time. The ovarian volume and number of primordial follicles were estimated by stereological methods. Results: The results showed a decrease in the ovarian volume, number of primordial follicles, and level of gonadotropins in the ND-treated animals compared with the vehicle groups. In the rats treated with 3 mg/kg of ND with hMG, an increase in the ovarian volume and number of primordial follicles was shown as compared to the rats treated with the same dose of ND without hMG. Conclusion: ND exerted detrimental effects on the dimensions of the ovary, number of follicles, and level of sex hormones. However, hMG, prevented the harmful effects of ND (at least in a low dose) on the ovarian follicles. PMID:24453393

  7. Comparison of recombinant human follicle stimulating hormone (rhFSH), human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) on semen parameters after varicocelectomy: a randomized clinical trial

    PubMed Central

    Amirzargar, Mohammad Ali; Yavangi, Mahnaz; Basiri, Abbass; Hosseini Moghaddam, Sayyed Mahdi; Babbolhavaeji, Hooshang; Amirzargar, Nasibeh; Amirzargar, Hossein; Moadabshoar, Leila

    2012-01-01

    Background: The most frequent physical finding in infertile men is varicocele, in which one of the mechanisms that can affect seminal parameters is oxidative stress. Objective: Our study aimed, for the first time, to compare the efficacy of recombinant human follicle-stimulating hormone (rhFSH), human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) on sperm parameters and fertility after varicocelectomy. Materials and Methods: 113 infertile men with varicocele were divided into four groups. Group A received HCG 5000 IU weekly, group B received HMG 75 IU three times a week, group C received rhFSH 75 IU three times a week and group D received no medical treatment after varicocelectomy. Results: After three months, in group A sperm morphology improved (p=0.007), causing a 32% pregnancy rate. In group B, sperm motility (p=0.023) and morphology (p=0.014) improved, causing a 57% pregnancy rate. In group C, all of the investigated semen parameters increased (p<0.05), causing a 62.5% pregnancy rate. Only rhFSH improved sperm concentrations to >20×106 mL (p=0.027). In group D, sperm morphology increased (p=0.038), but other parameters remained unchanged and no pregnancies occurred. Conclusion: It can be concluded that drugs can reduce induction time for spermatogenesis and fertility in comparison with varicocelectomy alone. For these purposes, rhFSH is more effective than other drugs. PMID:25246910

  8. Prepubertal increases in gonadotropin-releasing hormone mRNA, gonadotropin-releasing hormone precursor, and subsequent maturation of precursor processing in male rats.

    PubMed Central

    Dutlow, C M; Rachman, J; Jacobs, T W; Millar, R P

    1992-01-01

    Changes in gonadotropins and gonadal steroids during sexual maturation in rats and humans are well documented but little is known about hypothalamic gonadotropin-releasing hormone (GnRH) gene expression in relation to these events. This study measured hypothalamic proGnRH mRNA, GnRH precursor, and fully processed GnRH from postnatal day 8 until day 62 in male rats. GnRH precursor increased on day 22, reached a peak on day 24, declined on day 25 and returned to infantile levels by day 28. A secondary rise in precursor occurred at about day 40 when testosterone levels increased. GnRH mRNA increased on day 22 and remained elevated over the study period to day 26. GnRH increased on day 24 and remained at this level until a secondary rise occurred coincident with the testosterone rise at about day 40. The ratio of GnRH precursor to GnRH was high until day 24 and was low from day 26 onwards, reflecting a maturation of the processing enzyme system between these 2 d. Thus, an abrupt increase in GnRH gene transcription (mRNA) occurs early in juvenile male rats (day 22), well before the onset of puberty. An increase in GnRH precursor accompanies these early changes and this is followed by the maturation of processing as evidenced by the rapid decline of precursor and increase in GnRH from day 24 onward. Images PMID:1469100

  9. Isolation and 2,4-D-degrading characteristics of Cupriavidus campinensis BJ71.

    PubMed

    Han, Lizhen; Zhao, Degang; Li, Cuicui

    2015-06-01

    An indigenous bacterial strain capable of utilizing 2,4-dichlorophenoxyacetic acid as the sole carbon and energy source was isolated from a soil used for grown wheat with a long-term history of herbicide use in Beijing, China. The strain BJ71 was identified as Cupriavidus campinensis based on its 16S rRNA sequence analysis and morphological, physiological, and biochemical characteristics. The degradation characteristics of strain BJ71 were evaluated. The optimal conditions for 2,4-D degradation were as follows: pH 7.0, 30 °C, 3% (v/v) inoculum size, and an initial 2,4-D concentration of 350 mg L(-1). Up to 99.57% of the 2,4-D was degraded under optimal conditions after 6 days of incubation. Strain BJ71 was also able to degrade quizalofop and fluroxypyr. This is the first report of a 2,4-D-degrader containing tfdA gene that can utilize these two herbicides. In a biodegradation experiment, 87.13% and 42.53% of 2,4-D (initial concentration, 350 mg kg(-1)) was degraded in non-sterile and sterilized soil inoculated with BJ71, respectively, after 14 days. The 2,4-D degradation was more rapid in a soil microcosm including BJ71 than in a soil microcosm without BJ71. These results indicate that strain BJ71 is a potential candidate for the bioremediation of soil contaminated with the herbicide 2,4-D. PMID:26273258

  10. Finger length ratio (2D:4D) in adults with gender identity disorder.

    PubMed

    Kraemer, Bernd; Noll, Thomas; Delsignore, Aba; Milos, Gabriella; Schnyder, Ulrich; Hepp, Urs

    2009-06-01

    From early childhood, gender identity and the 2nd to 4th finger length ratio (2D:4D) are discriminative characteristics between sexes. Both the human brain and 2D:4D may be influenced by prenatal testosterone levels. This calls for an examination of 2D:4D in patients with gender identity disorder (GID) to study the possible influence of prenatal testosterone on gender identity. Until now, the only study carried out on this issue suggests lower prenatal testosterone levels in right-handed male-to-female GID patients (MtF). We compared 2D:4D of 56 GID patients (39 MtF; 17 female-to-male GID patients, FtM) with data from a control sample of 176 men and 190 women. Bivariate group comparisons showed that right hand 2D:4D in MtF was significantly higher (feminized) than in male controls, but similar to female controls. The comparison of 2D:4D ratios of biological women revealed significantly higher (feminized) values for right hands of right handed FtM. Analysis of variance confirmed significant effects for sex and for gender identity on 2D:4D ratios but not for sexual orientation or for the interaction among variables. Our results indirectly point to the possibility of a weak influence of reduced prenatal testosterone as an etiological factor in the multifactorially influenced development of MtF GID. The development of FtM GID seems even more unlikely to be notably influenced by prenatal testosterone. PMID:17906922

  11. Isolation and 2,4-D-degrading characteristics of Cupriavidus campinensis BJ71

    PubMed Central

    Han, Lizhen; Zhao, Degang; Li, Cuicui

    2015-01-01

    An indigenous bacterial strain capable of utilizing 2,4-dichlorophenoxyacetic acid as the sole carbon and energy source was isolated from a soil used for grown wheat with a long-term history of herbicide use in Beijing, China. The strain BJ71 was identified as Cupriavidus campinensis based on its 16S rRNA sequence analysis and morphological, physiological, and biochemical characteristics. The degradation characteristics of strain BJ71 were evaluated. The optimal conditions for 2,4-D degradation were as follows: pH 7.0, 30 °C, 3% (v/v) inoculum size, and an initial 2,4-D concentration of 350 mg L−1. Up to 99.57% of the 2,4-D was degraded under optimal conditions after 6 days of incubation. Strain BJ71 was also able to degrade quizalofop and fluroxypyr. This is the first report of a 2,4-D-degrader containing tfdA gene that can utilize these two herbicides. In a biodegradation experiment, 87.13% and 42.53% of 2,4-D (initial concentration, 350 mg kg−1) was degraded in non-sterile and sterilized soil inoculated with BJ71, respectively, after 14 days. The 2,4-D degradation was more rapid in a soil microcosm including BJ71 than in a soil microcosm without BJ71. These results indicate that strain BJ71 is a potential candidate for the bioremediation of soil contaminated with the herbicide 2,4-D. PMID:26273258

  12. Challenges of radiotherapy: report on the 4D treatment planning workshop 2013.

    PubMed

    Knopf, Antje; Nill, Simeon; Yohannes, Indra; Graeff, Christian; Dowdell, Stephen; Kurz, Christopher; Sonke, Jan-Jakob; Biegun, Aleksandra K; Lang, Stephanie; McClelland, Jamie; Champion, Benjamin; Fast, Martin; Wölfelschneider, Jens; Gianoli, Chiara; Rucinski, Antoni; Baroni, Guido; Richter, Christian; van de Water, Steven; Grassberger, Clemens; Weber, Damien; Poulsen, Per; Shimizu, Shinichi; Bert, Christoph

    2014-11-01

    This report, compiled by experts on the treatment of mobile targets with advanced radiotherapy, summarizes the main conclusions and innovations achieved during the 4D treatment planning workshop 2013. This annual workshop focuses on research aiming to advance 4D radiotherapy treatments, including all critical aspects of time resolved delivery, such as in-room imaging, motion detection, motion managing, beam application, and quality assurance techniques. The report aims to revise achievements in the field and to discuss remaining challenges and potential solutions. As main achievements advances in the development of a standardized 4D phantom and in the area of 4D-treatment plan optimization were identified. Furthermore, it was noticed that MR imaging gains importance and high interest for sequential 4DCT/MR data sets was expressed, which represents a general trend of the field towards data covering a longer time period of motion. A new point of attention was work related to dose reconstructions, which may play a major role in verification of 4D treatment deliveries. The experimental validation of results achieved by 4D treatment planning and the systematic evaluation of different deformable image registration methods especially for inter-modality fusions were identified as major remaining challenges. A challenge that was also suggested as focus for future 4D workshops was the adaptation of image guidance approaches from conventional radiotherapy into particle therapy. Besides summarizing the last workshop, the authors also want to point out new evolving demands and give an outlook on the focus of the next workshop. PMID:25172392

  13. Resolution enhancement of lung 4D-CT data using multiscale interphase iterative nonlocal means

    SciTech Connect

    Zhang Yu; Yap, Pew-Thian; Wu Guorong; Feng Qianjin; Chen Wufan; Lian Jun; Shen Dinggang

    2013-05-15

    Purpose: Four-dimensional computer tomography (4D-CT) has been widely used in lung cancer radiotherapy due to its capability in providing important tumor motion information. However, the prolonged scanning duration required by 4D-CT causes considerable increase in radiation dose. To minimize the radiation-related health risk, radiation dose is often reduced at the expense of interslice spatial resolution. However, inadequate resolution in 4D-CT causes artifacts and increases uncertainty in tumor localization, which eventually results in extra damages of healthy tissues during radiotherapy. In this paper, the authors propose a novel postprocessing algorithm to enhance the resolution of lung 4D-CT data. Methods: The authors' premise is that anatomical information missing in one phase can be recovered from the complementary information embedded in other phases. The authors employ a patch-based mechanism to propagate information across phases for the reconstruction of intermediate slices in the longitudinal direction, where resolution is normally the lowest. Specifically, the structurally matching and spatially nearby patches are combined for reconstruction of each patch. For greater sensitivity to anatomical details, the authors employ a quad-tree technique to adaptively partition the image for more fine-grained refinement. The authors further devise an iterative strategy for significant enhancement of anatomical details. Results: The authors evaluated their algorithm using a publicly available lung data that consist of 10 4D-CT cases. The authors' algorithm gives very promising results with significantly enhanced image structures and much less artifacts. Quantitative analysis shows that the authors' algorithm increases peak signal-to-noise ratio by 3-4 dB and the structural similarity index by 3%-5% when compared with the standard interpolation-based algorithms. Conclusions: The authors have developed a new algorithm to improve the resolution of 4D-CT. It outperforms

  14. Capillary Deposition of Complement C4d and C3d in Chinese Renal Allograft Biopsies

    PubMed Central

    Lv, Rong; Zhang, Wei; Han, Fei; Liu, Guangjun; Xie, Wenqing

    2015-01-01

    Background. C3d is a product of both the classic and the alternative complement cascades; however, few studies have addressed the role of C3d in renal biopsies and its relationship with long-term graft survival rate is not very clear. Methods. 94 patients with biopsy-proven acute rejection episodes were included in the study. We investigated the associations between histological findings, clinical examinations, and outcome. Results. The overall prevalence for C4dPTC and C3dPTC was 42.6% and 29.8%. There was a significant association between C3dPTC and C4dPTC (P < 0.001). C3dPTC and C4dPTC were related with histological types (P = 0.024 and P < 0.001, resp.). The long-term survival rate for C4dPTC positive transplants was lower than that of C4dPTC negative transplants, but it was not statistic significant in our study (P = 0.150). The survival rate of C3dPTC positive group was much lower than the negative group (P = 0.014). Patients with double positives for C4dPTC and C3dPTC exhibited the lowest survival rate significantly different from those of the C3dPTC only and C4dPTC only groups (P = 0.01 and P = 0.0037). Conclusions. This longitudinal cohort study has demonstrated that C3d deposition in the PTC was closely related to renal dysfunction and pathological changes. PMID:25821339

  15. Evaluation of a 4D cone-beam CT reconstruction approach using a simulation framework.

    PubMed

    Hartl, Alexander; Yaniv, Ziv

    2009-01-01

    Current image-guided navigation systems for thoracic abdominal interventions utilize three dimensional (3D) images acquired at breath-hold. As a result they can only provide guidance at a specific point in the respiratory cycle. The intervention is thus performed in a gated manner, with the physician advancing only when the patient is at the same respiratory cycle in which the 3D image was acquired. To enable a more continuous workflow we propose to use 4D image data. We describe an approach to constructing a set of 4D images from a diagnostic CT acquired at breath-hold and a set of intraoperative cone-beam CT (CBCT) projection images acquired while the patient is freely breathing. Our approach is based on an initial reconstruction of a gated 4D CBCT data set. The 3D CBCT images for each respiratory phase are then non-rigidly registered to the diagnostic CT data. Finally the diagnostic CT is deformed based on the registration results, providing a 4D data set with sufficient quality for navigation purposes. In this work we evaluate the proposed reconstruction approach using a simulation framework. A 3D CBCT dataset of an anthropomorphic phantom is deformed using internal motion data acquired from an animal model to create a ground truth 4D CBCT image. Simulated projection images are then created from the 4D image and the known CBCT scan parameters. Finally, the original 3D CBCT and the simulated X-ray images are used as input to our reconstruction method. The resulting 4D data set is then compared to the known ground truth by normalized cross correlation(NCC). We show that the deformed diagnostic CTs are of better quality than the gated reconstructions with a mean NCC value of 0.94 versus a mean 0.81 for the reconstructions. PMID:19964143

  16. Effects of light-emitting diode spectra on the vertebrate ancient long opsin and gonadotropin hormone in the goldfish Carassius auratus.

    PubMed

    Song, Jin Ah; Kim, Na Na; Choi, Young Jae; Choi, Ji Yong; Kim, Bong-Seok; Choi, Cheol Young

    2016-08-01

    We determined the molecular mechanism underlying the environmental (photoperiodic) regulation of sexual maturation in fish, we examined the expression of sexual maturation-related hormones and vertebrate ancient long opsin (VAL-opsin) in goldfish (Carassius auratus) exposed to different light spectra (red and green light-emitting diodes). We further evaluated the effect of exogenous gonadotropin hormone (GTH) on the expression of VAL-opsin under different light conditions. Our results demonstrated that the expression of GTHs was higher in the fish exposed to green light, and VAL-opsin levels were increased in the fish receiving GTH injection. Therefore, we have uncovered a molecular mechanism underlying the environmental (light)-induced trigger for sexual maturation: VAL-opsin is activated by green light and GTH, which promotes the expression of sexual maturation genes. PMID:27255995

  17. Intra-Testicular Signals Regulate Germ Cell Progression and Production of Qualitatively Mature Spermatozoa in Vertebrates

    PubMed Central

    Meccariello, Rosaria; Chianese, Rosanna; Chioccarelli, Teresa; Ciaramella, Vincenza; Fasano, Silvia; Pierantoni, Riccardo; Cobellis, Gilda

    2014-01-01

    Spermatogenesis, a highly conserved process in vertebrates, is mainly under the hypothalamic–pituitary control, being regulated by the secretion of pituitary gonadotropins, follicle stimulating hormone, and luteinizing hormone, in response to stimulation exerted by gonadotropin releasing hormone from hypothalamic neurons. At testicular level, gonadotropins bind specific receptors located on the somatic cells regulating the production of steroids and factors necessary to ensure a correct spermatogenesis. Indeed, besides the endocrine route, a complex network of cell-to-cell communications regulates germ cell progression, and a combination of endocrine and intra-gonadal signals sustains the production of high quality mature spermatozoa. In this review, we focus on the recent advances in the area of the intra-gonadal signals supporting sperm development. PMID:24847312

  18. Squelching of ETS2 transactivation by POU5F1 silences the human chorionic gonadotropin CGA subunit gene in human choriocarcinoma and embryonic stem cells.

    PubMed

    Gupta, Rangan; Ezashi, Toshihiko; Roberts, R Michael

    2012-05-01

    The subunit genes encoding human chorionic gonadotropin, CGA, and CGB, are up-regulated in human trophoblast. However, they are effectively silenced in choriocarcinoma cells by ectopically expressed POU domain class 5 transcription factor 1 (POU5F1). Here we show that POU5F1 represses activity of the CGA promoter through its interactions with ETS2, a transcription factor required for both placental development and human chorionic gonadotropin subunit gene expression, by forming a complex that precludes ETS2 from interacting with the CGA promoter. Mutation of a POU5F1 binding site proximal to the ETS2 binding site does not alter the ability of POU5F1 to act as a repressor but causes a drop in basal promoter activity due to overlap with the binding site for DLX3. DLX3 has only a modest ability to raise basal CGA promoter activity, but its coexpression with ETS2 can up-regulate it 100-fold or more. The two factors form a complex, and both must bind to the promoter for the combination to be transcriptionally effective, a synergy compromised by POU5F1. Similarly, in human embryonic stem cells, which express ETS2 but not CGA, ETS2 does not occupy its binding site on the CGA promoter but is found instead as a soluble complex with POU5F1. When human embryonic stem cells differentiate in response to bone morphogenetic protein-4 and concentrations of POU5F1 fall and hCG and DLX3 rise, ETS2 then occupies its binding site on the CGA promoter. Hence, a squelching mechanism underpins the transcriptional silencing of CGA by POU5F1 and could have general relevance to how pluripotency is maintained and how the trophoblast lineage emerges from pluripotent precursor cells. PMID:22446105

  19. 4D cone-beam CT reconstruction using multi-organ meshes for sliding motion modeling.

    PubMed

    Zhong, Zichun; Gu, Xuejun; Mao, Weihua; Wang, Jing

    2016-02-01

    A simultaneous motion estimation and image reconstruction (SMEIR) strategy was proposed for 4D cone-beam CT (4D-CBCT) reconstruction and showed excellent results in both phantom and lung cancer patient studies. In the original SMEIR algorithm, the deformation vector field (DVF) was defined on voxel grid and estimated by enforcing a global smoothness regularization term on the motion fields. The objective of this work is to improve the computation efficiency and motion estimation accuracy of SMEIR for 4D-CBCT through developing a multi-organ meshing model. Feature-based adaptive meshes were generated to reduce the number of unknowns in the DVF estimation and accurately capture the organ shapes and motion. Additionally, the discontinuity in the motion fields between different organs during respiration was explicitly considered in the multi-organ mesh model. This will help with the accurate visualization and motion estimation of the tumor on the organ boundaries in 4D-CBCT. To further improve the computational efficiency, a GPU-based parallel implementation was designed. The performance of the proposed algorithm was evaluated on a synthetic sliding motion phantom, a 4D NCAT phantom, and four lung cancer patients. The proposed multi-organ mesh based strategy outperformed the conventional Feldkamp-Davis-Kress, iterative total variation minimization, original SMEIR and single meshing method based on both qualitative and quantitative evaluations. PMID:26758496

  20. 4D cone-beam CT reconstruction using multi-organ meshes for sliding motion modeling

    NASA Astrophysics Data System (ADS)

    Zhong, Zichun; Gu, Xuejun; Mao, Weihua; Wang, Jing

    2016-02-01

    A simultaneous motion estimation and image reconstruction (SMEIR) strategy was proposed for 4D cone-beam CT (4D-CBCT) reconstruction and showed excellent results in both phantom and lung cancer patient studies. In the original SMEIR algorithm, the deformation vector field (DVF) was defined on voxel grid and estimated by enforcing a global smoothness regularization term on the motion fields. The objective of this work is to improve the computation efficiency and motion estimation accuracy of SMEIR for 4D-CBCT through developing a multi-organ meshing model. Feature-based adaptive meshes were generated to reduce the number of unknowns in the DVF estimation and accurately capture the organ shapes and motion. Additionally, the discontinuity in the motion fields between different organs during respiration was explicitly considered in the multi-organ mesh model. This will help with the accurate visualization and motion estimation of the tumor on the organ boundaries in 4D-CBCT. To further improve the computational efficiency, a GPU-based parallel implementation was designed. The performance of the proposed algorithm was evaluated on a synthetic sliding motion phantom, a 4D NCAT phantom, and four lung cancer patients. The proposed multi-organ mesh based strategy outperformed the conventional Feldkamp-Davis-Kress, iterative total variation minimization, original SMEIR and single meshing method based on both qualitative and quantitative evaluations.

  1. Using 2D: 4D digit ratios to determine motor skills in children.

    PubMed

    Wang, Y; Wang, H-L; Li, Y-H; Zhu, F-L; Li, S-J; Ni, H

    2016-03-01

    In past few decades, there has an outburst of research surrounding second to fourth finger digit ratio (2D:4D) and its relation to prenatal sex steroids including both testosterone and estrogen. In utero, testosterone and estrogen are responsible for the differences in digit ratio between the genders. Recent research has tried to extend past the influence of steroids and look at the potential effect of digit ratios on fine and gross motor skills in children. We compiled the current understanding of the connection between sex hormones and the development of the 2D:4D ratio as well as the effect the ratio has on motor skills. There seems to be a significant positive correlation between 2D:4D digit ratio and precision of fine motor skill. In addition, there is a negative correlation between 2D:4D ratio and speed of fine motor activity. In this review, we will outline the use of 2D:4D ratio as a biomarker for prenatal sex steroids and through that, a proxy marker for fine and gross motor skills. PMID:27010133

  2. Cloning and expression of the 4D8 gene from Hyalomma asiaticum tick.

    PubMed

    Liu, Z Q; Xia, J; Wang, G L; Kuermanali, N

    2016-01-01

    Hyalomma asiaticum tick, an important ectozoic parasite causes tickle, pain, anemia, weight loss, and paralysis in its hosts, which include humans, cattle, sheep, horses, camels, and hares. The 4D8 gene can be a potential vaccine candidate antigen for H. asiaticum. In the present study, we cloned and expressed the 4D8 gene of H. asiaticum from Xinjiang Province. Primers were designed according to the H. asiaticum tick 4D8 gene sequence available in GenBank. The gene was amplified by reverse transcription-polymerase chain reaction and the fragments were subcloned into the prokaryotic expression vector pET30a and the recombinant vector pET30a-4D8 was constructed. The expressed recombinant protein was purified and its biological activity was investigated by western blot. Results revealed that the recombinant protein was a biologically active fusion protein with a molecular weight of 20 kDa. The purified 4D8 protein would provide a strong foundation for further studies on this protein. PMID:27323189

  3. Allowing for model error in strong constraint 4D-Var

    NASA Astrophysics Data System (ADS)

    Howes, Katherine; Lawless, Amos; Fowler, Alison

    2016-04-01

    Four dimensional variational data assimilation (4D-Var) can be used to obtain the best estimate of the initial conditions of an environmental forecasting model, namely the analysis. In practice, when the forecasting model contains errors, the analysis from the 4D-Var algorithm will be degraded to allow for errors later in the forecast window. This work focusses on improving the analysis at the initial time by allowing for the fact that the model contains error, within the context of strong constraint 4D-Var. The 4D-Var method developed acknowledges the presence of random error in the model at each time step by replacing the observation error covariance matrix with an error covariance matrix that includes both observation error and model error statistics. It is shown that this new matrix represents the correct error statistics of the innovations in the presence of model error. A method for estimating this matrix using innovation statistics, without requiring prior knowledge of the model error statistics, is presented. The method is demonstrated numerically using a non-linear chaotic system with erroneous parameter values. We show that that the new method works to reduce the analysis error covariance when compared with a standard strong constraint 4D-Var scheme. We discuss the fact that an improved analysis will not necessarily provide a better forecast.

  4. Are 2D:4D finger-length ratios an indicator of androgenetic alopecia in males?*

    PubMed Central

    Bilgic, Özlem; Altınyazar, Hilmi Cevdet; Eryılmaz, Dilek; Tuğrul, Zehra Ayça

    2016-01-01

    BACKGROUND Although the pathogenesis of androgenetic alopecia is not completely understood, the roles of genetic susceptibility and androgens are well-known. A lower ratio of the second digit (index finger = 2D) to the fourth digit (ring finger = 4D) length has been hypothesized to reflect prenatal androgen exposure and/or higher sensitivity to androgens. OBJECTIVES To determine the relationship between the second to fourth digit length ratio and androgenetic alopecia. METHODS Finger length measurements were made by a digital vernier calliper. Androgenetic alopecia severity was assessed using the Hamilton-Norwood scale. Subjects with an androgenetic alopecia score of grade III or more were included in the study. RESULTS A total of 189 males with androgenetic alopecia and 171 healthy controls were enrolled in the study. The age range of participants was 19-65 years. The 2D:4D ratios in patients with androgenetic alopecia were significantly lower than those of healthy controls for the right hand; however, no significant difference was found for the left hand. Average 2D:4D ratios in androgenetic alopecia patients were also lower than in controls. No significant relationship was observed between androgenetic alopecia severity and 2D:4D ratios. CONCLUSION Our data support the anatomical evidence of in utero androgen exposure and/or an individual’s sensitivity to androgens in patients with androgenetic alopecia. Furthermore, the right hand 2D:4D ratio might be an indicator of androgenetic alopecia development. PMID:27192513

  5. Adaptive 4D MR Imaging Using Navigator-Based Respiratory Signal for MRI-Guided Therapy

    PubMed Central

    Tokuda, Junichi; Morikawa, Shigehiro; Haque, Hasnine A.; Tsukamoto, Tetsuji; Matsumiya, Kiyoshi; Liao, Hongen; Masamune, Ken; Dohi, Takeyoshi

    2010-01-01

    For real-time 3D visualization of respiratory organ motion for MRI-guided therapy, a new adaptive 4D MR imaging method based on navigator echo and multiple gating windows was developed. This method was designed to acquire a time series of volumetric 3D images of a cyclically moving organ, enabling therapy to be guided by synchronizing the 4D image with the actual organ motion in real time. The proposed method was implemented in an open-configuration 0.5T clinical MR scanner. To evaluate the feasibility and determine optimal imaging conditions, studies were conducted with a phantom, volunteers, and a patient. In the phantom study the root mean square (RMS) position error in the 4D image of the cyclically moving phantom was 1.9 mm and the imaging time was ≈10 min when the 4D image had six frames. In the patient study, 4D images were successfully acquired under clinical conditions and a liver tumor was discriminated in the series of frames. The image quality was affected by the relations among the encoding direction, the slice orientation, and the direction of motion of the target organ. In conclusion, this study has shown that the proposed method is feasible and capable of providing a real-time dynamic 3D atlas for surgical navigation with sufficient accuracy and image quality. PMID:18429011

  6. Association between PDE4D gene and ischemic stroke: recent advancements.

    PubMed

    Das, Satrupa; Roy, Sitara; Munshi, Anjana

    2016-07-01

    Stroke is a severe complication and a leading cause of death worldwide and genetic studies among different ethnicities has provided the basis for involvement of phosphodiesterase 4D (PDE4D) gene in cerebrovascular diseases. Recent advancements have evaluated the role of this gene in stroke and these studies have provided a stronger support for the involvement of this gene in stroke development and few studies also suggest that it may influence outcome. Furthermore, case-control studies and meta-analysis studies have provided strong evidence for certain variants in PDE4D to predispose to stroke only among certain ethnicities. Thus, this review focuses on recent progress made in PDE4D gene research involving genetic, molecular and pharmacological aspect. A strong conclusion has emerged that clearly indicates a pivotal role played by this gene in ischemic stroke globally. Studies have also noticeably highlighted that PDE4D gene/pathway can be a suitable drug target for managing stroke; however, a more comprehensive research is still required to understand the molecular and cellular intricacies this gene plays in stroke development, progression and its outcome. PMID:26004910

  7. Impact of 4D image quality on the accuracy of target definition.

    PubMed

    Nielsen, Tine Bjørn; Hansen, Christian Rønn; Westberg, Jonas; Hansen, Olfred; Brink, Carsten

    2016-03-01

    Delineation accuracy of target shape and position depends on the image quality. This study investigates whether the image quality on standard 4D systems has an influence comparable to the overall delineation uncertainty. A moving lung target was imaged using a dynamic thorax phantom on three different 4D computed tomography (CT) systems and a 4D cone beam CT (CBCT) system using pre-defined clinical scanning protocols. Peak-to-peak motion and target volume were registered using rigid registration and automatic delineation, respectively. A spatial distribution of the imaging uncertainty was calculated as the distance deviation between the imaged target and the true target shape. The measured motions were smaller than actual motions. There were volume differences of the imaged target between respiration phases. Imaging uncertainties of >0.4 cm were measured in the motion direction which showed that there was a large distortion of the imaged target shape. Imaging uncertainties of standard 4D systems are of similar size as typical GTV-CTV expansions (0.5-1 cm) and contribute considerably to the target definition uncertainty. Optimising and validating 4D systems is recommended in order to obtain the most optimal imaged target shape. PMID:26577711

  8. Uptake of 2,4-D in higher plants from artificial rain

    SciTech Connect

    Lokke, H.

    1984-02-01

    Sinapis alba L., Lapsana communis L., Achillea millefolium L., Brassica napus L., Lactuca sativa L., and Lycopersicum esculentum L. were exposed to 2,4-dichlorophenoxy (2-/sup 14/C)acetic acid (2,4-D) at 10 micrograms liter-1 in artificial rain, pH 6.5 and 3.3. The 2,4-D was absorbed in all species tested. Concentrations of parent 2,4-D appeared at the highest level in Achillea (0.1 mg kg-1 dry wt), and at zero level in Lycopersicum. Twenty-one daily treatments at pH 6.5 for 30-min periods increased dry-matter concentrations in the leaves of Achillea and decreased those in Brassica. No change in dry-matter concentration was observed in the leaves of Brassica by seven daily treatments for 30-min periods at pH 3.3.

  9. Soccer players awarded one or more red cards exhibit lower 2D:4D ratios.

    PubMed

    Mailhos, Alvaro; Buunk, Abraham P; Del Arca, Denise; Tutte, Verónica

    2016-09-01

    Anatomical, cognitive and behavioral sex differences are widely recognized in many species. It has been proposed that some of these differences might result from the organizing effects of prenatal sex steroids. In humans, males usually exhibit higher levels of physical aggression and prowess. In this study, we analyze the relationship between second-to-fourth digit (2D:4D) ratios-a proxy for prenatal androgen levels-and foul play and sporting performance in a sample of junior soccer players from a professional Uruguayan soccer club. Our results show that the most aggressive players (i.e., those awarded one or more red cards) have a more masculine finger pattern (lower 2D:4D ratio), while no relationship could be found between sporting performance and 2D:4D ratios. The results are discussed in the context of previous findings. Aggr. Behav. 42:417-426, 2016. © 2015 Wiley Periodicals, Inc. PMID:26699684

  10. Live 4D optical coherence tomography for early embryonic mouse cardiac phenotyping

    NASA Astrophysics Data System (ADS)

    Lopez, Andrew L.; Wang, Shang; Larin, Kirill V.; Overbeek, Paul A.; Larina, Irina V.

    2016-03-01

    Studying embryonic mouse development is important for our understanding of normal human embryogenesis and the underlying causes of congenital defects. Our research focuses on imaging early development in the mouse embryo to specifically understand cardiovascular development using optical coherence tomography (OCT). We have previously developed imaging approaches that combine static embryo culture, OCT imaging and advanced image processing to visualize the whole live mouse embryos and obtain 4D (3D+time) cardiodynamic datasets with cellular resolution. Here, we present the study of using 4D OCT for dynamic imaging of early embryonic heart in live mouse embryos to assess mutant cardiac phenotypes during development, including a cardiac looping defect. Our results indicate that the live 4D OCT imaging approach is an efficient phenotyping tool that can reveal structural and functional cardiac defects at very early stages. Further studies integrating live embryonic cardiodynamic phenotyping with molecular and genetic approaches in mouse mutants will help to elucidate the underlying signaling defects.

  11. Attosecond delay of xenon 4 d photoionization at the giant resonance and Cooper minimum

    NASA Astrophysics Data System (ADS)

    Magrakvelidze, Maia; Madjet, Mohamed El-Amine; Chakraborty, Himadri S.

    2016-07-01

    A Kohn-Sham time-dependent local-density-functional scheme is utilized to predict attosecond time delays of xenon 4 d photoionization that involves the 4 d giant dipole resonance and Cooper minimum. The fundamental effect of electron correlations to uniquely determine the delay at both regions is demonstrated. In particular, for the giant dipole resonance, the delay underpins strong collective effect, emulating the recent prediction at C60 giant plasmon resonance [T. Barillot et al., Phys. Rev. A 91, 033413 (2015), 10.1103/PhysRevA.91.033413]. For the Cooper minimum, a qualitative similarity with a photorecombination experiment near argon 3 p minimum [S. B. Schoun et al., Phys. Rev. Lett. 112, 153001 (2014), 10.1103/PhysRevLett.112.153001] is found. The result should encourage attosecond measurements of Xe 4 d photoemission.

  12. Proximal femoral focal deficiency of the fetus - early 3D/4D prenatal ultrasound diagnosis.

    PubMed

    Kudla, Marek J; Beczkowska-Kielek, Aleksandra; Kutta, Katarzyna; Partyka-Lasota, Justyna

    2016-09-01

    Proximal Femoral Focal Deficiency (PFFD) is a rare congenital syndrome of unknown etiology. Additional disorders can be present up to 70% of PFFD cases. Management (including termination) depends on the severity of the malformation. We present a case of a 32-year-old woman referred for routine ultrasound examination in the 12th week of pregnancy. Detailed 3D/4D evaluation revealed asymmetry of lower limbs and diagnosis of isolated PFFD was established. Parents were fully informed and decided to continue the pregnancy. We stress here the importance of early 3D/4D ultrasound diagnosis. Our paper presents the earliest case where the diagnosis of PFFD was established with 3D/4D ultrasound. PMID:27622419

  13. Exact Solutions of Embedding the 4d Universe in a 5d Einstein Manifold

    NASA Astrophysics Data System (ADS)

    Meng, Xin-He; Ren, Jie; Zhang, Hong-Guang

    One of the simplest ways to extend 4D cosmological models is to add another spatial dimension to make them 5D. In particular, it has been shown that the simplest of such 5D models, i.e. one in which the right-hand side of the Einstein equation is empty, induces a 4D nonempty universe. Accordingly, the origin of matter in a real 4D universe might be mathematically attributed to the existence of one (fictitious) extra spatial dimension. Here we consider the case of an empty 5D universe possessing a cosmological constant Λ and obtain exact solutions for both positive and negative values of the Λ. It is seen that such a model can naturally reduce to a power law ΛCDM model for the real universe. Further, it can be seen that the arbitrary constants and functions appearing in this model are endowed with definite physical meanings.

  14. The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma

    SciTech Connect

    Zhou, Hua; Yang, Ying-Hua; Binmadi, Nada O.; Proia, Patrizia; Basile, John R.

    2012-08-15

    Growth and metastasis of solid tumors requires induction of angiogenesis to ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing transformed cells. Through either mutations, hypoxia generated by cytoreductive therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a change from an avascular to a neovascular phenotype, a transition mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular endothelial growth factor (VEGF) is one example of a gene whose transcription is stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and survival by stimulating new blood vessel growth in response to such stresses as chemotherapy or radiotherapy-induced hypoxia, and it therefore has become a tempting target for neutralizing antibodies in the treatment of advanced neoplasms. Emerging evidence has shown that the semaphorins, proteins originally associated with control of axonal growth and immunity, are regulated by changes in oxygen tension as well and may play a role in tumor-induced angiogenesis. Through the use of RNA interference, in vitro and in vivo angiogenesis assays and tumor xenograft experiments, we demonstrate that expression of semaphorin 4D (SEMA4D), which is under the control of the HIF-family of transcription factors, cooperates with VEGF to promote tumor growth and vascularity in oral squamous cell carcinoma (OSCC). We use blocking antibodies to show that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of OSCC and other solid tumors. -- Highlights: Black-Right-Pointing-Pointer Similar to VEGF, SEMA4D promotes angiogenesis in vitro and in vivo. Black-Right-Pointing-Pointer Both VEGF and SEMA4D are produced by OSCC cells in a HIF-dependent manner. Black-Right-Pointing-Pointer These factors combine to elicit a robust pro-angiogenic phenotype in OSCC. Black-Right-Pointing-Pointer Anti-SEMA4D

  15. The 2D:4D-Ratio and Neuroticism Revisited: Empirical Evidence from Germany and China.

    PubMed

    Sindermann, Cornelia; Li, Mei; Sariyska, Rayna; Lachmann, Bernd; Duke, Éilish; Cooper, Andrew; Warneck, Lidia; Montag, Christian

    2016-01-01

    The 2D:4D-Ratio, as an indirect measure of the fetal testosterone to estradiol ratio, is potentially very important for understanding and explaining different personality traits. It was the aim of the present study to replicate the findings from Fink et al. (2004) about the relation between individual differences in 2D:4D-Ratios and the Five Factor Model in different cultural groups. Therefore a sample of n = 78 Chinese and n = 370 German participants was recruited. Every participant provided hand scans of both hands, from which 2D:4D-Ratios were computed. Moreover, all participants filled in the NEO Five Factor Inventory (NEO-FFI). Significant sex differences were found for ratios of both hands in the expected direction, with females showing higher ratios than males. With respect to links between personality and the digit ratio, a positive association was observed between 2D:4D-Ratio and Neuroticism in females, as shown in the earlier study. These findings were observed in both female subsamples from China and Germany, as well as in the full sample of participants. But in contrast to the results for the whole and the German female sample, where 2D:4D-Ratio of both hands were related to Neuroticism, in the Chinese female sample only left hand 2D:4D-Ratio was significantly and positively related to Neuroticism. There were no significant correlations found in any of the male samples. Thus, prenatal exposure to sex steroids appears to influence the personality factor Neuroticism in females specifically. This finding potentially has implications for mental health, as Neuroticism has been shown to be a risk factor for various forms of psychopathology. PMID:27375513

  16. Respiratory motion correction in 4D-PET by simultaneous motion estimation and image reconstruction (SMEIR)

    NASA Astrophysics Data System (ADS)

    Kalantari, Faraz; Li, Tianfang; Jin, Mingwu; Wang, Jing

    2016-08-01

    In conventional 4D positron emission tomography (4D-PET), images from different frames are reconstructed individually and aligned by registration methods. Two issues that arise with this approach are as follows: (1) the reconstruction algorithms do not make full use of projection statistics; and (2) the registration between noisy images can result in poor alignment. In this study, we investigated the use of simultaneous motion estimation and image reconstruction (SMEIR) methods for motion estimation/correction in 4D-PET. A modified ordered-subset expectation maximization algorithm coupled with total variation minimization (OSEM-TV) was used to obtain a primary motion-compensated PET (pmc-PET) from all projection data, using Demons derived deformation vector fields (DVFs) as initial motion vectors. A motion model update was performed to obtain an optimal set of DVFs in the pmc-PET and other phases, by matching the forward projection of the deformed pmc-PET with measured projections from other phases. The OSEM-TV image reconstruction was repeated using updated DVFs, and new DVFs were estimated based on updated images. A 4D-XCAT phantom with typical FDG biodistribution was generated to evaluate the performance of the SMEIR algorithm in lung and liver tumors with different contrasts and different diameters (10–40 mm). The image quality of the 4D-PET was greatly improved by the SMEIR algorithm. When all projections were used to reconstruct 3D-PET without motion compensation, motion blurring artifacts were present, leading up to 150% tumor size overestimation and significant quantitative errors, including 50% underestimation of tumor contrast and 59% underestimation of tumor uptake. Errors were reduced to less than 10% in most images by using the SMEIR algorithm, showing its potential in motion estimation/correction in 4D-PET.

  17. Advances in 4D Treatment Planning for Scanned Particle Beam Therapy — Report of Dedicated Workshops

    PubMed Central

    Bert, Christoph; Graeff, Christian; Riboldi, Marco; Nill, Simeon; Baroni, Guido; Knopf, Antje-Christin

    2014-01-01

    We report on recent progress in the field of mobile tumor treatment with scanned particle beams, as discussed in the latest editions of the 4D treatment planning workshop. The workshop series started in 2009, with about 20 people from 4 research institutes involved, all actively working on particle therapy delivery and development. The first workshop resulted in a summary of recommendations for the treatment of mobile targets, along with a list of requirements to apply these guidelines clinically. The increased interest in the treatment of mobile tumors led to a continuously growing number of attendees: the 2012 edition counted more than 60 participants from 20 institutions and commercial vendors. The focus of research discussions among workshop participants progressively moved from 4D treatment planning to complete 4D treatments, aiming at effective and safe treatment delivery. Current research perspectives on 4D treatments include all critical aspects of time resolved delivery, such as in-room imaging, motion detection, beam application, and quality assurance techniques. This was motivated by the start of first clinical treatments of hepato cellular tumors with a scanned particle beam, relying on gating or abdominal compression for motion mitigation. Up to date research activities emphasize significant efforts in investigating advanced motion mitigation techniques, with a specific interest in the development of dedicated tools for experimental validation. Potential improvements will be made possible in the near future through 4D optimized treatment plans that require upgrades of the currently established therapy control systems for time resolved delivery. But since also these novel optimization techniques rely on the validity of the 4DCT, research focusing on alternative 4D imaging technique, such as MRI based 4DCT generation will continue. PMID:24354749

  18. The 2D:4D-Ratio and Neuroticism Revisited: Empirical Evidence from Germany and China

    PubMed Central

    Sindermann, Cornelia; Li, Mei; Sariyska, Rayna; Lachmann, Bernd; Duke, Éilish; Cooper, Andrew; Warneck, Lidia; Montag, Christian

    2016-01-01

    The 2D:4D-Ratio, as an indirect measure of the fetal testosterone to estradiol ratio, is potentially very important for understanding and explaining different personality traits. It was the aim of the present study to replicate the findings from Fink et al. (2004) about the relation between individual differences in 2D:4D-Ratios and the Five Factor Model in different cultural groups. Therefore a sample of n = 78 Chinese and n = 370 German participants was recruited. Every participant provided hand scans of both hands, from which 2D:4D-Ratios were computed. Moreover, all participants filled in the NEO Five Factor Inventory (NEO-FFI). Significant sex differences were found for ratios of both hands in the expected direction, with females showing higher ratios than males. With respect to links between personality and the digit ratio, a positive association was observed between 2D:4D-Ratio and Neuroticism in females, as shown in the earlier study. These findings were observed in both female subsamples from China and Germany, as well as in the full sample of participants. But in contrast to the results for the whole and the German female sample, where 2D:4D-Ratio of both hands were related to Neuroticism, in the Chinese female sample only left hand 2D:4D-Ratio was significantly and positively related to Neuroticism. There were no significant correlations found in any of the male samples. Thus, prenatal exposure to sex steroids appears to influence the personality factor Neuroticism in females specifically. This finding potentially has implications for mental health, as Neuroticism has been shown to be a risk factor for various forms of psychopathology. PMID:27375513

  19. Complement Factor C4d Is a Common Denominator in Thrombotic Microangiopathy.

    PubMed

    Chua, Jamie S; Baelde, Hans J; Zandbergen, Malu; Wilhelmus, Suzanne; van Es, Leendert A; de Fijter, Johan W; Bruijn, Jan A; Bajema, Ingeborg M; Cohen, Danielle

    2015-09-01

    Complement activation has a major role in thrombotic microangiopathy (TMA), a disorder that can occur in a variety of clinical conditions. Promising results of recent trials with terminal complement-inhibiting drugs call for biomarkers identifying patients who might benefit from this treatment. The primary aim of this study was to determine the prevalence and localization of complement factor C4d in kidneys of patients with TMA. The secondary aims were to determine which complement pathways lead to C4d deposition and to determine whether complement activation results in deposition of the terminal complement complex. We examined 42 renal sections with histologically confirmed TMA obtained from a heterogeneous patient group. Deposits of C4d, mannose-binding lectin, C1q, IgM, and C5b-9 were scored in the glomeruli, peritubular capillaries, and arterioles. Notably, C4d deposits were present in 88.1% of TMA cases, and the various clinical conditions had distinct staining patterns within the various compartments of the renal vasculature. Classical pathway activation was observed in 90.5% of TMA cases. C5b-9 deposits were present in 78.6% of TMA cases and in 39.6% of controls (n=53), but the staining pattern differed between cases and controls. In conclusion, C4d is a common finding in TMA, regardless of the underlying clinical condition. Moreover, C5b-9 was present in >75% of the TMA samples, suggesting that terminal complement inhibitors may have a beneficial effect in these patients. C4d and C5b-9 should be investigated as possible diagnostic biomarkers in the clinical work-up of patients suspected of having complement-mediated TMA. PMID:25573909

  20. Digit ratio (2D:4D) and gender inequalities across nations.

    PubMed

    Manning, John T; Fink, Bernhard; Trivers, Robert

    2014-01-01

    Gender inequality varies across nations, where such inequality is defined as the disproportionate representation of one sex over the other in desirable social, economic, and biological roles (typically male over female). Thus in Norway, 40% of parliamentarians are women, in the USA 17%, and in Saudi Arabia 0%. Some of this variation is associated with economic prosperity but there is evidence that this cause and effect can go in either direction. Here we show that within a population the average ratio of index (2D) to ring (4D) finger lengths (2D:4D)-a proxy measure of the relative degree to which offspring is exposed in utero to testosterone versus estrogen-is correlated with measures of gender inequality between nations. We compared male and female 2D:4D ratios to female parliamentary representation, labor force participation, female education level, maternal mortality rates, and juvenile pregnancy rates per nation in a sample of 29 countries. We found those nations who showed higher than expected female fetal exposure to testosterone (low 2D:4D) and lower than expected male exposure to fetal testosterone (high 2D:4D) had higher rates of female parliamentary representation, and higher female labor force participation. In short, the more similar the two sexes were in 2D:4D, the more equal were the two sexes in parliamentary and labor force participation. The other variables were not as strongly correlated. We suggest that higher than expected fetal testosterone in females and lower fetal testosterone in males may lead to high female representation in the national labor force and in parliament. PMID:25300052

  1. C4 Glomerulopathy: A Disease Entity Associated With C4d Deposition.

    PubMed

    Sethi, Sanjeev; Quint, Patrick S; O'Seaghdha, Conall M; Fervenza, Fernando C; Bijol, Vanesa; Dorman, Anthony; Dasari, Surendra; Smith, Richard J H; Kurtin, Paul J; Rennke, Helmut G

    2016-06-01

    Complement-mediated glomerulonephritis, which includes C3 glomerulopathy, is characterized by dominant staining of C3 with minimal or no immunoglobulin deposits on immunofluorescence studies. We describe a new entity of complement-mediated glomerulonephritis that is characterized by bright C4d staining but with no or minimal C3 or immunoglobulin deposits on immunofluorescence studies. We label this entity as C4 glomerulopathy. C4 glomerulopathy includes C4 dense deposit disease and C4 glomerulonephritis. C4 dense deposit disease is characterized by bright C4d staining and dense deposits along glomerular basement membranes. C4 glomerulonephritis is characterized by bright C4d staining and many mesangial electron-dense deposits, with or without rare intramembranous electron-dense deposits. We describe clinical features and kidney biopsy results in a short series of 3 patients to highlight these findings. All 3 patients presented with proteinuria, and 2 patients also had hematuria. Kidney function was preserved in 2 patients, whereas 1 patient presented with declining kidney function. Evaluation for autoimmune disease, infection, and paraprotein yielded negative results in all patients. Complement levels were normal, although 1 patient had borderline low C4 levels. Kidney biopsy showed mesangial proliferative or membranoproliferative glomerulonephritis with bright C4d staining and absent or minimal C1q, C3, and immunoglobulin. Laser microdissection and mass spectrometry of glomeruli in all 3 patients showed large to moderate numbers of spectra matching C4. Furthermore, analysis of amino acid sequences showed that they were localized to the C4d portion of C4, consistent with immunofluorescence findings. Further studies are required to determine the underlying cause. In summary, we describe a novel complement-mediated glomerulonephritis that is characterized by bright glomerular C4d staining with minimal or absent staining for C1q, C3, and immunoglobulin. PMID

  2. Respiratory motion correction in 4D-PET by simultaneous motion estimation and image reconstruction (SMEIR).

    PubMed

    Kalantari, Faraz; Li, Tianfang; Jin, Mingwu; Wang, Jing

    2016-08-01

    In conventional 4D positron emission tomography (4D-PET), images from different frames are reconstructed individually and aligned by registration methods. Two issues that arise with this approach are as follows: (1) the reconstruction algorithms do not make full use of projection statistics; and (2) the registration between noisy images can result in poor alignment. In this study, we investigated the use of simultaneous motion estimation and image reconstruction (SMEIR) methods for motion estimation/correction in 4D-PET. A modified ordered-subset expectation maximization algorithm coupled with total variation minimization (OSEM-TV) was used to obtain a primary motion-compensated PET (pmc-PET) from all projection data, using Demons derived deformation vector fields (DVFs) as initial motion vectors. A motion model update was performed to obtain an optimal set of DVFs in the pmc-PET and other phases, by matching the forward projection of the deformed pmc-PET with measured projections from other phases. The OSEM-TV image reconstruction was repeated using updated DVFs, and new DVFs were estimated based on updated images. A 4D-XCAT phantom with typical FDG biodistribution was generated to evaluate the performance of the SMEIR algorithm in lung and liver tumors with different contrasts and different diameters (10-40 mm). The image quality of the 4D-PET was greatly improved by the SMEIR algorithm. When all projections were used to reconstruct 3D-PET without motion compensation, motion blurring artifacts were present, leading up to 150% tumor size overestimation and significant quantitative errors, including 50% underestimation of tumor contrast and 59% underestimation of tumor uptake. Errors were reduced to less than 10% in most images by using the SMEIR algorithm, showing its potential in motion estimation/correction in 4D-PET. PMID:27385378

  3. Biomarker correlations of urinary 2,4-D levels in foresters: genomic instability and endocrine disruption.

    PubMed Central

    Garry, V F; Tarone, R E; Kirsch, I R; Abdallah, J M; Lombardi, D P; Long, L K; Burroughs, B L; Barr, D B; Kesner, J S

    2001-01-01

    Forest pesticide applicators constitute a unique pesticide use group. Aerial, mechanical-ground, and focal weed control by application of herbicides, in particular chlorophenoxy herbicides, yield diverse exposure scenarios. In the present work, we analyzed aberrations in G-banded chromosomes, reproductive hormone levels, and polymerase chain reaction-based V(D)J rearrangement frequencies in applicators whose exposures were mostly limited to chlorophenoxy herbicides. Data from appliers where chlorophenoxy use was less frequent were also examined. The biomarker outcome data were compared to urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) obtained at the time of maximum 2,4-D use. Further comparisons of outcome data were made to the total volume of herbicides applied during the entire pesticide-use season.Twenty-four applicators and 15 minimally exposed foresters (control) subjects were studied. Categorized by applicator method, men who used a hand-held, backpack sprayer in their applications showed the highest average level (453.6 ppb) of 2,4-D in urine. Serum luteinizing hormone (LH) values were correlated with urinary 2,4-D levels, but follicle-stimulating hormone and free and total testosterone were not. At the height of the application season; 6/7 backpack sprayers, 3/4 applicators who used multinozzle mechanical (boom) sprayers, 4/8 aerial applicators, and 2/5 skidder-radiarc (closed cab) appliers had two or more V(D)J region rearrangements per microgram of DNA. Only 5 of 15 minimally exposed (control) foresters had two or more rearrangements, and 3 of these 5 subjects demonstrated detectable levels of 2,4-D in the urine. Only 8/24 DNA samples obtained from the exposed group 10 months or more after their last chlorophenoxy use had two rearrangements per microgram of DNA, suggesting that the exposure-related effects observed were reversible and temporary. Although urinary 2,4-D levels were not correlated with chromosome aberration frequency, chromosome

  4. Four-dimensional (4D) tracking of high-temperature microparticles

    NASA Astrophysics Data System (ADS)

    Wang, Zhehui; Liu, Q.; Waganaar, W.; Fontanese, J.; James, D.; Munsat, T.

    2016-11-01

    High-speed tracking of hot and molten microparticles in motion provides rich information about burning plasmas in magnetic fusion. An exploding-wire apparatus is used to produce moving high-temperature metallic microparticles and to develop four-dimensional (4D) or time-resolved 3D particle tracking techniques. The pinhole camera model and algorithms developed for computer vision are used for scene calibration and 4D reconstructions. 3D positions and velocities are then derived for different microparticles. Velocity resolution approaches 0.1 m/s by using the local constant velocity approximation.

  5. A hybrid reconstruction algorithm for fast and accurate 4D cone-beam CT imaginga)

    PubMed Central

    Yan, Hao; Zhen, Xin; Folkerts, Michael; Li, Yongbao; Pan, Tinsu; Cervino, Laura; Jiang, Steve B.; Jia, Xun

    2014-01-01

    Purpose: 4D cone beam CT (4D-CBCT) has been utilized in radiation therapy to provide 4D image guidance in lung and upper abdomen area. However, clinical application of 4D-CBCT is currently limited due to the long scan time and low image quality. The purpose of this paper is to develop a new 4D-CBCT reconstruction method that restores volumetric images based on the 1-min scan data acquired with a standard 3D-CBCT protocol. Methods: The model optimizes a deformation vector field that deforms a patient-specific planning CT (p-CT), so that the calculated 4D-CBCT projections match measurements. A forward-backward splitting (FBS) method is invented to solve the optimization problem. It splits the original problem into two well-studied subproblems, i.e., image reconstruction and deformable image registration. By iteratively solving the two subproblems, FBS gradually yields correct deformation information, while maintaining high image quality. The whole workflow is implemented on a graphic-processing-unit to improve efficiency. Comprehensive evaluations have been conducted on a moving phantom and three real patient cases regarding the accuracy and quality of the reconstructed images, as well as the algorithm robustness and efficiency. Results: The proposed algorithm reconstructs 4D-CBCT images from highly under-sampled projection data acquired with 1-min scans. Regarding the anatomical structure location accuracy, 0.204 mm average differences and 0.484 mm maximum difference are found for the phantom case, and the maximum differences of 0.3–0.5 mm for patients 1–3 are observed. As for the image quality, intensity errors below 5 and 20 HU compared to the planning CT are achieved for the phantom and the patient cases, respectively. Signal-noise-ratio values are improved by 12.74 and 5.12 times compared to results from FDK algorithm using the 1-min data and 4-min data, respectively. The computation time of the algorithm on a NVIDIA GTX590 card is 1–1.5 min per phase

  6. Fast X-ray micro-CT for real-time 4D observation

    NASA Astrophysics Data System (ADS)

    Takano, H.; Yoshida, K.; Tsuji, T.; Koyama, T.; Tsusaka, Y.; Kagoshima, Y.

    2009-09-01

    Fast X-ray computed tomography (CT) system with sub-second order measurement for single CT acquisition has been developed. The system, consisting of a high-speed sample rotation stage and a high-speed X-ray camera, is constructed at synchrotron radiation beamline in order to utilize fully intense X-rays. A time-resolving CT movie (i.e. 4D CT) can be available by operating the fast CT system continuously. Real-time observation of water absorbing process of super-absorbent polymer (SAP) has been successfully performed with the 4D CT operation.

  7. No relation between 2D : 4D fetal testosterone marker and dyslexia.

    PubMed

    Boets, Bart; De Smedt, Bert; Wouters, Jan; Lemay, Katrien; Ghesquière, Pol

    2007-09-17

    It has been suggested that high levels of prenatal testosterone exposure are implied in the aetiology of dyslexia and its frequently co-occurring sensory problems. This study examined 2D : 4D digit ratio (a marker of fetal testosterone exposure) in dyslexic and normal reading children. No group differences in 2D : 4D were observed. Digit ratio did not show the postulated relation with reading, spelling, phonological ability, speech perception, auditory processing and visual processing. These findings challenge the validity of theories that allocate a prominent role to fetal testosterone exposure in the aetiology of dyslexia and its sensory impairments. PMID:17712280

  8. A hybrid reconstruction algorithm for fast and accurate 4D cone-beam CT imaging

    SciTech Connect

    Yan, Hao; Folkerts, Michael; Jiang, Steve B. E-mail: steve.jiang@UTSouthwestern.edu; Jia, Xun E-mail: steve.jiang@UTSouthwestern.edu; Zhen, Xin; Li, Yongbao; Pan, Tinsu; Cervino, Laura

    2014-07-15

    Purpose: 4D cone beam CT (4D-CBCT) has been utilized in radiation therapy to provide 4D image guidance in lung and upper abdomen area. However, clinical application of 4D-CBCT is currently limited due to the long scan time and low image quality. The purpose of this paper is to develop a new 4D-CBCT reconstruction method that restores volumetric images based on the 1-min scan data acquired with a standard 3D-CBCT protocol. Methods: The model optimizes a deformation vector field that deforms a patient-specific planning CT (p-CT), so that the calculated 4D-CBCT projections match measurements. A forward-backward splitting (FBS) method is invented to solve the optimization problem. It splits the original problem into two well-studied subproblems, i.e., image reconstruction and deformable image registration. By iteratively solving the two subproblems, FBS gradually yields correct deformation information, while maintaining high image quality. The whole workflow is implemented on a graphic-processing-unit to improve efficiency. Comprehensive evaluations have been conducted on a moving phantom and three real patient cases regarding the accuracy and quality of the reconstructed images, as well as the algorithm robustness and efficiency. Results: The proposed algorithm reconstructs 4D-CBCT images from highly under-sampled projection data acquired with 1-min scans. Regarding the anatomical structure location accuracy, 0.204 mm average differences and 0.484 mm maximum difference are found for the phantom case, and the maximum differences of 0.3–0.5 mm for patients 1–3 are observed. As for the image quality, intensity errors below 5 and 20 HU compared to the planning CT are achieved for the phantom and the patient cases, respectively. Signal-noise-ratio values are improved by 12.74 and 5.12 times compared to results from FDK algorithm using the 1-min data and 4-min data, respectively. The computation time of the algorithm on a NVIDIA GTX590 card is 1–1.5 min per phase

  9. Clinical Utility of 4D FDG-PET/CT Scans in Radiation Treatment Planning

    SciTech Connect

    Aristophanous, Michalis; Sher, David J.; Allen, Aaron M.; Larson, Elysia; Chen, Aileen B.

    2012-01-01

    Purpose: The potential role of four-dimensional (4D) positron emission tomography (PET)/computed tomography (CT) in radiation treatment planning, relative to standard three-dimensional (3D) PET/CT, was examined. Methods and Materials: Ten patients with non-small-cell lung cancer had sequential 3D and 4D [{sup 18}F]fluorodeoxyglucose PET/CT scans in the treatment position prior to radiation therapy. The gross tumor volume and involved lymph nodes were contoured on the PET scan by use of three different techniques: manual contouring by an experienced radiation oncologist using a predetermined protocol; a technique with a constant threshold of standardized uptake value (SUV) greater than 2.5; and an automatic segmentation technique. For each technique, the tumor volume was defined on the 3D scan (VOL3D) and on the 4D scan (VOL4D) by combining the volume defined on each of the five breathing phases individually. The range of tumor motion and the location of each lesion were also recorded, and their influence on the differences observed between VOL3D and VOL4D was investigated. Results: We identified and analyzed 22 distinct lesions, including 9 primary tumors and 13 mediastinal lymph nodes. Mean VOL4D was larger than mean VOL3D with all three techniques, and the difference was statistically significant (p < 0.01). The range of tumor motion and the location of the tumor affected the magnitude of the difference. For one case, all three tumor definition techniques identified volume of moderate uptake of approximately 1 mL in the hilar region on the 4D scan (SUV maximum, 3.3) but not on the 3D scan (SUV maximum, 2.3). Conclusions: In comparison to 3D PET, 4D PET may better define the full physiologic extent of moving tumors and improve radiation treatment planning for lung tumors. In addition, reduction of blurring from free-breathing images may reveal additional information regarding regional disease.

  10. 4d/5d correspondence for the black hole potential and its critical points

    NASA Astrophysics Data System (ADS)

    Ceresole, Anna; Ferrara, Sergio; Marrani, Alessio

    2007-11-01

    We express the d=4, {\\cal N}=2 black hole effective potential for cubic holomorphic F functions and generic dyonic charges in terms of d = 5 real special geometry data. The 4d critical points are computed from the 5d ones, and their relation is elucidated. For symmetric spaces, we identify the BPS and non-BPS classes of attractors and the respective entropies. These always derive from simple interpolating formulae between four and five dimensions, depending on the volume modulus and on the 4d magnetic (or electric) charges.

  11. Enhanced response of granulosa and theca cells from sheep carriers of the FecB mutation in vitro to gonadotropins and bone morphogenic protein-2, -4, and -6.

    PubMed

    Campbell, B K; Souza, C J H; Skinner, A J; Webb, R; Baird, D T

    2006-04-01

    The FecB (Booroola) mutation, which leads to increased ovulation rates and multiple births in sheep, is now known to occur in the signaling domain of the bone morphogenic protein (BMP)-1B receptor. We examined the effect of the mutation on the responsiveness of granulosa (GC) and theca cells (TC) to BMPs and other local regulators using tissue from animals with (Fec(B/B)) and without (Fec(+/+)) the FecB mutation. Experiments examined the effect of BMP-2, -4, and -6 (0.005-50 ng/ml), and their interaction with IGF-I (0.1-10 ng/ml LR3 analog) and gonadotropins, on the proliferation and differentiation of GCs and TCs isolated from small (<2 mm) antral follicles and maintained in serum-free culture for up to 8 d. Dose-finding studies using ovaries from wild-type sheep obtained from the abbattoir showed no difference among the different BMPs in stimulating (P < 0.001) estradiol (E2) production by GCs cultured with FSH (10 ng/ml), but there was a clear interaction (P < 0.001) with IGF-I. BMPs had no effect on GC proliferation or the sensitivity of GCs to FSH. In contrast, higher doses of BMPs (5-50 ng/ml) inhibited LH-stimulated androstenedione production by TCs, whereas lower doses (0.005-0.05 ng/ml) stimulated TC proliferation (P < 0.01). Regardless of dose of IGF-I, at the end of culture (96-192 h) hormone production by GCs (E2, inhibin A) and TCs (androstenedione) was 4- to 5-fold greater (P < 0.001) by cells from Fec(B/B), compared with Fec(+/+) ewes exposed to the same dose of gonadotropin. In the presence of low concentrations of IGF-I (0.1 ng/ml), the maximum increase in the production of E2 and inhibin A by GCs from FF ewes in response to BMPs was observed at doses that were 3- to 10-fold lower (3-10 ng/ml) than ++ (30 ng/ml; P < 0.001). Low doses of BMPs stimulated proliferation of TCs from ++ (P < 0.01) but not FF ewes. Immunohistochemistry confirmed BMP-6 protein expression in the oocyte, granulosa, and thecal layers of antral follicles from both genotypes

  12. WE-G-BRF-09: Force- and Image-Adaptive Strategies for Robotised Placement of 4D Ultrasound Probes

    SciTech Connect

    Kuhlemann, I; Bruder, R; Ernst, F; Schweikard, A

    2014-06-15

    Purpose: To allow continuous acquisition of high quality 4D ultrasound images for non-invasive live tracking of tumours for IGRT, image- and force-adaptive strategies for robotised placement of 4D ultrasound probes are developed and evaluated. Methods: The developed robotised ultrasound system is based on a 6-axes industrial robot (adept Viper s850) carrying a 4D ultrasound transducer with a mounted force-torque sensor. The force-adaptive placement strategies include probe position control using artificial potential fields and contact pressure regulation by a PD controller strategy. The basis for live target tracking is a continuous minimum contact pressure to ensure good image quality and high patient comfort. This contact pressure can be significantly disturbed by respiratory movements and has to be compensated. All measurements were performed on human subjects under realistic conditions. When performing cardiac ultrasound, rib- and lung shadows are a common source of interference and can disrupt the tracking. To ensure continuous tracking, these artefacts had to be detected to automatically realign the probe. The detection is realised by multiple algorithms based on entropy calculations as well as a determination of the image quality. Results: Through active contact pressure regulation it was possible to reduce the variance of the contact pressure by 89.79% despite respiratory motion of the chest. The results regarding the image processing clearly demonstrate the feasibility to detect image artefacts like rib shadows in real-time. Conclusion: In all cases, it was possible to stabilise the image quality by active contact pressure control and automatically detected image artefacts. This fact enables the possibility to compensate for such interferences by realigning the probe and thus continuously optimising the ultrasound images. This is a huge step towards fully automated transducer positioning and opens the possibility for stable target tracking in

  13. Inhibitory action of gonadotropin-inhibitory hormone on the signaling pathways induced by kisspeptin and vasoactive intestinal polypeptide in GnRH neuronal cell line, GT1-7.

    PubMed

    Son, You Lee; Ubuka, Takayoshi; Soga, Tomoko; Yamamoto, Kazutoshi; Bentley, George E; Tsutsui, Kazuyoshi

    2016-06-01

    Gonadotropin-inhibitory hormone (GnIH) acts as a negative regulator of reproduction by acting on gonadotropes and gonadotropin-releasing hormone (GnRH) neurons. Despite its functional significance, the molecular mechanism of GnIH action in the target cells has not been fully elucidated. To expand our previous study on GnIH actions in gonadotropes, we investigated the potential signal transduction pathway that conveys the inhibitory action of GnIH in GnRH neurons by using the GnRH neuronal cell line, GT1-7. We examined whether GnIH inhibits the action of kisspeptin and vasoactive intestinal polypeptide (VIP), positive regulators of GnRH neurons. Although GnIH significantly suppressed the stimulatory effect of kisspeptin on GnRH release in hypothalamic culture, GnIH had no inhibitory effect on kisspeptin stimulation of serum response element and nuclear factor of activated T-cell response element activities and ERK phosphorylation, indicating that GnIH may not directly inhibit kisspeptin signaling in GnRH neurons. On the contrary, GnIH effectively eliminated the stimulatory effect of VIP on p38 and ERK phosphorylation, c-Fos mRNA expression, and GnRH release. The use of pharmacological modulators strongly demonstrated the specific inhibitory action of GnIH on the adenylate cyclase/cAMP/protein kinase A pathway, suggesting a common inhibitory mechanism of GnIH action in GnRH neurons and gonadotropes.-Son, Y. L., Ubuka, T., Soga, T., Yamamoto, K., Bentley, G. E., Tsutsui, K. Inhibitory action of gonadotropin-inhibitory hormone on the signaling pathways induced by kisspeptin and vasoactive intestinal polypeptide in GnRH neuronal cell line, GT1-7. PMID:26929433

  14. Evidence that obesity and androgens have independent and opposing effects on gonadotropin production from puberty to maturity.

    PubMed

    Rosenfield, Robert L; Bordini, Brian

    2010-12-10

    Optimal fat mass is necessary for normal gonadotropin levels in adults, and both undernutrition and overnutrition suppress gonadotropins: thus, the gonadotropin response to relative adipose mass is biphasic. Adult obesity is associated with blunted luteinizing hormone (LH) pulse amplitude that is partially attributable to increased LH clearance rate. Testosterone appears to have a biphasic effect on gonadotropin production in females. Moderate elevations of testosterone appear to stimulate LH production at both the hypothalamic and pituitary level, while very high levels of testosterone suppress LH. Thus, obesity per se appears to suppress gonadotropin production, and moderate hyperandrogenemia in women appears to stimulate LH. The ordinary hypergonadotropic hyperandrogenism of obese women appears to be an exception to this model because it is usually due to polycystic ovary syndrome (PCOS), a condition in which intrinsic functional ovarian hyperandrogenism and excess adiposity share a common origin that involves insulin-resistant hyperinsulinemia. LH elevation seems to be secondary to hyperandrogenemia and is absent in the most obese cases. Overweight early pubertal girls have significant blunting of sleep-related LH production, which is the first hormonal change of puberty. The data are compatible with the possibility that excess adiposity may paradoxically subtly suppress hypothalamic-pituitary-gonadal function in early puberty although it is known to contribute to the early onset of puberty. PMID:20816944

  15. A method for deriving a 4D-interpolated balanced planning target for mobile tumor radiotherapy

    SciTech Connect

    Roland, Teboh; Hales, Russell; McNutt, Todd; Wong, John; Simari, Patricio; Tryggestad, Erik

    2012-01-15

    Purpose: Tumor control and normal tissue toxicity are strongly correlated to the tumor and normal tissue volumes receiving high prescribed dose levels in the course of radiotherapy. Planning target definition is, therefore, crucial to ensure favorable clinical outcomes. This is especially important for stereotactic body radiation therapy of lung cancers, characterized by high fractional doses and steep dose gradients. The shift in recent years from population-based to patient-specific treatment margins, as facilitated by the emergence of 4D medical imaging capabilities, is a major improvement. The commonly used motion-encompassing, or internal-target volume (ITV), target definition approach provides a high likelihood of coverage for the mobile tumor but inevitably exposes healthy tissue to high prescribed dose levels. The goal of this work was to generate an interpolated balanced planning target that takes into account both tumor coverage and normal tissue sparing from high prescribed dose levels, thereby improving on the ITV approach. Methods: For each 4DCT dataset, 4D deformable image registration was used to derive two bounding targets, namely, a 4D-intersection and a 4D-composite target which minimized normal tissue exposure to high prescribed dose levels and maximized tumor coverage, respectively. Through definition of an ''effective overlap volume histogram'' the authors derived an ''interpolated balanced planning target'' intended to balance normal tissue sparing from prescribed doses with tumor coverage. To demonstrate the dosimetric efficacy of the interpolated balanced planning target, the authors performed 4D treatment planning based on deformable image registration of 4D-CT data for five previously treated lung cancer patients. Two 4D plans were generated per patient, one based on the interpolated balanced planning target and the other based on the conventional ITV target. Plans were compared for tumor coverage and the degree of normal tissue sparing

  16. Efficacy and Mechanism of a Glycoside Compound Inhibiting Abnormal Prion Protein Formation in Prion-Infected Cells: Implications of Interferon and Phosphodiesterase 4D-Interacting Protein

    PubMed Central

    Nishizawa, Keiko; Oguma, Ayumi; Kawata, Maki; Sakasegawa, Yuji; Teruya, Kenta

    2014-01-01

    ABSTRACT A new type of antiprion compound, Gly-9, was found to inhibit abnormal prion protein formation in prion-infected neuroblastoma cells, in a prion strain-independent manner, when the cells were treated for more than 1 day. It reduced the intracellular prion protein level and significantly modified mRNA expression levels of genes of two types: interferon-stimulated genes were downregulated after more than 2 days of treatment, and the phosphodiesterase 4D-interacting protein gene, a gene involved in microtubule growth, was upregulated after more than 1 day of treatment. A supplement of interferon given to the cells partly restored the abnormal prion protein level but did not alter the normal prion protein level. This interferon action was independent of the Janus activated kinase-signal transducer and activator of transcription signaling pathway. Therefore, the changes in interferon-stimulated genes might be a secondary effect of Gly-9 treatment. However, gene knockdown of phosphodiesterase 4D-interacting protein restored or increased both the abnormal prion protein level and the normal prion protein level, without transcriptional alteration of the prion protein gene. It also altered the localization of abnormal prion protein accumulation in the cells, indicating that phosphodiesterase 4D-interacting protein might affect prion protein levels by altering the trafficking of prion protein-containing structures. Interferon and phosphodiesterase 4D-interacting protein had no direct mutual link, demonstrating that they regulate abnormal prion protein levels independently. Although the in vivo efficacy of Gly-9 was limited, the findings for Gly-9 provide insights into the regulation of abnormal prion protein in cells and suggest new targets for antiprion compounds. IMPORTANCE This report describes our study of the efficacy and potential mechanism underlying the antiprion action of a new antiprion compound with a glycoside structure in prion-infected cells, as well as

  17. Adaptive phenotypic modulation of human arterial endothelial cells to fluid shear stress-encoded signals: modulation by phosphodiesterase 4D-VE-cadherin signalling.

    PubMed

    Rampersad, Sarah N; Wudwud, Alie; Hubert, Fabien; Maurice, Donald H

    2016-07-01

    Although cAMP-signalling regulates numerous functions of vascular endothelial cells (VECs), including their ability to impact vascular resistance in response to changes in blood flow dynamics, few of the mechanisms underlying these effects have yet to be described. In addition to forming stable adherens junctions (AJs) in static VEC cultures, VE-cadherin (VECAD) has emerged as a critical component in a key mechanosensor responsible for linking altered blood flow dynamics and the VEC-mediated control of vascular resistance. Previously, a cAMP phosphodiesterase, PDE4D, was shown to coordinate the VEC permeability limiting effects of cAMP-elevating agents in human arterial VECs (HAECs). Herein, we report that PDE4D acts to allow cAMP-elevating agents to regulate VECADs' role as a sensor of flow-associated fluid shear stress (FSS)-encoded information in HAECs. Thus, we report that PDE4 activity is increased in HAECs exposed to laminar FSS and that this effect contributes to controlling how FSS impacts the morphological and gene expression changes in HAECs exposed to flow. More specifically, we report that PDE4D regulates the efficiency with which VECAD, within its mechanosensor, controls VEGFR2 and Akt activities. Indeed, we show that PDE4D knockdown (KD) significantly blunts responses of HAECs to levels of FSS characteristically found in areas of the vasculature in which stenosis is prevalent. We propose that this effect may provide a new therapeutic avenue in modulating VEC behaviour at these sites by promoting an adaptive and vasculo-protective phenotype. PMID:26658094

  18. Evaluation of dual trigger with gonadotropin-releasing hormone agonist and human chorionic gonadotropin in improving oocyte maturity rates: A prospective randomized study

    PubMed Central

    Mahajan, Nalini; Sharma, Shilpa; Arora, Puneet Rana; Gupta, Shalu; Rani, Kumkum; Naidu, Padmaja

    2016-01-01

    BACKGROUND: Mature oocytes are prerequisite for achieving the process of in vitro fertilization. Human chorionic gonadotropin (hCG) is the standard trigger used for stimulating ovulation but is associated with ovarian hyperstimulation syndrome (OHSS). Gonadotropin-releasing hormone agonist trigger achieves oocyte maturation and lowers the incidence of OHSS, but it has limitations of higher pregnancy loss rate and miscarriage rates. Coadministration of both hormones is found to improve the pregnancy rates and the number of mature oocytes retrieved. We aimed to assess if the dual trigger is better than the conventional hCG in triggering oocyte maturation. METHODOLOGY: The study included 76 female patients aged 24–43 years who were randomly divided into two groups with 38 patients in each arm. The study included patients with antimullerian hormone (AMH) <4 ng/ml, antral follicle counts (AFCs)/ovary <12. The study excluded high responders-AMH >4 ng/ml and AFC/ovary >12 to avoid OHSS risk with hCG trigger. RESULTS: The study showed statistically insignificant differences between dual group versus hCG group in terms of the number of oocytes retrieved (10.0 ± 5.6 vs. 8.7 ± 5.0; P = 0.2816), the number of mature oocytes recovered (8.4 ± 5.0 vs. 7.2 ± 4.0; P = 0.2588), fertilization rate (5.9 ± 4.2 vs. 5.6 ± 3.3; P = 0.7390), and the number of usable embryos on day 3 (4.0 ± 3.0 vs. 4.0 ± 2.4; P = 0.8991). CONCLUSION: The dual trigger is equivalent to hCG in triggering oocyte maturation. PMID:27382235

  19. Gonadotropin-binding sites in the rhesus monkey ovary: role of the vasculature in the selective distribution of human chorionic gonadotropin to the preovulatory follicle

    SciTech Connect

    Zeleznik, A.J.; Schuler, H.M.; Reichert, L.E. Jr.

    1981-08-01

    These experiments were initiated to determine if differences exist in the vasculature of individual follicles in the rhesus monkey ovary during the late follicular phase of the menstrual cycle and to determine whether differences in vascularity result in differential exposure of certain follicles to gonadotropic hormones. The density of blood vessels within the thecal layer of the dominant follicle and other antral follicles was determined in ovaries from four animals removed on day 9 or 10 of the menstrual cycle. Blood vessels were identified using a histochemical stain for hemoglobin. Morphometric analysis indicated that the percentage of the thecal layer occupied by blood vessels in the dominant follicles (48%) was significantly greater (P less than 0.005) than that of other smaller antral follicles either within the same ovary as the dominant follicle (24%) or in the contralateral ovary (26%). To determine if differences in vascularity result in a differential supply of gonadotropins to the dominant follicle, we studied, by autoradiography, the in vivo and in vitro binding of (125I)hCG in four rhesus monkeys on day 9 of the menstrual cycle. Results of in vitro binding studies indicated that the thecal layer of virtually every antral follicle possessed hCG-binding sites. However, when (125I)hcg was injected iv into animals and allowed to distribute via the vasculature, the dominant follicle was heavily labeled while other smaller antral follicles accumulated little, if any, radioiodinated hCG. These observations indicate that increased vascularization of individual follicles results in preferential delivery of gonadotropins, and suggest that blood flow to individual follicles may play an instrumental role in the selective maturation of the preovulatory follicle in the rhesus monkey.

  20. Effects of progesterone inclusion in a gonadotropin-prostaglandin-gonadotropin programme on follicular dynamics and ovulation synchronisation of pasture-based dairy cows with anoestrous.

    PubMed

    Sahu, S K; Cockrem, J F; Parkinson, T J; Laven, R A

    2015-10-01

    The aim of this study was to evaluate how the addition of a progesterone device to a gonadotropin-prostaglandin-gonadotropin (GPG) programme in dairy cows with postpartum anovulatory anoestrus affected ovarian follicular dynamics and the synchronisation of ovulation. Twenty-two dairy cows were randomly assigned to either GPG (Day 0: 100 μg GnRH, Day 7: 500 μg PGF2α, Day 9: 100 μg GnRH, Day 0-7: Day 10) or GPG with a progesterone device from Day 0 to 7 (GPG+P4). Ovarian follicular dynamics and ovulation synchronisation were studied using transrectal ultrasonography. Compared to the GPG+P4, GPG alone resulted in a relatively larger mean dominant follicle size and a higher mean peripheral oestradiol concentration (74.9 pg ∗ day vs. 60.6 pg ∗ day; P=0.002); however, there was much greater variation in follicle diameter in the group treated with GPG (7.8-22 mm vs. 10.8-17.5mm in GPG+P4) and this may, at least partly explain why only 7/11 cows in this group ovulated within 48 h of the Day 9 GnRH injection compared to 10/10 of the cows in the GPG+P4 group. These results suggest that differences in follicular dynamics between GPG and GPG+P4 programmes are not a key driver of the difference in conception rate, but further studies are required to better assess the role of ovulation synchronisation. PMID:26412544

  1. Knockdown of phosphodiesterase 4D inhibits nasopharyngeal carcinoma proliferation via the epidermal growth factor receptor signaling pathway

    PubMed Central

    XU, TING; WU, SIHAI; YUAN, YUAN; YAN, GUOXIN; XIAO, DAJIANG

    2014-01-01

    Phosphodiesterase 4D (PDE4D) is a subtype of metallohydrolases, and it has been reported that PDE4D functions as a proliferation promoting factor in certain types of cancer, including head and neck cancer. The present study first investigated the function of PDE4D in nasopharyngeal carcinoma (NPC). Western blot analysis was applied to detect PDE4D expression in NPC samples and cells. A lentiviral infection technique was used to stabilize the knockdown of PDE4D, which was subsequently examined in vitro and in vivo. The results showed that PDE4D was overexpressed in the NPC tissues and cells. Knockdown of PDE4D inhibited the growth of CNE2 and 5–8F, inducing cell cycle arrest in the G0/G1 phase in CNE2. These effects could be reversed by epidermal growth factor (EGF) stimulation. Furthermore, knockdown of PDE4D significantly inhibited the phosphorylation of epidermal growth factor receptor (EGFR) and AKT. The results were further validated in an NPC xenograft in nude mice. In conclusion, this study demonstrated that PDE4D may function as a proliferation promoting factor in NPC, by affecting the EGFR/PI3K/AKT signaling pathway. Therefore, the targeting of PDE4D may be a rational strategy in the treatment of NPC. PMID:25289091

  2. Experimental investigation of irregular motion impact on 4D PET-based particle therapy monitoring.

    PubMed

    Tian, Y; Stützer, K; Enghardt, W; Priegnitz, M; Helmbrecht, S; Bert, C; Fiedler, F

    2016-01-21

    Particle therapy positron emission tomography (PT-PET) is an in vivo and non-invasive imaging technique to monitor treatment delivery in particle therapy. The inevitable patient respiratory motion during irradiation causes artefacts and inaccurate activity distribution in PET images. Four-dimensional (4D) maximum likelihood expectation maximisation (4D MLEM) allows for a compensation of these effects, but has up to now been restricted to regular motion for PT-PET investigations. However, intra-fractional motion during treatment might differ from that during acquisition of the 4D-planning CT (e.g. amplitude variation, baseline drift) and therefore might induce inaccurate 4D PET reconstruction results. This study investigates the impact of different irregular analytical one-dimensional (1D) motion patterns on PT-PET imaging by means of experiments with a radioactive source and irradiated moving phantoms. Three sorting methods, namely phase sorting, equal amplitude sorting and event-based amplitude sorting, were applied to manage the PET list-mode data. The influence of these sorting methods on the motion compensating algorithm has been analysed. The event-based amplitude sorting showed a superior performance and it is applicable for irregular motions with ⩽ 4 mm amplitude elongation and drift. For motion with 10 mm baseline drift, the normalised root mean square error was as high as 10.5% and a 10 mm range deviation was observed. PMID:26733104

  3. 77 FR 23135 - 2,4-D; Order Denying NRDC's Petition To Revoke Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-18

    ... and thyroid hormonal pathways and ecological effects. (63 FR 71542, 71544, December 28, 1998). The... battery of screening assays in a Federal Register Notice issued January 24, 2008 (73 FR 4216). EPA... October 21, 2009 for 67 chemicals including 2,4-D. (74 FR 54422, 54425). With regard to endocrine...

  4. Experimental investigation of irregular motion impact on 4D PET-based particle therapy monitoring

    NASA Astrophysics Data System (ADS)

    Tian, Y.; Stützer, K.; Enghardt, W.; Priegnitz, M.; Helmbrecht, S.; Bert, C.; Fiedler, F.

    2016-01-01

    Particle therapy positron emission tomography (PT-PET) is an in vivo and non-invasive imaging technique to monitor treatment delivery in particle therapy. The inevitable patient respiratory motion during irradiation causes artefacts and inaccurate activity distribution in PET images. Four-dimensional (4D) maximum likelihood expectation maximisation (4D MLEM) allows for a compensation of these effects, but has up to now been restricted to regular motion for PT-PET investigations. However, intra-fractional motion during treatment might differ from that during acquisition of the 4D-planning CT (e.g. amplitude variation, baseline drift) and therefore might induce inaccurate 4D PET reconstruction results. This study investigates the impact of different irregular analytical one-dimensional (1D) motion patterns on PT-PET imaging by means of experiments with a radioactive source and irradiated moving phantoms. Three sorting methods, namely phase sorting, equal amplitude sorting and event-based amplitude sorting, were applied to manage the PET list-mode data. The influence of these sorting methods on the motion compensating algorithm has been analysed. The event-based amplitude sorting showed a superior performance and it is applicable for irregular motions with  ⩽4 mm amplitude elongation and drift. For motion with 10 mm baseline drift, the normalised root mean square error was as high as 10.5% and a 10 mm range deviation was observed.

  5. Prenatal influences on sexual orientation: digit ratio (2D:4D) and number of older siblings.

    PubMed

    Kangassalo, Katariina; Pölkki, Mari; Rantala, Markus J

    2011-01-01

    Prenatal androgen levels are suggested to influence sexual orientation in both sexes. The 2D:4D digit ratio has been found to associate with sexual orientation, but published findings have often been contradictory, which may partly be due to the large ethnic diversity between and within studied populations. In men, number of older brothers has been found to correlate positively with homosexuality. This phenomenon has been explained with a maternal immune reaction, which is provoked only by male fetuses and which gets stronger after each pregnancy. Here we assessed the relationship of sexual orientation to 2D:4D ratios and number of older siblings in Finland, where the population is found to be genetically relatively homogeneous. As in many previous studies, heterosexual men had lower 2D:4D than non-heterosexual men, which supports the notion that non- heterosexual men experience higher androgen levels in utero than population norms. Contrary to previous reports, non-heterosexual women had higher 2D:4D than heterosexual women. Non-heterosexual men had more older brothers and older sisters than heterosexual men. The greater number of older sisters in non-heterosexual men indicates that there are other factors that contribute to the higher birth order of homosexual men than the maternal immunization. PMID:22947989

  6. Symbolic perception-based autonomous driving in dynamic environments using 4D/RCS

    NASA Astrophysics Data System (ADS)

    Foedisch, M.,; Madhavan, R.; Schlenoff, C.

    2007-04-01

    4D/RCS is a hierarchical architecture designed for the control of intelligent systems. One of the main areas that 4D/RCS has been applied to recently is the control of autonomous vehicles. To accomplish this, a hierarchical decomposition of on-road driving activities has been performed which has resulted in implementation of 4D/RCS tailored towards this application. This implementation has seven layers and ranges from a journey manager which determines the order of the places you wish to drive to, through a destination manager which provides turn-by-turn directions on how to get to a destination, through a route segment, drive behavior, elemental maneuver, goal path trajectory, and then finally to servo controllers. In this paper, we show, within the 4D/RCS architecture, how knowledge-driven top-down symbolic representations combined with low-level bottom-up tasks can synergistically provide valuable information for on-road driving better than what is possible with either of them alone. We demonstrate these ideas using field data obtained from an Unmanned Ground Vehicle (UGV) traversing urban on-road environments.

  7. Five cycles of selection for 2,4-D resistance in red clover

    Technology Transfer Automated Retrieval System (TEKTRAN)

    2,4-D and other auxin-like mode of action herbicides are used to control broadleaf weeds in pastures. Unfortunately such herbicides also kill beneficial forage legumes in pastures. Although transgene-conferred herbicide-resistance is utilized in some crops, it is unlikely that transgenic breeding ap...

  8. Enhancing 4D PC-MRI in an aortic phantom considering numerical simulations

    NASA Astrophysics Data System (ADS)

    Kratzke, Jonas; Schoch, Nicolai; Weis, Christian; Müller-Eschner, Matthias; Speidel, Stefanie; Farag, Mina; Beller, Carsten J.; Heuveline, Vincent

    2015-03-01

    To date, cardiovascular surgery enables the treatment of a wide range of aortic pathologies. One of the current challenges in this field is given by the detection of high-risk patients for adverse aortic events, who should be treated electively. Reliable diagnostic parameters, which indicate the urge of treatment, have to be determined. Functional imaging by means of 4D phase contrast-magnetic resonance imaging (PC-MRI) enables the time-resolved measurement of blood flow velocity in 3D. Applied to aortic phantoms, three dimensional blood flow properties and their relation to adverse dynamics can be investigated in vitro. Emerging "in silico" methods of numerical simulation can supplement these measurements in computing additional information on crucial parameters. We propose a framework that complements 4D PC-MRI imaging by means of numerical simulation based on the Finite Element Method (FEM). The framework is developed on the basis of a prototypic aortic phantom and validated by 4D PC-MRI measurements of the phantom. Based on physical principles of biomechanics, the derived simulation depicts aortic blood flow properties and characteristics. The framework might help identifying factors that induce aortic pathologies such as aortic dilatation or aortic dissection. Alarming thresholds of parameters such as wall shear stress distribution can be evaluated. The combined techniques of 4D PC-MRI and numerical simulation can be used as complementary tools for risk-stratification of aortic pathology.

  9. WELLTON GOVERNMENT CAMP, TEMPORARY RESIDENCE TYPE 4D. PLAN, SECTION, AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    WELLTON GOVERNMENT CAMP, TEMPORARY RESIDENCE TYPE 4D. PLAN, SECTION, AND ELEVATIONS. Drawing 50-308-4566, dated July 16, 1949. U.S. Department of the Interior, Bureau of Reclamation, Yuma, Arizona - Wellton-Mohawk Irrigation System, Building No. 6 A-B (Duplex), 30651 & 30653 Wellton-Mohawk Drive, Wellton, Yuma County, AZ

  10. 4-D Cardiac MR Image Analysis: Left and Right Ventricular Morphology and Function

    PubMed Central

    Wahle, Andreas; Johnson, Ryan K.; Scholz, Thomas D.; Sonka, Milan

    2010-01-01

    In this study, a combination of active shape model (ASM) and active appearance model (AAM) was used to segment the left and right ventricles of normal and Tetralogy of Fallot (TOF) hearts on 4-D (3-D+time) MR images. For each ventricle, a 4-D model was first used to achieve robust preliminary segmentation on all cardiac phases simultaneously and a 3-D model was then applied to each phase to improve local accuracy while maintaining the overall robustness of the 4-D segmentation. On 25 normal and 25 TOF hearts, in comparison to the expert traced independent standard, our comprehensive performance assessment showed subvoxel segmentation accuracy, high overlap ratios, good ventricular volume correlations, and small percent volume differences. Following 4-D segmentation, novel quantitative shape and motion features were extracted using shape information, volume-time and dV/dt curves, analyzed and used for disease status classification. Automated discrimination between normal/TOF subjects achieved 90%–100% sensitivity and specificity. The features obtained from TOF hearts show higher variability compared to normal subjects, suggesting their potential use as disease progression indicators. The abnormal shape and motion variations of the TOF hearts were accurately captured by both the segmentation and feature characterization. PMID:19709962

  11. ADULT AND CHILDREN'S EXPOSURE TO 2,4-D FROM MULTIPLE SOURCES AND PATHWAYS

    EPA Science Inventory

    In this study, we investigated the 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide exposures of 135 preschool-aged children and their adult caregivers at 135 homes in North Carolina (NC) and Ohio (OH). Participants were randomly recruited from six NC and six OH counties. Monito...

  12. Geometric engineering, mirror symmetry and 6{d}_{(1,0)}to 4{d}_{(N=2)}

    NASA Astrophysics Data System (ADS)

    Del Zotto, Michele; Vafa, Cumrun; Xie, Dan

    2015-11-01

    We study compactification of 6 dimensional (1,0) theories on T 2. We use geometric engineering of these theories via F-theory and employ mirror symmetry technology to solve for the effective 4d N=2 geometry for a large number of the (1 ,0) theories including those associated with conformal matter. Using this we show that for a given 6d theory we can obtain many inequivalent 4d N=2 SCFTs. Some of these respect the global symmetries of the 6d theory while others exhibit SL(2 , ℤ) duality symmetry inherited from global diffeomorphisms of the T 2. This construction also explains the 6d origin of moduli space of 4d affine ADE quiver theories as flat ADE connections on T 2. Among the resulting 4 d N=2 CFTs we find theories whose vacuum geometry is captured by an LG theory (as opposed to a curve or a local CY geometry). We obtain arbitrary genus curves of class S with punctures from toroidal compactification of (1 , 0) SCFTs where the curve of the class S theory emerges through mirror symmetry. We also show that toroidal compactification of the little string version of these theories can lead to class S theories with no punctures on arbitrary genus Riemann surface.

  13. RELATIVE AIRBORNE LOSSES OF COMMERCIAL 2,4-D FORMULATIONS FROM A SIMULATED WHEAT FIELD

    EPA Science Inventory

    The relative airborne losses of seven commercial 2,4-D (2,4-dichlorophenoxyacetic acid) formulations were evaluated in a simulated wheat field. The formulations tested were butyl ester, isooctyl ester, two propylene glycol butyl ether esters, ethanol/isopropyl amine, and two dime...

  14. DBI action of real linear superfield in 4D N = 1 conformal supergravity

    NASA Astrophysics Data System (ADS)

    Aoki, Shuntaro; Yamada, Yusuke

    2016-06-01

    We construct the Dirac-Born-Infeld (DBI) action of a real linear multiplet in 4D N = 1 supergravity. Based on conformal supergravity, we derive the general condition under which the DBI action can be realized, and show that it can be constructed in the new minimal supergravity. We also generalize it to the matter coupled system.

  15. Analysis of free breathing motion using artifact reduced 4D CT image data

    NASA Astrophysics Data System (ADS)

    Ehrhardt, Jan; Werner, Rene; Frenzel, Thorsten; Lu, Wei; Low, Daniel; Handels, Heinz

    2007-03-01

    The mobility of lung tumors during the respiratory cycle is a source of error in radiotherapy treatment planning. Spatiotemporal CT data sets can be used for studying the motion of lung tumors and inner organs during the breathing cycle. We present methods for the analysis of respiratory motion using 4D CT data in high temporal resolution. An optical flow based reconstruction method was used to generate artifact-reduced 4D CT data sets of lung cancer patients. The reconstructed 4D CT data sets were segmented and the respiratory motion of tumors and inner organs was analyzed. A non-linear registration algorithm is used to calculate the velocity field between consecutive time frames of the 4D data. The resulting velocity field is used to analyze trajectories of landmarks and surface points. By this technique, the maximum displacement of any surface point is calculated, and regions with large respiratory motion are marked. To describe the tumor mobility the motion of the lung tumor center in three orthogonal directions is displayed. Estimated 3D appearance probabilities visualize the movement of the tumor during the respiratory cycle in one static image. Furthermore, correlations between trajectories of the skin surface and the trajectory of the tumor center are determined and skin regions are identified which are suitable for prediction of the internal tumor motion. The results of the motion analysis indicate that the described methods are suitable to gain insight into the spatiotemporal behavior of anatomical and pathological structures during the respiratory cycle.

  16. Clastogenicity of pentachlorophenol, 2,4-D and butachlor evaluated by Allium root tip test.

    PubMed

    Ateeq, Bushra; Abul Farah, M; Niamat Ali, M; Ahmad, Waseem

    2002-02-15

    The meristematic mitotic cells of Allium cepa is an efficient cytogenetic material for chromosome aberration assay on environmental pollutants. For assessing genotoxicity of pentachlorophenol (PCP), 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-chloro-2,6-diethyl-N-(butoxymethyl) acetanilide (butachlor), 50% effective concentration (EC(50)), c-mitosis, stickiness, chromosome breaks and mitotic index (MI) were used as endpoints of genotoxicity. EC(50) values for PCP and butachlor are 0.73 and 5.13 ppm, respectively. 2,4-D evidently induced morphological changes at higher concentrations. Some changes like crochet hooks, c-tumours and broken roots were unique to 2,4-D at 5-20 ppm. No such abnormalities were found in PCP and butachlor treated groups, however, root deteriorated and degenerated at higher concentrations (<3 ppm) in PCP. MI in 2,4-D showed a low average of 14.32% followed by PCP (19.53%), while in butachlor it was recorded 71.6%, which is near to the control value. All chemicals induced chromosome aberrations at statistically significant level. The highest chromosome aberration frequency (11.90%) was recorded in PCP at 3 ppm. Large number of c-mitotic anaphases indicated that butachlor acts as potent spindle inhibitor, whereas, breaks, bridges, stickiness and laggards were most frequently found in PCP showing that it is a potent clastogen. PMID:11815249

  17. Assimilation of DMSP/SSUSI UV data into IDA4D

    NASA Astrophysics Data System (ADS)

    Gelinas, L. J.; Bust, G. S.; Brinkman, D. G.; Straus, P. R.; Swartz, R. L.

    2014-12-01

    Ionospheric Data Assimilation Four-Dimensional (IDA4D) is a continuous-time, three-dimensional imaging algorithm that can produce 4D electron density specifications for various science investigations [e.g., Bust et al., 2007]. IDA4D is based on three-dimensional variational (3DVAR) data assimilation [Daley and Barker, 2001]. The algorithm combines various data sources and their associated error covariances with a background model (in this case the IRI) and its covariances to produce an ionospheric specification with formal uncertainties. IDA4D employs a Gauss- Markov Kalman filter technique similar to that used by operational assimilation models. The model can ingest a broad spectrum of data types that are either linearly or non-linearly related to electron density, including ground-based TEC, space-based TEC as measured by GPS occultation sensors and UV emissions associated with nightside recombination of O+. IDA4D has been undergoing testing at The Aerospace Corporation to determine its performance with respect to combinations of input data sets under different conditions (solar minimum, solar maximum, geomagnetic activity). The results presented here summarize the performance of IDA4D when UV data is ingested, both with and without additional TEC measurements. The UV data used in the study summarized here are 135.6 nm emissions measured the SSUSI instruments on F16 and F18 DMSP. We discuss the process by which UV data is ingested into IDA4D, including data binning, error estimation and correction of 135.6 nm contamination from mutual neutralization of O+ and O-. Model performance is then assessed using comparisons to various ground truth data, including ISR data, Jason VTEC, CNOF/S in-situ plasma density and ionosonde-derived NmF2 values. The results of this study show that UV data improves model performance, particularly when TEC data coverage is sparse. Bust, G. S., G. Crowley, T. W. Garner, T. L. Gaussiran II, R. W. Meggs, C. N. Mitchell, P. S. J. Spencer, P

  18. Evaluation of the Elekta Symmetry ™ 4D IGRT system by using a moving lung phantom

    NASA Astrophysics Data System (ADS)

    Shin, Hun-Joo; Kim, Shin-Wook; Kay, Chul Seung; Seo, Jae-Hyuk; Lee, Gi-Woong; Kang, Ki-Mun; Jang, Hong Seok; Kang, Young-nam

    2015-07-01

    Purpose: 4D cone-beam computed tomography (CBCT) is a beneficial tool for the treatment of movable tumors because it can help us to understand where the tumors are actually located and it has a precise treatment plan. However, general CBCT images have a limitation in that they cannot perfectly perform a sophisticated registration. On the other hand, the Symmetry TM 4D image-guided radiation therapy (IGRT) system of Elekta offers a 4D CBCT registration option. In this study, we evaluated the usefulness of Symmetry TM . Method and Materials: Planning CT images of the CIRS moving lung phantom were acquired 4D multi-detector CT (MDCT), and the images were sorted as 10 phases from 0% phase to 90% phase. The thickness of the CT images was 1 mm. Acquired MDCT images were transferred to the contouring software, and a virtual target was generated. A one-arc volumetric-modulated arc therapy (VMAT) plan was performed by using the treatment planning system on the virtual target. Finally, the movement of the phantom was verified by using the XVI Symmetry TM system. Results: The physical movement of the CIRS moving lung phantom was ±10.0 mm in the superiorinferior direction, ±1.0 mm in the lateral direction, and ±2.5 mm in the anterior-posterior direction. The movement of the phantom was measured from the 4D MDCT registration as ±10.2 mm in the superior-inferior direction, ±0.9 mm in the lateral direction, and ±2.45 mm in the anterior-posterior direction. The movement of the phantom was measured from the SymmetryTM registration as ±10.1 mm in the superior-inferior direction, ±0.9 mm in the lateral direction, and ±2.4 mm in the anterior-posterior direction. Conclusion: We confirmed that 4D CBCT is a beneficial tool for the treatment of movable tumors, and that the 4D registration of SymmetryTM can increase the precision of the registration when a movable tumor is the target of radiation treatment.

  19. Improved Dynamic Cardiac Phantom Based on 4D NURBS and Tagged MRI.

    PubMed

    Segars, W Paul; Lalush, David S; Frey, Eric C; Manocha, Dinesh; King, Michael A; Tsui, Benjamin M W

    2009-10-01

    We previously developed a realistic phantom for the cardiac motion for use in medical imaging research. The phantom was based upon a gated magnetic resonance imaging (MRI) cardiac study and using 4D non-uniform rational b-splines (NURBS). Using the gated MRI study as the basis for the cardiac model had its limitations. From the MRI images, the change in the size and geometry of the heart structures could be obtained, but without markers to track the movement of points on or within the myocardium, no explicit time correspondence could be established for the structures. Also, only the inner and outer surfaces of the myocardium could be modeled. We enhance this phantom of the beating heart using 4D tagged MRI data. We utilize NURBS surfaces to analyze the full 3D motion of the heart from the tagged data. From this analysis, time-dependent 3D NURBS surfaces were created for the right (RV) and left ventricles (LV). Models for the atria were developed separately since the tagged data only covered the ventricles. A 4D NURBS surface was fit to the 3D surfaces of the heart creating time-continuous 4D NURBS models. Multiple 4D surfaces were created for the left ventricle (LV) spanning its entire volume. The multiple surfaces for the LV were spline-interpolated about an additional dimension, thickness, creating a 4D NURBS solid model for the LV with the ability to represent the motion of any point within the volume of the LV myocardium at any time during the cardiac cycle. Our analysis of the tagged data was found to produce accurate models for the RV and LV at each time frame. In a comparison with segmented structures from the tagged dataset, LV and RV surface predictions were found to vary by a maximum of 1.5 mm's and 3.4 mm's respectively. The errors can be attributed to the tag spacing in the data (7.97 mm's). The new cardiac model was incorporated into the 4D NURBS-based Cardiac-Torso (NCAT) phantom widely used in imaging research. With its enhanced abilities, the model

  20. Distribution of LPXRFa, a gonadotropin-inhibitory hormone ortholog peptide, and LPXRFa receptor in the brain and pituitary of the tilapia.

    PubMed

    Ogawa, Satoshi; Sivalingam, Mageswary; Biran, Jakob; Golan, Matan; Anthonysamy, Rachel Shalini; Levavi-Sivan, Berta; Parhar, Ishwar S

    2016-10-01

    In vertebrates, gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH), respectively, regulate reproduction in positive and negative manners. GnIH belongs to the LPXRFa family of peptides previously identified in mammalian and nonmammalian vertebrates. Studying the detailed distribution of LPXRFa as well as its receptor (LPXRFa-R) in the brain and pituitary is important for understanding their multiple action sites and potential functions. However, the distribution of LPXRFa and LPXRFa-R has not been studied in teleost species, partially because of the lack of fish-specific antibodies. Therefore, in the present study, we generated specific antibodies against LPXRFa and its receptor from Nile tilapia (Oreochromis niloticus), and examined their distributions in the brain and pituitary by immunohistochemistry. Tilapia LPXRFa-immunoreactive neurons lie in the posterior ventricular nucleus of the caudal preoptic area, whereas LPXRFa-R-immunoreactive cells are distributed widely. Double immunofluorescence showed that neither LPXRFa-immunoreactive fibers nor LPXRFa-R is closely associated or coexpressed with GnRH1, GnRH3, or kisspeptin (Kiss2) neurons. In the pituitary, LPXRFa fibers are closely associated with gonadotropic endocrine cells [expressing luteinizing hormone (LH) and follicle-stimulating hormone (FSH)], with adrenocorticomelanotropic cells [corticotropin (ACTH) and α-melanotropin (α-MSH)], and with somatolactin endocrine cells. In contrast, LPXRFa-R are expressed only in LH, ACTH, and α-MSH cells. These results suggest that LPXRFa and LPXRFa-R signaling acts directly on the pituitary cells independent from GnRH or kisspeptin and could play multiple roles in reproductive and nonreproductive functions in teleosts. J. Comp. Neurol. 524:2753-2775, 2016. © 2016 Wiley Periodicals, Inc. PMID:26917324

  1. Expression profiles of gonadotropins and their receptors during 17α-methyltestosterone implantation-induced sex change in the orange-spotted grouper (Epinephelus coioides).

    PubMed

    Hu, Xuesong; Liu, Xiaochun; Zhang, Haifa; Zhang, Yong; Li, Shuisheng; Sang, Qing; Wang, Qian; Luo, Wenna; Liu, Qizhi; Lu, Danqi; Meng, Zining; Lin, Haoran

    2011-06-01

    It is known that the hypothalamic-pituitary-gonadal axis participates in the sex change of hermaphrodite teleosts, and gonadal steroid hormones mediate this physiological process. The secretion of gonadal steroids is directly regulated by signaling pathways involving gonadotropins (GtHs) and gonadotropin receptors (GtHRs) in teleosts. To gain insight into the involvement of GtH/GtHR systems in the sex change process, cDNAs encoding follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) were firstly isolated from gonads of orange-spotted grouper (Epinephelus coioides), a protogynous hermaphrodite fish. Reverse transcription-PCR (RT-PCR) analysis demonstrated that the expression of the FSHR was confined to the brain, pituitary gland, ovary, and testis, while the LHR was expressed only in the brain, ovary, and testis. Furthermore, the expression profiles of GtH subunits (FSHβ and LHβ) and their receptors were analyzed in parallel with the serum levels of estradiol-17β (E(2) ), testosterone (T), and 11-ketotestosterone (11-KT) during 17α-methyltestosterone (MT)-induced sex change. Quantitative real-time PCR determined that the abundances of FSHβ and FSHR were significantly inhibited after MT treatment for 2 and 4 weeks, but subsequently returned to the control level after 6 weeks. In contrast, the mRNA levels of LHβ and LHR were significantly elevated throughout the sex change process. During MT-induced sex change, serum concentrations of E(2) remained constant while T and 11-KT levels were significantly increased. Taken together, our results suggest that GtH/GtHR systems are involved in MT-induced sex change, and two signaling pathways may have distinct roles in modulating the variations of the corresponding steroid hormones in the orange-spotted grouper. PMID:21567650

  2. VMAT QA: Measurement-guided 4D dose reconstruction on a patient

    SciTech Connect

    Nelms, Benjamin E.; Opp, Daniel; Robinson, Joshua; Wolf, Theresa K.; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

    2012-07-15

    Purpose: To develop and validate a volume-modulated arc therapy (VMAT) quality assurance (QA) tool that takes as input a time-resolved, low-density ({approx}10 mm) cylindrical surface dose map from a commercial helical diode array, and outputs a high density, volumetric, time-resolved dose matrix on an arbitrary patient dataset. This first validation study is limited to a homogeneous 'patient.'Methods: A VMAT treatment is delivered to a diode array phantom (ARCCHECK, Sun Nuclear Corp., Melbourne, FL). 3DVH software (Sun Nuclear) derives the high-density volumetric dose using measurement-guided dose reconstruction (MGDR). MGDR cylindrical phantom results are then used to perturb the three-dimensional (3D) treatment planning dose on the patient dataset, producing a semiempirical volumetric dose grid. Four-dimensional (4D) dose reconstruction on the patient is also possible by morphing individual sub-beam doses instead of the composite. For conventional (3D) dose comparison two methods were developed, using the four plans (Multi-Target, C-shape, Mock Prostate, and Head and Neck), including their structures and objectives, from the AAPM TG-119 report. First, 3DVH and treatment planning system (TPS) cumulative point doses were compared to ion chamber in a cube water-equivalent phantom ('patient'). The shape of the phantom is different from the ARCCHECK and furthermore the targets were placed asymmetrically. Second, coronal and sagittal absolute film dose distributions in the cube were compared with 3DVH and TPS. For time-resolved (4D) comparisons, three tests were performed. First, volumetric dose differences were calculated between the 3D MGDR and cumulative time-resolved patient (4D MGDR) dose at the end of delivery, where they ideally should be identical. Second, time-resolved (10 Hz sampling rate) ion chamber doses were compared to cumulative point dose vs time curves from 4D MGDR. Finally, accelerator output was varied to assess the linearity of the 4D MGDR with

  3. Gonadotropin-releasing hormone II receptor (GnRHR-II) knockdown reduces testis size and decreases testosterone secretion during pubertal development in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The second mammalian isoform of gonadotropin-releasing hormone (GnRH-II) functions quite differently from the classical form (GnRH-I) as it is a poor stimulator of gonadotropin release. Unlike most species, a functional GnRHR-II has been identified in swine. Our laboratory detected GnRHR-IIs on Leyd...

  4. CDK5-mediated phosphorylation of p19INK4d avoids DNA damage-induced neurodegeneration in mouse hippocampus and prevents loss of cognitive functions.

    PubMed

    Ogara, María Florencia; Belluscio, Laura M; de la Fuente, Verónica; Berardino, Bruno G; Sonzogni, Silvina V; Byk, Laura; Marazita, Mariela; Cánepa, Eduardo T

    2014-07-01

    DNA damage, which perturbs genomic stability, has been linked to cognitive decline in the aging human brain, and mutations in DNA repair genes have neurological implications. Several studies have suggested that DNA damage is also increased in brain disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. However, the precise mechanisms connecting DNA damage with neurodegeneration remain poorly understood. CDK5, a critical enzyme in the development of the central nervous system, phosphorylates a number of synaptic proteins and regulates dendritic spine morphogenesis, synaptic plasticity and learning. In addition to these physiological roles, CDK5 has been involved in the neuronal death initiated by DNA damage. We hypothesized that p19INK4d, a member of the cell cycle inhibitor family INK4, is involved in a neuroprotective mechanism activated in response to DNA damage. We found that in response to genotoxic injury or increased levels of intracellular calcium, p19INK4d is transcriptionally induced and phosphorylated by CDK5 which provides it with greater stability in postmitotic neurons. p19INK4d expression improves DNA repair, decreases apoptosis and increases neuronal survival under conditions of genotoxic stress. Our in vivo experiments showed that decreased levels of p19INK4d rendered hippocampal neurons more sensitive to genotoxic insult resulting in the loss of cognitive abilities that rely on the integrity of this brain structure. We propose a feedback mechanism by which the neurotoxic effects of CDK5-p25 activated by genotoxic stress or abnormal intracellular calcium levels are counteracted by the induction and stabilization of p19INK4d protein reducing the adverse consequences on brain functions. PMID:24703879

  5. Photocatalytic oxidation of low concentration 2,4-D solution with new TiO2 fiber catalyst in a continuous flow reactor.

    PubMed

    Terashima, Y; Ozaki, H; Giri, R R; Tano, T; Nakatsuji, S; Takanami, R; Taniguchi, S

    2006-01-01

    Environmental pollution by low concentrations of 2,4-Dichlorophenoxyacetic acid (2,4-D) is a concern these days due to ever increasingly stringent regulations. Photocatalysis with immobilized TiO2 fiber is a promising oxidation method. Laboratory experiments on photocatalytic degradation of 0.045 mmol l(-1) 2,4-D with the world's first high-strength TiO2 fiber catalyst were carried out in a continuous flow reactor in which the degradations were, in general, similar to those with high 2,4-D concentrations investigated elsewhere. Degradation and mineralization of 2,4-D were significantly enhanced with no initial pH adjustments. The rate constants for total organic carbon (TOC) without pH adjustment were about two-fold bigger than the pH adjustment cases. CO2 gas measurement and carbon mass-balance were carried out for the first time, where about 34% organic carbon converted into CO2 gas during four-hour oxidation. 2,4-Dichlorophenol (2,4-DCP), phenol, benzyl alcohol and two unknowns (RT = 2.65 and 3.78 min.) were detected as aromatic intermediates while Phenol was the new aromatic in HPLC analysis. Dechlorination efficiencies were high (> 70%) in all the cases, and more than 90% efficiencies were observed in chloride mass balance. Bigger flow rates and solution temperature fixed at 20 degrees C without pH adjustment greatly enhanced 2,4-D mineralization. These results can be an important basis in applying the treatment method for dioxin-contaminated water and wastewater. PMID:17163013

  6. Chlorothalonil and 2,4-D losses in surface water discharge from a managed turf watershed.

    PubMed

    King, K W; Balogh, J C

    2010-08-01

    Managed turf sites (golf courses) are the most intensively managed landscapes in the urban environment. Yet, long-term watershed scale studies documenting the environmental transport of agrichemicals applied to these systems are rare. The objective of this study was to quantify the surface discharge losses of two commonly applied pesticides (chlorothalonil and 2,4-D) resulting from prevailing practices on a managed golf course. Inflow and outflow discharge waters on a subarea of Northland Country Club located in Duluth, MN were measured for both quantity and quality from April through November from 2003 to 2008. The median chlorothalonil outflow concentration (0.58 microg L(-1)) was significantly greater (p < 0.05) than the inflow concentration, which was below the detection limit (0.07 microg L(-1)). Similarly, the median outflow 2,4-D concentration (0.85 microg L(-1)) was significantly greater (p < 0.05) than the inflow concentration (0.31 microg L(-1)). Chlorothalonil concentrations occasionally exceeded acute toxicity levels (7.6 microg L(-1)) reported for rainbow trout. No 2,4-D concentrations exceeded any human or aquatic species published toxicity level; however, the maximum measured 2,4-D concentration (67.1 microg L(-1)), which rarely occurred, did approach the 70 microg L(-1) maximum contaminant level (MCL) for that compound. Losses of both pesticides were detectable throughout the annual sampling period. Mean annual chlorothalonil loading was 10.5 g ha(-1) or 0.3% of applied, while mean annual 2,4-D loading was 4.9 g ha(-1) or 0.5% of applied. The findings of this study provide quantifiable evidence of agrichemical transport resulting from typical turfgrass management and highlight the need for implementation of best management practices to combat the offsite transport of agrichemicals used in professional turf management. PMID:20526481

  7. 4D/RCS: a reference model architecture for intelligent unmanned ground vehicles

    NASA Astrophysics Data System (ADS)

    Albus, James S.

    2002-07-01

    4D/RCS consists of a multi-layered multi-resolutional hierarchy of computational nodes each containing elements of sensory processing (SP), world modeling (WM), value judgment (VJ), and behavior generation (BG). At the lower levels, these elements generate goal-seeking reactive behavior. At higher levels, they enable goal-defining deliberative behavior. At low levels, range in space and time is short and resolution is high. At high levels, distance and time are long and resolution is low. This enables high-precision fast-action response over short intervals of time and space at low levels, while long-range plans and abstract concepts are being formulated over broad regions of time and space at high levels. 4D/RCS closes feedback loops at every level. SP processes focus attention (i.e., window regions of space or time), group (i.e., segment regions into entities), compute entity attributes, estimate entity state, and assign entities to classes at every level. WM processes maintain a rich and dynamic database of knowledge about the world in the form of images, maps, entities, events, and relationships at every level. Other WM processes use that knowledge to generate estimates and predictions that support perception, reasoning, and planning at every level. 4D/RCS was developed for the Army Research Laboratory Demo III program. To date, only the lower levels of the 4D/RCS architecture have been fully implemented, but the results have been extremely positive. It seems clear that the theoretical basis of 4D/RCS is sound and the architecture is capable of being extended to support much higher levels of performance.

  8. [Effects of EDTA on the Reductive Dechlorination of 2,4-D by Pd/Fe].

    PubMed

    Zhou, Hong-yi; Nie, Ya-zhong; Chen, Yong; Lei, Shuang-jian

    2016-02-15

    In Pd/Fe system, zero-valent iron (ZVI) passivation layer is easily formed on the particle surface during the catalytic reductive dechlorination of chlorinated organics, hindering further dechlorination of target contaminants. In this paper, the passivation layer on the Pd/Fe particle surfaces could be eliminated by the chelation of disodium edetate (EDTA) with Fe2+, Fe3+, making the reductive dechlorination continue. The experiment investigated the effects of EDTA addition manner and dosage, pH, Pd loading and temperature on dechlorination of 2,4-dichlorophenoxyacetic acid (2,4-D) by Pd/Fe. The conclusions can be summarized as follows: (1) Phenoxyacetic acid (PA) generation ratio reached 90. 7% within 20 min with EDTA concentration of 25.0 mmol x L(-1) and flow rate of 20 mL x h(-1), while it was only 74.5% after 210 min in the system without EDTA. (2) The EDTA could chelate the Fe2+ and Fe3+ generated from the process of 2,4-D dechlorination by Pd/Fe, preventing or slowing down the formation of passivation layer, and accelerating the reduction efficiency. (3) The appropriate experimental parameters for 2,4-D removal were as follows: EDTA flow rate of 20 mL x h(-1), CEDTA of 25.0 mmol x L(-1), Pd loading of 0.050%, 200 r x min(-1), pH 4.2 and 30.0 degrees C. The removal percentage of 20.0 mg x L(-1) 2,4-D reached nearly up to 100% within 210 min under these conditions. (4) The intermediates of 2, 4-D catalytic dechlorination included 2-chlorophenoxvacetic acid (2-CPA) and trace 4-chloronhenoxyacetic acid (4-CPA), and the end product was PA. PMID:27363149

  9. Soil depth and temperature effects on microbial degradation of 2,4-D

    SciTech Connect

    Veeh, R.H.; Camper, A.K.; Inskeep, W.P.

    1996-01-01

    Numerous soil factors and climatic conditions affect the degradation rate of pesticides in soils. A major soil factor influencing herbicide degradation is the composition and abundance of the microbiota, which has been shown to vary considerably with soil depth. Another important variable affecting microbial growth and degradation kinetics is temperature. Soil samples from 0- to 30-, 30- to 60-, and 60- to 120-cm depths of two Montana soils were placed in reaction flasks and treated with {sup 14}C-labeled 2,4-D at representative field use rates at temperatures of 10, 17, and 24{degrees}C. A carrier gas was used to continuously evacuate evolved {sup 14}CO{sub 2} into NaOH traps as a measure of 2,4-D degradation. Comparisons of the effects of soil depth and temperature were made by fitting experimental data to both first-order and logistic kinetic models. Degradation rates of 2,4-D decreased significantly with increasing soil depth and were positively correlated with bacterial plate counts. Effects of temperature on degradation rate constants were adequately described using the Arrhenius equation. Degradation rates of 2,4-D and bacterial enumerations were positively correlated with changes in soil organic C as a function of soil depth. These results support the idea that changes in organic C with soil depth could be used as a parameter for estimating changes in degradation rate as a function of soil depth. Efforts to model the transport of 2,4-D in soils should account for variation in degradation rate as a function of soil depth and temperature. 46 refs., 4 figs., 3 tabs.

  10. Graph-based retrospective 4D image construction from free-breathing MRI slice acquisitions

    NASA Astrophysics Data System (ADS)

    Tong, Yubing; Udupa, Jayaram K.; Ciesielski, Krzysztof C.; McDonough, Joseph M.; Mong, Andrew; Campbell, Robert M.

    2014-03-01

    4D or dynamic imaging of the thorax has many potential applications [1, 2]. CT and MRI offer sufficient speed to acquire motion information via 4D imaging. However they have different constraints and requirements. For both modalities both prospective and retrospective respiratory gating and tracking techniques have been developed [3, 4]. For pediatric imaging, x-ray radiation becomes a primary concern and MRI remains as the de facto choice. The pediatric subjects we deal with often suffer from extreme malformations of their chest wall, diaphragm, and/or spine, as such patient cooperation needed by some of the gating and tracking techniques are difficult to realize without causing patient discomfort. Moreover, we are interested in the mechanical function of their thorax in its natural form in tidal breathing. Therefore free-breathing MRI acquisition is the ideal modality of imaging for these patients. In our set up, for each coronal (or sagittal) slice position, slice images are acquired at a rate of about 200-300 ms/slice over several natural breathing cycles. This produces typically several thousands of slices which contain both the anatomic and dynamic information. However, it is not trivial to form a consistent and well defined 4D volume from these data. In this paper, we present a novel graph-based combinatorial optimization solution for constructing the best possible 4D scene from such data entirely in the digital domain. Our proposed method is purely image-based and does not need breath holding or any external surrogates or instruments to record respiratory motion or tidal volume. Both adult and children patients' data are used to illustrate the performance of the proposed method. Experimental results show that the reconstructed 4D scenes are smooth and consistent spatially and temporally, agreeing with known shape and motion of the lungs.

  11. Fully 4D list-mode reconstruction applied to respiratory-gated PET scans

    NASA Astrophysics Data System (ADS)

    Grotus, N; Reader, A J; Stute, S; Rosenwald, J C; Giraud, P; Buvat, I

    2009-03-01

    18F-fluoro-deoxy-glucose (18F-FDG) positron emission tomography (PET) is one of the most sensitive and specific imaging modalities for the diagnosis of non-small cell lung cancer. A drawback of PET is that it requires several minutes of acquisition per bed position, which results in images being affected by respiratory blur. Respiratory gating techniques have been developed to deal with respiratory motion in the PET images. However, these techniques considerably increase the level of noise in the reconstructed images unless the acquisition time is increased. The aim of this paper is to evaluate a four-dimensional (4D) image reconstruction algorithm that combines the acquired events in all the gates whilst preserving the motion deblurring. This algorithm was compared to classic ordered subset expectation maximization (OSEM) reconstruction of gated and non-gated images, and to temporal filtering of gated images reconstructed with OSEM. Two datasets were used for comparing the different reconstruction approaches: one involving the NEMA IEC/2001 body phantom in motion, the other obtained using Monte-Carlo simulations of the NCAT breathing phantom. Results show that 4D reconstruction reaches a similar performance in terms of the signal-to-noise ratio (SNR) as non-gated reconstruction whilst preserving the motion deblurring. In particular, 4D reconstruction improves the SNR compared to respiratory-gated images reconstructed with the OSEM algorithm. Temporal filtering of the OSEM-reconstructed images helps improve the SNR, but does not achieve the same performance as 4D reconstruction. 4D reconstruction of respiratory-gated images thus appears as a promising tool to reach the same performance in terms of the SNR as non-gated acquisitions while reducing the motion blur, without increasing the acquisition time.

  12. Trauma-related altered states of consciousness: exploring the 4-D model.

    PubMed

    Frewen, Paul A; Lanius, Ruth A

    2014-01-01

    Frewen and Lanius (in press) recently articulated a 4-D model as a framework for classifying symptoms of posttraumatic stress into those that potentially occur within normal waking consciousness (NWC) versus those that intrinsically represent dissociative experiences of trauma-related altered states of consciousness (TRASC). Four dimensions were specified: time-memory, thought, body, and emotion. The 4-D model further hypothesizes that in traumatized persons, symptoms of TRASC, compared with NWC forms of distress, will be (a) observed less frequently; (b) less intercorrelated, especially as measured as moment-to-moment states; (c) observed more frequently in people with high dissociative symptomatology as measured independently; and (d) observed more often in people who have experienced repeated traumatization, particularly early developmental trauma. The aim of the present research was to begin to evaluate these 4 predictions of the 4-D model. Within a sample of 74 women with posttraumatic stress disorder (PTSD) primarily due to histories of childhood trauma, as well as within a 2nd sample of 504 undergraduates (384 females), the 1st 2 hypotheses of the 4-D model were supported. In addition, within the PTSD sample, the 3rd hypothesis was supported. However, inconsistent with the 4th hypothesis, severity of childhood trauma history was not strongly associated with TRASC. We conclude that the hypotheses articulated by the 4-D model were generally supported, although further research in different trauma-related disorders is needed, and the role of childhood trauma history in the etiology of TRASC requires further research. PMID:24650122

  13. Nitric oxide mediates gonadotropin-releasing hormone effects on frog pituitary.

    PubMed

    Gobbetti, A; Zerani, M

    1998-06-01

    We studied the possible role of nitric oxide (NO) in GnRH-induced gonadotropin secretion in the female water frog, Rana esculenta. During pre-reproduction, pre-ovulation, ovulation, post-ovulation, refractory, recovery and hibernation, pituitaries were incubated with medium-alone, GnRH, NO donor (NOd), NO synthase inhibitor (NOSi), cyclic GMP analogue (cGMPa), soluble guanylate cyclase inhibitor (sGCi), GnRH plus NOSi, GnRH plus sGCi, and NOd plus sGCi. Because antisera raised against gonadotropins are not available for this species, we measured these hormones indirectly through their effects on ovarian progesterone secretion. The ovaries were superfused with the pituitaries pre-incubated as reported above. In addition, NOS activity and cGMP levels were determined in the pre-incubated pituitaries. Those pre-incubated with medium-alone and with GnRH increased progesterone secretion during pre-reproduction, pre-ovulation, ovulation and recovery; the increase induced by GnRH was higher than that induced by medium-alone during pre-reproduction, pre-ovulation and recovery. NOd and cGMPa increased progesterone in all considered reproductive phases except ovulation; the increase induced by NOd and cGMP was higher than that induced by medium-alone during pre-reproduction, pre-ovulation and recovery. NOS activity was highest during ovulation and lowest during post-ovulation, refractory and hibernation. GnRH increased NOS activity during pre-reproduction, pre-ovulation and recovery. Cyclic GMP levels were highest during ovulation and lowest during post-ovulation, refractory and hibernation. GnRH increased cGMP levels during pre-reproduction, pre-ovulation and recovery, NOd during all considered reproductive phases. These results suggest that NO mediates basal and GnRH-induced gonadotropin secretion in female Rana esculenta. PMID:9688343

  14. Gonadotropin-inhibitory hormone receptor signaling and its impact on reproduction in chickens.

    PubMed

    Bédécarrats, Grégoy Y; McFarlane, Heather; Maddineni, Sreenivasa R; Ramachandran, Ramesh

    2009-09-01

    In birds, as in other vertebrates, reproduction is controlled by the hypothalamo-pituitary-gonadal axis with each component secreting specific neuropeptides or hormones. Until recently, it was believed this axis is exclusively under the stimulatory control of hypothalamic gonadotropin-releasing hormone I (GnRH-I) which in turn, stimulates luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from the pituitary gland. However, the discovery of a novel inhibitory hypothalamic peptide able to reduce LH secretion (gonadotropin-inhibitory hormone: GnIH) challenged this dogma. Furthermore, with the characterization of its specific receptor (GnIHR), progress has been made to clarify the physiological relevance of GnIH in birds. This short review discusses the recent advances in GnIHR signaling at the level of the pituitary gland and the gonads. GnIHR is a member of the G-protein coupled receptor (GPCR) family which couples to G(alphai) and, upon activation inhibits adenylyl cyclase (AC) activity, thus reducing intracellular cAMP levels. This implies that GnIH interferes with signaling of any GPCR coupled to G(alphas), including GnRH, LH and FSH receptors. In the chicken pituitary gland, the GnRHR-II/GnIHR ratio changes during sexual maturation in favor of GnRHR-II that appears to result in hypothalamic control of gonadotropin secretion shifting from inhibitory to stimulatory, with corresponding changes in GnRH-induced cAMP levels. Within the gonads, GnIH and its receptor may act in an autocrine/paracrine manner and may interfere with LH and FSH signaling to influence ovarian follicular maturation and recruitment, as